Risankizumab Induction Therapy Achieves Early Symptom Improvements That Are Associated With Future Clinical and Endoscopic Outcomes in Crohn's Disease: Post Hoc Analysis of the ADVANCE, MOTIVATE, and FORTIFY Phase 3 Studies.

BACKGROUND AND AIMS: Crohn's disease (CD) symptoms are a main driver for impaired quality of life and fast relief is important for patient care. Stool frequency (SF) and abdominal pain score (APS) are patient reported outcomes (PROs) measuring symptom severity, which are supported as treatment targets by the STRIDE-II consensus. This post hoc analysis examined the efficacy of risankizumab (RZB), a humanised monoclonal antibody with high specificity for interleukin-23 p19, for providing early symptom relief, along with the prognostic value of early symptom relief for achieving future clinical and endoscopic endpoints. METHODS: Individual and combined measures of SF and AP at weeks 1, 2, and 3 were assessed in patients with moderate to severe CD who received 600 mg intravenous RZB or placebo (PBO) in the ADVANCE or MOTIVATE induction studies. Multivariate logistic regression was used to examine the predictiveness of early symptom improvement for clinical and endoscopic outcomes following RZB induction and maintenance. RESULTS: Higher rates of SF/APS clinical remission and enhanced clinical response were observed as early as week 1 with RZB versus PBO. A larger proportion of patients achieved clinical endpoints with RZB versus PBO, irrespective of prior bio-failure status. Early PRO improvement was associated with a greater likelihood of achieving clinical and endoscopic improvement following 12-weeks induction and 52-weeks maintenance RZB dosing. CONCLUSIONS: After the first intravenous RZB induction dose, significantly greater rates of symptom improvement versus PBO were achieved. Improvements could be observed as early as week 1 and were predictive of week 12 and 52 clinical and endoscopic improvement.

Early symptom change contributes to the outcome prediction of cognitive behavioral therapy for depression patients: A machine learning approach.

BACKGROUND: Limited evidence exists regarding the association between early symptom change and later outcomes of cognitive behavioral therapy (CBT). This study aimed to apply machine learning algorithms to predict continuous treatment outcomes based on pre-treatment predictors and early symptom changes and to uncover whether additional variance could be explained compared to regression methods. Additionally, the study examined early subscale symptom changes to determine the most significant predictors of treatment outcome. METHODS: We investigated CBT outcomes in a large naturalistic dataset (N = 1975 depression patients). The sociodemographic profile, pre-treatment predictors, and early symptom change, including total and subscale scores were used to predict the Symptom Questionnaire (SQ)48 score at the 10th session as a continuous outcome. Different machine learners were compared to linear regression. RESULTS: Early symptom change and baseline symptom score were the only significant predictors. Models with early symptom change explained 22.0 % to 23.3 % more variance than those without early symptom change. Specifically, the baseline total symptom score, and the early symptom score changes of the subscales pertaining to depression and anxiety were the top three predictors of treatment outcome. LIMITATION: Excluded patients with missing treatment outcomes had slightly higher symptom scores at baseline, indicating possible selection bias. CONCLUSION: Early symptom change improved the prediction of treatment outcomes. The prediction performance achieved is far from clinical relevance: the best learner could only explain 51.2 % of the variance in outcomes. Compared to linear regression, more sophisticated preprocessing and learning methods did not substantially improve performance.

Predictive value of Post-stroke Depression Prediction Scale combined with the Early Symptom Measurement of Post-Stroke Depression-Short Form for post-stroke depression / 中国实用护理杂志

Objective:To analyze the efficacy of the Post-stroke Depression Prediction Scale (DePreS) combined with the Early Symptom Measurement of Post-Stroke Depression-Short Form (ESMPSD-SF) in predicting post stroke depression (PSD).Methods:This study was a cross-sectional survey, using convenience sampling method to select 185 stroke patients admitted to Henan Provincial People′s Hospital from June 2019 to May 2021 as the research subjects. The DePreS, ESMPSD-SF, and general information questionnaire were used to investigate them.Results:The incidence of PSD was 36.76% (68/185). The DePreS and ESMPSD-SF scores in the PSD patients were (6.29 ± 8.77), (33.83 ± 6.78) points, respectively, significantly higher than those in the non-PSD patients (-2.05 ± 5.70), (26.51 ± 5.56) points, with statistically significant differences ( t=7.06, 7.97, both P<0.05). Logistic regression analysis showed that DePreS and ESMPSD-SF scores, marital status, and the number of comorbidities were predictive factors for PSD occurrence ( P<0.05). The AUC of DePreS for diagnosing PSD was 0.777, with an optimal diagnostic point of 2 points, a sensitivity of 59.42%, and a specificity of 80.71%; the AUC of the ESMPSD-SF for diagnosing PSD was 0.792, with an optimal diagnostic point of 28 points, a sensitivity of 78.26%, and a specificity of 74.14%. The sensitivity, specificity, and AUC of DePreS combined with ESMPSD-SF in the diagnosis of PSD were 82.61%, 83.62%, and 0.886, respectively. The differences were statistically significant compared to the AUC evaluated separately by DePreS or ESMPSD-SF ( Z=3.21, 3.49, both P<0.05). Conclusions:The combination of DePreS and ESMPSD-SF had a higher detection efficiency for PSD, and the combination of the two is more suitable for assessing PSD risk in stroke patients.

Early clinical signs and treatment of Menkes disease.

Menkes disease (MD) is an X-linked recessive disorder caused by mutations in ATP7A. Patients with MD exhibit severe neurological and connective tissue disorders due to copper deficiency and typically die before 3 years of age. Early treatment with copper injections during the neonatal period, before the occurrence of neurological symptoms, can alleviate neurological disturbances to some degree. We investigated whether early symptoms can help in the early diagnosis of MD. Abnormal hair growth, prolonged jaundice, and feeding difficulties were observed during the neonatal period in 20 of 69, 16 of 67, and 3 of 18 patients, respectively. Only three patients visited a physician during the neonatal period; MD diagnosis was not made at that point. The mean age at diagnosis was 8.7 months. Seven patients, who were diagnosed in the prenatal stage or soon after birth, as they had a family history of MD, received early treatment. No diagnosis was made based on early symptoms, highlighting the difficulty in diagnosing MD based on symptoms observed during the neonatal period. Patients who received early treatment lived longer than their elderly relatives with MD. Three patients could walk and did not have seizures. Therefore, effective newborn screening for MD should be prioritized.

Distinct early symptoms in neuropathologically proven frontotemporal lobar degeneration.

OBJECTIVES: Frontotemporal lobar degeneration (FTLD) is associated with accumulation of neurodegeneration-related protein, such as tau, TAR DNA-binding protein 43 (TDP-43), or fused in sarcoma protein (FUS). There have been very few systematic studies of the early symptoms of clinical phenotypes: behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA). Clinical subtypes and the patterns of atrophy reflect protein-accumulation patterns, but the relationship between early symptoms and pathological findings remains unclear. METHODS: We retrospectively investigated the clinical records and examined the neuropathology of 39 bvFTD and 6 svPPA patients to identify symptoms appearing within 2 years of the first clinically apparent changes. RESULTS: The bvFTD group consisted of 13 FTLD-tau, 18 FTLD-TDP, and 8 FTLD-FUS, and the svPPA group consisted of 6 FTLD-TDP. Age at death is significantly younger in FTLD-FUS (52.8 ± 12.6; P = 0.0104 < 0.05). Over 50% of bvFTD patients show apathy or inertia, and distinct language features appear early in svPPA. Interestingly, bvFTD and svPPA frequently present additional symptoms, not included in the diagnostic criteria, such as physical signs, reticence, dazed condition, and delusions. Stereotyped behaviors, hyperorality and dietary changes are prominent in FTLD-FUS, while linguistic deficits are greater in FTLD-TDP. CONCLUSIONS: Specific symptoms tend to appear in the early stage of FTLD in each pathological background. They might reflect the morphological features and pathological progression, and should be helpful in the stratification of patients for future therapeutic trials based on the proteinopathies.

A randomised clinical trial to evaluate the acceptability and efficacy of an early phase, online, guided augmentation of outpatient care for adults with anorexia nervosa.

BACKGROUND: Outpatient interventions for adult anorexia nervosa typically have a modest impact on weight and eating disorder symptomatology. This study examined whether adding a brief online intervention focused on enhancing motivation to change and the development of a recovery identity (RecoveryMANTRA) would improve outcomes in adults with anorexia nervosa. METHODS: Participants with anorexia nervosa (n = 187) were recruited from 22 eating disorder outpatient services throughout the UK. They were randomised to receiving RecoveryMANTRA in addition to treatment as usual (TAU) (n = 99; experimental group) or TAU only (n = 88; control group). Outcomes were measured at end-of-intervention (6 weeks), 6 and 12 months. RESULTS: Adherence rates to RecoveryMANTRA were 83% for the online guidance sessions and 77% for the use of self-help materials (workbook and/or short video clips). Group differences in body mass index at 6 weeks (primary outcome) were not significant. Group differences in eating disorder symptoms, psychological wellbeing and work and social adjustment (at 6 weeks and at follow-up) were not significant, except for a trend-level greater reduction in anxiety at 6 weeks in the RecoveryMANTRA group (p = 0.06). However, the RecoveryMANTRA group had significantly higher levels of confidence in own ability to change (p = 0.02) and alliance with the therapist at the outpatient service (p = 0.005) compared to the control group at 6 weeks. CONCLUSIONS: Augmenting outpatient treatment for adult anorexia nervosa with a focus on recovery and motivation produced short-term reductions in anxiety and increased confidence to change and therapeutic alliance.

Early Symptom Trajectories as Predictors of Treatment Outcome for Citalopram Versus Placebo.

OBJECTIVES: The high percentage of failed clinical trials for anti-depressant medications, especially in elderly populations, obscures the fact that some patients may benefit greatly from treatment. Early detection of patients who may benefit most from antidepressant medication may improve treatment decisions. We examined whether depressed patients in a large clinical trial exhibit distinct trajectories of early symptom change that predict differential response to medication or placebo. METHODS: We reanalyzed data of 174 patients aged 75 years and older with unipolar depression who were randomly assigned to citalopram or placebo. We used growth mixture modeling to identify trajectories of early change (weeks 1-4) on the Hamilton Rating Scale for Depression in the citalopram and placebo conditions. RESULTS: In the citalopram condition, two distinct trajectories of early change were detected that were associated with significantly different symptom reduction, but only one trajectory was detected for the placebo condition. One of the early trajectories of patients receiving citalopram (N = 33) showed significantly better symptomatic change than placebo; the other trajectory (N = 51) did not differ significantly from placebo. Poor baseline functional scores predicted trajectory membership, so that individuals with a score below 4.5 on baseline instrumental activities of daily living showed a higher tendency to be in the trajectory that outperformed placebo. CONCLUSIONS: The subgroup of citalopram-treated patients exhibiting better symptom trajectory early in a trial are likely to have beneficial outcomes relative to placebo. Future research should focus on developing reliable pre-treatment clinical and biological measures to identify this subgroup.

Analysis of early symptoms of autism spectrum disorder children based on three-minute videos / 中华实用儿科临床杂志

Objective To explore the difference in early symptoms between 2-3 years old autism spectrum disorder (ASD) children and healthy children through video analysis,in order to provide evidence for the identification and screening of ASD children.Methods The study involved 25 cases of ASD children who were admitted to Children Development and Behavior Center,the Third Affiliated Hospital,Sun Y at-Sen University,and confirmed with diagnosis standards of Diagnosis and Statistical Manual of Medical Disorder 5th edition (DSM-5) and 21 healthy children recruited in community.Three-minute videos of children in standard procedure were collected.Mter that,all the videos were scored on 5 items by 2 professional evaluators,unaware of diagnostic status.Comparison analysis of video scores between ASD and the healthy controls was made,and the sensitivity and specificity of video analysis were evaluated.Results Response to roll-call score was higher in ASD children [2 (2) scores] than that of the healthy children [0 (0) scores],response to audible object score was higher in ASD children [0(1) scores] than that of the healthy children [0(0) scores],social smiling score was higher in ASD children [1 (1) scores] than that of the healthy children [0 (1) scores],and total score was higher in ASD children [4 (2) scores] than that of the healthy children [2 (0) scores],and the differences were statistically significant (Z =2.272,P =0.000;Z =0.976,P =0.010;Z =1.763,P =0.001;Z =2.355,P =0.000).But,no difference was found in speech and finger pointing (all P ＞ 0.05).The consistency between three-minute video analysis and standard diagnosis was 0.652 (P =0.000),with 80.0％ of sensitivity and 85.7％ of specificity.Conclusions The ASD children perform worse than the healthy children in response to roll-call,response to audible object and social smiling.Three-minute standard video analysis can help to detect the early symptoms of ASD children.This result also demonstrates the potential of video-based analysis used as a ASD screening instrument in 2-3 years old children.

Early symptom change in adult outpatients: Relationship with patient characteristics and therapeutic alliance.

OBJECTIVE: This study has three aims: (1) to identify early change trajectories, (2) to examine patient characteristics predicting trajectory classes, and (3) to investigate the moderating effect of trajectory class membership on the working alliance. METHOD: In a sample of 402 outpatients (M age = 38.27, 64.9% women), outcome scores (OQ-45) on three time points (sessions 1, 3, and 5) were analysed by means of Latent Class Growth Curve Analysis. A multinomial logistic regression was used to investigate whether patient's age, gender, initial distress (OQ-45), and personality traits (Dimensional Assessment of Personality Pathology-Short Form) predicted trajectory class membership. A repeated-measures ANOVA examined whether differences in trajectory classes moderated the alliance quality (Working Alliance Inventory-Short version) over time. RESULTS: Four trajectory classes were identified: High distress-no change; moderate/high distress-small improvement, low distress-moderate improvement, and moderate/low distress-strong improvement. Gender, initial distress, and emotion dysregulation significantly predicted patients' trajectory class membership. The Task/Goal alliance component increased linearly over time, whereas the Bond component followed a reversed U-shaped pattern. The alliance was not moderated by trajectory class membership. CONCLUSIONS: Four clinically relevant subgroups could be identified on the basis of the early symptom change trajectories. Gender, initial psychological distress, and emotion dysregulation predicted patient's trajectory class membership. Trajectory class membership did not influence the development of the early working alliance. PRACTITIONER POINTS: As early change in highly distressed patients (Axis I and II) is not characterized by significant symptom change, clinicians should support and facilitate emotion regulation and social skills. Investing in a strong alliance is recommended, although it does not differentiate early responders from non-responders.

Early Symptoms and Clinical Manifestations in Korean Patients with Multiple Endocrine Neoplasia / 대한내분비외과학회지

PURPOSE: Multiple endocrine neoplasia (MEN) syndrome is an inherited, autosomal dominant disease that presents as a combination of several endocrine tumors. Early diagnosis of this syndrome is difficult, because of the nonspecific symptoms and signs. This study analyzed early manifestations and clinical characteristics in patients with MEN syndrome. METHODS: Medical records were retrospectively reviewed and telephone interviews were conducted with 35 patients diagnosed as MEN syndrome at Samsung Medical Center from December 1994 to December 2009. RESULTS: The 35 patients had been diagnosed as MEN1 (n=14), MEN2A (n=19) and MEN2B (n=2). The early manifestations of the 14 MEN1 patients were related with hyperparathyroidism (n=5), pituitary tumor (n=3), and pancreatic endocrine tumor (n=2). There were tumors of the parathyroid gland in all 14 patients, anterior pituitary in eight patients, and pancreatic islet cells in seven patients. Four cases were incidentally detected during the screening examination. Six cases harbored a MEN1 gene mutation. The twenty-one patients diagnosed with MEN2 comprised medullary thyroid cancer (n=20), adrenal pheochromocytoma (n=15), and hyperparathyroidism (n=4). The MTC-related symptoms in the 21 MEN2 patients included neck mass or discomfort in 12 patients and pheochromocytoma-related symptoms in seven patients. Two cases were detected through familial genetic screening test. The RET gene mutationwas detected in 19 cases. CONCLUSION: Early manifestations of MEN syndrome were very different between the types of MEN and the types of its presenting tumor. The early diagnosis and proper management of MEN requires awareness of the clinical characteristics of each expressed tumor and is influenced by genetic screening methods.