Clinical Meaningfulness Research Articles

Impact of walk advice alone or in combination with supervised or home-based structured exercise on patient-reported physical function and generic and disease-specific health related quality of life in patients with intermittent claudication, a secondary analysis in a randomized clinical trial

BackgroundSupervised exercise is an integral part of the recommended first-line treatment for patients with intermittent claudication (IC). By reflecting the patients’ perspectives, patient-reported outcome measurements provide additional knowledge to the biomedical endpoints and are important outcomes to include when evaluating exercise interventions in patients with IC. We aimed to evaluate the one-year impact of three strategies: unsupervised Nordic pole walk advice (WA), WA + six months of home-based structured exercise (HSEP) or WA + six months of hospital-based supervised exercise (SEP) on health-related quality of life and patient-reported physical function in patients with IC.MethodsThis secondary exploratory analysis of a multi-center, randomized clinical trial compared three exercise strategies. The primary outcome of the secondary analysis was the one-year change in the 36-Item Short-Form (SF-36). Secondary outcomes were three- and six-months SF-36 changes alongside three, six- and 12-months changes in the disease-specific Vascular Quality of Life instrument (VascuQoL) and the Patient-Specific Functional Scale (PSFS). The Kruskal–Wallis test with Bonferroni-adjusted post-hoc tests were used for between-group comparisons. Effect size calculations were used to describe the size of observed treatment effects, and the clinical meaningfulness of observed changes in the VascuQoL summary score at one year was studied using established minimally important difference (MID) thresholds.ResultsA total of 166 patients with IC, mean age: 72.1 (SD 7.4) years, 41% women, were randomized. No significant between-group differences were observed over time for the SF-36 or the PSFS scores whereas some significant between-group differences were observed in the VascuQoL domain and summary scores over time, favoring SEP and/or HSEP over WA. The observed SF-36 and VascuQoL domain and summary score effect sizes were small to moderate, and many domain score effect sizes also remained unchanged over time. A significantly higher proportion of the patients in the SEP group reached the VascuQoL summary score MID of improvement in one year.ConclusionClinically important improvements were observed in SEP using the VascuQoL, while we did not observe any significant between-group differences using the SF-36. Whereas effect sizes for the observed changes over time were generally small, a significantly higher proportion of patients in SEP reached the VascuQoL MID of improvement.Trial registrationNCT02341716, January 19, 2015 (retrospectively registered).

Avacopan (Tavneos)


 CADTH recommends that Tavneos not be reimbursed by public drug plans as adjunctive treatment for adults with severe active antineutrophil cytoplasmic autoantibody-associated vasculitis (ANCA-AV) (granulomatosis with polyangiitis [GPA] and microscopic polyangiitis [MPA]).
 One clinical trial demonstrated that Tavneos in combination with ANCA-AV background therapy (including glucocorticoids and drugs that reduce immune system function) was as good as oral prednisone (60 mg dose reduced over 20 weeks) in combination with ANCA-AV background therapy for showing a reduction in disease symptoms at week 26 and was better than oral prednisone for maintaining symptom improvement at week 52. However, it was unclear if Tavneos offered a meaningful clinical benefit over other treatments used for ANCA-AV mainly because rituximab was not used as maintenance therapy in the trial, as is currently recommended by Canadian guidelines, and there is uncertainty around the clinical meaningfulness of the differences between the treatment groups for outcomes that assessed renal function, relapse, and Short Form [36] Health Survey version 2 (SF-36v2).
 There was not enough evidence to conclude that Tavneos met patients’ needs for a treatment that reduces or eliminates the use of glucocorticoids and their side effects as well as improves their health-related quality of life (HRQoL).

Assessing the validity and clinical meaningfulness of skin pain response (NRS30) assessed using numerical rating scale in hidradenitis suppurativa: Results from the SUNSHINE and SUNRISE trials

Assessing the validity and clinical meaningfulness of skin pain response (NRS30) assessed using numerical rating scale in hidradenitis suppurativa: Results from the SUNSHINE and SUNRISE trials

Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings.

The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics. We investigated 123 participants-23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME-who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy. Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance. JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.

Patient reported outcome measure for upper limb in Duchenne muscular dystrophy: correlation with PUL2.0.

The increasing pressure to include non ambulant Duchenne muscular dystrophy (DMD) boys in clinical trials has highlighted the need for outcome measures that could address the impact of upper limb function on activities of daily living. The aim of the present study was to establish the correlation between the recently developed Patient Reported Outcome Measure for the upper limb (PROM UL) and the observer rated functional scale Performance of Upper Limb (PUL 2.0) in a large cohort of DMD boys and young adults. As part of a larger natural history study, non ambulant DMD patients were assessed using PUL2.0 and PROM UL. One hundred and twenty-five concurrent PUL 2.0 and PROM UL evaluations from 60 non ambulant DMD boys were taken into consideration. The total PROM UL scores showed a strong correlation with both PUL 2.0 total scores and with PUL 2.0 entry item score. The strong correlation between the two tools confirms the clinical meaningfulness of the PUL2.0 and that the PROM UL can help to detect the gradient of progression of upper limb involvement.

Evaluating meaningful changes in physical functioning and cognitive declines in metachromatic leukodystrophy: a caregiver interview study

BackgroundMetachromatic leukodystrophy (MLD) is a rare lysosomal storage disease caused by deficient activity of arylsulfatase A (ASA). Treatment options for patients are limited; gene therapy based on haematopoietic stem cell transplantation is the only approved treatment for some subtypes of MLD. Any therapeutic benefit of treatments must be meaningful for patients and their families. We evaluated the clinical meaningfulness of slowing the decline in gross motor function as measured by the Gross Motor Function Classification in MLD (GMFC-MLD) from the caregiver perspective via semi-structured telephone interviews with caregivers of children with late-infantile MLD. We also evaluated the perceived significance of declines in communication abilities measured by the Expressive Language Function Classification in MLD (ELFC-MLD). This work could help to inform the endpoints of a phase 2 clinical trial (NCT03771898) assessing the efficacy of intrathecal recombinant human ASA in MLD.ResultsTwelve caregivers were recruited, reporting on 12 children with MLD. Children had a mean age of 6.1 years; mean age at symptom onset was 17.6 months. Most children (10/12) progressed from walking without support (categories 0–1) to a loss of locomotion (categories 5–6) in ≤ 2 years. Caregivers felt that GMFC-MLD and ELFC-MLD accurately described motor and language declines in their children, respectively. Most caregivers (10/12) reported that the idea of delaying disease progression would be meaningful. Further, a slowing of motor function decline in GMFC-MLD, from category 1 to category 3 or from category 2 to category 4 over 2 years, was seen as meaningful by all caregivers asked; however, only 3/12 caregivers reported that delayed decline would be meaningful if baseline category was ≥ 3. Caregivers also reported that delaying expressive language decline at any level that did not indicate a complete loss of expressive language (indicated by categories 1–3) would be meaningful.ConclusionsCaregivers of children with MLD felt that a delayed decline in gross motor function, as assessed by the GMFC-MLD, would be meaningful, supporting the selection of primary and secondary endpoints for the phase 2 clinical trial. Communication abilities were another area of significance for consideration in future clinical trial design.

Selecting an optimal real-time fMRI neurofeedback method for alcohol craving control training.

Real-time fMRI neurofeedback (rt-fMRI-NF) is a technique in which information about an individual's neural state is given back to them, typically to enable and reinforce neuromodulation. Its clinical potential has been demonstrated in several applications, but lack of evidence on optimal parameters limits clinical utility of the technique. This study aimed to identify optimal parameters for rt-fMRI-NF-aided craving regulation training in alcohol use disorder (AUD). Adults with AUD (n = 30) participated in a single-session study of four runs of rt-fMRI-NF where they downregulated "craving-related" brain activity. They received one of three types of neurofeedback: multi-region of interest (ROI), support vector machine with continuous feedback (cSVM), and support vector machine with intermittent feedback (iSVM). Performance was assessed on the success rate, change in neural downregulation, and change in self-reported craving for alcohol. Participants had more successful trials in run 4 versus 1, as well as improved downregulation of the insula, anterior cingulate, and dorsolateral prefrontal cortex (dlPFC). Greater downregulation of the latter two regions predicted greater reduction in craving. iSVM performed significantly worse than the other two methods. Downregulation of the striatum and dlPFC, enabled by ROI but not cSVM neurofeedback, was correlated with a greater reduction in craving. rt-fMRI-NF training for downregulation of alcohol craving in individuals with AUD shows potential for clinical use, though this pilot study should be followed with a larger randomized-control trial before clinical meaningfulness can be established. Preliminary results suggest an advantage of multi-ROI over SVM and intermittent feedback approaches.

#5834 ALBUMINURIA AND RENAL RESISTIVE INDEX ARE ASSOCIATED WITH MICROVASCULAR REMODELING IN PATIENTS WITH SEVERE OBESITY

Abstract Background and Aims Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in severe obesity, its noninvasive assessment with ultrasound still fails to provide pathophysiologic and clinical meaningfulness. The aim of the study is to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity. Method We enrolled forty-eight patients affected by severe obesity with an indication for bariatric surgery referring to our Clinic. Patients underwent an extensive renal examination with evaluation of eGFR with EPI-Cr formula, albuminuria and urinary TGF-β as indirect markers of kidney fibrosis, paired with Doppler ultrasound to measure renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L), wall-cross sectional area (WCSA) and vascular response to acetylcholine (ACh), alone or co-incubated with L-NAME, were measured. Results Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower eGFR and higher RRI compared to NT. The presence and extent of albuminuria were similar between the two groups, while TGF-β was slightly higher in the HT group (p = 0.059). Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT (p = 0.039). Multivariable analysis showed a relationship between M/L and RRI (p = 0.022, St.β 0.38) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation (p = 0.039, St. β = -0.36). Notably, all these correlations were consistent also after adjustment for confounding factors. Conclusion The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal hemodynamics and microcirculatory disruption.

Quality of Life Benefit and Clinical Predictors of Complete Skin Clearance in Psoriasis: A Multicenter, Prospective, Real-World Study

Background: Newer biologics, such as interleukin (IL)-17 inhibitors, make it possible to achieve complete skin clearance (CSC) in patients with moderate-to-severe psoriasis. However, the clinical meaningfulness and predictive factors of CSC in daily practice have not yet been fully investigated. Objective: The study was conducted to, first, assess the impact of CSC on quality of life (QoL) improvements compared with treatment responses without clearance and, second, identify clinical parameters as predictors of CSC response in psoriasis patients treated with ixekizumab. Methods: Patients attending 26 dermatology centers across China were recruited into this real-world setting between August 2020 and May 2022. Prospective cohort study in which response to ixekizumab was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI). The absolute DLQI score and DLQI (0) response at week 12 were compared between groups achieving various levels of skin clearance. A stepwise logistic regression analysis was applied to identify which baseline clinical characteristics were predictive factors for CSC. Results: After 12 weeks of treatment, 226 of 511 (44.2%) patients achieved CSC, defined as 100% improvement in PASI score (PASI-100). A significantly higher proportion of patients with CSC versus almost clear skin (PASI 90-99) achieved DLQI score of 0, corresponding to the experience of no impairment on QoL (54.4% vs. 37.7%, p = 0.001). Females patients were more likely than males to achieve CSC response (odds ratio [OR] = 1.83; 95% confidence interval [CI]: 1.24–2.70), while previous biologic treatment (OR = 0.43; 95% CI: 0.24–0.81) and joint affected (OR = 0.61; 95% CI: 0.42–0.89) were significantly associated with less CSC response. Conclusions: This study highlights the fact that clinical parameters are important in determining CSC response in psoriasis. In daily practice, achieving CSC represents a clinically meaningful treatment goal, especially from the patient perspective.

Patient-reported outcomes (PROs) among men receiving talazoparib (TALA) + enzalutamide (ENZA) vs placebo (PBO) + ENZA as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC): Results from a phase 3 study (TALAPRO-2).

5013 Background: TALAPRO-2 (NCT03395197) showed statistically significant improvement in radiographic progression free survival with TALA + ENZA (n=402) vs PBO + ENZA (n=403) (HR=0.63 95% CI 0.51-0.78; P<0.001) in men receiving 1L treatment for mCRPC. Here we report PRO endpoints from TALAPRO-2. Methods: PROs were assessed at day 1 (baseline) and at scheduled visits until radiographic progression (every 4 weeks until week 53, and then every 8 weeks) using the EORTC QLQ-C30 and its prostate cancer module, QLQ-PR25. Prespecified PRO analyses included overall mean change from baseline (per longitudinal repeated measures mixed-effects model) and time to definitive clinically meaningful (≥10-point change) deterioration (TTD). Between-arm comparisons of TTD were made using a stratified log-rank test and a Cox proportional hazards model. Results: Of the 805 men randomized and treated, 793 had a baseline score followed by at least 1 post-baseline score; TALA + ENZA (n=395), PBO + ENZA (n=398). Although the treatment effect on global health status (GHS)/quality of life (QoL) significantly favored PBO + ENZA, the predefined threshold of clinical meaningfulness was not met; moreover, no significant differences between the arms were observed in any functioning scales. A significantly longer TTD in GHS/QoL was observed for TALA + ENZA; HR=0.780 (95% CI: 0.62, 0.99), P=0.038; median: 30.8 months vs 25.0 months. A numerical greater delay in TTD in urinary symptoms was longer for TALA + ENZA; HR=0.759 (95% CI: 0.543, 1.061), P=0.105; median not reached vs 35.9 months. Additional PRO results will be presented. Conclusions: Compared with PBO + ENZA, in the TALA + ENZA arm there was 1) a modest deterioration disfavoring GHS/QoL (deterioration was not clinically meaningful based on the predefined threshold), and 2) a maintenance in all functioning scales. TTD in GHS/QoL was significantly longer with TALA + ENZA vs PBO + ENZA, reflecting improved disease control. These results complement the benefit-risk assessment of TALAPRO-2. Clinical trial information: NCT03395197 . [Table: see text]

Change over time in functional capacity and self-perceived health status for patients with chronic musculoskeletal pain: a registry-based longitudinal study

Chronic musculoskeletal pain is a major public health problem worldwide. Both self-reported functional capacity and self-perceived health status are reduced in patients with chronic musculoskeletal pain. Previous studies mostly assessed functional capacity through self-reported questionnaires instead of objective measurements. The aim of this study, therefore, is to assess the amount of change over time and its clinical meaningfulness in functional capacity and self-perceived health status of patients with chronic musculoskeletal pain undergoing Bern Ambulatory Interprofessional Rehabilitation (BAI-Reha). The registry-based longitudinal cohort study with prospectively collected data from a rehabilitation programme took place in a real-life setting. Patients (n = 81) with chronic musculoskeletal pain took part in the BAI-Reha. The main outcomes were the six-minute-walk test (6MWT), the safe maximum floor-to-waist lift (SML) and the European Quality of Life and Health measure visual analogue scale (EQ VAS). Timepoints of measurement were at baseline and post-BAI-Reha (i.e., at 4 months). The quantity of interest was the adjusted time effect (point estimate, 95% confidence interval, and p-value for testing the null hypothesis of no change over time). Statistical significance (α= 0.05) and clinical meaningfulness of the mean value change over time were assessed using predefined thresholds (six-minute-walk test 50 m, SML 7 kg, and EQ VAS 10 points). The linear mixed model analysis showed a statistically significant change over time for the six-minute-walk test (mean value change 56.08 m, 95% CI [36.13, 76.03]; p <0.001), SML (mean value change 3.92 kg, 95% CI [2.66, 5.19]; p <0.001), and EQ VAS (mean value change 9.58 points, 95% CI [4.87, 14.28]; p <0.001). Moreover, the improvement in the six-minute-walk test is clinically meaningful (mean value change 56.08 m) and almost clinically meaningful (mean value change 9.58 points) in the EQ VAS. Patients walk further, lift more weight, and feel healthier after interprofessional rehabilitation when compared to baseline measurement. These findings confirm and add to previous results. We encourage other providers of rehabilitation for patients with chronic musculoskeletal pain to measure functional capacity with objective outcome variables and to use self-reported outcome measures in addition to self-perceived health status. The well-established assessments used in this study are suitable for this purpose.

Defining Clinical Meaningfulness in Huntington's Disease.

Minimal clinically important difference (MCID) represents the smallest within-person change on an outcome measure considered meaningful to the patient. Anchor-based MCID methods evaluate the relationship between changes in an outcome measure and the patient-reported clinical importance of that change. This study aims to estimate longitudinal MCID for clinically relevant outcome measures for individuals who have Stages 2 or 3 disease as measured by the Huntington's Disease Integrated Staging System (HD-ISS). Data were drawn from Enroll-HD, a large global longitudinal, observational study and clinical research platform for HD family members. We analyzed HD participants (N = 11,070) by staging group using time frames ranging from 12 to 36 months. The anchor was the physical component summary score of the 12-item short-form health survey. HD-relevant motor, cognitive, and functional outcome measures were independent, external criterion outcomes. Complex analysis was conducted using multiple, independent, linear mixed effect regression models with decomposition to calculate MCID for each external criterion by group. MCID estimates varied by progression stage. MCID estimates increased as stage progression increased and as the time frame increased. MCID values for key HD measures are provided. For example, starting in HD-ISS stage 2, meaningful group change over 24 months equals an average increase of 3.6 or more points on the Unified Huntington's Disease Rating Scale Total Motor Score. This is the first study to examine MCID estimation thresholds for HD. The results can be used to improve clinical interpretation of study outcomes and enable treatment recommendations to support clinical decision-making and clinical trial methodology. © 2023 International Parkinson and Movement Disorder Society.

‘Time Saved’ As a Demonstration of Clinical Meaningfulness and Illustrated Using the Donanemab TRAILBLAZER-ALZ Study Findings

In Alzheimer’s disease (AD) clinical trials, disease-modifying therapies are expected to slow the rate of disease progression. Treatment effects are evaluated using a validated clinical scale as the difference between treatment and placebo in mean change from baseline to endpoint. Understanding the clinical relevance of this metric is not necessarily intuitive. Expressing active treatment-placebo difference as a time metric (i.e., months saved with treatment) has potential to provide a metric that is more easily and consistently interpreted. Using data from the TRAILBLAZER-ALZ study, time component tests (TCTs) were employed to determine the time saved with donanemab (an amyloid lowering drug) treatment. At study endpoint (Week 76), disease progression was delayed by 5.3 months and 5.2 months as measured by the Integrated Alzheimer’s Disease Rating Scale (iADRS) and the Clinical Dementia Rating Sum of Boxes (CDR-SB), respectively.

Abstract #1368352: Significance of LH Estimation While Evaluating Erectile Dysfunction in Male Subjects with Type 2 Diabetes Mellitus

Erectile Dysfunction (ED) is quite common in male subjects with Type 2 Diabetes Mellitus and many of them have Hypogonadism (low testosterone). There are subjects having ED despite having normal testosterone levels and among them some may have Compensated hypogonadism (CH), an entity characterized by normal testosterone with an increase in LH level and is associated with a unique symptomatology. The objective was to determine the prevalence of CH in male subjects with type 2 diabetes having ED and to evaluate its correlations. It was a cross-sectional study among the T2DM subjects attending the OPD of an Endocrinology Specialty Hospital. 500 male subjects with T2DM were screened for ED using International Index of Erectile Function-5 (IIEF-5) questionnaire, which consists of 5 items; a sum score of 21 or less indicates the presence of ED. Out of these 127 (25.4%) subjects were diagnosed as having ED. These subjects underwent clinical and biochemical evaluation including Lipid profile, HbA1c, Testosterone, LH, TSH, Prolactin. Compensated hypogonadism was defined (European Male Aging Study) as total testosterone > 10.5 nmol / L and LH > 9.4 IU /L. The mean age of the participants was 56.4 ± 6.7 years and the mean duration of diabetes was 11.9 ± 7.4 years. Hypertension was present in 51.5% and CAD in 26.6% of subjects. Among the participants 44.2% had hypogonadism (low T) whereas compensated hypogonadism was present in additional 9.5%. CH was positively correlated with older age (>55yrs) (p<0.01), the severity of ED (p-0.02), Hypertension (p-0.02), CAD (p<0.01) and LDL (p-0.012) but not with HbA1c. There was a statistically significant negative correlation between LH level and IIEF-5 score. Hypogonadism is common in males with T2DM and is characterized by clinical and biochemical evidence of testosterone deficiency. Compensated hypogonadism (CH) is a subclinical deficiency of testosterone (normal testosterone and high LH). Symptoms of CH may include ED, low moods, decreased muscle mass, sleep disturbances, mobility issues and fatigue. Our study shows CH to be correlating with sexual dysfunction, hypertension, CAD and LDL in subjects with T2DM. Hypogonadism is treated with testosterone but in CH only limited studies have demonstrated some positive effects of testosterone therapy and the clinical meaningfulness of these findings remains debatable. The present management strategies for CH include healthy lifestyle habits, exercise, nutritious diet, reducing stress and getting good sleep. We suggest larger studies to validate our findings, to essentially include LH estimation in the workup of ED and consider formation of guidelines regarding management of CH in subjects with T2DM including the place of testosterone therapy.

Patient Concept Elicitation Interviews: Insights into Multiple System Atrophy (MSA) Patient Experiences and Relevance of a modified United Multiple System Atrophy Rating Scale (P8-9.003)

Patient Concept Elicitation Interviews: Insights into Multiple System Atrophy (MSA) Patient Experiences and Relevance of a modified United Multiple System Atrophy Rating Scale (P8-9.003)

Personal meaningfulness of potential FDA-approved treatments: Perspectives of individuals living with Alzheimer's disease.

With the emergence of new clinical trial data on disease-modifying therapies in several. Alzheimer's disease (AD) studies, the Alzheimer's Association convened individuals living with AD to gain their perspective on meaningfulness and new treatments.A total of 30 Alzheimer's Association National Early Stage Advisory Group members participated in a focus group or an online survey to gain insights on what is wanted from a first-in-class treatment that could stop the progression of their disease at the earliest stage. Participants felt that researchers and regulators need to consider personal meaningfulness alongside clinical meaningfulness. At the same time, individuals living with AD felt that access, education, choice, and affordability were all important considerations moving forward.

The renal resistive index is associated with microvascular remodeling in patients with severe obesity.

Renal hemodynamics is impaired since the early stage of cardiometabolic disease. However, in obesity, its noninvasive ultrasound assessment still fails to provide pathophysiologic and clinical meaningfulness. We aimed to explore the relationship between peripheral microcirculation and renal hemodynamics in severe obesity. We enrolled fifty severely obese patients with an indication for bariatric referring to our outpatient clinic. Patients underwent an extensive reno-metabolic examination, paired with Doppler ultrasound and measurement of the renal resistive index (RRI). On the day of the surgery, visceral fat biopsies were collected to perform an ex-vivo complete microcirculatory assessment. Media-to-lumen ratio (M/L) and vascular response to acetylcholine (ACh), alone or co-incubated with N G -nitro arginine methyl ester (L-NAME), were measured. Patients were stratified according to their normotensive (NT) or hypertensive (HT) status. HT had lower estimated glomerular filtration rate and higher RRI compared to NT, while the presence and extent of albuminuria were similar between the two groups. Concerning microcirculatory assessment, there were no differences between groups as regards the microvascular structure, while the vasorelaxation to ACh was lower in HT ( P = 0.042). Multivariable analysis showed a relationship between M/L and RRI ( P = 0.016, St. β 0.37) and between albuminuria and the inhibitory response of L-NAME to Ach vasodilation ( P = 0.036, St. β = -0.34). Notably, all these correlations were consistent also after adjustment for confounding factors. The RRI and albuminuria relationship with microvascular remodeling in patients affected by severe obesity supports the clinical implementation of RRI to improve risk stratification in obesity and suggests a tight pathophysiologic connection between renal haemodynamics and microcirculatory disruption.

Response to van Dyck, O'Dell, & Mecca letter to the editor regarding Andrews etal. (2019).

Response to van Dyck, O'Dell, & Mecca letter to the editor regarding Andrews etal. (2019).

Session to Explore the Progress of Precision Psychiatry

Back to table of contents Previous article Next article Annual MeetingFull AccessSession to Explore the Progress of Precision PsychiatryNick ZagorskiNick ZagorskiSearch for more papers by this authorPublished Online:26 Feb 2023https://doi.org/10.1176/appi.pn.2023.03.3.33AbstractHow close is the psychiatric field to matching the right patients with the right treatment? Listen and find out. With innovation being one of the core themes of this year’s APA Annual Meeting, it is fitting that there will be a session focusing on a topic expected to play a major role in future psychiatric care: precision psychiatry.Taking concepts from the broader field of precision medicine, precision psychiatry aims for more individualization in patient care from the moment of diagnosis through treatment. “In psychiatry, we don’t classify disorders using biological systems the way a field like oncology does,” said session chair Daniel R. Karlin, M.D., the chief medical officer at MindMed, a company developing psychedelic and non-psychedelic psychiatric medicines and digital companion devices. Even in other fields like cardiology, physicians can rely on measurable physiological metrics (for example, stroke volume or blood pressure), whereas psychiatrists make a diagnosis based on phenomenology. “It’s how patients tell us they feel, and how we think they feel based on clinical observations,” he said. The result are disorders like depression that are highly likely to be biologically heterogenous.“What precision psychiatry asks is, Can we look at the information which we already have—such as a patient’s medical record and the patient’s behavioral phenomenology—with a finer grain so that we can make more precise diagnoses, ultimately working toward meaningfully incorporating biological information such as genomics?” Karlin said.This session will discuss the evolution of precision psychiatry, which was conceptualized as a field just recently but has a long tradition, Karlin explained. “If you think back to the early years of psychiatry and psychoanalysis, we had a rich system where doctors focused on what patients said and how they acted to develop robust diagnostic formulations and offer what could be called precision treatment in today’s vernacular—highly individualized psychotherapeutic interventions,” he said. Today, busy psychiatrists have to be more efficient with their time, but this is where machine learning programs and other digital tools can be helpful. Karlin and his co-presenters will highlight how technology is being used to collect more detailed patient data and discuss how soon some of these tools will be ready for routine use.“Part of the conversation will involve reigning in the hype,” Karlin said. “We would all love a future where a simple blood test could answer all of our questions, but if not developed with careful attention to clinical meaningfulness, today’s exciting advances in neuroscience or technology ultimately may not improve patient care.” But progress is being made, Karlin noted. The ability to monitor patients in real time with the help of mobile devices and acquire quantitative data on activity, sleep, and other characteristics could be transformative. “Psychiatry entails much observation, and our ability to observe improves daily.” ■ ISSUES NewArchived

Abstract P2-02-03: Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis

Abstract Background: Adjuvant regional nodal irradiation together with whole breast or chest wall irradiation is considered standard of care in most node positive early breast cancer. Existing data on adding internal mammary irradiation (IMNI) to the regional nodal fields are inconsistent. The objective of this study was to conduct a meta-analysis to explore the efficacy and safety of adding IMNI to adjuvant radiotherapy in early-stage, high risk breast cancer. Methods: A search of PubMed and EMBASE identified randomized trials that investigated the addition of IMNI to standard adjuvant radiation in early-stage breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for overall survival (OS), breast cancer specific survival (BCSS), disease-free survival (DFS) and distant-metastasis free survival (DMFS). The odds ratios (ORs) for regional and loco-regional recurrence, non-breast cancer mortality, secondary non-breast cancer, contralateral breast cancer and cardiovascular morbidity and mortality were also extracted. These data where pooled in a meta-analysis using RevMan 5.4. Results: Analysis included 5 trials comprising 10,994 patients. Compared to the control group, IMNI was associated with a small, but statistically significant improvement in OS (HR=0.91, 95% 0.85-0.97, p=0.004), BCSS (HR=0.84, 95%0.77-0.92, p&amp;lt; 0.001), DFS (HR=0.89, 95% CI 0.82-0.98, p= 0.01) and DMFS (HR=0.89, 95% 0.81-0.98, p=0.02). IMNI was also associated with reduced odds for regional (OR=0.58, 95% 0.44-0.75, p&amp;lt; 0.001) and loco-regional recurrence (OR=0.85, 95% CI 0.72-1.00, p=0.04). Subgroup analyses for OS by tumor location (medial/central vs. lateral) and by nodal burden showed similar benefit is all subgroups. The odds for cardiotoxicity were higher, but did not reach statistical significance (OR=1.23, 95% 0.99-1.53, p=0.07). There was no association with cardiovascular mortality (OR=1.00, 95% 0.69-1.46, p=1.00). There were also comparable odds for non-breast cancer mortality (OR=1.05, 95% 0.79-1.41, p=0.74), secondary cancer (OR=0.95, 95% 0.82-1.10, p=0.51) and contra-lateral breast cancer (OR=1.07, 95% 0.77-1.51, p=0.68). Conclusions: Compared to the control group the addition of IMNI in high-risk patients is associated with a statistically significant improvement in survival, albeit with a magnitude of questionable clinical meaningfulness. Non-significant association with increased cardiovascular toxicity requires further study in longer-term studies. Citation Format: Yasmin Korzets, Dina Levitas, Ahuva Grubstein, Ben W Corn, Eitan Amir, Hadar Goldvaser. Efficacy and Safety of the Addition of Internal Mammary Irradiation to Standard Adjuvant Radiation in Early-Stage Breast Cancer: A Systematic Review and Meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-02-03.