Response Trajectories Research Articles

Tunnels as Temples of 'New Green India': Dominant Narratives of Himalayan Dam Building

The dramatic unfolding of the Joshimath crisis in Uttarakhand, India, has brought the world’s attention once again to the Himalaya. The contribution of a 520-megawatt hydropower dam to land subsidence is squarely in the spotlight. River valleys with bumper-to-bumper hydropower dam building, especially in the North Western Himalaya, in the past decade and a half or so, have witnessed frequent slope de-stabilisation, landslides and seepages. Unlike the visible dispossession of rural—often adivasi and dalit— populations in reservoir based dam affected areas, even establishing and ‘scientifically’ correlating cascading hazards with human impacts of the ‘invisible’ activity of run-of-the-river dams in the relatively sparsely populated regions of the Himalaya, has been an uphill battle for impacted mountain people. This article examines the conflict around hydropower development in Himachal Pradesh to understand the trajectory of State policy, dominant narratives and responses of affected communities. Tracing the history of such contestation in the 180 MW Bajoli Holi hydropower project in Chamba’s tribal belt Bharmour, we illustrate the complicity of project proponents, regulatory institutions, political actors, scientists and the judiciary in transferring the project’s risks to local inhabitants and the environment. The burden of building fresh evidence, staking claims and posing counter-narratives lies unfairly with the dispossessed as they struggle for safety and survival.

An OMICS‐based analytical framework to identify metabolic predictors of the cognitive response to a multimodal intervention: preliminary findings from the PENSA Study

AbstractBackgroundNot all individuals may respond to a cognitive decline preventive intervention. However, the low frequency of cognitive assessments during short‐lasting interventions hampers the study of the heterogeneity of treatment effects (HTE). We have recently developed and validated an innovative method for remote monthly monitoring of executive functions, which leverages the performance indicators from cognitive training games (CTG) (Figure 1). Here, we aimed to examine the HTE to a multimodal intervention using this CTG measure and to identify which baseline glycaemic, lipidic, and inflammatory factors are associated with the cognitive response profiles.MethodsWe included N = 98 individuals (65.3% females; 67.2 ±4.6 years) APOE‐ɛ4 carriers with Subjective Cognitive Decline who had completed eight months of the PENSA Study multimodal intervention on January 2023. We analysed P = 62 baseline exposures that included: anthropometric factors, biochemical parameters, endocannabinoids, and plasma metabolites of the tryptophan and glutamine metabolism. First, we examined the HTE with the CTG measure as the outcome (6 repeated measures/subject) using growth mixture models. Second, we assessed the partial correlations between exposures using graphical LASSO with stability selection. Finally, we identified the most contributing predictors to the cognitive response profiles using stability selection‐based LASSO multinomial regression, fit on 500 random 80% subsamples of the data using the R package ‘sharp’.ResultsWe identified and labelled three different cognitive response trajectories: ‘average respondents’ (75.6%), ‘super respondents’ (16.3%), and ‘non‐respondents’ (8.2%) (Figure 2A). The network of exposures showed higher intra‐family than inter‐family correlations (Figure 2B). Finally, four out of 62 exposures were identified as stable predictors of the cognitive response profiles (Figure 2C). Compared to ‘average respondents’ the ‘super‐respondents’ and ‘non‐respondents’ presented higher carnitine and serotonin concentrations. However, fasting plasma glucose and total cholesterol were lower in ‘super‐respondents’ (OR = 0.63 and OR = 0.69) and higher in ‘non‐respondents’ (OR = 6.07 and OR = 2.40).ConclusionsThis study shows that not all individuals at high risk of Alzheimer’s disease respond to an intensive lifestyle‐based multimodal intervention, and that baseline cholesterol and glycaemic homeostasis could determine the success of preventive interventions for cognitive decline. Further cholesterol‐ and glycaemic‐related metabolites should be analysed to better understand the underlying mechanisms of these findings.

A O03 Host phenotypic adversity independently predicts progression to resection in neoadjuvantly-treated pancreatic cancer

Abstract Background Neoadjuvant treatment (NAT) offers a modest survival benefit to the otherwise dismal outcomes of pancreatic ductal adenocarcinoma (PDAC), however methods for assessing treatment response and disease trajectory during NAT are limited. Cachexia and sarcopenia are hallmark features of PDAC and defining host phenotypic adversity is crucial in understanding the tumour-host relationship and its influence on clinical outcomes. We sought to determine the relationship between body composition, systemic inflammation, and outcomes in NAT PDAC to lay foundations for improving assessment of treatment response. Methods This is a retrospective, observational study with an intention-to-treat design, analysing resected (n = 109) and non-resected (n = 117) NAT PDAC (total n = 226) from the tertiary West of Scotland Pancreatic Unit, Glasgow Royal Infirmary. Patients were included if they had resectable or borderline resectable disease and received NAT. Patients were excluded if they had locally advanced or metastatic disease. Body composition was determined by single-slice L3 cross-sectional measurements. Results Patients with an adverse phenotype defined by change in body composition were less likely to progress to resection (40.9% vs 68.8%, p < 0.001). Logistic regression confirms the independence of this effect (OR 3.79, 95% CI 1.99-7.22, p < 0.001). There was a trend towards systemic inflammation in the non-resected group (CRP rise 51.4% vs 29.9%, p = 0.008). Patients treated with Folfirinox who required dose reduction received higher doses of irinotecan, 5-fluorouracil (bolus) and 5-fluorouracil (infusion) per unit muscle mass (7.3 vs 6.9mg/cm2⋅m-2, p = 0.010; 16.2 vs 14.7mg/cm2⋅m-2, p = 0.002; 96.5 vs 91.1mg/cm2⋅m-2, p = 0.026). Conclusions Host phenotypic adversity during NAT presents a potentially valuable addition to a limited arsenal of tools to aid decision making in resectable and borderline resectable PDAC. Early assessment of body composition trend during chemotherapy may present an opportunity to switch the host phenotype from adverse to favourable in some patients, or highlight the futility of continuing aggressive treatment in others. Chemotherapeutic prescribing by body surface area overlooks crucial differences in lean body mass and may be exposing patients to avoidable and burdensome toxicities.

Expressed emotion and early treatment response in family-based treatment for adolescent anorexia nervosa

ABSTRACT This study examined the effect of pre-treatment levels of parental expressed emotion (EE) on early treatment response for adolescent anorexia nervosa (AN). Data were collected from 121 adolescents, ages 12–18, who met DSM-IV criteria for AN excluding the amenorrhea criterion, and their parents. Participants were randomized to family-based treatment (FBT) or adolescent-focused therapy (AFT). To examine the effects of different thresholds of EE, we used two different levels of EE in analyses. Results demonstrated that adolescents who had at least one parent with elevated EE indicated by a lower threshold (i.e. even mild levels) at baseline were less likely to achieve an early treatment response, suggesting that EE might interfere with treatment success from the start of treatment. When high EE was defined by a higher threshold, these effects were no longer significant, regardless of treatment type (FBT or AFT). These findings suggest that adolescents with AN may be more sensitive to EE than other mental illnesses, such that lower thresholds of EE impact the speed with which they are able to reduce symptoms and gain weight in treatment. It may be necessary to target parental EE prior to or early in treatment or pivot to parent-focused treatment to change the trajectory of treatment response. Future research is needed to explore ways parental EE can be reduced.

Developmental Trajectory of the Frequency-Following Response During the First 6 Months of Life.

The aim of the present study is to characterize the maturational changes during the first 6 months of life in the neural encoding of two speech sound features relevant for early language acquisition: the stimulus fundamental frequency (fo), related to stimulus pitch, and the vowel formant composition, particularly F1. The frequency-following response (FFR) was used as a snapshot into the neural encoding of these two stimulus attributes. FFRs to a consonant-vowel stimulus /da/ were retrieved from electroencephalographic recordings in a sample of 80 healthy infants (45 at birth and 35 at the age of 1 month). Thirty-two infants (16 recorded at birth and 16 recorded at 1 month) returned for a second recording at 6 months of age. Stimulus fo and F1 encoding showed improvements from birth to 6 months of age. Most remarkably, a significant improvement in the F1 neural encoding was observed during the first month of life. Our results highlight the rapid and sustained maturation of the basic neural machinery necessary for the phoneme discrimination ability during the first 6 months of age.

Ruxolitinib add-on therapy in steroid-refractory graft-vs-host disease following hematopoietic cell transplantation: A single institutional experience

Steroid-refractory graft-vs-host disease (SR-GVHD) remains a significant cause of mortality after allogeneic hematopoietic cell transplantation (HCT), and the trajectory of treatment response for that vary. In our case series, we introduced six cases experiencing SR-GVHD who achieved better disease control after applying ruxolitinib (RUX). Of the six cases, five of them achieved symptoms-free while one of them, unfortunately, died of invasive fungal infection. Three alive cases were weaned off the RUX treatment successfully, while the remaining were on a medication tapering program. We demonstrated mixed efficacy in patients with SR-GVHD, suggesting that the RUX add-on may be a useful therapeutic adjunct in combination with other immunosuppressants.

Single trajectory treatment response for predominant negative symptoms: Post-hoc analysis of a clinical trial with cariprazine and risperidone.

Examining the heterogeneity of negative symptoms of schizophrenia contributes to the identification of available treatment targets. Generally, prior evidence classified three to four symptom treatment response trajectory groups over the course of positive symptoms, yet, no evidence exists regarding the heterogeneity of medium-term response to predominant negative symptoms. The current post-hoc analysis aims to identify the heterogeneity in negative symptom treatment response trajectories among patients with predominant negative symptoms who received either cariprazine or risperidone for 26weeks. Treatment response was analyzed based on the: the Positive and Negative Syndrome Scale Factor Score for Negative Symptoms (PANSS-FSNS), and the Clinical Global Impression Severity (CGIS) and Improvement (CGII) scales. To identify subgroups of patients with a similar course of treatment response, group-based trajectory modelling was utilized. Results demonstrated that in comparison with competing models, a single trajectory best described the treatment response of patients with predominant negative symptoms. The results indicate that patients with predominant negative symptoms with over ten years of schizophrenia respond rapidly to adequate treatment and follow a course of steady improvement.

Quantifying the impact of immunotherapy on RNA dynamics in cancer

BackgroundCheckpoint inhibitor (CPI) immunotherapies have provided durable clinical responses across a range of solid tumor types for some patients with cancer. Nonetheless, response rates to CPI vary greatly between cancer...

Co-evolution of SARS-CoV-2 variants and host immune response trajectories underlie COVID-19 pandemic to epidemic transition

COVID-19 pandemic saw emergence of multiple SAR-CoV-2 variants. Exacerbated risk of severe outcome and hospital admissions led us to comprehend differential host-immune kinetics associated with SARS-CoV-2 variants. Longitudinal investigation was conducted through different time periods of Pre-VOC and VOCs (Delta& Omicron) mapping host transcriptome features. Robust antiviral type-1 interferon response marked Omicron infection, which was largely missing during Pre-VOC and Delta waves. SARS-CoV-2-host protein-protein interactions and docking complexes highlighted N protein to interact with HNRNPA1 in Pre-VOC, demonstrating its functional role for enhanced viral replication. Omicron revealed enhanced binding efficiency of LARP1 to N protein, probably potentiating antiviral effects of LARP1. Differential expression of zinc finger protein genes, especially in Omicron, mechanistically support induction of strong IFN (Interferon) response, thereby strengthening early viral clearance. Study highlights eventual adaptation of host to immune activation patterns that interrupt virus evolution with enhanced immune-evasion mutations and counteraction mechanisms, delimiting the next phase of COVID-19 pandemic.

Mental Distress Among Norwegian Adults During the COVID-19 Pandemic: Predictors in Initial Response and Subsequent Trajectories.

Objectives: To identify factors associated with change in mental distress at the onset of the COVID-19 pandemic, relative to pre-pandemic levels, and with changes during the following 1.5years. Methods: The prospective Norwegian Mother, Father and Child Cohort Study collected eight waves of data during the pandemic (March 2020-September 2021) in 105,972 adult participants used for this analyses. A piecewise latent growth model was fitted to identify initial level and longitudinal changes in mental distress. Results: Mental distress peaked at the beginning of the pandemic. Factors associated with initial increases were: medical conditions, living alone, history of psychiatric disorders, lower education, female sex, younger age, and obesity. Being quarantined or infected with SARS-CoV-2 were associated with increasing distress while being vaccinated was associated with reduced mental distress. Conclusion: Having a chronic disease and being quarantined or infected by the SARS-CoV-2 virus were associated with more mental distress during the pandemic. This knowledge is important for planning interventions to support individuals during future pandemics and other societal crises.

Plasmodium Infection-Cure Cycles Increase the Capacity of Phagocytosis in Conventional Dendritic Cells.

Malaria stands as one of the most pervasive human infectious diseases globally and represents a prominent cause of mortality. Immunity against clinical malaria disease is achieved through multiple infection and treatment cycles, culminating in a substantial reduction in parasite burden. To investigate this phenomenon, we established a murine model involving repeated infection-cure cycles, whereby mice were infected with the lethal rodent malarial parasite Plasmodium berghei ANKA and subsequently treated with the anti-malarial drug pyrimethamine. Our earlier study revealed a significant decrease in the capacity of conventional dendritic cells (cDCs) to produce cytokines upon stimulation in infection-cured mice. In the present study, we aimed to further elucidate the modulation of cDC functionality during repeated infection-cure cycles by examining their phagocytic capacity. Administering fluorescent beads to mice resulted in no significant difference in the total number of bead-positive cells within the spleens of both uninfected and 3-cure (three cycles of infection-cure) mice. However, the proportion of the CD11c+F4/80- population within bead-positive cells was notably higher in 3-cure mice compared to uninfected mice. Subsequent in vitro analysis of bead phagocytosis by purified CD11c+cDCs revealed that the cDC2 subset from 3-cure mice exhibited significantly enhanced phagocytic capacity in comparison to their uninfected counterparts. These findings underscore the substantial impact of repeated infection-cure cycles on various facets of cDC function, potentially influencing the trajectory of immune responses against subsequent malaria infections.

A fractional order PID tuning tool for automatic voltage regulator using marine predators algorithm

The fractional-order proportional-integral-derivative (FOPID) controller stands as a widely embraced choice for the task of automatic voltage regulation (AVR) when it comes to maintaining the voltage output of synchronous generators. Nevertheless, fine-tuning the FOPID controller presents a formidable challenge, mainly because it possesses five tuning gains, in contrast to the conventional PID controller, which has three gains. Consequently, this paper introduces a novel tuning tool tailored to the AVR system by utilizing the marine predators algorithm (MPA). To gauge the effectiveness of the proposed approach, two key evaluation criteria are employed: step response analysis and trajectory tracking analysis. The results of this research reveal that the MPA-FOPID controller demonstrates exceptional performance criteria, notably enhancing the AVR transient response in comparison to other FOPID controllers optimized through recent metaheuristic algorithms.

Variability of vaccine responsiveness in early life

Vaccinations in early life elicit variable antibody and cellular immune responses, sometimes leaving fully vaccinated children unprotected against life-threatening infectious diseases. Specific immune cell populations and immune networks may have a critical period of development and calibration in a window of opportunity occurring during the first 100 days of early life. Among the early life determinants of vaccine responses, this review will focus on modifiable factors involving development of the infant microbiota and metabolome: antibiotic exposure, breast versus formula feeding, and Caesarian section versus vaginal delivery of newborns. How microbiota may serve as natural adjuvants for vaccine responses and how microbiota-derived metabolites influence vaccine responses are also reviewed. Early life poor vaccine responsiveness can be linked to increased infection susceptibility because both phenotypes share similar immunity dysregulation profiles. An early life pre-vaccination endotype, when interventions have the highest potential for success, should be sought that predicts vaccine response trajectories.

“Trajectories of treatment response in a cognitive-behavioral therapy intervention for depression and adherence in persons with HIV in South Africa”

BackgroundPeople with HIV (PHW) are at greater risk of depression than the general population. Insight into the time-to-treatment-response and predictors of response to psychotherapy may improve implementation in primary care. MethodsWe assessed depression treatment response among 80 participants in a trial of cognitive-behavioral therapy for adherence and depression (CBT-AD) for PWH with MDD and suboptimal antiretroviral therapy (ART) adherence. Participants self-reported depressive symptoms (CESD) at each therapy session. Clinicians assessed participants' depression (HAMD), along with potential predictors of response, every four months for one year. Latent class analyses examined classes of responders for the active and the post-treatment phases. Regression analyses identified predictors of class membership for each phase. ResultsDuring the active treatment phase (CESD) we identified an early response (at session 2 and with continued trajectory of improvement) and a non-response group. There were also two classes during post-treatment (HAM-D): early responders (4-month) and late responders (12-month). Distress aversion was associated with lower likelihood of early response to CBT-AD (aOR = 0.74, 95%CI[0.56–0.90], p = .009), and social support was associated with increased likelihood of early response (aOR = 2.24, 95%CI[1.07–5.46], p = .045). LimitationsSelf-reported depression during the treatment phase may have resulted from social desirability bias. ConclusionsMost participants responded to CBT-AD early during treatment (89 %) and had sustained improvements in depression by 4 months (80 %). Distress aversion was a risk factor for late response, and social support was protective. Future research is needed to assess the optimal dose of CBT-AD in resource limited settings.

The levels of immunosuppressive checkpoint protein PD-L1 and tumor-infiltrating lymphocytes were integrated to reveal the glioma tumor microenvironment.

In spite of significant strides in the realm of cancer biology and therapeutic interventions, the clinical prognosis for patients afflicted with glioblastoma (GBM) remains distressingly dismal. The tumor immune microenvironment (TIME), a crucial player in the progression, treatment response, and prognostic trajectory of glioma, warrants thorough exploration. Within this intricate microcosm, the immunosuppressive checkpoint protein PD-L1 and tumor-infiltrating lymphocytes (TILs) emerge as pivotal constituents, underscoring their potential role in deciphering glioma biology and informing treatment strategies. However, prognostic models based on the association between PD-L1 expression and TIL infiltration in the tumor immune microenvironment have not been established. The aim of this study was to explore TIME genes associated with PD-L1 expression and TIL invasion and to construct a risk score for predicting the overall survival (OS) of GBM patients based on these genes. The samples were separately classified according to the PD-L1 expression level and TIL score and TIME-related genes were identified using differential expression and weighted gene co-expression network analysis. The DEGs were subjected to least absolute contraction and selection operator (LASSO) -Cox regression to construct TIME associated risk score (TIMErisk). A TIMErisk was developed based on STEAP3 and CXCL13 genes. The STLEAP3 was demonstrated to be involved in glioma progression. The results showed that the patients in the high TIMErisk group had poor OS compared with subjects in the low TIMErisk group. The biological phenotypes associated with TIMErisk were analyzed in terms of functional enrichment, tumor immune profile, and tumor mutation profile. The results on tumor immune dysfunction and exclusion dysfunction (TIDE) score and immune surface score (IPS) showed that GBM patients with different TIME risks had different responses to immunotherapy. Tumor purity analysis indicated that PD-L1 and TIL scores were positively correlated with TIMErisk score and negatively correlated with tumor purity. These results show that the TIMErisk-based prognostic model had high predictive value for the prognosis and immune characteristics of GBM patients. Immunohistochemical staining images of patients in the high and low TIMErisk groups were analyzed, showing that the degree of immune cell infiltration was higher in the high TIMErisk group relative to the low TIMErisk group. The present study provides a basis for understanding glioma tumor microenvironment and a foundation for conducting comprehensive immunogenomic analysis.

Relationship between heart rate variability and differential patterns of cortisol response to acute stressors in mid-life adults: A data-driven investigation.

Cortisol and heart rate variability (HRV) are well-established biomarkers of the human stress response system. While a relationship between cortisol and HRV is assumed, few studies have found evidence of their correlation within single study designs. One complication for isolating such a relationship may lie in individual variability in the cortisol response to stress such that atypical cortisol responding (i.e., elevated or blunted) occurs. To-date, studies on the cortisol response have employed traditional mean-difference-based approaches to examine average magnitude change in cortisol over time. Alternatively, data-driven trajectory modelling, such as latent growth mixture modelling, may be advantageous for quantifying cortisol based on patterns of response over time. Latent growth mixture modelling was used in N=386 adults to identify subgroups based on trajectories of cortisol responses to stress. The relationship between cortisol and HRV was tested within subgroups. Results revealed a 'prototypical' subgroup characterised by expected rise and fall in cortisol response to stress (n=309), a 'decline' subgroup (n=28) that declined in cortisol after stress, and a 'rise' subgroup (n=49) that increased in cortisol after stress. Within the 'prototypical' subgroup, greater HRV during stress was associated with decline in cortisol after stress from its maximum (r (306)=0.19, p<0.001). This relationship failed to emerge in the 'decline' and 'rise' subgroups (p>0.271). Results document different patterns of cortisol response to stress; among those who exhibit a 'prototypical' response, changes in HRV during stress are related to changes in cortisol after stress.

Prior SARS-CoV-2 Infection Enhances Initial mRNA Vaccine Response with a Lower Impact on Long-Term Immunity.

Spike-encoding mRNA vaccines in early 2021 effectively reduced SARS-CoV-2-associated morbidity and mortality. New booster regimens were introduced due to successive waves of distinct viral variants. Therefore, people now have a diverse immune memory resulting from multiple SARS-CoV-2 Ag exposures, from infection to following vaccination. This level of community-wide immunity can induce immunological protection from SARS-CoV-2; however, questions about the trajectory of the adaptive immune responses and long-term immunity with respect to priming and repeated Ag exposure remain poorly explored. In this study, we examined the trajectory of adaptive immune responses following three doses of monovalent Pfizer BNT162b2 mRNA vaccination in immunologically naive and SARS-CoV-2 preimmune individuals without the occurrence of breakthrough infection. The IgG, B cell, and T cell Spike-specific responses were assessed in human blood samples collected at six time points between a moment before vaccination and up to 6 mo after the third immunization. Overall, the impact of repeated Spike exposures had a lower improvement on T cell frequency and longevity compared with IgG responses. Natural infection shaped the responses following the initial vaccination by significantly increasing neutralizing Abs and specific CD4+ T cell subsets (circulating T follicular helper, effector memory, and Th1-producing cells), but it had a small benefit at long-term immunity. At the end of the three-dose vaccination regimen, both SARS-CoV-2-naive and preimmune individuals had similar immune memory quality and quantity. This study provides insights into the durability of mRNA vaccine-induced immunological memory and the effects of preimmunity on long-term responses.

S900 Response Trajectory by the Clinical Decision Support Tool Probability Groups in Vedolizumab-Treated Patients With Crohn’s Disease: A Pooled Analysis of GEMINI 2, VISIBLE 2, and VERSIFY

S900 Response Trajectory by the Clinical Decision Support Tool Probability Groups in Vedolizumab-Treated Patients With Crohn’s Disease: A Pooled Analysis of GEMINI 2, VISIBLE 2, and VERSIFY

Prospective Longitudinal Assessment of Quality of Life after Stereotactic Ablative Radiotherapy for Oligometastases: Analysis of the Population-Based SABR-5 Phase II Trial

To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases. The SABR-5 trial was a population-based single-arm phase II study of SABR to up to 5 sites of oligometastases, conducted in 6 regional cancer centers in British Columbia from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and 3, 6, 9, 12, 15, 18, 21, 24, 30, and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal, and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and baseline score of individual patients. Mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with "stable," "improved," or "worsened" QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI Functional Interference Score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3). All enrolled patients with baseline QoL assessment and at least 1 follow-up assessment were analyzed (n = 135). On equivalence testing, patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% CI [1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% CI [1.15 to 2.21]; FACIT-AD TOI mean difference: -8.76, 90% CI [-11.29 to -6.24]; POSI mean difference: -4.61, 90% CI [-6.09 to -3.14]). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). The majority of patients reported stable QoL at all time points (range: BPI worst pain 71-82%, BPI FIS 45-78%, FACIT-AD TOI 50-100%, POSI 25-73%). Clinically significant stability, worsening, and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months. SABR in the oligometastatic setting can lead to transient decreases in QoL. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterize patients at greatest risk for decreased QoL.

Determination of the most appropriate ACR response definition for contemporary drug approval trials in rheumatoid arthritis

ObjectivesTo evaluate which American College of Rheumatology (ACR) response definition (ACR20, 50 or 70) should primarily be used for efficacy claims in future drug approval trials of rheumatoid arthritis (RA).MethodsWe...