UNASSIGNED: Previously, we had observed that immediate pain reduction after one acupuncture treatment was associated with high temporal summation of pain (TS) at a pain free control site and younger age in a mixed population of chronic pain patients. The aim of the present study was to verify these results in chronic non-specific low back pain (LBP) and to collect pilot data on the association between TS and the response to an acupuncture series.
UNASSIGNED: TS at a pain free control site (back of dominant hand) and at the pain site was quantified by the pin-prick induced wind-up ratio (WUR) in 60 LBP patients aged 50 years or younger. Response to one acupuncture treatment was assessed by change in pain intensity and pressure pain threshold (PPT) at the pain site. The primary hypothesis was that a high TS (WUR > 2.5) would be associated with a clinically relevant reduction in pain intensity of at least 30%. In study part two, 26 patients received nine additional treatments. Response to the acupuncture series was assessed by the pain intensity during the last week, the PPT and the Hannover functional ability questionnaire (FFbH-R).
UNASSIGNED: An immediate reduction in pain intensity of at least 30% was frequent irrespective of TS at the control site (low vs. high TS 58% vs. 72%, p = 0.266). High TS at the pain site was also not significantly associated with a clinically relevant immediate reduction in pain intensity (low vs. high TS 46% vs. 73%, p = 0.064). The PPT was not changed after one acupuncture treatment. Study part two did not reveal a consistent association between TS at the control site and any of the outcome measures but also a trend toward a higher chance for a clinically relevant response along with low TS at the pain site.
UNASSIGNED: Our results do not suggest an important role of TS for predicting a clinically important acupuncture effect or the response to a series of 10 acupuncture treatments in patients with chronic non-specific LBP. Overall high response rates imply that acupuncture is a suitable treatment option for LBP patients irrespective of their TS.

OBJECTIVE: This study aimed to develop a reliable and effective nomogram model to identify high-risk populations with non-response to prone position ventilation (PPV) in acute respiratory distress syndrome (ARDS) patients.
METHODS: This retrospective cohort study included 175 patients with ARDS undergoing PPV. An improvement of ≥ 20 mmHg in the PaO2/FiO2 after the first PPV was defined as a \'response\'. For the construction of the model, all patients were randomly assigned to the train and validation cohort according to 2:1. Multivariate logistic regression was useed to develop the nomogram. The area under the receiver operating characteristic curve (AUC), decision curve and calibration curve were assessed to evaluate the efficiency, clinical utility and calibration of the model.
RESULTS: The overall rate of non-response to PPV in ARDS patients was approximately 32.6 %. In the training cohort and validation cohort, the rate are 29.9 % and 34.5 % respectively. Murray score ≥ 2.5 (OR: 4.29), procalcitonin (PCT) ≥ 2 ng/mL (OR: 2.52), N-terminal pro-B-type natriuretic peptide (Nt-proBNP) ≥ 2000 pg/ml (OR: 2.44), and hemoglobin ≤ 90 g/L (OR: 2.39) were independently associated with the rate of non-response to PPV and combined in prediction model. The model demonstrated good predictive value with AUC of 0.817 and 0.828 in the train and validation cohort. Calibration curve showed good calibration and decision curve analysis indicated favorable clinical utility.
CONCLUSIONS: This study constructed a risk prediction model for non-response to PPV, which demonstrated good predictive value and clinical utility.
CONCLUSIONS: Early identification of prone position response in ARDS is essential for timely alternative treatments, improving patient prognosis and healthcare efficiency. The predictive model included representative indicators of patients with ARDS, encompassing parameters such as the acute lung injury (Murray score), cardiac function (Nt-proBNP), infectious status (PCT), and hemoglobin levels.

BACKGROUND: Exercise potentially improves gait, balance, and habitual physical activity in Parkinson\'s disease (PD). However, given the heterogeneous nature of the disease, it is likely that people respond differently to exercise interventions. Factors determining responsiveness to exercise interventions remain unclear.
OBJECTIVE: To address this uncertainty, we explored the responsiveness to our highly challenging balance and gait intervention (HiBalance) in people with PD.
METHODS: Thirty-nine participants with mild-moderate PD who underwent the HiBalance intervention from our randomized controlled trial were included. We defined response in three domains: (1) balance based on Mini-BESTest, (2) gait based on gait velocity, and (3) physical activity based on accelerometry-derived steps per day. In each domain, we explored three responsiveness levels: high, low, or non-responders according to the change from pre- to post-intervention. Separate Random Forests for each responder domain classified these responsiveness levels and identified variable importance.
RESULTS: Only the Random Forest for the balance domain classified all responsiveness levels above the chance level indicated by a Cohen\'s kappa of \"slight\" agreement. Variable importance differed among the responsiveness levels. Slow gait velocity indicated high responders in the balance domain but showed low probabilities for low and non-responders. For low and non-responders, fall history or no falls, respectively, were more important.
CONCLUSIONS: Among three responder domains and responsiveness levels, we could moderately classify responders in the balance domain, but not for the gait or physical activity domain. This can guide inclusion criteria for balance-targeted, personalized intervention studies in people with PD.

OBJECTIVE: To date, there is no reported effective biomarker that can predict which Alzheimer\'s disease (AD) patients will respond to donepezil and which will not. This study aimed to investigate whether baseline values of Aβ oligomers (AβOs), measured by the Multimer Detection System-Oligomeric Aβ (MDS-OAβ), can be used to predict responders after 6 months of donepezil medication.
METHODS: The study enrolled 104 patients diagnosed with probable AD. After 6 months of donepezil medication, the response to treatment was evaluated by re-assessing the Korean version of the Mini-Mental State Examination (K-MMSE) and Clinical Dementia Rating scale-Sum of Box (CDR-SB) scales conducted at baseline. The patients were categorized into two groups according to the baseline MDS-OAβ values known as the cut-off for AD diagnosis: a group with values below 0.78 and another group with values equal to or above 0.78.
RESULTS: After 6 months of medication, the number of responders was 50 (49.5%). Responders exhibited significantly worse baseline CDR, CDR-SB, K-MMSE, and Barthel index compared with non-responders. There was a significantly higher number of responders among patients with MDS-OAβ values below the cut-off of 0.78 compared with those with values equal to or above this threshold. Furthermore, there was a significant improvement in the K-MMSE and CDR-SB after 6 months of donepezil medication in patients with MDS-OAβ values below 0.78 compared with those with values equal to or above 0.78.
CONCLUSIONS: Baseline MDS-OAβ values might constitute a novel biochemical marker for the efficacy of 6 months of donepezil treatment in AD. Geriatr Gerontol Int 2024; ••: ••-••.

BACKGROUND: The fibrosis-5 (FIB-5) index is a noninvasive marker for assessing the progression of liver fibrosis and predictor in patients with heart failure (HF). This study investigated the association between the FIB-5 index and response to cardiac resynchronization therapy (CRT) and evaluated its predictive value for prognosis.
METHODS: In total, 203 patients who underwent CRT/CRT-defibrillator (CRT-D) implantation were retrospectively included. The FIB-5 index was calculated using blood samples obtained before and after CRT/CRT-D. Response to CRT was defined as a relative reduction in left ventricular end-systolic volume of ≥15% 6 months after CRT/CRT-D. We compared the prognosis after CRT/CRT-D between the groups according to the FIB-5 index.
RESULTS: One hundred and twenty-three patients (61%) responded to CRT. The responder group demonstrated a significantly higher FIB-5 index than the nonresponder group (-2.76 ± 3.85 vs. -4.67 ± 3.29, p < 0.001). Receiver-operating characteristic analysis demonstrated that the area under the curve of the FIB-5 index was 0.660 with a cutoff value of -4.00 for responders. In multivariate analysis, FIB-5 index ≥ -4.00 was an independent predictor for CRT response (odds ratio: 3.665, p = 0.003), in addition to QRS duration ≥ 150 ms and echocardiographic dysynchrony. The FIB-5 index increased significantly after 6 months in the responder group but not in the nonresponder group. The FIB-5 index ≥ -4.00 group showed a significantly better prognosis for cardiac death, HF hospitalization, and composite endpoint than the FIB-5 index < -4.00 group.
CONCLUSIONS: The FIB-5 index in addition to classical predictors may be a useful marker for predicting response to CRT.

BACKGROUND: Severe asthma (SA) presents a considerable healthcare challenge despite optimal standard treatment. Dupilumab, which is effective in type 2 (T2) SA patients, demonstrates variable responses, categorizing patients as non-responders, partial responders, or those achieving clinical remission. However, real-world response rates remain underexplored. Additionally, understanding the characteristics of patients achieving clinical remission is crucial for predicting favourable responses to dupilumab.
OBJECTIVE: To investigate responder types and identify predictors of clinical remission and non-response induced by dupilumab in a real-world cohort of SA patients.
METHODS: We analyzed retrospective data from SA patients undergoing dupilumab treatment in a study conducted at Franciscus Gasthuis & Vlietland hospital. Data were collected at baseline and at a 12 to 24-months follow-up (T = 12). Response rates were evaluated at T = 12. Predictors of non-response and clinical remission were investigated using multivariate logistic regression analysis with a stepwise forward variable selection approach.
RESULTS: Among the 175 patients screened, 136 met the inclusion criteria. At T = 12, 31.6 % achieved clinical remission, 47.1 % were partial responders and 21.3 % were non-responders. Predictors associated with clinical remission included high baseline blood eosinophil counts (BEC) and male sex. Conversely, younger age at baseline, low baseline total immunoglobin E (IgE) and low baseline fractional exhaled nitric oxide (FeNO) levels were identified as predictors of non-response.
CONCLUSIONS: Dupilumab results in clinical disease remission in one-third of the treated patients. Clinical remission is predicted by high BEC and male sex, whereas low total IgE, low FeNO and younger age indicate a lower likelihood of response.

Objective.Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive method of stimulating the vagus nerve, simultaneously affects the autonomic nervous system (ANS) and central nervous system (CNS) through efferent and afferent pathways. The purpose of this study is to analyze the effect of taVNS on the ANS and CNS through heart rate variability (HRV) and electroencephalography (EEG) parameters of identified responders.Approach.Two sets of data were collected from each of 10 healthy adult male subjects in their 20 s, and five HRV parameters from the time domain (RMSSD, pNN50, pNN30, pNN20, ppNNx) and two EEG parameters (power of alpha band, power of delta band) were extracted.Main results.Based on pNN50, responders to taVNS were identified; among them, pNN50 (p= 0.0041) and ppNNx (p= 0.0037) showed significant differences before and after taVNS. At the same time, for alpha power and delta power of EEG, significant difference (p< 0.05) was observed in most channels after taVNS compared to before stimulation.Significance.This study demonstrated the validity of identifying responders using pNN50 and the influence of taVNS on both the ANS and CNS. We conclude that taVNS can be used to treat a variety of diseases and as a tool to help control the ANS and CNS.

Background and Objective: Patients with spinal muscular atrophy (SMA) treated with a disease-modifying therapy (DMT) are often classified as responders or non-responders based on the attainment of a specific improvement threshold on validated functional scales. This categorization may significantly impact treatment reimbursement in some countries. The aim of this research is to evaluate the perception of treatments and their benefit by patients considered as responders or non-responders. Methods: In this non-commercial multicenter study, 99 post-symptomatically treated SMA type I-III patients with a median age of 11.2 (0.39-57.4) years at treatment initiation were stratified into three groups based on their treatment outcomes, i.e., those exhibiting clinically significant improvement (N = 41), those with non-clinically significant improvement (N = 18), or those showing no improvement (N = 40). Fifteen months after treatment, the initiation patients or patients\' caregivers were assessed using a patient-rated scoring system based on the Patient Global Impression of Change (PGIC) scale, comprising 22 questions targeting important aspects and tasks in the daily life of patients with SMA. Results: We found no statistical difference in the patient perception of treatment benefits in 17 out of 22 domains across patient groups. Conclusions: Our results suggest that functional motor scales do not recapitulate patients\' and patients\' caregivers\' experience of the effect of nusinersen treatment in SMA.

BACKGROUND: Several studies have evaluated the role of QRS duration (QRSd) or QRS narrowing as a predictor of response to cardiac resynchronization therapy (CRT) to reduce nonresponders.
OBJECTIVE: Our study aimed to determine the correlation between the relative change in QRS index (QI) compared to clinical outcome and prognosis in patients who underwent CRT implantation.
METHODS: A three-centers study involving 398 patients with a CRT device was conducted. Clinical, echocardiographic and pharmacological variables, QRSd before and after CRT implantation and QI were measured.
RESULTS: In a 6-month follow-up, a significant improvement in left ventricular ejection fraction (LVEF), left ventricular end-diastolic and systolic volumes (LVEDV and LVESV) were observed. QI was related to reverse remodeling (multiple r-squared: 0.48, adjusted r-squared: 0.43, p = .001), and the cut-off value that best predicted LV reverse remodeling after 6 months of CRT was 12.25% (AUC 0.7, p = .001). At 24 months, a statistically significant difference was found between patients with a QI ≤ 12.25% and those with a QI > 12.25% regarding NYHA class worsening (p = .04). The mean of the QI of patients who died from cardiovascular causes was lower than patients who died of other causes (p = .0179). A correlation between pre-CRT QRSd/LVEDV and QI was observed (r = + 0.20; p = .0003). A higher QRSd/LVEDV ratio was associated with an improved LVEF, LVEDV, and LVESV (p < .0001) at follow-up.
CONCLUSIONS: QI narrowing after CRT was related to greater echocardiographic reverse remodeling and a lower rate of adverse events (death or cardiovascular hospitalizations). The QI can improve the prediction of adverse events in a population with CRT regardless of comorbidities according to the Charlson Comorbidity Index. QI could be used to predict CRT response.

BACKGROUND: Vasomotor symptoms (VMS), the characteristic symptoms of menopausal transition, are often the primary reason women seek treatment. Current treatment options for VMS include fezolinetant, a nonhormonal, selective neurokinin 3 receptor antagonist. This study aimed to define a clinically meaningful threshold for reduction of moderate-to-severe VMS in postmenopausal women treated with fezolinetant and then apply it in a responder analysis of the pooled trial data.
METHODS: This analysis pooled data from two identical phase 3, double-blind, placebo-controlled studies that randomized women with moderate-to-severe VMS to once-daily fezolinetant 30 mg, 45 mg, or placebo (SKYLIGHT 1 and 2). The frequency of VMS was collected daily using an electronic diary. Patients completed the Patient Global Impression of Change in VMS (PGI-C VMS) instrument, which assessed changes in hot flushes/night sweats at weeks 4 and 12 compared with baseline using a seven-point Likert scale. VMS frequency data were anchored to PGI-C VMS data; the anchor level for meaningful within-patient change in PGI-C VMS was \"moderately better.\"
RESULTS: In the pooled population (N = 1022), the mean (standard deviation) estimated thresholds for a meaningful within-patient change in moderate-to-severe VMS frequency were - 5.73 (3.47) at week 4 and - 6.20 (5.18) at week 12. Applying the thresholds for meaningful within-patient change to responder analyses (\"missing as non-responder\" imputation method) indicated a favorable clinical benefit: greater proportions of responders were observed in the fezolinetant 30-mg and 45-mg groups compared with placebo at week 4 (odds ratio range 2.48-2.91; P < 0.001) and week 12 (odds ratio range 1.908-2.68; P < 0.001).
CONCLUSIONS: PGI-C VMS is sensitive to change and correlates with VMS frequency: a reduction of approximately six VMS episodes per day from baseline to week 12 was meaningful at the individual patient level. Fezolinetant provides a meaningful clinical benefit for women with moderate-to-severe VMS associated with menopause and represents an important nonhormonal treatment option.
BACKGROUND: NCT04003155 and NCT04003142.