Imaging Predictors of Neurologic Outcome After Pediatric Arterial Ischemic Stroke.

BACKGROUND AND PURPOSE: To assess whether initial imaging characteristics independently predict 1-year neurological outcomes in childhood arterial ischemic stroke patients. METHODS: We used prospectively collected demographic and clinical data, imaging data, and 1-year outcomes from the VIPS study (Vascular Effects of Infection in Pediatric Stroke). In 288 patients with first-time stroke, we measured infarct volume and location on the acute magnetic resonance imaging studies and hemorrhagic transformation on brain imaging studies during the acute presentation. Neurological outcome was assessed with the Pediatric Stroke Outcome Measure. We used univariate and multivariable ordinal logistic regression models to test the association between imaging characteristics and outcome. RESULTS: Univariate analysis demonstrated that infarcts involving uncinate fasciculus, angular gyrus, insular cortex, or that extended from cortex to the subcortical nuclei were significantly associated with poorer outcomes with odds ratios ranging from 1.95 to 3.95. All locations except the insular cortex remained significant predictors of poor outcome on multivariable analysis. When infarct volume was added to the model, the locations did not remain significant. Larger infarct volumes and younger age at stroke onset were significantly associated with poorer outcome, but the strength of the relationships was weak. Hemorrhagic transformation did not predict outcome. CONCLUSIONS: In the largest pediatric arterial ischemic stroke cohort collected to date, we showed that larger infarct volume and younger age at stroke were associated with poorer outcomes. We made the novel observation that the strength of these associations was modest and limits the ability to use these characteristics to predict outcome in children. Infarcts affecting specific locations were significantly associated with poorer outcomes in univariate and multivariable analyses but lost significance when adjusted for infarct volume. Our findings suggest that infarcts that disrupt critical networks have a disproportionate impact upon outcome after childhood arterial ischemic stroke.

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry.

BACKGROUND & AIMS: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. METHODS: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. RESULTS: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). CONCLUSIONS: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. LAY SUMMARY: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes.

Predicting Recovery and Outcome after Pediatric Stroke: Results from the International Pediatric Stroke Study.

OBJECTIVE: To characterize predictors of recovery and outcome following pediatric arterial ischemic stroke, hypothesizing that age influences recovery after stroke. METHODS: We studied children enrolled in the International Pediatric Stroke Study between January 1, 2003 and July 31, 2014 with 2-year follow-up after arterial ischemic stroke. Outcomes were defined at discharge by clinician grading and at 2 years by the Pediatric Stroke Outcome Measure. Demographic, clinical, and radiologic outcome predictors were examined. We defined changes in outcome from discharge to 2 years as recovery (improved outcome), emerging deficit (worse outcome), or no change. RESULTS: Our population consisted of 587 patients, including 174 with neonatal stroke and 413 with childhood stroke, with recurrent stroke in 8.2% of childhood patients. Moderate to severe neurological impairment was present in 9.4% of neonates versus 48.8% of children at discharge compared to 8.0% versus 24.7% after 2 years. Predictors of poor outcome included age between 28 days and 1 year (compared to neonates, odds ratio [OR] = 3.58, p < 0.05), underlying chronic disorder (OR = 2.23, p < 0.05), and involvement of both small and large vascular territories (OR = 2.84, p < 0.05). Recovery patterns differed, with emerging deficits more common in children <1 year of age (p < 0.05). INTERPRETATION: Outcomes after pediatric stroke are generally favorable, but moderate to severe neurological impairments are still common. Age between 28 days and 1 year appears to be a particularly vulnerable period. Understanding the timing and predictors of recovery will allow us to better counsel families and target therapies to improve outcomes after pediatric stroke. ANN NEUROL 2020;87:840-852.

Validation of the pediatric stroke outcome measure for classifying overall neurological deficit.

BACKGROUND: The pediatric stroke outcome measure (PSOM) is a standardized, disease-specific outcome measure. We aimed to validate the overall classification of neurological deficit severity using PSOM. METHODS: We identified 367 neonates/children with arterial ischemic stroke (AIS) (Derivation Cohort). We analyzed the PSOM subscales (scored as 0 [no deficit], 0.5 [minimal/mild deficit; normal function], 1 [moderate deficit; slowing function], or 2 [severe deficit; missing function]) to derive severity levels using latent class analysis (LCA). We validated a severity classification scheme (PSOM-SCS) in: (a) children who had Pediatric Evaluation of Disability Inventory (PEDI; n = 63) and/or the Pediatric Quality-of-Life Inventory (PedsQL; n = 97) scored; and (b) an external cohort (AIS; n = 102) with concurrently scored modified Rankin Scale (mRS), King's Outcome Scale for Childhood Head-Injury (KOSCHI) and PSOM. RESULTS: Within the Derivation Cohort, LCA identified three severity levels: "normal/mild," "moderate," and "severe" (83.7%, 13.3%, and 3%, respectively). We developed severity classification based on PSOM subscale scores: "normal/mild"-normal function in all domains or slowing in one domain, "moderate"-slowing in ≥2 domains or missing function in one domain, and "severe"-missing function in ≥2 domains or slowing in ≥1 plus missing in one domain. PEDI and PedsQL both differed significantly across the severity groups. PSOM-SCS displayed high concordance with mRS (agreement coefficient [AC2] = 0.88) and KOSCHI (AC2 = 0.79). CONCLUSION: The PSOM-SCS constitutes a valid tool for classifying overall neurological severity emphasizing function and encompassing the full range of severity in pediatric stroke. IMPACT: Arithmetic summing of the PSOM subscales scores to assess severity classification is inadequate.The prior severity classification using PSOM overestimates poor outcomes.Three distinct severity profiles using PSOM subscales are identified.The PSOM-SCS is in moderate to excellent agreement with other disability measures.PSOM-SCS offers a valid tool for classifying the overall neurological deficit severity.

Long-term cognitive outcomes after cerebral sinovenous thrombosis in childhood.

AIM: To assess long-term cognitive function in children after cerebral sinovenous thrombosis (CSVT). METHOD: Children with CSVT, who had neuropsychological testing for intellectual ability, executive function, attention, language, or behavior, were included in a prospective observational study. Outcomes were compared with normative means using one-sample t-tests. Predictors of abnormal function were examined using logistic regression. RESULTS: Fifty children with CSVT were included (median age at diagnosis 2y 10mo, interquartile range 7d-6y 10mo; 35 males, 15 females). The median follow-up time was 4 years 2 months (interquartile range 2y 8mo-6y 4mo). Compared with normative means, children with CSVT had lower mean (± standard deviation) full-scale IQ, working memory, and processing speed scores (93.3±16, p=0.01; 93.6±16, p=0.04; 93.7±15.3, p=0.02 respectively). They also had lower scores in executive function, attention, and language domains. Refractory seizure at presentation was associated with a trend in behavioral problems (odds ratio [OR] 6.3, 95% confidence interval [CI] 0.9-46, p=0.07). Females were less likely to experience processing speed difficulties (OR 0.22, 95% CI 0.04-1.3, p=0.09). Incomplete recanalization was associated with a greater risk of abnormal verbal comprehension (OR 5.3, 95% CI 0.93-30.5, p=0.059). INTERPRETATION: Children with CSVT as a group performed below age expectations on standardized neuropsychological tests, although there was variability across individuals and cognitive domains. Larger studies are needed to evaluate predictors of cognitive deficits in children with CSVT.

Patients With Fibromyalgia Reporting Severe Pain but Low Impact of the Syndrome: Clinical and Pain-Related Cognitive Features.

BACKGROUND: Fibromyalgia (FM) is a prevalent and highly disabling chronic pain syndrome. However, differences among patients regarding how pain impacts on daily life are remarkable. The main aim of this study was to identify clinical and pain-related cognitive variables characterizing patients reporting high adaptability despite experiencing severe chronic pain. METHODS: Two hundred and eighty-three Spanish patients with FM with high levels of pain were classified into 2 groups: (1) those reporting low impact of the syndrome, and (2) those with moderate-to-high impact. Perceived stress, anxiety, and depressive symptoms along with pain catastrophizing, psychological inflexibility, and perceived control over pain were evaluated. Differences in sociodemographics, years with FM, past/current major depressive disorder comorbidity, and health-related economic costs (ie, medications, use of medical services, lost productivity due to sick leave) were also assessed. Stepwise logistic regression analyses predicting group membership from clinical variables and pain-related cognitive processes as predictors were performed. RESULTS: Lower stress, anxiety, and depressive symptoms, along with reduced pain catastrophism, psychological inflexibility, and perceived control over pain, were found in the low-impact group. Significant predictors of group membership (low-impact vs. moderate-to-high impact) in regression analyses were "cognitive fusion" (psychological inflexibility), "helplessness" (pain catastrophizing), and depressive symptomatology, together with pain intensity and other FM symptoms. CONCLUSIONS: The present study provides further evidence on resilience resources in chronic pain by identifying some variables (ie, reduced depressive symptomatology, pain catastrophizing, and psychological inflexibility) differentially characterizing a profile of patients with FM who are especially able to adapt to high levels of pain.

Arterial Wall Imaging in Pediatric Stroke.

BACKGROUND AND PURPOSE: Arteriopathy is common in childhood arterial ischemic stroke (AIS) and predicts stroke recurrence. Currently available vascular imaging techniques mainly image the arterial lumen rather than the vessel wall and have a limited ability to differentiate among common arteriopathies. We aimed to investigate the value of a magnetic resonance imaging-based technique, namely noninvasive arterial wall imaging (AWI), for distinguishing among arteriopathy subtypes in a consecutive cohort of children presenting with AIS. METHODS: Children with confirmed AIS and magnetic resonance angiography underwent 3-Tesla AWI including T1-weighted 2-dimensional fluid-attenuated inversion recovery fast spin echo sequences pre- and post-gadolinium contrast. AWI characteristics, including wall enhancement, wall thickening, and luminal stenosis, were documented for all. RESULTS: Twenty-six children with AIS had AWI. Of these, 9 (35%) had AWI enhancement. AWI enhancement was associated with anterior circulation magnetic resonance angiography abnormality and cortical infarction in 8 of 9 (89%) children and normal magnetic resonance angiography with posterior circulation subcortical infarction in 1 (1 of 9; 11%) child. AWI enhancement was not seen in 17 (65%), 10 (59%) of whom had an abnormal magnetic resonance angiography. Distinct patterns of pre- and postcontrast signal abnormality were demonstrated in the vessel wall in the region of interest in children with transient cerebral arteriopathy, arterial dissection, primary central nervous system angiitis, dissecting aneurysm, and cardioembolic stroke. CONCLUSIONS: AWI is a noninvasive, high-resolution magnetic resonance AWI technique, which can be successfully used in children presenting with AIS. Patterns of AWI enhancement are recognizable and associated with specific AIS pathogeneses. Further studies are required to assess the additional diagnostic utility of AWI over routine vascular imaging techniques, in childhood AIS.

Pelvic floor dysfunction in women with fibromyalgia and control subjects: Prevalence and impact on overall symptomatology and psychosocial function.

AIMS: To evaluate the prevalence, distress, and impact of pelvic floor dysfunction (PFD) symptomatology in women with fibromyalgia and control women. We also aimed to evaluate the impact of PFD symptomatology on several psychosocial measures such as mood, sleep, pain, and quality of life. METHODS: We conducted a cross-sectional study in women with fibromyalgia and control women from the general population. Using a structured survey, we collected sociodemographic and clinical data, assessed the prevalence of PFD and evaluated the distress (PFDI-20) and the impact (PFIQ-7) caused by its symptomatology. Using Spanish-validated questionnaires, we also evaluated mood and sleep disturbances, bodily pain, and quality of life in subjects with and without PFD. In participants with fibromyalgia, we assessed the severity and impact of the disease using the Fibromyalgia Impact Questionnaire (FIQR). RESULTS: Two hundred and twenty-six patients with fibromyalgia and 222 control women completed the surveys. Two hundred and twenty patients (93%) and 140 controls (63%) reported PFD-related symptoms. Both the scores of distress (143.1 ± 5.7 vs 96.1 ± 4.8, P < 0.0001) and impact (122.4 ± 5.6 vs 100.6 ± 6.4, P < 0.0001) caused by PFD symptoms were significantly higher in women with fibromyalgia than in controls. There was a significant positive relationship between fibromyalgia severity and both PFDI-20 (r2 = 0.32, P < 0.0001) and PFIQ-7 scores (r2 = 0.375, P < 0.0001). Depression severity, sleep disturbances, bodily pain, and low quality of life were highest in women with fibromyalgia and PFD and lowest in control women without PFD. CONCLUSIONS: PFD-related symptoms were significantly more frequent in women with fibromyalgia than in controls. PFD symptomatology, when present, negatively influenced mood, sleep quality, and quality of life of both patients with fibromyalgia and controls.

Suicidal behaviors in patients with rheumatic diseases: a narrative review.

Chronic rheumatic disorders are characterized by inflammation and chronic pain, and both anxiety and depression have been frequently observed in these patients. Depression and chronic pain are recognized as risk factors for the development of suicidal behaviors. Accordingly, the objective of the present review is to provide a comprehensive review of suicidal behaviors associated with rheumatic diseases. Medline and EMBASE were searched for English language publications using key words related with rheumatic diseases, suicide, suicide attempts, and suicidal ideation. 34 records (30 full-length published papers and 4 studies published in abstract form) that included data related to the frequency and/or potential determinants of suicidal behaviors in rheumatic diseases were included in the review. It was found that both suicidal ideation and completed suicide seem to be more frequent in patients experiencing systemic lupus erythematosus, fibromyalgia and arthritis. Major determinants were comorbid depression in fibromyalgia and arthritis, and neuropsychiatric disease in systemic lupus erythematosus. Based on these findings, suicide risk should be assessed in patients suffering from systemic lupus erythematosus, fibromyalgia and/or arthritis.

The Effects of a Gluten-free Diet Versus a Hypocaloric Diet Among Patients With Fibromyalgia Experiencing Gluten Sensitivity-like Symptoms: A Pilot, Open-Label Randomized Clinical Trial.

BACKGROUND AND AIMS: Patients with fibromyalgia frequently present with symptoms similar to those experienced by patients with gluten-related disorders, raising the possibility that a subgroup of these patients could be experiencing underlying gluten sensitivity. This study aimed to evaluate the effects of a gluten-free diet (GFD) compared with a hypocaloric diet (HCD) among patients with fibromyalgia. METHODS: Adult patients diagnosed with fibromyalgia were randomly allocated to receive a GFD or a HCD over a 24-week period. The primary outcome measure was the change in the number of gluten sensitivity symptoms. The following secondary outcomes were evaluated: body mass index, Revised Fibromyalgia Impact Questionnaire, Pittsburgh Sleep Quality Index, Brief Pain Inventory, Beck Depression Inventory-II, State-Trait Anxiety Inventory, Short-Form Health Survey, Patient Global Impression Scale of Severity, Patient Global Impression Scale of Improvement, and adverse events. RESULTS: Seventy-five subjects were randomly allocated to receive either a GFD (n=35) or an HCD (n=40). The least squares mean change in the total number of gluten sensitivity symptoms from baseline did not differ significantly between the GFD and HCD groups (-2.44±0.40 for the GFD; -2.10±0.37 for the HCD; P=0.343). Similarly, the 2 dietary interventions did not differ in any of the remaining measured secondary outcomes. Both dietary interventions were well tolerated. CONCLUSIONS: Both dietary interventions were associated with similar beneficial outcomes in reducing gluten sensitivity symptoms and other secondary outcomes. However, despite its specificity, GFD was not superior to HCD in reducing the number of gluten sensitivity symptoms or secondary outcomes.

An insight into the gastrointestinal component of fibromyalgia: clinical manifestations and potential underlying mechanisms.

Fibromyalgia syndrome is characterized by chronic generalized pain accompanied by a broad symptomatologic spectrum. Besides chronic fatigue, sleep disturbances, headaches and cognitive dysfunction that are extensively described in the literature, a considerable proportion of patients with fibromyalgia experience gastrointestinal symptoms that are commonly overlooked in the studies that are not specifically dedicated to evaluate these manifestations. Nevertheless, various attempts were undertaken to explore the gastrointestinal dimension of fibromyalgia. Several studies have demonstrated an elevated comorbidity of irritable bowel syndrome (IBS) among patients with fibromyalgia. Other studies have investigated the frequency of presentation of gastrointestinal symptoms in fibromyalgia in a nonspecific approach describing several gastrointestinal complaints frequently reported by these patients such as abdominal pain, dyspepsia and bowel changes, among others. Several underlying mechanisms that require further investigation could serve as potential explanatory hypotheses for the appearance of such manifestations. These include sensitivity to dietary constituents such as gluten, lactose or FODMAPs or alterations in the brain-gut axis as a result of small intestinal bacterial overgrowth or subclinical enteric infections such as giardiasis. The gastrointestinal component of fibromyalgia constitutes a relevant element of the multidisciplinary pathophysiologic mechanisms underlying fibromyalgia that need to be unveiled, as this would contribute to the adequate designation of relevant treatment alternatives corresponding to these manifestations.

Celiac symptoms in patients with fibromyalgia: a cross-sectional study.

Fibromyalgia is a chronic pain syndrome associated with numerous somatic symptoms including gastrointestinal manifestations of nonspecific nature. Celiac disease and nongluten sensitivity frequently evolve in adults with gastrointestinal and extraintestinal symptoms similar to those found among patients with fibromyalgia. The objective of the present study was to evaluate the presence of celiac-type symptoms among patients with fibromyalgia in comparison with healthy subjects and with those experienced by adult celiac patients and subjects with gluten sensitivity. A list of typical celiac-type symptoms was developed, comparing the frequency of presentation of these symptoms between patients with fibromyalgia (N = 178) and healthy subjects (N = 131), in addition to those of celiac patients and gluten-sensitive patients reported in the literature. The frequency of presentation of every celiac-type symptom, excepting anemia, was significantly higher among patients with fibromyalgia compared to controls (p < 0.0001). Regarding the existing data in the literature, the prevalence of fatigue, depression, cognitive symptoms and cutaneous lesions predominated among patients with fibromyalgia, whereas the prevalence of gastrointestinal symptoms was higher among patients with fibromyalgia compared to gluten-sensitive patients and was similar among patients with fibromyalgia and celiac disease patient. The symptomatological similarity of both pathologies, especially gastrointestinal symptoms, suggests that at least a subgroup of patients with fibromyalgia could experience subclinical celiac disease or nonceliac gluten intolerance.

Health-Related Quality of Life and Psychosocial Variables in Women with Colorectal Pelvic Floor Dysfunction: A Cross-Sectional Study.

Pelvic floor dysfunction comprises various disorders, including urinary incontinence, fecal incontinence, pelvic organ prolapse, and chronic pelvic pain. This study aimed to evaluate health-related quality of life (HRQoL), anxiety, depression, sleep disturbance, and sexual functioning in women with pelvic floor dysfunction of colorectal etiology compared with control women. Patients were recruited from a specialized colorectal unit and controls were selected from among the patients' friends and relatives. Sociodemographic and clinical data were collected. Pelvic floor dysfunction distress and impact, HRQoL, depression, anxiety, insomnia, and sexual functioning were assessed using the following validated questionnaires: Short-Form Pelvic Floor Distress Inventory (PFDI-20), Short Form Pelvic Floor Impact Questionnaire (PFIQ-7), 36-Item Short-Form Health Survey (SF-36), Beck Depression Inventory II (BDI-II), Beck Anxiety Inventory (BAI), Insomnia Severity Index (ISI), and Changes in Sexual Functioning Scale (CSFQ). Statistical analyses included Welch's t-test, Fisher's exact test, and Spearman's correlation coefficients. Eighty-four patients and 57 controls were included. Compared with controls, patients were more likely to be obese or overweight, have had higher numbers of deliveries, more vaginal deliveries, more frequent use of forceps, and have had more associated comorbidities, mainly in the urinary, neurological, and psychiatric domains. As expected, patients scored significantly higher than controls on both the PFDI-20 and PFIQ-7 and their respective sub-scales, with the highest mean values in the patient group on the sub-scales related to the colorectal-anal domain. QoL, depression, anxiety, insomnia, and sexual functioning were significantly worse in patients than in controls (p < 0.0001 in every case). In patients, PFIQ-7 scores correlated significantly with HRQoL (p < 0.001 for the physical component and p < 0.01 for the mental component), depression (p < 0.001), anxiety (p < 0.001), insomnia (p < 0.05), and sexual functioning scores (p < 0.05). Colorectal pelvic floor dysfunction had a markedly deleterious impact on the HRQoL, depression, anxiety, sleep disturbance, and sexual functioning of patients. It is concluded that colorectal pelvic floor dysfunction exerts a considerable burden on patients' lives. Addressing these issues in clinical settings could significantly improve patients' well-being.

Handling related publications reporting real-world evidence in network meta-analysis: a case study in multiple sclerosis.

Aim: The presence of two or more publications that report on overlapping patient cohorts poses a challenge for quantitatively synthesizing real-world evidence (RWE) studies. Thus, we evaluated eight approaches for handling such related publications in network meta-analyses (NMA) of RWE studies. Methods: Bayesian NMAs were conducted to estimate the annualized relapse rate (ARR) of disease-modifying therapies in multiple sclerosis. The NMA explored the impact of hierarchically selecting one pivotal study from related publications versus including all of them while adjusting for correlations. Results: When selecting one pivotal study from related publications, the ARR ratios were mostly similar regardless of the pivotal study selected. When including all related publications, there were shifts in the point estimates and the statistical significance. Conclusion: An a priori hierarchy should guide the selection among related publications in NMAs of RWE. Sensitivity analyses modifying the hierarchy should be considered for networks with few or small studies.

Belimumab versus anifrolumab in adults with systemic lupus erythematosus: an indirect comparison of clinical response at 52 weeks.

OBJECTIVE: To generate comparative efficacy evidence of belimumab versus anifrolumab in SLE that can inform treatment practices. METHODS: The SLE Responder Index (SRI)-4 response at 52 weeks of belimumab versus anifrolumab was evaluated with an indirect treatment comparison. The evidence base consisted of randomised trials that were compiled through a systemic literature review.A feasibility assessment was performed to comprehensively compare the eligible trials and to determine the most appropriate indirect treatment comparison analysis method. A multilevel network meta-regression (ML-NMR) was implemented that adjusted for differences across trials in four baseline characteristics: SLE Disease Activity Index-2K, anti-double-stranded DNA antibody positive, low complement (C)3 and low C4. Additional analyses were conducted to explore if the results were robust to different sets of baseline characteristics included for adjustment, alternative adjustment methods and changes to the trials included in the evidence base. RESULTS: The ML-NMR included eight trials: five belimumab trials (BLISS-52, BLISS-76, NEA, BLISS-SC, EMBRACE) and three anifrolumab trials (MUSE, TULIP-1, TULIP-2). Belimumab and anifrolumab were comparable in terms of SRI-4 response (OR (95% credible interval), 1.04 (0.74-1.45)), with the direction of the point estimate slightly favouring belimumab. Belimumab had a 0.58 probability of being the more effective treatment. The results were highly consistent across all analysis scenarios. CONCLUSIONS: Our results suggest that the SRI-4 response of belimumab and anifrolumab are similar at 52 weeks in the general SLE population, but the level of uncertainty around the point estimate means we cannot rule out the possibility of a clinically meaningful benefit for either treatment. It remains to be seen if specific groups of patients could derive a greater benefit from anifrolumab or from belimumab, and there is certainly an unmet need to identify robust predictors towards more personalised selection of available biological agents in SLE.

Efficacy of Bimekizumab and Other Biologics in Moderate to Severe Plaque Psoriasis: A Systematic Literature Review and a Network Meta-Analysis.

INTRODUCTION: Biologic treatments are increasingly being used in the management of moderate to severe plaque psoriasis (PSO). Bimekizumab is a selective inhibitor of both interleukin (IL)-17A and IL-17F approved for the treatment of moderate to severe PSO. Although bimekizumab trials provide comparisons to secukinumab, adalimumab and ustekinumab, there are no further head-to-head comparisons of bimekizumab to other biologics. This network meta-analysis (NMA) aimed to compare the short-term efficacy of bimekizumab versus other biologic systemic therapies for moderate to severe PSO. METHODS: A systematic literature review was conducted to identify randomised controlled trials (RCTs) in patients with moderate to severe PSO. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews and PsycINFO were searched on July 1, 2020. An enhanced multinomial Bayesian NMA model was used to evaluate the comparative efficacy in 50%, 75%, 90% and 100% improvement from baseline Psoriasis Area and Severity Index (PASI 50/75/90/100) at 10-16 weeks. The model was also adjusted for baseline risk, given the variable placebo responses across the trials. RESULTS: Eighty-six RCTs (including 34,476 patients) were included in the NMA. IL-17 and IL-23 inhibitors were the most effective treatments across all PASI levels. At 10-16 weeks, bimekizumab had the highest probability of achieving PASI 75 (92.3%), PASI 90 (84.0%) and PASI 100 (57.8%). Bimekizumab demonstrated statistical superiority over all biologics in achieving PASI 90 and PASI 100 thresholds. For PASI 75, the benefit of bimekizumab was statistically significant compared to all other treatments except risankizumab and ixekizumab. CONCLUSION: This analysis demonstrated that IL-17 and IL-23 inhibitors were highly effective in achieving short-term improvement among patients with moderate to severe PSO. Patients receiving bimekizumab were significantly more likely to achieve PASI 90 or PASI 100 within 10-16 weeks of the first injection than all other biologics.

Fronto-Parietal and White Matter Haemodynamics Predict Cognitive Outcome in Children with Moyamoya Independent of Stroke.

Moyamoya disease is a major arteriopathy characterised by progressive steno-occlusion of the arteries of the circle of Willis. Studies in adults with moyamoya suggest an association between abnormal fronto-parietal and white matter regional haemodynamics and cognitive impairments, even in the absence of focal infarction. However, these associations have not been investigated in children with moyamoya. We examined the relationship between regional haemodynamics and ratings of intellectual ability and executive function, using hypercapnic challenge blood oxygen level-dependent magnetic resonance imaging of cerebrovascular reactivity in a consecutive cohort of children with confirmed moyamoya. Thirty children were included in the final analysis (mean age: 12.55 ± 3.03 years, 17 females, 15 idiopathic moyamoya and 15 syndromic moyamoya). Frontal haemodynamics were abnormal in all regardless of stroke history and comorbidity, but occipital lobe haemodynamics were also abnormal in children with syndromic moyamoya. Executive function deficits were noted in both idiopathic and syndromic moyamoya, whereas intellectual ability was impaired in syndromic moyamoya, even in the absence of stroke. Analysis of the relative effect of regional abnormal haemodynamics on cognitive outcomes demonstrated that executive dysfunction was predominantly explained by right parietal and white matter haemodynamics independent of stroke and comorbidity, while posterior circulation haemodynamics predicted intellectual ability. These results suggest that parietal and posterior haemodynamics play a compensatory role in overcoming frontal vulnerability and cognitive impairment.

Marital Adjustment in Patients with Cancer: Association with Psychological Distress, Quality of Life, and Sleep Problems.

Marital adjustment plays a key role in the physical and psychosocial wellbeing. We conducted a cross-sectional study to evaluate marital adjustment and its association with psychological distress, suicidal ideation, sleep problems, and quality of life in patients with cancer. We collected demographic and clinical information using a structured survey. We assessed marital adjustment, quality of life, psychological distress profile, and sleep problems of participants using validated instruments: the Locke and Wallace Marital Adjustment Test (LWMAT), the Short-Form Health Survey-12, the Beck's Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), and the Insomnia Severity Index (ISI). Suicidal ideation was assessed with item nine of the BDI. Of the 130 patients (52.3% females, mean age 57.9 ± 12.4 years) enrolled, 20 (15%) were classified as experiencing poor marital adjustment. Moderate to severe depression, anxiety, and insomnia were found in 25.4%, 34.6%, and 24.7% of participants, respectively. Positive suicidal ideation was documented in 13.8% of participants. We found a significant association between poor marital adjustment and depression, anxiety, suicidal ideation, and poor sleep. Our study confirms the relevance of marital adjustment in relation to the psychological wellbeing of patients with cancer. Depression, anxiety, and poor sleep were found to be significantly associated with poor marital adjustment.