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1.
Salivary Electrostimulation in the Treatment of Radiation Therapy-Induced Xerostomia (LEONIDAS-2): A Multicenter, Randomized, Double-Masked, Sham-Controlled, Phase 3 Trial.
Mercadante, V, Hamad, AA, McCaul, J, Nutting, C, Harrington, K, Carnell, D, Urbano, TG, Kalavrezos, N, Barber, JA, Porter, SR, et al
International journal of radiation oncology, biology, physics. 2024;(1):142-153
Abstract
PURPOSE Radiation therapy-induced xerostomia significantly affects quality of life in head and neck cancer survivors. Neuro-electrostimulation of the salivary glands may safely increase natural salivation and reduce dry mouth symptoms. METHODS AND MATERIALS This multicenter, double-masked, randomized, sham-controlled clinical trial assessed the long-term effects of a commercially available intraoral neuro-electrostimulating device in lessening xerostomia symptoms, increasing salivary flow, and improving quality of life in individuals with radiation therapy-induced xerostomia. Using a computer-generated randomization list, participants were assigned (1:1) to an active intraoral custom-made removable electrostimulating device or a sham device to be used for 12 months. The primary outcome was the proportion of patients reporting a 30% improvement on the xerostomia visual analog scale at 12 months. A number of secondary and exploratory outcomes were also assessed through validated measurements (sialometry and visual analog scale) and quality-of-life questionnaires (EORTC QLQ-H&N35, OH-QoL16, and SF-36). RESULTS As per protocol, 86 participants were recruited. Intention-to-treat analyses showed no statistical evidence of a difference between the study groups with respect to the primary outcome or for any of the secondary clinical or quality-of-life outcomes. Exploratory analyses showed a statistically significant difference in the changes over time of the dry mouth subscale score of the EORTC QLQ-H&N35 in favor of the active intervention. CONCLUSIONS LEONIDAS-2 did not meet the primary and secondary outcomes.
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2.
Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.
Aronne, LJ, Sattar, N, Horn, DB, Bays, HE, Wharton, S, Lin, WY, Ahmad, NN, Zhang, S, Liao, R, Bunck, MC, et al
JAMA. 2024;(1):38-48
Abstract
IMPORTANCE The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. OBJECTIVE To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. DESIGN, SETTING, AND PARTICIPANTS This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. INTERVENTIONS Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. MAIN OUTCOMES AND MEASURES The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. RESULTS Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. CONCLUSIONS AND RELEVANCE In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT04660643.
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3.
Orthostatic hypotension, orthostatic hypertension, and ambulatory blood pressure in patients with chronic kidney disease in CRIC.
Ghazi, L, Cohen, JB, Townsend, RR, Drawz, PE, Rahman, M, Pradhan, N, Cohen, DL, Weir, MR, Rincon-Choles, H, Juraschek, SP
Journal of hypertension. 2024;(2):329-336
Abstract
BACKGROUND Orthostatic changes in blood pressure (BP), either orthostatic hypotension or orthostatic hypertension (OHTN), are common among patients with chronic kidney disease. Whether they are associated with unique out-of-office BP phenotypes is unknown. METHODS CRIC is a prospective, multicenter, observational cohort study of participants with CKD. BP measured at 2 min after standing and ambulatory BP monitoring (ABPM) were obtained on 1386 participants. Orthostatic hypotension was defined as a 20 mmHg drop in SBP or 10 mmHg drop in DBP when changing from seated to standing positions. Systolic and diastolic night-to-day ratio was also calculated. OHTN was defined as a 20 or 10 mmHg rise in SBP or DBP when changing from a seated to a standing position. White-coat effect (WCE) was defined as seated minus daytime ambulatory BP. RESULTS Of the 1386 participants (age: 58 ± 10 years, 44% female, 39% black), 68 had orthostatic hypotension and 153 had OHTN. Postural reduction in SBP or DBP was positively associated with greater systolic and diastolic WCE and systolic and diastolic night-to-day ratio. Orthostatic hypotension was positively associated with diastolic WCE (β = 3 [0.2, 5.9]). Diastolic OHTN was negatively associated with systolic WCE (β = -4 [-7.2, -0.5]) and diastolic WCE (β = -6 [-8.1, -4.2]). CONCLUSION Postural change in BP was associated with WCE and night-to-day-ratio. Orthostatic hypotension was positively associated with WCE and OHTN was negatively associated with WCE. These findings strengthen observations that postural changes in BP may associate with distinct BP patterns throughout the day. These observations are informative for subsequent research tailoring orthostatic hypotension and OHTN treatment to specific BP phenotypes.
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4.
Decline in Estimated Glomerular Filtration Rate After Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Prespecified Secondary Analysis of the DELIVER Randomized Clinical Trial.
Mc Causland, FR, Claggett, BL, Vaduganathan, M, Desai, A, Jhund, P, Vardeny, O, Fang, JC, de Boer, RA, Docherty, KF, Hernandez, AF, et al
JAMA cardiology. 2024;(2):144-152
Abstract
IMPORTANCE An initial decline in estimated glomerular filtration rate (eGFR) is expected after initiating a sodium-glucose cotransporter-2 inhibitor (SGLT2i) and has been observed across patients with diabetes, chronic kidney disease, and heart failure. OBJECTIVE To examine the implications of initial changes in eGFR among patients with heart failure with mildly reduced ejection fraction (HFmrEF) or preserved ejection fraction (HFpEF) enrolled in the Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure (DELIVER) trial. DESIGN, SETTING, AND PARTICIPANTS This was a prespecified analysis of the results of the DELIVER randomized clinical trial, which was an international multicenter study of patients with EF greater than 40% and eGFR greater than or equal to 25. The DELIVER trial took place from August 2018 to March 2022. Data for the current prespecified study were analyzed from February to October 2023. INTERVENTION Dapagliflozin, 10 mg per day, or placebo. MAIN OUTCOMES AND MEASURES In this prespecified analysis, the frequency of an initial eGFR decline (baseline to month 1) was compared between dapagliflozin and placebo. Cox models adjusted for baseline eGFR and established prognostic factors were fit to estimate the association of an initial eGFR decline with cardiovascular (cardiovascular death or heart failure event) and kidney (≥50% eGFR decline, eGFR<15 or dialysis, death from kidney causes) outcomes, landmarked at month 1, stratified by diabetes. RESULTS Study data from 5788 participants (mean [SD] age, 72 [10] years; 3253 male [56%]) were analyzed. The median (IQR) change in eGFR level from baseline to month 1 was -1 (-6 to 5) with placebo and -4 (-9 to 1) with dapagliflozin (difference, -3; P < .001). A higher proportion of patients assigned to dapagliflozin developed an initial eGFR decline greater than 10% vs placebo (1144 of 2892 [40%] vs 737 of 2896 [25%]; odds ratio, 1.9; 95% CI, 1.7-2.1; P difference <.001). An initial eGFR decline of greater than 10% (vs ≤10%) was associated with a higher risk of the primary cardiovascular outcome among those randomized to placebo (adjusted hazard ratio [aHR], 1.33; 95% CI, 1.10-1.62) but not among those randomized to dapagliflozin (aHR, 0.90; 95% CI, 0.74-1.09; P for interaction = .01). Similar associations were observed when alternative thresholds of initial eGFR decline were considered and when analyzed as a continuous measure. An initial eGFR decline of greater than 10% was not associated with adverse subsequent kidney composite outcomes in dapagliflozin-treated patients (aHR, 0.94; 95% CI, 0.49-1.82). CONCLUSIONS AND RELEVANCE Among patients with HFmrEF or HFpEF treated with dapagliflozin, an initial eGFR decline was frequent but not associated with subsequent risk of cardiovascular or kidney events. These data reinforce clinical guidance that SGLT2is should not be interrupted or discontinued in response to an initial eGFR decline. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03619213.
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5.
Self-Reported Nutritional Status and Breakfast Characterization in Latin American University Students.
Saavedra Clarke, S, Parra-Soto, S, Murillo, G, Carpio-Arias, V, Landaeta-Díaz, L, Nava-González, EJ, Ríos-Castillo, I, Nuñez-Martínez, BE, Gómez, G, Araneda-Flores, J, et al
Journal of the American Nutrition Association. 2024;(3):252-260
Abstract
OBJECTIVE To associate breakfast consumption frequency with self-reported nutritional status and dietary patterns of Latin American university students by human development. MATERIAL AND METHODS This was a cross-sectional, multicenter observational study. University students from 11 Latin American countries (Argentina, Chile, Colombia, Costa Rica, Ecuador, Guatemala, Mexico, Peru, Paraguay, Panama and Uruguay) were invited to participate by answering an online self-administered questionnaire on food consumption and sociodemographic indicators, associations were investigated using logistic regression. RESULTS The logistic regression analysis showed significant associations between breakfast consumption and the crude model, models 2 and 3 in countries with very high and upper-middle/high human development. However, after adjustment in the most comprehensive model, the association is no longer statistically significant. In the fully adjusted model of the variables, a significant relationship was observed between breakfast consumption and both healthy and unhealthy dietary patterns. Specifically, students who typically consume breakfast exhibit greater consumption of oatmeal and fruits, as well as healthier dinner choices. Conversely, they exhibit lower consumption of fast food, sugary drinks, and juices. In particular, in highly developed countries, along with the mentioned foods, consumption of dairy was linked to breakfast consumption in a positive way, while alcohol consumption was negatively associated. CONCLUSION University students who eat breakfast on a regular basis maintain a healthier diet in comparison to those who do not, irrespective of their country's level of human development.
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Adaptation of nutritional risk screening tools may better predict response to nutritional treatment: a secondary analysis of the randomized controlled trial Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT).
Wunderle, C, Siegenthaler, J, Seres, D, Owen-Michaane, M, Tribolet, P, Stanga, Z, Mueller, B, Schuetz, P
The American journal of clinical nutrition. 2024;(3):800-808
Abstract
BACKGROUND Nutritional screening tools have proven valuable for predicting clinical outcomes but have failed to determine which patients would be most likely to benefit from nourishment interventions. The Nutritional Risk Screening 2002 (NRS) and the Mini Nutritional Assessment (MNA) are 2 of these tools, which are based on both nutritional parameters and parameters reflecting disease severity. OBJECTIVES We hypothesized that the adaptation of nutritional risk scores, by removing parameters reflecting disease severity, would improve their predictive value regarding response to a nutritional intervention while providing similar prognostic information regarding mortality at short and long terms. METHODS We reanalyzed data of 2028 patients included in the Swiss-wide multicenter, randomized controlled trial EFFORT (Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial) comparing individualized nutritional support with usual care nutrition in medical inpatients. The primary endpoint was 30-d all-cause mortality. RESULTS Although stratifying patients by high compared with low NRS score showed no difference in response to nutritional support, patients with high adapted NRS showed substantial benefit, whereas patients with low adapted NRS showed no survival benefit [adjusted hazard ratio: 0.55 [95% confidence interval (CI): 0.37, 0.80]] compared with 1.17 (95% CI: 0.70, 1.93), a finding that was significant in an interaction analysis [coefficient: 0.48 (95% CI: 0.25, 0.94), P = 0.031]. A similar effect regarding treatment response was found when stratifying patients on the basis of MNA compared with the adapted MNA. Regarding the prognostic performance, both original scores were slightly superior in predicting mortality than the adapted scores. CONCLUSIONS Adapting the NRS and MNA by including nutritional parameters only improves their ability to predict response to a nutrition intervention, but slightly reduces their overall prognostic performance. Scores dependent on disease severity may best be considered prognostic scores, whereas nutritional risk scores not including parameters reflecting disease severity may indeed improve a more personalized treatment approach for nourishment interventions. The trial was registered at clinicaltrials.gov as NCT02517476.
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Randomised controlled trial of adjunctive triamcinolone acetonide in eyes undergoing vitreoretinal surgery following open globe trauma: The ASCOT study.
Casswell, EJ, Cro, S, Cornelius, VR, Banerjee, PJ, Zvobgo, TM, Tudor Edwards, R, Ezeofor, V, Anthony, B, Shahid, SM, Bunce, C, et al
The British journal of ophthalmology. 2024;(3):440-448
Abstract
BACKGROUND/AIMS: To investigate the clinical effectiveness of adjunctive triamcinolone acetonide (TA) given at the time of vitreoretinal surgery following open globe trauma (OGT). METHODS A phase 3, multicentre, double-masked randomised controlled trial of patients undergoing vitrectomy following OGT comparing adjunctive TA (intravitreal and subtenons) against standard care (2014-2020). The primary outcome was the proportion of patients with at least 10 Early Treatment Diabetic Retinopathy Study (ETDRS) letter improvement in corrected visual acuity (VA) at 6 months. Secondary outcomes included: change in ETDRS, retinal detachment (RD) secondary to PVR, retinal reattachment, macular reattachment, tractional RD, number of operations, hypotony, elevated intraocular pressure and quality of life. RESULTS 280 patients were randomised over 75 months, of which 259 completed the study. 46.9% (n=61/130) of patients in the treatment group had a 10-letter improvement in VA compared with 43.4% (n=56/129) of the control group (difference 3.5% (95% CI -8.6% to 15.6%), OR=1.03 (95% CI 0.61 to 1.75), p=0.908)). Secondary outcome measures also failed to show any treatment benefit. For two of the secondary outcome measures, stable complete retinal and macular reattachment, outcomes were worse in the treatment group compared with controls, respectively, 51.6% (n=65/126) vs 64.2% (n=79/123), OR=0.59 (95% CI 0.36 to 0.99), and 54.0% (n=68/126) vs 66.7% (n=82/123), OR=0.59 (95% CI 0.35 to 0.98), for TA vs control. CONCLUSION The use of combined intraocular and sub-Tenons capsule TA is not recommended as an adjunct to vitrectomy surgery following OGT. TRIAL REGISTRATION NUMBER NCT02873026.
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8.
Empagliflozin after Acute Myocardial Infarction.
Butler, J, Jones, WS, Udell, JA, Anker, SD, Petrie, MC, Harrington, J, Mattheus, M, Zwiener, I, Amir, O, Bahit, MC, et al
The New England journal of medicine. 2024;(16):1455-1466
Abstract
BACKGROUND Empagliflozin improves cardiovascular outcomes in patients with heart failure, patients with type 2 diabetes who are at high cardiovascular risk, and patients with chronic kidney disease. The safety and efficacy of empagliflozin in patients who have had acute myocardial infarction are unknown. METHODS In this event-driven, double-blind, randomized, placebo-controlled trial, we assigned, in a 1:1 ratio, patients who had been hospitalized for acute myocardial infarction and were at risk for heart failure to receive empagliflozin at a dose of 10 mg daily or placebo in addition to standard care within 14 days after admission. The primary end point was a composite of hospitalization for heart failure or death from any cause as assessed in a time-to-first-event analysis. RESULTS A total of 3260 patients were assigned to receive empagliflozin and 3262 to receive placebo. During a median follow-up of 17.9 months, a first hospitalization for heart failure or death from any cause occurred in 267 patients (8.2%) in the empagliflozin group and in 298 patients (9.1%) in the placebo group, with incidence rates of 5.9 and 6.6 events, respectively, per 100 patient-years (hazard ratio, 0.90; 95% confidence interval [CI], 0.76 to 1.06; P = 0.21). With respect to the individual components of the primary end point, a first hospitalization for heart failure occurred in 118 patients (3.6%) in the empagliflozin group and in 153 patients (4.7%) in the placebo group (hazard ratio, 0.77; 95% CI, 0.60 to 0.98), and death from any cause occurred in 169 (5.2%) and 178 (5.5%), respectively (hazard ratio, 0.96; 95% CI, 0.78 to 1.19). Adverse events were consistent with the known safety profile of empagliflozin and were similar in the two trial groups. CONCLUSIONS Among patients at increased risk for heart failure after acute myocardial infarction, treatment with empagliflozin did not lead to a significantly lower risk of a first hospitalization for heart failure or death from any cause than placebo. (Funded by Boehringer Ingelheim and Eli Lilly; EMPACT-MI ClinicalTrials.gov number, NCT04509674.).
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9.
Prevalence of chronic kidney disease in Tunisian diabetics: the TUN-CKDD survey.
Labidi, J, Harzallah, A, Kaab, BB, Mami, I, Agrebi, S, Azzabi, A, Chargui, S, Hadj-Brahim, M, Hammouda, M, Azaiez, S, et al
BMC nephrology. 2024;(1):67
Abstract
BACKGROUND In Tunisia, the prevalence of diabetes mellitus increased from 15.5% on 2016 to 23% by 2023. While Chronic Kidney Disease (CKD) stills the most dreaded complications of diabetes, studies on the prevalence of chronic kidney disease non-dialysis diet are scarce. The aim of this study was to assess the prevalence of chronic kidney disease among the Tunisian diabetic population based on investigators' specialty, demographic criteria (gender, age, duration of diabetes and geographic distribution) and diagnosis criteria (albuminuria and/or eGFR). METHODS This observational, multicentric, and cross-sectional study enrolled all diabetic subjects from all regions of Tunisia with at least 3 months of follow-up before the inclusion date, from 09 January to 08 February 2023. CKD diagnosis was established based on the KDIGO guidelines. The study was carried out at medical departments and ambulatory clinics of different healthcare providers. Baseline data were collected by investigators using an electronic case report form (eCRF). Continuous variables were described by means, median, standard deviation, and quartiles. Categorical data were tabulated in frequencies and percentages. RESULTS The overall prevalence of CKD among the 10,145 enrolled patients with diabetes mellitus was 38.7% with a 95%CI [37.8-39.6%]. 50.9% were male, with a mean age of 67.5 (± 11.3) years. The mean diabetes duration was 16.1 years (± 8.9). The highest CKD prevalence was noted among nephrologists (82.2%), while it was similar between the cardiologists and the primary care physicians (30.0%). CKD prevalence was highest among males (43.0% versus 35.1%) and increased proportionally with patients' age and diabetes duration. CKD was more frequent in the Mid-East Area when compared to other regions (49.9% versus 25.3 to 40.1% in other regions). Albuminuria was present within 6.6% of subjects with CKD, and it was found an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² within 13.3% of subjects wit h CKD. 18.9% had both criteria. CONCLUSIONS In Tunisia, CKD among diabetics had a prevalence of 38.7%, approaching European prevalence. The prevalence discrepancy worldwide of CKD can be improved with a larger population size and by implementing standardized practices.
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The phase 2 LYSA study of prednisone, vinblastine, doxorubicin, and bendamustine for untreated Hodgkin lymphoma in older patients.
Ghesquières, H, Krzisch, D, Nicolas-Virelizier, E, Kanoun, S, Gac, AC, Guidez, S, Touati, M, Laribi, K, Morschhauser, F, Bonnet, C, et al
Blood. 2024;(11):983-995
Abstract
Older patients with classical Hodgkin lymphoma (cHL) require more effective and less toxic therapies than younger patients. In this multicenter, prospective, phase 2 study, we investigated a new firstline therapy regimen comprising 6 cycles of prednisone (40 mg/m2, days 1-5), vinblastine (6 mg/m2, day 1), doxorubicin (40 mg/m2, day 1), and bendamustine (120 mg/m2, day 1) (PVAB regimen) every 21 days for patients with newly diagnosed cHL aged ≥61 years with an advanced Ann Arbor stage. A Mini Nutritional Assessment score ≥17 was the cutoff value for patients aged ≥70 years. The primary end point was the complete metabolic response (CMR) rate after 6 cycles. The median age of the 89 included patients was 68 years (range, 61-88 years), with 35 patients (39%) aged ≥70 years. Seventy-eight patients (88%) completed the 6 cycles. The toxicity rate was acceptable, with a 20% rate of related serious adverse events. CMR was achieved by 69 patients (77.5%; 95% confidence interval [CI], 67-86). After a median follow-up of 42 months, 31 patients progressed or relapsed (35%), and 24 died (27%) from HL (n = 11), toxicity during treatment (n = 4), secondary cancers (n = 6), or other causes (n = 3). The 4-year progression-free survival (PFS) and overall survival rates were 50% and 69%, respectively. Multivariate analysis showed that liver involvement (P = .001), lymphopenia (P = .001), CRP (P = .0005), and comedications (P = .003) were independently associated with PFS. The PVAB regimen yielded a high CMR rate with acceptable toxicity. Over long-term follow-up, survival end points were influenced by unrelated lymphoma events. This trial was registered at www.clinicaltrials.gov as #NCT02414568 and at EudraCT as 2014-001002-17.