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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.

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

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).

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

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

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 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.

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.

Background and Aims This study evaluated the minimal clinically important short-term improvement in the Modified Multiplier Simple Endoscopic Score for crohn’s Disease [MM-SES-CD], a novel modified scoring system of the SES-CD, which reliably predicted 1-year endoscopic remission [ER]. Methods This post-hoc analysis of two CD clinical trial programmes pooled data of 198 participants with baseline ulcers and SES-CD ≥3, who had baseline, post-induction [8–12 weeks], and 1-year endoscopic assessments. Different cut-off values for endoscopic response were evaluated using receiver operating characteristic [ROC] curves, positive likelihood ratios [PLR], and negative likelihood ratios [NLR]. ER [SES-CD Results MM-SES-CD ≥40% reduction from baseline was selected as the cut-off maximising PLR and minimising NLR. Among 7.6% [15/198] participants achieving this cut-off post-induction, 1-year ER was 46.7%. One-year ER was 16.9% among those not achieving this cut-off. This threshold predicted 1-year ER with 95.0% (95% confidence interval [CI] 90.4%–97.8%) specificity and a PLR of 3.7 [95% CI 1.4–9.5], which was higher than traditional endoscopic response criteria of SES-CD ≥50% reduction [specificity 62.5%, 95% CI 54.5%–70.0%; PLR 1.9, 95% CI 1.4–2.5]. Lower thresholds of MM-SES-CD reduction also were highly specific for 1-year ER [e.g., MM-SES-CD ≥20% reduction was achieved in 19.7% of patients with 83.1% specificity]. Conclusions In CD patients, post-induction endoscopic response defined by MM-SES-CD ≥40% reduction from baseline identified patients most likely to achieve 1-year ER.

ObjectiveTo assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality.MethodsIn the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation of infection, showing non-inferiority. Haemoglobin (Hgb) levels were measured at randomisation. Primary outcomes were all-cause mortality after 6 months and 3 years. Patients who underwent valve surgery were excluded due to competing reasons for anaemia.ResultsOut of 400 patients with IE, 248 (mean age 70.6 years (SD 11.1), 62 women (25.0%)) were medically managed; 37 (14.9%) patients had no anaemia, 139 (56.1%) had mild anaemia (Hgb ConclusionModerate to severe anaemia was present in 29% of patients with medically treated IE after stabilisation of infection and was independently associated with higher mortality within the following 3 years. Further investigations are warranted to determine whether intensified treatment of anaemia in patients with IE might improve outcome.

Objectives Our aim in this work was to document sleep/insomnia, fruit and vegetable (FV) consumption and physical activity (PA) according to diabetes presence and type and biologic sex, as these 3 lifestyle habits may influence glycemic control and prevention of diabetes-related complications. Methods Adults between 18 and 64 years of age were invited to complete validated web-based self-reported questionnaires assessing sleep, insomnia, FV consumption and PA. Pregnant women and shift workers were excluded from the study. Results A total of 151 adults (80.1% women), of whom 54 had diabetes (type 1 [T1D], n=30; type 2 [T2D], n=24), completed the questionnaires. Sleep quality scores were significantly higher, indicating poorer sleep quality, according to diabetes presence (diabetes, 7.2±3.5; no diabetes, 5.4±3.5; p=0.0024) and type (T1D, 6.1±2.9; T2D, 8.7±3.8; p=0.0072). Sleep duration was significantly shorter among adults living with diabetes (diabetes, 7.0±1.7 hours/night; no diabetes, 7.8±1.3 hours/night; p=0.0019), regardless of type. More adults living with diabetes had moderate to severe clinical insomnia (diabetes, 25.9%; no diabetes, 10.4%; p=0.0129), especially those with T2D (T1D, 13.3%; T2D, 41.7%; p=0.0182). FV consumption and PA did not vary significantly according to diabetes presence and type. Only PA differed by biologic sex, with lower PA among women. Conclusions The results suggest that adults living with diabetes, especially those with T2D, are at higher risk for short and poor sleep quality, and clinical insomnia. Adults living with diabetes, especially those with T2D, should have access to effective sleep interventions to prevent complications associated with elevated glucose levels.

Traumatic brain injury (TBI) is a major clinical and public health problem with few therapeutic interventions successfully translated to the clinic. Identifying imaging-based biomarkers characterizing injury severity and predicting long-term functional and cognitive outcomes in TBI patients is crucial for treatment. TBI results in white matter (WM) injuries, which can be detected using diffusion tensor imaging (DTI). Trauma-induced pathologies lead to accumulation of free water (FW) in brain tissue, and standard DTI is susceptible to the confounding effects of FW. In this study, we applied FW DTI to estimate free water volume fraction (FW-VF) in patients with moderate-to-severe TBI and demonstrated its association with injury severity and long-term outcomes. DTI scans and neuropsychological assessments were obtained longitudinally at 3, 6, and 12 months post-injury for 34 patients and once in 35 matched healthy controls. We observed significantly elevated FW-VF in 85 of 90 WM regions in patients compared to healthy controls (p

Psoriasis is a common inflammatory disorder with potentially severe systemic and dermatologic consequences. As traditional treatments for this condition fail, biologics are emerging as the next promising therapy for moderate-to-severe cases, especially for the lower extremity. This review examines current research on monoclonal antibodies that target specific cytokines including interleukin-23 (IL-23), IL-12, tumor necrosis factor alpha, and IL-17 involved in pathologic inflammatory processes.

Background Surgeons performing Minimally Invasive Surgery (MIS) report significant neck/shoulder problems and visual symptoms. Headache is another commonly reported symptom but publications about the characteristics and associated risk factors are limited. Purpose of the study To determine the characteristics of headache among MIS surgeons and the associations of headache with neck/shoulder problems, visual symptoms and other associated factors. Design A cross-sectional study. Methods A comprehensive online survey was sent to MIS surgeons inclusive of 63 questions about individual and workplace physical factors, characteristics of headache, neck/shoulder problems and visual symptoms. Binary logistic regression models were conducted to determine the associations of the prevalence and severity of headache with risk factors. The main findings Headaches in the last 7 days were reported by 36% of surgeons, with 37% of these of moderate to severe intensity. Frequent intense headaches were often preceded by neck pain. Surgeons with headache were eight times more likely to also experience visual symptoms and four times more likely to experience neck/shoulder problems. Several factors (frequently adopting forward head movement, surgical specialty, sex and age) were significantly associated with headaches (p ≤ 0.05). Conclusions This study revealed headaches were present in one-third of MIS surgeons. During surgery, surgeons report adopting non-neutral neck/shoulder/head positions, which may explain headaches, neck/shoulder problems and visual symptoms. Evidence based strategies to assist surgeons better manage these symptoms are warranted.

Background: Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting. Objective: To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation. Methods: This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation. Results: A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group ( P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population ( P = 0.55). No fatal bleeding or thromboembolic events occurred. Conclusion and Relevance: DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.

PURPOSE Our study aims to examine the midterm outcomes of the loop technique for extended mitral valve (MV) prolapse patients. METHODS From October 2008 to August 2020, we performed MV repairs in 407 patients with severe mitral regurgitation (MR). Follow-up ranged in duration from 287 to 2899 days (median, 872 days). The prolapse extensiveness (p-score) was determined based on the ratio of prolapsing segment's areas to whole area. We divided the whole MV into 10 segments (A1, A2 medial, A2 lateral, A3, P1, P2 medial, P2 lateral, P3, AC, and PC). Patients were categorized into three groups according to the p-score: simple (0.1-0.2), intermediate (0.3-0.4), and extensive (0.5-0.9). RESULTS All patients underwent MV repair with the loop technique. The rates of freedom from significant (moderate to severe or severe) MR at 5 and 7 years after surgery were 91% and 91%, respectively. There were 252, 115, and 40 patients in simple group, intermediate group, and extensive group, respectively. The following were significantly increased in extended group: Barlow disease (23/40 patients, p

The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot remains unknown.We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for soft-tissue infections of the diabetic foot results in similar rates of clinical remission and adverse events (AE).The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace.This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of "clinical remission at 2-months follow-up".Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm ( P = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; P = 0.71), and remission in the per-protocol population (25/32 vs 18/27; P = 0.32). Overall, 8 soft tissue DFIs in the 10-day arm and 5 cases in the 20-day arm recurred as a new osteomyelitis [8/35 (23%) versus 5/31 (16%); P = 0.53]. Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (intention-to-treat population, hazard ratio 0.6, 95%CI 0.3-1.1; per-protocol population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course.In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way.ClinicalTrials NCT03615807.

Objectives Although the efficacy of the addition of ipratropium bromide (IB) to short-acting β2-agonists (SABAs) for treating children with moderate to severe asthma exacerbations has been demonstrated, evidence of its cost-effectiveness is scarce. The aim of the present study was to evaluate the cost-effectiveness of treatment with a combination of SABAs and IB compared with SABAs alone for the treatment of children with moderate to severe asthma exacerbations. Methods To achieve the objectives of the study, a decision-analysis model was adapted. Effectiveness parameters were obtained from a systematic review of the literature with meta-analysis. Cost data were obtained from hospital bills and from the national manual of drug prices in Colombia. The study was carried out from the perspective of the national healthcare system in Colombia. The main outcome of the model was avoidance of hospital admission. Results In children with moderate to severe asthma exacerbations, the base-case analysis showed that compared to SABAs alone, treatment with a combination of SABAs and IB was associated with lower overall treatment costs (US$126.24 vs. US$170.69 mean cost per patient) and a higher probability of hospital admission avoided (0.7999 vs. 0.7100), thus leading to dominance. For children with severe asthma exacerbations, these values were US$132.99 versus US$170.69 and 0.7883 versus 0.7100, respectively. Conclusions In Colombia, when compared to therapy with SABAs alone, therapy with a combination of SABAs and IB for treating pediatric patients with moderate to severe asthma exacerbations involves a lower probability of hospital admission at lower treatment costs.

Background It is not clear which method is more cost-effective: To initially provide all depressed patients with combination therapy (COMB; i.e. cognitive behavioural therapy plus pharmacotherapy), followed by antidepressant treatment (AD) for those still in depression; or, to first provide AD for all patients, followed by COMB for non-remission patients. The aim is to investigate whether a COMB-first strategy would be more cost-effective than an AD-first strategy, in treating depression. Methods A Markov model was developed to perform the analysis. The primary outcome was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) at 104 weeks. Probabilistic sensitivity analysis and scenario analysis were performed, to investigate the uncertainty associated with the clinical parameters and the impact of CBT's cost on the results, respectively. Results The ICER per QALY at 104 week, was JPY 591,822 (USD 5,725) for moderate depression and JPY 499,487 (USD 4,832) for severe one. The scenario analysis revealed the ICER became JPY 1,147,518 (USD 11,101) for moderate and JPY 968,484 (USD 9,369) for severe when the CBT cost was set as JPY 14,400 (USD 139)(i.e. GBP 96: the unit cost of CBT in UK), which is well below the threshold recommended by NICE (i.e. GBP 20,000–30,000). Limitations This is a model-based analysis which was conducted from the health insurance perspective. Then, the analysis from the societal perspective would generate different results. Conclusions The results suggest that a COMB-first strategy would be more cost effective than an AD-first strategy.

Background This study sought to classify the level of quality of life in patients with moderate to severe hand trauma, and explore differences in their potential profile characteristics based on the Patient-Reported Outcomes Measurement Information System (PROMIS). Methods This was a survey research. A convenience sampling method was used to investigate 296 patients with moderate to severe hand trauma. A general information questionnaire (which was used to gather general demographic data and disease-related data) and PROMIS-57 were administered form November 2020 to May 2021. A latent profile analysis and Chi square test were conducted to analyze the data. Results Based on quality of life, patients with moderate to severe hand trauma were divided into the following 3 groups: (I) Group C1: the psychosocial-pain low-impact group (38.9%); (II) Group C2: the psychosocial-moderate-impact severe-pain group (43.9%); and (III) Group C3: the psychosocial-pain high-impact group (17.2%). There were significant differences in the distribution of age, educational level, marital status, occupation, monthly income, medical insurance type, family role, subsequent financial resources, cause of the injury, satisfaction with the appearance of the hand, degree of the injury, and impact of the injury on daily life among patients in the different groups (P Conclusions The quality of life in patients with moderate to severe hand trauma can be identified to provide precise care.

Burnout has been previously assessed in head and neck microvascular reconstructive surgeons (HNMVS), but not in the context of modifiable workplace factors.Anonymous, cross-sectional survey. The Abbreviated Maslach Burnout Inventory - Human Services Survey for Medical Personnel (aMBI-HSS) was utilized to assess emotional exhaustion (EE), depersonalization (DP), and personal achievement (PA). Modifiable risk factors were also evaluated.High risk of burnout by EE, DP, and PA was demonstrated in 24%, 9%, and 27% of respondents, respectively. EE was associated with10% dedicated research time, lack of autonomy over clinic schedule, inadequate inpatient support, and lack of supportive clinical partner. DP was associated with3 operative days, difficulty balancing academic commitments, and lack of supportive clinical partner. Dedicated research time and two or fewer days of block time were protective.Burnout was associated with several modifiable workplace factors. Addressing these may prevent moderate to severe burnout in HNMVS.

Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. Though corticosteroids are the cornerstone of therapy, the Janus kinase inhibitor abrocitinib has shown promise in recent clinical trials for the treatment of AD.To assess the overall efficacy and safety of abrocitinib in moderate to severe AD.All randomized controlled trials (RCTs) evaluating the efficacy and safety of abrocitinib in moderate to severe AD were included in the meta-analysis.The pooled analysis revealed a significant proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.52, 95% CI; 2.78-4.46,This meta-analysis showed that abrocitinib had a significant beneficial effect and tolerable adverse effect profile in patients of AD. Dose regimens of 200 and 100 mg seemed to have similar benefits. However, long-term trials are needed for corroboration.Key pointsAbrocitinib is emerging as a potential treatment option for moderate to severe atopic dermatitis.The pooled analysis from 4 RCTs demonstrated significant effectiveness of abrocitinib in both physician and patient-reported outcomes like IGA, EASI, and PP-NRS. The drug was also well-tolerated across the trials.The number needed to treat (NNT) for all efficacy outcomes was low suggesting clinically desirable benefits with the use of abrocitinib.

BackgroundThe significance of spiritual care needs among chronic diseases patients has been emphasized across countries and cultures in many studies. However, there were few studies on spiritual care needs among elderly patients with moderate-to-severe chronic heart failure (CHF) in China.ObjectiveTo investigate spiritual care needs and associated influencing factors among elderly patients with moderate-to-severe CHF, and to examine the relationships among spiritual care needs, self-perceived burden, symptom management self-efficacy, and perceived social support.MethodsA cross-sectional design was implemented, and the STROBE Checklist was used to report the study. A convenience sample of 474 elderly patients with moderate-to-severe CHF were selected from seven hospitals in Tianjin, China. The sociodemographic characteristics questionnaire, the Spiritual Needs Questionnaire Scale, the Self-Perceived Burden Scale, the Self-efficacy for Symptom Management Scale, and the Perceived Social Support Scale were used. Descriptive statistics, univariate, multiple linear regression, and Pearson's correlation analysis were used to analyze data.ResultsThe total score of spiritual care needs among 474 elderly patients with moderate-to-severe CHF was 37.95 ± 14.71, which was moderate. Religious belief, educational background, self-perceived burden, symptom management self-efficacy, and perceived social support were the main factors affecting spiritual care needs, and spiritual care needs were negatively correlated with self-perceived burden (r = −0.637, p < 0.01) and positively correlated with symptom management self-efficacy (r = 0.802, p < 0.01) and social support (r = 0.717, p < 0.01).Significance of resultsThe spiritual care needs of elderly patients with moderate-to-severe CHF were moderate, which were influenced by five factors. It is suggested that clinical nurses, families, and society should take targeted spiritual care measures to improve patients’ symptom management self-efficacy and perceived social support from many aspects, and reduce self-perceived burden to meet their spiritual care needs and improve the quality and satisfaction of spiritual care in nursing practice.

Purpose Guselkumab, an interleukin (IL)-23 inhibitor, effectively treats moderate-to-severe plaque psoriasis. Materials and methods ECLIPSE, was a Phase 3, multicenter, 56-week, double-blinded, active-comparator study of guselkumab vs. secukinumab (IL-17A inhibitor) in patients with moderate-to-severe psoriasis. Patients were treated with guselkumab 100 mg (n = 534) or secukinumab 300 mg (n = 514) through week 44. Efficacy (at least a 90% and 100% improvement from baseline in Psoriasis Area and Severity Index [PASI 90 and PASI 100], Investigator's Global Assessment [IGA] 0/1, and IGA 0) was analyzed across subpopulations defined by baseline: age ( Results Overall, 1048 patients were randomized. At week 48, numerically greater proportions of patients achieved PASI 90, PASI 100, IGA 0/1, and IGA 0 with guselkumab vs. secukinumab regardless of baseline age, body weight, BMI, disease severity, body region, and prior medication. The largest differences were in patients ≥65 years old and patients weighing >100 kg. Conclusions Guselkumab treatment provided greater efficacy vs. secukinumab at week 48 in most subpopulations of patients with psoriasis.

Kellgren-Lawrence grades (KLG) are frequently used for patient selection in clinical trials. The Ahlback radiographic grading system has been developed for moderate and severe knee OA. KLG 3 is comparable to Ahlback 1 and KLG 4 is subdivided into Ahlback 2–5. The objective of this study was to investigate if the Ahlback scoring system is able to subdivide patients with moderate to severe knee OA (KLG 3/4) into groups with different sensitivity to change in cartilage thickness. This study was based on 108 Osteoarthritis Initiative (OAI) participants with KLG 3/4. Baseline KLG scores were available from the OAI database; Ahlback scores were performed using the same x-rays. Cartilage thickness change in the weight-bearing femorotibial cartilage was analysed from baseline and year 1 3D FLASH MRI for the entire femorotibial joint (FTJ), the medial (MFTC) and the lateral compartment (LFTC) and for the location-independent ordered values 1 and 16 (OV 1/OV 16) representing the subregions with largest loss (OV 1) and gain (OV 16) within each knee. Of the 108 patients, n = 30/78 had KLG 3/4. The corresponding Ahlback scores (1–5) were n = 30/33/36/9/10. Cartilage thickness changes between Ahlback groups showed no statistically significant difference for FTJ, MFTC, LFTC and OV 1, but change in OV 16 was significantly higher in Ahlback 4 knees (p = 0.03) compared to Ahlback 1–3 knees. Radiographic knee OA grading with Ahlback scores was not superior to KLG for prediction of cartilage thickness loss over 1 year, in patients with moderate and severe knee OA supporting the continuous use of the easier and more widely used KLG.

Dupilumab is a relatively new treatment option for patients with moderate to severe atopic dermatitis. There is a lack of knowledge about the effects of treatment with dupilumab during conception for both men and women, as well as during pregnancy and lactation in women. We report four patients (two men, two women) who expressed a wish to conceive during treatment with dupilumab in daily practice. Both men conceived during dupilumab treatment, while the two women discontinued dupilumab because of anticipated pregnancy. Apart from disease flares in both of the patients who discontinued treatment, no complications were reported concerning the ability to conceive, the course of the pregnancy or the fetal outcome. We present an overview of the current available literature on dupilumab during conception, pregnancy and lactation, which can guide considerations for patients on dupilumab wishing to conceive a child. Until more data are available, preference should be given to treatment with topical corticosteroids, phototherapy, systemic corticosteroids and ciclosporin.

Objective We systematically reviewed the evidence of published original research to determine the role of remdesivir in the management of patients with COVID-19 and a moderate-to-severe course of illness. Methods A systematic search of articles was conducted in scientific databases, with the latest update in May 2021. This paper systematically reviewed the clinical evidence available (randomized controlled trials, compassionate use studies, and case reports) on the use of remdesivir for patients with moderate or severe COVID-19. Results A total of eleven studies were included: four studies based on compassionate use of remdesivir, three randomized, double-blind, placebo-controlled, multicentre trials, three randomized, open-label, phase III trials, and one case report. Clinical improvement and mortality rates in patients who used remdesivir varied across studies. Conclusion Given the current evidence, there is insufficient data to confidently recommend the use of remdesivir alone for the treatment of adult hospitalized patients with moderate-to-severe COVID-19. However, remdesivir may be considered along with an anti-inflammatory agent in patients with pneumonia, on oxygen support, provided there is close monitoring of clinical and laboratory parameters and adverse events.

Introduction Peppermint oil is often used to treat irritable bowel syndrome (IBS); however, the overall quality of previous studies is low, and findings have been heterogeneous. This study aimed to compare the effects of peppermint oil vs placebo in relieving IBS symptoms. Methods In a 6-week, randomized, double-blind, placebo-controlled trial at a single academic center in the United States, individuals diagnosed with IBS (Rome IV criteria), with moderate to severe symptoms based on the IBS Severity Scoring System (IBS-SSS score ≥175), were randomized to enteric-coated peppermint oil 180 mg 3 times daily vs placebo in a 1:2 ratio. The primary outcome was mean change in IBS-SSS scores from baseline to 6-week endpoint. Results A modified intent-to-treat analysis revealed that there were substantial mean improvements from baseline to 6-week endpoint in the main outcome measure (IBS-SSS) for both peppermint oil (90.8, SD = 75.3) and placebo (100.3, SD = 99.6). Although the peppermint oil group reported numerically lower improvement than the placebo group, the effect size was small (d = -0.11), and the difference between the groups was not statistically significant (P = 0.97). Similarly, both groups reported substantial improvements on the secondary endpoints; but again, there were no statistically significant differences between the groups on any of the secondary measures. Sensitivity analyses using multiple imputation to replace missing data produced similar results and revealed no significant differences between peppermint oil and placebo on any outcome measure. Discussion Peppermint oil and placebo both showed clinically meaningful improvement in IBS symptoms. However, there were no significant differences between the groups. Further large, rigorous trials are needed to evaluate the role of peppermint oil for the treatment of IBS.

BACKGROUND Acute wheezing is one of the most common hospital presentations for young children. Respiratory syncytial virus (RSV) and rhinovirus (RV) species A, B and the more recently described species C are implicated in the majority of these presentations. However, the relative importance and age-specificities of these viruses have not been defined. Hence, this study aimed to establish these relationships in a large cohort of prospectively recruited hospitalized children. METHODS The study cohort was 390 children 0-16 years of age presenting with acute wheezing to a children's emergency department, 96.4% being admitted. A nonwheezing control population of 190 was also recruited. Nasal samples were analyzed for viruses. RESULTS For the first 6 months of life, RSV was the dominant virus associated with wheezing (P < 0.001). From 6 months to 2 years, RSV, RV-A and RV-C were all common but none predominated. From 2 to 6 years, RV-C was the dominant virus detected (50-60% of cases), 2-3 times more common than RV-A and RSV, RSV decreasing to be absent from 4 to 7 years. RV-B was rare at all ages. RV-C was no longer dominant in children more than 10 years of age. Overall, RV-C was associated with lower mean oxygen saturation than any other virus (P < 0.001). Controls had no clear age distribution of viruses. CONCLUSION This study establishes a clear profile of age specificity of virus infections causing moderate to severe wheezing in children: RSV as the dominant cause in the first 6 months and RV-C in preschool-age children.

BACKGROUND Bullying is destructive and pervasive. Although the literature suggests children with chronic health conditions are at higher risk of being bullied, there is minimal research regarding the prevalence of bullying among children with orthopaedic conditions. Our study aimed to assess the prevalence of bullying among pediatric orthopaedic outpatients and evaluate the association of orthopaedic conditions and use of orthopaedic devices with perceptions of bullying. METHODS Patients in outpatient pediatric orthopaedic clinics, ages 10 to 17 and their parents were surveyed using the Child-Adolescent Bullying Scale-9. Basic demographic, information about the child's orthopaedic condition, and parent's perception of their child being subject to bullying were also collected. Children were asked if they had used any orthopaedic devices in the last 3 months, whether they were bullied because of their device, and if bullying affected their compliance with device use. The analysis utilized a t test or analysis of variance to compare mean Child-Adolescent Bullying Scale-9 scores across different groups. RESULTS Among the 198 patients surveyed, 61% (N=121) perceived no-to-minimal exposure to bullying, 36% (N=72) moderate exposure, and 3% (N=5) severe exposure. Children ages 10 to 13 (N=100) and children ages 14 to 17 (N=98) reported similar rates of bullying (P=0.97). Higher rates of moderate to severe bullying were reported by patients with foot deformity (80%), multiple orthopaedic diagnoses (55%), chronic pain (39%), fracture/acute injury (37%), and scoliosis (33%). Moderate to severe bullying was reported by 37% of patients who wore a cast, 40% who wore a brace/orthotic, and 52% who used multiple orthopaedic devices. Parental concern that their child was being bullied was highly correlated with their child's bullying score (P=0.0002). CONCLUSIONS More than one third of our pediatric orthopaedic outpatients (39%) experience moderate to severe levels of bullying, which is higher than the general population's reported rates of 20% to 35%. Exposure to bullying may be higher in certain diagnoses or with use of certain orthopaedic devices. Further research is needed to delineate who is at highest risk. LEVEL OF EVIDENCE Level IV.

The effectiveness of minimally invasive surgery (MIS)-distal chevron metatarsal osteotomy (DCMO) for the correction of moderate-to-severe hallux valgus deformity is unclear. This study aimed to compare the radiographic and clinical outcomes of our novel MIS-proximal chevron metatarsal osteotomy (PCMO) with those of MIS-DCMO performed during the same timeframe. We prospectively compared the outcomes of patients who underwent MIS-PCMO (n = 20 patients; 22 cases) with those of patients who underwent MIS-DCMO (n = 23 patients; 26 cases) for moderate-to-severe hallux valgus deformity (hallux valgus angle [HVA] ≥ 30° and first-to-second intermetatarsal angle [IMA] ≥ 13°) between June 2017 and January 2019. The minimum follow-up duration for study inclusion was two years. The HVA, IMA, distal metatarsal articular angle (DMAA), relative length of the second metatarsal, medial sesamoid position, and Meary’s angle to evaluate the degree of deformity correction and its maintenance were measured pre-operatively and at the final follow-up. Compared with MIS-DCMO, MIS-PCMO resulted in significantly greater correction of the HVA (P

Supplemental digital content is available in the text., Background Itch, the most bothersome symptom in atopic dermatitis, is largely mediated by pruritogenic cytokines via Janus kinase 1 signaling in cutaneous sensory neurons. Objectives The aims of the study were to assess the magnitude and rapidity of itch relief with the Janus kinase 1 selective inhibitor abrocitinib and to evaluate the extent to which the effect of abrocitinib on itch relief is independent of overall disease improvement. Methods Pooled data from 1 phase 2b (NCT02780167) and 2 phase 3 (NCT03349060, NCT03575871) double-blind, randomized, placebo-controlled monotherapy trials in moderate to severe atopic dermatitis (N = 942) were analyzed. Results Abrocitinib produced significant and clinically meaningful itch relief versus placebo from week 2 through week 12 (end of treatment) that was associated with marked sleep and quality-of-life improvements. Mean percentage reductions in itch scores 24 hours after the first dose were greater for both abrocitinib doses (200 and 100 mg) versus placebo. Itch improvement occurred regardless of baseline itch severity, sex, race, body mass index, or Investigator Global Assessment response, suggesting that abrocitinib-associated itch relief is at least partially independent of overall disease improvement. Conclusions Abrocitinib showed a rapid and profound antipruritic effect, partially independent of improvement in overall disease.

As a chronic inflammatory disease, ulcerative colitis has significant negative impact on the quality of life (QoL) of patients. Since the disease affects many aspects of QoL, comprising multiple domains, treatments that induce and maintain remission can provide benefits beyond hard clinical endpoints. Effective treatment of ulcerative colitis can restore QoL and return it to normal or near normal levels. Biological therapies have shown consistent improvement in the QoL of patients with ulcerative colitis during the induction phase, with benefits that are generally maintained in the long-term. Current medical treatment options broadly comprise aminosalicylates, corticosteroids, thiopurines, and calcineurin inhibitors, as well as biologic therapies. Conventional therapies do not always adequately control disease in a sizeable portion of patients, while anti-TNF antibodies are associated with several issues such as contraindications, intolerance, primary non-response, and loss of response in some patients. JAK inhibitors have been associated with clinical improvements in disease manifestations and long-term improvement in QoL outcomes. However, additional studies are needed to better understand the comparative effects of different treatments on QoL and patient preferences for therapy. Herein, the available evidence is reviewed regarding the impact of various treatments on QoL in patients with moderate to severe ulcerative colitis.

Objectives: This cross-sectional study investigated the stages of periodontitis in obstructive sleep apnea (OSA) patients and risk factors associated with periodontitis severity among them. Materials and methods: A total of 194 patients underwent a polysomnography/polygraphy and were referred to periodontal examination. According to apnea-hypopnea index (AHI), patients were classified as mild OSA (AHI < 15) and moderate to severe OSA (AHI ≥ 15), whereas periodontitis severity was determined by the clinical attachment level (CAL) according to the recent Classification of Periodontal Diseases and Conditions. Patients were grouped into two categories: stages 1 and 2, and stages 3 and 4. Results: Higher AHI values were reported in OSA patients exhibiting periodontitis stages 3 and 4 compared to OSA patients with periodontitis stages 1 and 2 (p = 0.043) and the non- periodontitis group (p = 0.044). A positive correlation was found between AHI and mean CAL (r = 0.215 ; p = 0.004), and between AHI and plaque scores (r = 0.292 ; p < 0.001). Following a multivariable regression analysis, AHI was a significant predictor of mean CAL (β = 0.169 ; p = 0.031), explaining 16.4% of variability in mean CAL (adjusted R2 = 0.164 ; p < 0.001). Older patients had higher odds for an increased mean CAL (β = 0.266 ; p = 0.001), as well as patients smoking or formerly smoking (β = 0.305 ; p < 0.001) whereas visiting a dental medicine doctor once a year or more often was associated with a decreased mean CAL (β = - 0.182 ; p = 0.02). Conclusions: OSA was associated with severe stages of periodontitis along with increased age, smoking, low frequency of dental visits, and poor oral hygiene. Clinical relevance: Screening for periodontitis is recommended for patients with more severe forms of OSA.

Introduction: Ixekizumab (IXE), a high affinity humanized monoclonal antibody that selectively targets interleukin-17A, is approved in the United States (US) and the European Union (EU) for pediatric patients with moderate to severe plaque psoriasis. This review summarizes ixekizumab use in the phase 3, randomized, double-blind, placebo-controlled study in pediatric patients with moderate to severe plaque psoriasis and provides some clinical pearls we have learned after using the drug in the pediatric population for the past 3 years.Areas covered: Review of IXORA-PEDS trial data, general literature review pertaining to the systemic treatment of pediatric psoriasis as well as our clinical experience with IXEExpert opinion: IXE is the only IL17 antagonist for pediatric psoriasis and is a welcome addition to our armamentarium.

Rituximab appears to be effective for treating pemphigus, although there are limited long-term data.This retrospective single-center study evaluated patients with conventional treatment-resistant pemphigus who received rituximab during September 2010-December 2019. The first rituximab cycle was based on the rheumatoid arthritis protocol in all patients except one patient, and additional single doses (500 mg or 1000 mg) were administered after clinical and/or serological relapse. The consensus definitions were used for complete remission off therapy, complete remission on minimal therapy, and clinical relapse. Serological relapse was defined as a progressive ≥2-fold increase in anti-desmoglein titers (vs. previous the measurement).The study included 52 patients with pemphigus vulgaris and 1 patient with pemphigus foliaceus. The mean number of infusions was 5 and the average follow-up after the first infusion was 56 months. The average time to clinical and/or serological relapse was 12 months. Complete remission was achieved in 84.9% of patients, including after the first rituximab cycle in 25 patients (47.1%). Two patients died during the follow-up period.Additional rituximab cycles may help achieve and prolong remission in patients with moderate-to-severe pemphigus resistant to conventional therapies. However, prospective trials are needed to identify the optimal dosing protocol.

The incidence of airway obstruction in patients with complex CHD other than vascular rings and absent pulmonary valve syndrome is unknown. We reviewed pre-operative CT and clinical data of children with conotruncal abnormalities to assess for airway obstruction. Airway obstruction was common (41% of patients), often moderate to severe, of diverse aetiology, and most commonly associated with a right aortic arch. Patients with airway obstruction showed a trend towards a higher mortality rate. Patients with complex conotruncal abnormalities should be assessed for airway obstruction as it may help predict the need for additional interventions and assist with prognostication.

Two-step irradiance schedule (2-SIS) has been shown to significantly reduce pain during topical 5-aminolevulinic acid photodynamic therapy (ALA-PDT) on non-melanoma skin cancer (NMSC) and condyloma acuminatum (CA).1, 2 Few studies focused on 2-SIS pain control during PDT for acne.

Describe driving patterns following moderate-to-severe traumatic brain injury (TBI). Participants: Adults (N = 438) with TBI that required inpatient acute rehabilitation who had resumed driving.Cross-sectional, observational design.Eight TBI Model System sites.A driving survey was completed at phone follow-up.Most respondents reported driving daily, although 41% reported driving less than before their injury. Driving patterns were primarily associated with employment, family income, sex, residence, and time since injury, but not injury severity. Confidence in driving was high for most participants and was associated with a perception that the TBI had not diminished driving ability. Lower confidence and perceived loss of ability were associated with altered driving patterns.Most people with moderate-to-severe TBI resume driving but perhaps not at pre-injury or normal levels compared to healthy drivers. Some driving situations are restricted. The relationship between low confidence/perceived loss of ability and driving patterns/restrictions suggests people with TBI are exhibiting some degree of caution consistent with those perceptions. Careful assessment of driving skills and monitoring during early stages of RTD is warranted, particularly for younger, male, and/or single drivers who express higher levels of confidence.

Introduction To compare the cost-effectiveness of vedolizumab with that of conventional therapy in patients with moderate-to-severe active Crohn’s disease (CD) in China. Methods A decision tree and Markov model were built to predict the lifetime cost and health outcomes in the induction phase and maintenance phase of vedolizumab treatment and conventional therapy (a combination of corticosteroids, immunosuppressants, and aminosalicylates) in adult patients with moderate-to-severe active CD from the perspective of China’s healthcare system. Clinical efficacy and health utility were derived from the GEMINI 2 and GEMINI 3 trials and published literature. Costs were mainly obtained from clinical physician surveys in China and are presented in 2020 US dollars. Health outcomes (quality-adjusted life years, QALYs) and costs were discounted at an annual rate of 5%. The incremental cost per QALY gained was used to compare the cost-effectiveness of the two treatments. One-way and probabilistic sensitivity analyses (PSAs) were performed to test the robustness of the model. Results The model predicted more QALYs (9.92 vs 9.00 QALYs) and lower incurred costs ($288,284 vs $309,680) in vedolizumab than in conventional therapy in a mixed population (anti-TNF-naïve and anti-TNF-failure populations) over a lifetime horizon in the base-case analysis. Similar results were observed in the anti-TNF-naïve and anti-TNF-failure subgroups of patients with CD. One-way sensitivity analysis results suggested that health state cost was the most influential factor in the model. The PSA results supported the dominance of vedolizumab in the base-case analysis. Conclusion Vedolizumab appears to be a cost-effective strategy option in the treatment of adult patients with moderate-to-severe active CD in China in both anti-TNF-naïve and anti-TNF-failure populations. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01806-7.

Background Adolescent patients with moderate to severe idiopathic scoliosis who have completed their skeletal growth face a significant choice in their treatment path: watchful waiting or spinal fusion. Shared decision making (SDM) assists patients and clinicians to find treatments that make intellectual, practical and emotional sense. Our objective was to develop a tool that supports SDM for patients with scoliosis and their families. Methods We used a user-centered design approach that included collaboration between patients, surgeons and SDM experts, observation of clinician encounters, and literature review. We focused on adolescent idiopathic scoliosis patients 13 or more years of age with less than 1 year of growth remaining (Risser stage 3 or greater) and curves between 40 and 65 degrees. Results We included 22 patients, and collected 22 video recordings. From these videos, we identified salient patient priorities for decision making including treatment benefits, surgical complications, pain, scheduling and recovery, and cost. For each theme, we conducted a focused review to obtain the best estimate of effect. Then, an expert SDM designer developed an electronic prototype called Scoliosis Choice. Conclusions The initial prototype of the scoliosis SDM was finalized and is currently being field tested in clinic. Scoliosis Choice may help patients and surgeons better understand the potential risks and benefits of spinal fusion vs. observation for scoliosis treatment and improve validated measures of quality in patient-parent-surgeon communication.