Median Weight Change Research Articles

Prognostic value of weight loss in hospitalized patients with heart failure.

Weight loss is a poor prognostic factor in patients with chronic heart failure (HF). However, whether the same is true for hospitalized patients with HF is unknown, even though hospitalization is the first opportunity for many patients to be diagnosed with HF. This study aimed to investigate the prognostic value of weight loss in patients hospitalized for HF. This was a post-hoc analysis of the FRAGILE-HF study, a prospective multi-center, observational study including 1,332 hospitalized older (≥65 years) patients with HF. The primary outcome was all-cause death within two years of discharge. Self-reported body weight data one year prior to hospital admission were available for 1,106 patients (83.0%) and were compared with their weight after decongestion therapy. The median weight change was -6.9% [-2.4 - -11.9] and 86.8% of the overall cohort experienced some weight loss. Whereas patients with weight loss ≥ 5%, which is a well-validated cut-off in chronic HF, had comparable mortality to those with less weight loss (p = 0.96 by log-rank test), patients with weight loss > 12%, the lowest quartile value, had higher mortality than those with less weight loss (p = 0.024 for all-cause mortality, p = 0.028 for non-cardiovascular mortality, and p = 0.28 for cardiovascular mortality, respectively). In a Cox proportional hazard model, > 12% weight loss was associated with high mortality after adjusting for known prognostic factors and history of malignancy (adjusted hazard ratio: 1.485 [1.070-2.062], p=0.018). Weight loss derived from patient-reported body weight one year before hospitalization was significantly associated with increased mortality after discharge, mainly due to non-cardiovascular etiology, in elderly patients hospitalized for HF.

Glucagon-like peptide-1 agonist use for obesity treatment in patients with left ventricular assist devices

Glucagon-like peptide-1 agonists are effective weight loss treatments, yet few data are available regarding their use in patients with durable left ventricular assist devices. We report our single-center experience with glucagon-like peptide-1 agonist use in 21 patients with World Health Organization class I-III obesity on durable left ventricular assist device support. During therapy, patients experienced a median weight change of -12.4 (-20.0 to -2.9) kgs and a -7.4% (-16.3 to -2.1) change in body weight with a median time on glucagon-like peptide-1 agonist therapy of 12 (6-22) months. Of these, 17/21 patients lost weight (median change -14.0 kg [-21.8 to -5.3], -9.5% [-18.0 to -4.0] body weight) and 9 of 21 had a speed reduction. No major adverse events were attributed to glucagon-like peptide-1 agonist therapy. At our center, glucagon-like peptide-1 agonists use was well-tolerated, safe and was associated with weight loss in patients with durable left ventricular assist devices.

Baseline Characteristics in the Remote Diet Intervention to REduce long-COVID Symptoms Trial (ReDIRECT).

The persistence of symptoms for ≥12 weeks after a COVID-19 infection is known as Long COVID (LC), a condition with unclear pathophysiology and no proven treatments to date. Living with obesity is a risk factor for LC and has symptoms which may overlap with and aggravate LC. ReDIRECT is a remotely delivered trial assessing whether weight management can reduce LC symptoms. We recruited people with LC and BMI >27kg/m 2. The intervention was delivered remotely by dietitians, with online data collection (medical and dietary history, COVID-19 infection and vaccination, body composition, LC history/symptoms, blood pressure, quality of life, sociodemographic data). Participants self-selected the dominant LC symptoms they most wanted to improve from the intervention. Participants (n=234) in England (64%) and Scotland (30%) were mainly women (85%) of white ethnicity (90%), with 13% living in the 20% most deprived areas, a mean age of 46 (SD10) years, and median BMI of 35kg/m 2 (IQR 32-40). Before starting the study, 30% reported more than one COVID-19 infection (82% confirmed with one or more positive tests). LC Diagnosis was mainly by GPs (71%), other healthcare professionals (9%), or self-diagnosed (21%). The median total number of symptoms was 6 (IQR 4-8). Self-selected dominant LC symptoms included fatigue (54%), breathlessness (16%), pain (12%), anxiety/depression (1%) and "other" (17%). At baseline, 82% were taking medication, 57% reported 1+ other medical conditions. Quality of life was poor; 20% were on long-term sick leave or reduced working hours. Most (92%) reported having gained weight since contracting COVID-19 (median weight change +11.5 kg, range -11.5 to +45.3 kg). Symptoms linked to LC and overweight are diverse and complex. Remote trial delivery enabled rapid recruitment across the UK yet certain groups (e.g. men and those from ethnic minority groups) were under-represented. ISRCTN registry ( ISRCTN12595520, 25/11/2021).

Switch to bictegravir/emtricitabine/tenofovir alafenamide from dolutegravir-based therapy.

To evaluate the efficacy and safety of 96 weeks of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) treatment in participants switching from dolutegravir (DTG)-based therapy. Studies 1489 (NCT02607930) and 1490 (NCT02607956) were phase 3 randomized, double-blind, active-controlled, first-line therapy trials in people with HIV-1. After 144 weeks of DTG-based or B/F/TAF treatment, participants could enter a 96-week open-label extension (OLE) of B/F/TAF. A pooled analysis evaluated viral suppression (HIV-1 RNA <50 copies/ml) and changes in CD4 + cell count at OLE Weeks 48 and 96, treatment-emergent resistance, safety, and tolerability after switch from a DTG-based regimen to B/F/TAF. Outcomes by prior treatment were summarized using descriptive statistics and compared by two-sided Wilcoxon rank sum test. At OLE Week 96, participants who switched to B/F/TAF ( N = 519) maintained high levels of virologic suppression (99.5 and 99.1% in those switching from DTG/abacavir/lamivudine and DTG+F/TAF, respectively) and CD4 + cell count, with no treatment-emergent resistance to B/F/TAF. Twenty-one participants experienced drug-related adverse events after switching, with diarrhea, weight gain, and headache occurring most commonly. There were no cases of proximal renal tubulopathy, drug-related Grade 4 adverse events, or serious adverse events. Two participants discontinued B/F/TAF due to treatment-related adverse events. Participants who switched from DTG/abacavir/lamivudine experienced statistically significant greater weight gain than those who switched from DTG+F/TAF; however, median weight change from the blinded phase baseline to OLE Week 96 was numerically similar across treatment groups. This medium-term analysis demonstrates the safety and efficacy of switching to B/F/TAF from a DTG-containing regimen in people with HIV-1.

Evaluation of Total Parenteral Nutrition in the Autologous Transplantation Setting in Patients with AML: A Retrospective Exploratory Analysis

Malnutrition remains a clinical challenge in AML patients undergoing autologous hematopoietic stem cell transplantation (ASCT), leading to physical deconditioning and prolonged hospitalization. Prospective data are mainly lacking to identify those patients who may particularly benefit from parenteral nutrition in this setting. This observational, non-randomized, retrospective, exploratory cohort study assessed the nutritional development in patients following high-dose chemotherapy (HDCT) with ASCT and explored their survival outcomes. The study included all consecutive AML patients who underwent HDCT with ASCT at a single academic center between January 2000 and January 2019. Patients were divided into two primary cohorts: those who received TPN following high-dose chemotherapy and ASCT and those who did not. We identified 126 patients with AML in first complete remission undergoing ASCT consolidation, including 75 patients receiving TPN after HDCT and ASCT and 51 patients without TPN. Neither group differed in gender, age, or subgroups of AML. The nutritional condition at first diagnosis and after induction chemotherapy was equal in both groups, as were median weight changes throughout the induction chemotherapy cycles. Finally, progression-free and overall survival rates were comparable in both groups. Our data suggest that the need to provide TPN for an average of 11 days following HDCT with ASCT for consolidation of first remission in AML patients does not affect the clinical outcome of these patients.

Disease and toxicity outcomes for a modern cohort of patients with squamous cell carcinoma of cutaneous origin involving the parotid gland: Comparison of volumetric modulated arc therapy and pencil beam scanning proton therapy

ObjectivesWe sought to describe outcomes for locally advanced cutaneous squamous cell carcinoma (SCC) involving the parotid treated with volumetric modulated arc therapy (VMAT) versus pencil beam scanning proton beam therapy (PBT). Materials and MethodsPatients were gathered from 2016 to 2022 from 5 sites of a large academic RT department; included patients were treated with RT and had parotid involvement by: direct extension of a cutaneous primary, parotid regional spread from a previously or contemporaneously resected but geographically separate cutaneous primary, or else primary parotid SCC (with a cutaneous primary ostensibly occult). Acute toxicities were provider-reported (CTCAE v5.0) and graded at each on treatment visit. Statistical analyses were conducted. ResultsMedian follow-up was 12.9 months (1.3 – 72.8); 67 patients were included. Positive margins/extranodal extension were present in 34 cases; gross disease in 17. RT types: 39 (58.2 %) VMAT and 28 (41.8 %) PBT. Concurrent systemic therapy was delivered in 10 (14.9 %) patients. There were 17 treatment failures (25.4 %), median time of 168 days. Pathologically positive neck nodes were associated with locoregional recurrence (p = 0.015). Oral cavity, pharyngeal constrictor, and contralateral parotid doses were all significantly lower for PBT. Median weight change was −3.8 kg (-14.1 – 5.1) for VMAT and −3 kg (-16.8 – 3) for PBT (p = 0.013). Lower rates of ≥ grade 1 xerostomia (p = 0.002) and ≥ grade 1 dysguesia (p < 0.001) were demonstrated with PBT. ConclusionsCutaneous SCC involving the parotid can be an aggressive clinical entity despite modern multimodal therapy. PBT offers significantly lower dose to organs at risk compared to VMAT, which seemingly yields diminished acute toxicities.

Association between fat-free mass and survival in critically ill patients with COVID-19: A prospective cohort study.

Most critically ill patients with COVID-19 experience malnutrition and weight loss associated with negative clinical outcomes. Our primary aim was to assess body composition during acute and late phase of illness in these patients in relation to clinical outcome and secondary to tailored nutrition support. This prospective cohort study included adult critically ill patients with COVID-19. Body composition (fat-free mass [FFM] [exposure of interest], fat mass [FM], skeletal muscle mass [SMM], and phase angle [PA]) was determined with multifrequency bioelectrical impedance analyses in the acute and late phase. Nutrition support data were collected simultaneously. Clinical outcome was defined as intensive care unit (ICU) survival (primary outcome) and 30-90 days thereafter, duration of mechanical ventilation, and length of ICU stay and length of hospital stay (LOS). Nonparametric tests and regression analyses were performed. We included 70 patients (73% male, median age 60 years). Upon admission, median BMI was 30 kg/m2 , 54% had obesity (BMI > 30 kg/m2 ). Median weight change during ICU stay was -3 kg: +3 kg FM and -6 kg FFM (-4 kg SMM). Body composition changed significantly (P < 0.001). Regarding clinical outcome, only low PA was associated with prolonged LOS (odds ratio = 0.83, 95% CI = 0.72-0.96; P = 0.015). Patients with optimal protein intake (>80%) during acute phase maintained significantly more FFM (2.7 kg, P = 0.047) in the late phase compared with patients who received <80%. FFM decreased significantly during acute and late phase of illness, but we observed no association with ICU survival. Only low PA was associated with prolonged LOS. FFM wasting likely occurred because of disease severity and immobility.

Long-term weight loss as a predictor of mortality in haemodialysis patients.

Serial weight decrease can be a prognostic predictor in chronic haemodialysis (HD) patients. We investigated the impact of long-term post-HD body weight (BW) changes on all-cause mortality among HD patients. This longitudinal cohort study and post-hoc analysis evaluated participants of a previous randomised controlled trial conducted between 2006 and 2011 who were followed up until 2018. Weight change slopes were generated with repeated measurements every 6 months during the trial for patients having ≥5 BW measurements. Participants were categorised into four groups based on quartiles of weight change slopes; the median weight changes per 6 months were -1.02 kg, -0.25 kg, +0.26 kg, and +0.86 kg. Cox proportional hazard regression was used to evaluate differences in subsequent survival among the four groups. BW trajectories were plotted with a backward time-scale and multilevel regression analysis to visualise the difference in BW trajectories between survivors and non-survivors. Among the 461 patients, 404 were evaluated, and 168 (41.6%) died within a median follow-up period of 10.2 years. The Cox proportional hazard regression adjusted for covariates and baseline BW showed that a higher rate of weight loss was associated with higher mortality. The hazard ratios were 2.02 (1.28-3.20), 1.77 (1.10-2.85), 1.00 (reference), and 1.11 (0.67-1.83) for the first, second, third (reference), and fourth quartiles, respectively. BW trajectories revealed a significant decrease in BW in non-survivors. Weight loss elucidated by serial BW measurements every 6 months is significantly associated with higher mortality among HD patients.

Weight Change over Ten Years Predicts Biological Aging in a Random Sample of 3070 U.S. Adults.

This investigation was designed to study the relationship between weight change over 10 years and leukocyte telomere length (LTL) in a large sample of 3070 randomly selected U.S. adults, 36-70 years old. The National Health and Nutrition Examination Survey (NHANES) data were used to examine the relationship between percent weight change and LTL. Potential mediating variables were controlled using partial correlation. After adjusting for age, race, year, and housing status, the association between percent weight change over 10 years and LTL was significant in women (F = 6.9, p = 0.0138). Adjusting for the demographic and several other covariates weakened the relationship slightly (F = 4.7, p = 0.0392). With all the covariates controlled, for each one percentage point increase in weight over the previous 10 years, telomeres were, on average, 3.48 base pairs (bp) shorter in women. Given that each one-year increase in age was associated with telomeres that were 15.0 bp shorter in women, the median weight change in U.S. women over the previous 10 years (an increase of 10.4%) was predictive of LTLs that were 36 bp shorter, on average, or an increase of 2.4 years of biological aging. Percent weight change over 10 years was not associated with LTL in U.S. men. Percent weight change over 10 years is a strong predictor of biological aging in U.S. women, but not in men.

The outcome of a multicomponent lifestyle intervention in patients with obesity: A cohort study

Persons with obesity are at risk of developing diseases. Furthermore, people with obesity are often stigmatized and struggle with how to improve their lifestyle despite perhaps already knowing what healthy habits consist of. Hence, there is a need for lifestyle interventions aimed at improving mental well-being in patients with obesity in order to induce lifestyle change. The aim of the study was to investigate the outcome of a multicomponent lifestyle intervention in a group of Danish patients with obesity (Body Mass Index (BMI) ≥30). The study was a cohort study for patients referred for a multicomponent lifestyle intervention (3 times/6 months) at a lifestyle rehabilitation center from 2016 to 2019 with a BMI ≥30. Patients completed questionnaires at baseline, 6 and 18 months regarding diet, physical activity, body weight, the Short-Form 12-Item Health Survey (SF-12) (minimal important change ≥5 points) and a question regarding satisfaction with treatment. A total of 1336 patients (mean age (standard deviation) 51(14) years, 25% men) were included. Median weight change (25th;75th quartile) was -5% (-2;-8%), p<0.001 from baseline to 6 months and -4% (0;-9%), p<0.001 at 18 months. After the intervention, only 8% patients had an unhealthy diet and patients reported increased participation in physical activities (+1 day/week) (p<0.001). Patients changed their mean [95%confidence interval] SF-12 physical score 4.0 [3.4;4.5] points (p<0.001) at 6 months follow up and 3.2 [2.4;3.8] points (p<0.001) at 18 months. Their SF-12 mental scores were changed 2.8 [2.2;3.4] points (p<0.001) at 6 months and 2.3 [1.5;3.1] points (p<0.001) at 18 months. 40–45% patients had a minimal important change in their SF-12 scores. 91% of the patients were highly satisfied with the treatment. Patients participating in a multicomponent lifestyle intervention focusing on improving mental factors had improved outcomes at 6 and 18 months follow up.

Bictegravir/emtricitabine/tenofovir alafenamide as initial treatment for HIV-1: five-year follow-up from two randomized trials.

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single-tablet regimen recommended for HIV-1 treatment. The safety and efficacy of B/F/TAF as initial therapy was established in two Phase 3 studies: 1489 (vs dolutegravir [DTG]/abacavir/lamivudine) and 1490 (vs DTG+F/TAF). After 144 weeks of randomized follow-up, an open-label extension evaluated B/F/TAF to 240 weeks. Of 634 participants randomized to B/F/TAF, 519 completed the double-blinded treatment, and 506/634 (80%) chose the 96-week open-label B/F/TAF extension, which was completed by 444/506 (88%) participants. Efficacy was based on the secondary outcome of the proportion of participants with HIV-1 RNA <50 copies/mL at Week 240 by missing=excluded and missing=failure methods. All 634 participants who were randomized to B/F/TAF and received at least one dose of B/F/TAF were included in efficacy and safety analyses. (Study 1489: ClinicalTrials.govNCT02607930; EudraCT 2015-004024-54. Study 1490: ClinicalTrials.govNCT02607956; EudraCT 2015-003988-10). Of those with available virologic data, 98.6% (95% CI [97.0%-99.5%], 426/432) maintained HIV-1 RNA <50 copies/mL at Week 240 (missing=excluded); when missing virologic data were considered as failure, 67.2% (95% CI [63.4%-70.8%], 426/634) maintained HIV-1 RNA <50 copies/mL. Mean (SD) change in CD4+ count from baseline was+338 (236.2) cells/μL. No treatment-emergent resistance to B/F/TAF was detected. Adverse events led to drug discontinuation in 1.6% (n=10/634) of participants (n=5 with events considered drug-related). No discontinuations were due to renal adverse events. Median (IQR) total cholesterol increased 21 (1,42) mg/dL from baseline; the change in total cholesterol:HDL was 0.1 (-0.5,0.6). Median (IQR) weight change from baseline was+6.1kg (2.0, 11.7) at Week 240. In Study 1489, hip and spine bone mineral density mean percent changes from baseline were ≤0.6%. Through 5 years of follow-up, B/F/TAF maintained high rates of virologic suppression with no treatment-emergent resistance and rare drug discontinuations due to adverse events. These results demonstrate the durability and safety of B/F/TAF in people with HIV. Gilead Sciences.

Abstract 15887: Bodyweight Changes and the Incidence of Atrial Fibrillation in Individuals With Obstructive Sleep Apnea

Introduction: Previous studies have demonstrated that obstructive sleep apnea (OSA) and obesity independently increase the risk for development of atrial fibrillation (AF). However, it is unknown whether weight changes in an OSA cohort also increase the risk of AF. Methods: This was a case control study from a single tertiary institution analyzing patients with a confirmed OSA diagnosis from 2013-2020. Patients with missing data on any of the key variables were excluded from these analyses. The covariates included smoking history, hypertension, congestive heart failure, chronic obstructive pulmonary disease, heart failure, and coronary artery disease. Patients’ weight at the time of AF diagnosis by electrocardiogram (ECG) was compared to the weight documented one year earlier. Weight at the time of the ECG closest to the sleep study date was compared to the weight one year prior for the control group. ​​Multivariate logistic regression analysis to examine the association between AF cases (versus controls) and weight percent change greater than 5%. Results: Among the 182 patients included in the analysis, the incidence of AF was 32.4% and the median weight change was -1.32± 11.69 lb (Table 1). About 36% of those diagnosed with AF had weight changes (gain or loss) above 5% compared to 23% in the control group (p = 0.07). The average weight change for those with diagnosed AF compared to individuals without AF was -2.5 ±11.8 lb vs. -0.76 ± 11.6 lb (p=0.19). The change in the adjusted odds of AF diagnosis among those with more than 5% weight gain or loss was 2.27 (95% CI =1.01, 5.09) compared to those with less or no weight change. Conclusions: Among individuals with OSA, those who exhibited weight changes greater than 5% over a one year period have increased odds for developing AF. Further large-scale studies need to be undertaken to understand the link between intentional versus unintentional weight loss.

ODP369 Weight Trajectory as a Predictor of Cushing's Disease

Abstract Cushing's syndrome, a disorder of cortisol excess, is associated with significant morbidity and mortality. Obesity, hypertension and glucose intolerance are common clinical findings in patients with Cushing's, but with the increasing incidence of obesity worldwide-- nearly 40% of the world's adult population is currently overweight– and the increasing incidence of obesity-associated comorbidities of hypertension and diabetes mellitus, deciding whom to screen for Cushing's can be very challenging and frequently delays timely diagnosis. We performed a retrospective study in patients with Cushing's disease (CD) and those with a clinically non-functioning ACTH-staining adenoma (NF-ACTH+) who underwent endoscopic endonasal resection at a large academic health center from 1/2015-7/2021 to investigate whether there are differences in weight-gain trajectories that can help differentiate patients with Cushing's from those without, even in a population that is predominantly overweight-obese. We hypothesized that patients with Cushing's would have significantly greater increases in weight in the six months preceding surgery compared to NF-ACTH+ patients with similar pre-operative evaluation and similar pre-operative BMI. Patients with CD (n=50) were younger (mean+SD: 45.9+15.4 years) compared to patients with NF-ACTH+ (n=34) (54.2+15.1 years, p=0. 02) and a higher percentage were female (CD: 86% versus NF-ACTH+: 50%, p=0. 0003). CD and NF-ACTH+ patients were of similar BMI (CD: 34.5+9.2 kg/m 2 and NF-ACTH+: 33.8+6.7 kg/m 2, p=0.93), even after controlling for age and sex (p=0.47), and &amp;gt;90% of both CD and NF-ACTH+ had a BMI of &amp;gt;25 kg/m 2 . Median weight change in the six months prior to surgery was 2.5 [0.3, 5.4] kg in CD and -0.5 [-2.7, 1.6] kg in NF-ACTH+ (p&amp;lt;0. 02); 77% of CD versus 43% of NF-ACTH+ gained weight during the six-month period (p=0. 02). Using a minimally clinically significant weight gain of 2kg, 56.4% of CD versus 21.4% of NF-ACTH+ gained &amp;gt;2kg in the six months preceding surgery (p=0. 02); using a 3kg cut off, 46% of CD versus only 14.3% of NF-ACTH+ gained &amp;gt;3kg in the six months preceding surgery (p=0. 03). After controlling for use of insulin in the setting of diabetes mellitus, the results remained significant with more CD patients than NF-ACTH+ gaining &amp;gt;2kg or &amp;gt;3kg in the six months prior to surgery (p&amp;lt;0. 04 for both analyses). These data demonstrate that patients with Cushing's are significantly more likely to gain at least 2kg (4.4 lbs) over a six-month period compared to a similarly overweight/obese population without clinical Cushing's, independent of the use of insulin in the setting of diabetes mellitus. A weight increase of at least 2kg can potentially allow weight to continue to be used as a helpful sign of Cushing's despite the increasing incidence of obesity. Collectively, these data suggest value in using weight trajectories, rather than absolute BMI, as a clinical variable when assessing the pretest probability of Cushing's. Presentation: No date and time listed

Predictors of weight reduction in a Nigerian family practice setting.

This study identified the predictors of weight reduction among adult obese patients in a Family Practice Setting and developed a statistical model to predict weight reduction. A prospective cohort design. The Family Practice Clinic, University College Hospital, Ibadan, Nigeria. Obese adults were recruited into a three-month weight reduction program. Patient Information Leaflets were used for counselling, while questionnaires were administered to obtain socio-demographic and lifestyle factors. Potential predictors were assessed using the Multidimensional Scale of Perceived Social Support, Zung Depression Scale, Rosenberg Self-Esteem scale, Garner's Eating Attitude Test-26 (EAT-26), 24-hour dietary recall and International Physical Activity Questionnaire-short form. Anthropometric indices, blood pressure and Fasting Lipid Profile were assessed. Descriptive and inferential statistics were used for analysis with a significance set at α0.05. Most 99(76.2%) of the 130 participants achieved weight reduction and had a median weight change of -2.3kg (IQR-4, -0.5), with 66 (66.7%) out of 99 attaining the weight reduction target of 10%. The regression model showed predictors of weight reduction to be Total Cholesterol [TC] (p=0.01) and Low-Density Lipoprotein Cholesterol [LDL-C] (p=0.03). The statistical model derived for Weight reduction = 0.0028 (LDL-C) -0.029 (TC)-0.053 (EAT-26) +0.041(High-Density Lipoprotein Cholesterol). The proportion of variance of the model tested was R2 = 0.3928 (adjusted R2 = 0.2106). Predictors of weight reduction among patients were eating attitude score, Total Cholesterol, Low-Density Lipid and High-Density Lipoprotein Cholesterol levels. A statistical model was developed for managing obesity among patients. Self-funded, with a discount from the Public-Private Partnership Laboratory obtained for the patients recruited.

Trajectories of body weight change and survival among patients with mCRC treated with systemic therapy: Pooled analysis from the ARCAD database

BackgroundHigher body mass index is associated with a higher incidence of colorectal cancer (CRC) but also with improved survival in metastatic CRC (mCRC). Whether weight change after mCRC diagnosis is associated with survival remains largely unknown. MethodsWe analysed individual patient data for previously untreated patients enrolled in five phase 3 randomised trials conducted between 1998 and 2006. Weight measurements were prospectively collected at baseline and up to 59.4 months after diagnosis. We used stratified multivariable Cox models to assess the prognostic associations of weight loss with overall and progression-free survival, adjusting for other factors. The primary end-point was a difference in overall survival (OS) between populations with weight loss and stable or increasing weight. FindingsData were available for 3504 patients. The median weight change at 3 months was −0.54% (IQR −3.9 … +1.5%). We identified a linear trend of increasing risk of death associated with progressive weight loss. Unstratified median OS was 20.5, 18.0, and 11.9 months (p < 0.001) for stable weight or gain, <5% weight loss, and ≥5% weight loss at 3 months, respectively. Weight loss was associated with a higher risk of death (<5% loss: aHR 1.18 [1.06–1.30], p < 0.002; ≥5% loss: aHR 1.87 [1.67–2.1], p < 0.001) as compared to stable or increasing weight at 3 months post-baseline (reference), while adjusting for age, sex, performance, and a number of metastatic sites. InterpretationPatients losing weight during systemic therapy for metastatic colorectal cancer have significantly shorter OS. The degree of weight loss is proportional to the observed increased risk of death and remains evident among underweight, normal weight, and obese individuals. On-treatment weight change could be used as an intermediate end-point. FundingThe creation and management of the database containing the individual patient data from the original randomised trials is supported by the Aide et Recherche en Cancérologie Digestive Foundation.

Archetypal analysis of visual fields in optic neuritis reveals functional biomarkers associated with outcome and treatment response

Background and objectivesArchetypal analysis (AA), a form of unsupervised machine learning, can identify quantifiable visual field (VF) patterns seen in optic neuritis (ON), known as archetypes (ATs). We hypothesized that AT weight changes over time would reflect the course of recovery and the effects of therapy in ON. We explored whether baseline AT weights would be associated with VF status at the clinical trial outcome and if ATs would indicate residual VF defects in eyes with mean deviation (MD) ≥ -2.00 at six months. MethodsWe used a published 16-AT model derived from 3892 Optic Neuritis Treatment Trial VFs (456 eyes) for all analyses. We measured AT weight changes over the six-month study period and used asymptotic regression to analyze the rate of change. We compared AT weights at six months between treatment groups. We evaluated associations between baseline AT weight thresholds and VF outcome or treatment effect. We calculated residual AT weights in eyes with MD ≥ -2.00 dB at six months. ResultsOver six months, AT1 (a normal VF pattern) demonstrated the greatest median weight change, increasing from 0.00% (IQR 0.00–0.00%) at baseline to 60.0% (IQR 38.3–70.8%) at six months (p < 0.001). At outcome, the intravenous methylprednisolone (IVMP) group had the highest median AT1 weight (IVMP: 63.3%, IQR 51.3–72.8%; placebo: 56.2%, IQR 35.1–71.6%; prednisone 58.3%, IQR 35.1–71.6%; p = 0.019). Eyes with AT1 weight ≥ 19% at baseline had superior median MD values (-0.91 vs. -2.07 dB, p < 0.001) and AT1 weights (70.8% vs. 57.8% p < 0.001) at six months. Only eyes with AT1 weight < 19% at baseline showed a treatment benefit for IVMP, with a higher six-month median AT1 weight compared to placebo (p = 0.015) and prednisone (p = 0.016), and a higher median MD compared to placebo (p = 0.027). At six months, 182 (80.2%) VFs with MD ≥ -2.00 had at least one abnormal AT. DiscussionChanges in quantifiable, archetypal patterns of VF loss reflect recovery in ON. Machine learning analysis of the VFs in optic neuritis reveals associations with response to therapy and VF outcome, and uncovers residual deficits, not readily seen with standard evaluations.

Short-term Neuropsychiatric and Body Weight Changes in Patients Switching From EVG/Cobi/FTC/TAF to BIC/FTC/TAF (PreEC/RIS69).

We report NP, clinical and laboratory changes in patients switching from EVG/Cobi/FTC/TAF to BIC/FTC/TAF in clinical practice. A group of subjects switching from EVG/Cobi/FTC/TAF to BIC/F/TAF was prospectively followed. A validated sleep quality questionnaire (Pittsburgh Sleep Quality Index), as well as the Hospital Anxiety and Depression Scale (HADS), were administered after 4 weeks from the treatment switch. Adverse events, side effects and discontinuation were recorded at weeks 4 and 24. Pretreatment switch and week 24 body weight and laboratory data were compared. A total of 96 virologically suppressed patients (86% male) were included. All patients received EVG/Cobi/FTC/TAF at least 1 year before the treatment switch. Median (IQR) nadir CD4 was 367 (263). The most common comorbidities were dyslipidemia, HTA and diabetes, 26%, 14% and 7%, respectively. Depression was reported by 8%. Five patients discontinued BIC/FTC/TAF before week 4 due to intolerance (2 insomnia, 1 headache and 2 GI symptoms). No changes in sleep quality, anxiety and depression outcomes were observed at week 4 (p = 0.1, p = 0.1 and p = 0.3, respectively). After 6 months, the median body weight change was statistically significant (0.6 kg, p = 0.003). All patients maintained HIV suppression. Except in a few cases, sleep quality, anxiety and depression symptoms remain stable in HIV virologically suppressed patients on EVG/Cobi/FTC/TAF who switch to BIC/F/TAF. NPAEs are mild and tend to occur in those with previous neuropsychiatric symptoms. Weight gain tends to be small but statistically significant. Long-term follow-up in "real-life" cohorts would be needed to confirm these findings.

Recruitment in randomized clinical trials: The MeMeMe experience.

IntroductionRecruitment is essential for the success of clinical trials. We are conducting a randomized clinical trial to test the effect of a Mediterranean dietary intervention with or without 1700 mg/day of metformin for the prevention of age-related chronic diseases, the MeMeMe trial (Trial registration number: EudraCT number: 2012-005427-32 ClinicalTrials.gov ID: NCT02960711). MeMeMe recruiting experience, highlighting strengths, limitations encountered and results is reported.Patients and methodsStatistical analysis focused on the reasons for withdrawal according to the recruitment method (“active” versus “passive” criterion) and the time of withdrawal. Logistic regression models were used to explore the associations between the risk of withdrawal and sex, recruitment method, randomization arm, and with markers of compliance to the intervention, such as one-year change in body weight.ResultsOut of 2035 volunteers, 660 (32.4%) were recruited “actively” and 1375 (67.6%) “passively”. Among people who dropped out of the trial after randomization, there were 19.5% for the “active” and 22.0% for the “passive” method (p = 0.28). The risk of withdrawal was significantly higher in women (OR:1.91; 95% CI:1.17–3.12; p = 0.01), in volunteers older at recruitment (OR:1.25; 95% CI:1.07–1.45; p = 0.004), and in those with a higher BMI at baseline (OR:1.23; 95% CI:1.07–1.43; p = 0.004). Volunteers who lost at least 2 kg (the median weight change) in the first year of intervention were significantly less (53%) likely to withdraw from the trial (OR:0.48; 95% CI:0.30–0.75; p = 0.001).ConclusionOur findings suggest that the “passive” recruitment method was more effective than the “active” one to advance recruitment. The benefits of “passive” recruitment hardly outweighed the drawbacks.Trial registrationTrial registration number: EudraCT number: 2012-005427-32. ClinicalTrials.gov ID: NCT02960711.

Longitudinal changes of blood parameters and weight in inoperable stage III NSCLC patients treated with concurrent chemoradiotherapy followed by maintenance treatment with durvalumab

BackgroundInvestigating dynamic changes in blood-parameters and weight in patients with locally advanced non-small cell lung cancer (NSCLC) receiving durvalumab maintenance therapy after chemoradiotherapy (cCRT). Laboratory outcomes were determined based on the number of durvalumab administrations received.MethodsTwenty-two patients completed platinum-based cCRT followed by maintenance treatment with durvalumab. Different parameters such as hemoglobin (Hb), leukocytes, Lactate dehydrogenase (LDH), C-reactive protein (CRP), body weight and albumin were analyzed before cCRT, after cCRT, 3, 6, 9 and 12 months after starting durvalumab maintenance.ResultsSixteen (72.7%) patients were male; twelve (54.5%) and fifteen (68.2%) patients had non-squamous histology and Union for International Cancer Control (UICC) stage IIIB-C disease, respectively. Median follow-up time was 24.4 months; 12- and 18-months- progression-free and overall-survival rates were 55.0% and 45.0 as well as 90.2 and 85.0%, respectively.During maintenance treatment Hb increased by 1.93 mg/dl (17.53%) after 9 months (p < 0.001) and 2.02 mg/dl (18.46%) after 12 months compared to the start of durvalumab (p < 0.001). LDH decreased by 29.86 U/l (− 11.74%) after 3 months (p = 0.022). Receipt of at least 12 cycles of durvalumab was beneficial in terms of Hb-recovery (Hb 6 months: 12.64 vs. 10.86 [mg/dl]; Hb 9 months: 13.33 vs 11.74 [mg/dl]; (p = 0.03)). Median weight change [kilogram (kg)] was + 6.06% (range: − 8.89 − + 18.75%) after 12 months. The number of durvalumab cycles significantly correlated with total weight gain [kg] (Spearman-Rho-correlation: r = 0.502*).ConclusionIn the investigated cohort, no severe hematologic toxicity occurred by laboratory blood tests within 1 year of durvalumab maintenance therapy after cCRT for unresectable stage III NSCLC. Receiving at least 12 cycles of durvalumab appears to have a significant effect on recovery of hemoglobin levels and body weight.

Medical weight management protects against weight gain during the COVID-19 pandemic.

BackgroundAmerican adults have gained weight during the COVID‐19 pandemic. Little is known about how patients who are medically managed for overweight and obesity, including patients who are prescribed antiobesity pharmacotherapy, have fared.ObjectiveTo assess the COVID‐19 pandemic's effect on weight, food choices, and health behaviors in patients receiving medical treatment for overweight or obesity.MethodsAdult patients treated at an urban academic weight management center between 1 May 2019 and 1 May 2020 were electronically surveyed between 23 February and 23 March 2021. The survey assessed changes in weight, eating, behaviors, and the use of antiobesity medications (AOMs) following issuance of social distancing/stay‐at‐home policies in March 2020.ResultsIn 970 respondents, median percent weight change for those taking AOMs was −0.459% [interquartile range −5.46%–(+3.73%)] compared to +2.33% [IQR −1.92%–(+6.52%)] for those not taking AOMs (p < 0.001). More participants achieved ≥5% weight loss if they were taking AOMs compared to those who were not (26.7% vs. 15.8%, p = 0.004), and weight gain ≥5% was also lower in those taking AOMs (19.8% vs. 30.3%, p = 0.004). Patients with pre‐pandemic BMI ≥30 kg/m2 taking AOMs experienced the greatest weight reduction, and there was greater weight loss associated with increased physical activity.Conclusions and RelevanceMedical weight management protected against weight gain during this period of the COVID‐19 pandemic. Increased physical activity, decreased alcohol intake, and use of AOMs were factors that contributed to this protective effect.