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1.
Early Weight Loss in Behavioral Treatment Predicts Later Rate of Weight Loss and Response to Pharmacotherapy.
Tronieri, JS, Wadden, TA, Chao, AM, Pearl, RL, Alamuddin, N, Berkowitz, RI
Annals of behavioral medicine : a publication of the Society of Behavioral Medicine. 2019;(3):290-295
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Abstract
BACKGROUND Early weight loss (EWL) in the first 1-2 months of behavioral treatment is a strong predictor of later total weight loss. It is not clear whether participants with lower early losses lose less in ongoing treatment or simply fail to overcome the smaller initial loss. Furthermore, no study has tested whether EWL in behavioral treatment predicts response to a different treatment modality, such as pharmacotherapy. METHODS Data were from 170 participants with obesity (baseline BMI = 40.8 ± 5.8 kg/m2, 87.6% female; 71.3% Black) enrolled in a two-phase trial. Data from the weight loss phase, which provided weekly lifestyle counseling and a meal replacement diet, were used to examine the relationship between 4-week EWL and subsequent rate of weight loss in behavioral treatment. Data from the maintenance phase, in which 137 participants who had lost ≥5% of initial weight were randomized to 52 weeks of maintenance counseling with lorcaserin or placebo, were used to determine whether EWL with behavioral treatment affects the benefit of pharmacotherapy. RESULTS EWL in the first 4 weeks of behavioral treatment (3.6 ± 1.7%) predicted greater total losses at Week 14 (r2 = 0.61, p < .001) and a faster rate of weight loss in the subsequent 9 weeks of the program (p < .001). During the maintenance phase, lower EWL in behavioral treatment predicted a greater benefit of lorcaserin, in comparison with placebo, for the maintenance of a ≥5% loss at Weeks 24 and 52. CONCLUSIONS These findings support recommendations to modify treatment for individuals with low EWL.
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Short- and Long-Term Changes in Health-Related Quality of Life with Weight Loss: Results from a Randomized Controlled Trial.
Pearl, RL, Wadden, TA, Tronieri, JS, Berkowitz, RI, Chao, AM, Alamuddin, N, Leonard, SM, Carvajal, R, Bakizada, ZM, Pinkasavage, E, et al
Obesity (Silver Spring, Md.). 2018;(6):985-991
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Abstract
OBJECTIVE The objective of this study was to determine the effects of weight loss and weight loss maintenance (WLM) on weight-specific health-related quality of life in a 66-week trial. METHODS Adults with obesity (N = 137, 86.1% female, 68.6% black, mean age = 46.1 years) who had lost ≥ 5% of initial weight in a 14-week intensive lifestyle intervention/low-calorie diet (LCD) program were randomly assigned to lorcaserin or placebo for an additional 52-week WLM program. The Impact of Weight on Quality of Life-Lite (IWQOL-Lite) scale (including five subscales), Patient Health Questionnaire-9 (depression), and Perceived Stress Scale were administered at the start of the 14-week LCD program, randomization, and week 52 of the randomized controlled trial (i.e., 66 weeks total). RESULTS Significant improvements in all outcomes, except weight-related public distress, were found following the 14-week LCD program (P values < 0.05). Improvements were largely maintained during the 52-week randomized controlled trial, despite weight regain of 2.0 to 2.5 kg across treatment groups. Participants who lost ≥ 10% of initial weight achieved greater improvements in physical function, self-esteem, sexual life, and the IWQOL-Lite total score than those who lost < 5% and did not differ from those who lost 5% to 9.9%. CONCLUSIONS Improvements in weight-specific health-related quality of life were achieved with moderate weight loss and were sustained during WLM.
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Diagnosis and management of hyponatraemia in the older patient.
Woodward, M, Gonski, P, Grossmann, M, Obeid, J, Scholes, R, Topliss, DJ
Internal medicine journal. 2018;:5-12
Abstract
Hyponatraemia (serum sodium concentration below 135 mmol/L) is the most common electrolyte disturbance and occurs commonly in older people. The causes can be complex to diagnose and treat and many published guidelines do not focus on the issues in an older patient group. Here, we are principally concerned with diagnosis and management of euvolaemic and hypervolaemic hyponatraemia in hospitalised patients over 70 years old. We also aim to increase awareness of hyponatraemia in residential aged care facilities and the community. Hyponatraemia can have many causes; in older people, chronic hyponatraemia can often be the result of medications used to treat chronic disease, particularly thiazide or thiazide-like drugs (such as indapamide) or drugs acting on the central nervous system. Where a reversible trigger (such as drug-induced hyponatraemia) can be identified, hyponatraemia may be treated relatively simply. Chronic hyponatraemia due to an irreversible cause will require ongoing treatment. Fluid restriction can be an effective therapy in dilutional hyponatraemia, although poor compliance and the burdensome nature of the restrictions are important considerations. Tolvaptan is an oral vasopressin receptor antagonist that can increase serum sodium concentrations by increasing electrolyte-free water excretion. Tolvaptan use is supported by clinical trial evidence in patients with hypervolaemic or euvolaemic hyponatraemia below 125 mmol/L. Clinical trial evidence also supports its use after a trial of fluid restriction in patients with symptomatic hyponatraemia above 125 mmol/L. The use of tolvaptan is affected by regulatory restriction of chronic therapy due to safety concern and the non-subsidised cost of treatment.
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Tolvaptan for Heart Failure in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis.
Sen, J, Chung, E, McGill, D
Heart, lung & circulation. 2018;(8):928-939
Abstract
BACKGROUND Heart failure (HF) is frequently associated with renal impairment. Tolvaptan is reported to be effective in treating congestion in HF without significant electrolyte loss compared to conventional diuretics. However, the safety and efficacy of its use in patients with chronic kidney disease (CKD) is uncertain. This systematic review and meta-analysis evaluated the efficacy and safety outcomes of tolvaptan for HF management in patients with CKD, with a focus at a physiologic basis related to safety. METHODS We searched for observational studies and randomised clinical trials (RCTs) that assessed the effects of tolvaptan against placebo or standard care in adult patients with HF and CKD. Our protocol was registered with PROSPERO (number CRD42017052775). RESULTS Seventeen studies were included in the qualitative review and six in the meta-analysis involving 1597 patients. Tolvaptan was associated with an increase in sodium concentration. No significant differences in change of eGFR and serum creatinine were found between tolvaptan and control groups. Urine flow rate appears to increase significantly with tolvaptan compared to baseline (p<0.0001). The meta-analysis demonstrated no heterogeneity between studies but the possibility of publication bias due to incomplete reporting in excluded studies and lack of RCTs. CONCLUSIONS The safety profile of tolvaptan appears acceptable for patients with HF and CKD. There is evidence for an improvement in serum sodium and reduction in body water without deterioration in renal function. Further research is needed to elucidate the long-term benefits of tolvaptan as an adjunct or alternative to diuretics in such patients.
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Association between the Serum Sodium Levels and the Response to Tolvaptan in Liver Cirrhosis Patients with Ascites and Hyponatremia.
Hayashi, M, Abe, K, Fujita, M, Okai, K, Takahashi, A, Ohira, H
Internal medicine (Tokyo, Japan). 2018;(17):2451-2458
Abstract
Objective Hyponatremia is closely associated with the pathophysiology of cirrhosis. However, the association between the serum sodium level and the response to tolvaptan is unclear. This study evaluated the factors related to the tolvaptan response and the prognosis in cirrhosis patients with ascites and hyponatremia. Methods We retrospectively reviewed the clinical records of cirrhosis patients hospitalized for treatment with tolvaptan. The associations of patient baseline characteristics with the tolvaptan response after one week and of the characteristics after one-month tolvaptan treatment with the prognosis were analyzed. Results We analyzed 83 cirrhosis patients with ascites, including 34 patients with hyponatremia. The response rates to tolvaptan in patients with serum sodium <130 mEq/L, 130-135 mEq/L, and >135 mEq/L were 20%, 66%, and 58%, respectively (p=0.22). The serum sodium level was associated with the response to tolvaptan [odds ratio=1.18; 95% confidence interval (CI) =1.02-1.37; p=0.029]. In patients with hyponatremia, the serum sodium level after 1-month tolvaptan treatment was increased compared to baseline (132 mEq/L vs. 136 mEq/L, p=0.006), and an increasing serum sodium level was associated with a lower risk of mortality (hazard ratio=0.85; 95% CI=0.75-0.97; p=0.016). The survival rate was higher in patients with an increase in the serum sodium level after 1 month than in patients with a decreased serum sodium level (p=0.023). Conclusion Tolvaptan treatment was effective in cirrhosis patients with ascites and hyponatremia, but a low serum sodium level was associated with non-responsiveness to tolvaptan. An increased serum sodium level after one-month tolvaptan treatment may positively influence the mortality risk in cirrhosis patients with hyponatremia.
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Tolvaptan treatment improves survival of cirrhotic patients with ascites and hyponatremia.
Wang, S, Zhang, X, Han, T, Xie, W, Li, Y, Ma, H, Liebe, R, Weng, H, Ding, HG
BMC gastroenterology. 2018;(1):137
Abstract
BACKGROUND Although tolvaptan treatment improves hyponatremia, only few studies have investigated whether tolvaptan actually benefits the survival of cirrhotic patients. This study evaluated the impact of tolvaptan on six-month survival of decompensated cirrhotic patients with and without hyponatremia. METHODS Two hundred forty-nine decompensated cirrhotic patients with or without hyponatremia were enrolled in a multicenter cohort study. Patients were divided into two groups according to receiving either tolvaptan or placebo treatment for 7-day. Subsequently, the patients were followed up for 6 months. RESULTS Two hundred thirty patients, including 98 with hyponatremia (tolvaptan vs. placebo: 69 vs. 29) finished the study. Tolvaptan did not alter serum sodium levels and survival outcome of decompensated cirrhotic patients without hyponatremia. However, tolvaptan treatment remarkably improved serum sodium levels and six-month survival in patients with hyponatremia. Following tolvaptan treatment, serum sodium levels were restored to normal in 63.8% of patients, whereas in patients receiving placebo, only 36.2% showed the same effect (P < 0.05). Compared to a six-month survival rate of 68.97% in patients receiving placebo, the survival rate in tolvapatan-treated patients was 89.94% (P < 0.05). Furthermore, six-month survival rate in the tolvaptan-treated hyponatremia patients with resolved serum sodium was 81.32%, whereas the survival in those with unresolved serum sodium was only 24% (P < 0.05). CONCLUSIONS Tolvaptan improves short term survival in most decompensated cirrhotic hyponatremia patients with resolved serum sodium. TRIALS REGISTRATION Clinical trial one: ClinicalTrials.gov ID: NCT00664014 , Registered on April 14, 2008. Clinical trial two: ClinicalTrials.gov ID: NCT01349335 , Registered on March 5, 2010. Clinical trial three: ClinicalTrials.gov ID: NCT01349348 , Registered on May 4, 2011.
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A randomized controlled trial of lorcaserin and lifestyle counselling for weight loss maintenance: changes in emotion- and stress-related eating, food cravings and appetite.
Chao, AM, Wadden, TA, Pearl, RL, Alamuddin, N, Leonard, SM, Bakizada, ZM, Pinkasavage, E, Gruber, KA, Walsh, OA, Berkowitz, RI, et al
Clinical obesity. 2018;(6):383-390
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Abstract
Anti-obesity medication may help people maintain diet-induced reductions in appetite. The present exploratory analysis assessed the effects of lorcaserin on changes at 24 weeks post-randomization in emotion- and stress-related eating, food cravings and other measures of appetite (i.e. binge eating, cognitive restraint, disinhibition, hunger, preoccupation with eating and fullness). The parent study investigated the efficacy of combined lorcaserin and behavioural treatment in facilitating weight loss maintenance (WLM) in 137 adults (mean age = 46.1 years, 86.1% female, 68.6% black) who had lost ≥5% of initial weight during a 14-week, low-calorie diet (LCD) run-in. Participants were randomly assigned to lorcaserin or placebo and were provided with group WLM counselling sessions. Emotion- and stress-related eating, food cravings and appetite were measured at the start of the LCD (week -14), randomization (0) and week 24. From randomization, lorcaserin-treated participants had significantly greater improvements in emotion- and stress-related eating compared to placebo-treated participants (P = 0.04). However, groups did not differ significantly after randomization in changes in the frequency of food cravings, binge eating or other measures of appetite (Ps > 0.05). Compared to placebo, lorcaserin may improve emotion- and stress-related eating.
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Administration of tolvaptan with reduction of loop diuretics ameliorates congestion with improving renal dysfunction in patients with congestive heart failure and renal dysfunction.
Hanatani, A, Shibata, A, Kitada, R, Iwata, S, Matsumura, Y, Doi, A, Sugioka, K, Takagi, M, Yoshiyama, M
Heart and vessels. 2017;(3):287-294
Abstract
In patients with congestive heart failure and renal dysfunction, high dose of diuretics are necessary to improve congestion, which may progress to renal dysfunction. We examined the efficacy of tolvaptan with reduction of loop diuretics to improve renal function in patients with congestive heart failure and renal dysfunction. We conducted a multicenter, prospective, randomized study in 44 patients with congestive heart failure and renal dysfunction (serum creatinine concentration ≥1.1 mg/dl) treated with conventional diuretics. Patients were randomly divided into two groups: tolvaptan (15 mg) with a fixed dose of diuretics or with reducing to a half-dose of diuretics for 7-14 consecutive days. We examined the change of urine volume, body weight, serum creatinine and electrolyte concentrations in each group. Both groups demonstrated significant urine volume increase (724 ± 176 ml/day in the fixed-dose group and 736 ± 114 ml/day in the half-dose group) and body weight reduction (1.6 ± 1.5 kg and 1.6 ± 1.9 kg, respectively) from baseline, with no differences between the two groups. Serum creatinine concentration was significantly increased in the fixed-dose group (from 1.60 ± 0.47 to 1.74 ± 0.66 mg/dl, p = 0.03) and decreased in the half-dose group (from 1.98 ± 0.91 to 1.91 ± 0.97 mg/dl, p = 0.10). So the mean changes in serum creatinine concentration from baseline significantly differed between the two groups (0.14 ± 0.08 mg/dl in the fixed-dose group and -0.07 ± 0.19 mg/dl in the half-dose group, p = 0.006). The administration of tolvaptan with reduction of loop diuretics was clinically effective to ameliorate congestion with improving renal function in patients with congestive heart failure and renal dysfunction.
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Effects of Tolvaptan Addition to Furosemide in Normo- and Hyponatremia Patients with Heart Failure and Chronic Kidney Disease Stages G3b-5: A Subanalysis of the K-STAR Study.
Tominaga, N, Kida, K, Inomata, T, Sato, N, Izumi, T, Akashi, YJ, Shibagaki, Y
American journal of nephrology. 2017;(5):417-426
Abstract
BACKGROUND Tolvaptan increases free water clearance (aquaresis) and thereby improves hyponatremia. Although hyponatremia on admission is common in patients with congestive heart failure (CHF), little is known regarding the response to tolvaptan in those who also have chronic kidney disease (CKD) with or without hyponatremia. The aim of this subanalysis was to investigate the differences in treatment response between normo- and hyponatremia patients with CHF and CKD stages G3b-5. METHODS The Kanagawa Aquaresis Investigators Trial of Tolvaptan on HF Patients with Renal Impairment (K-STAR) was a multicenter, open-label, randomized, controlled prospective clinical trial that included 81 Japanese patients with CHF and residual signs of congestion despite oral furosemide treatment (≥40 mg/day). All patients were randomly assigned to 7-day treatment with either ≤15 mg/day of new add-on tolvaptan or ≤40 mg/day of increased furosemide. A subanalysis was conducted for 73 patients, who were classified into 2 groups according to their assigned treatment, then further stratified into 2 subgroups according to their serum sodium concentration [Na+]. The differences between the urine and serum parameters from day 1 to 3 were compared between the groups and between the subgroups in each group. RESULTS The change (Δ) in urine volume (ΔUV) and Δurine osmolality were greater in the tolvaptan group than in the furosemide group; however, ΔUV and Δurine osmolality did not show significant differences between the normonatremia subgroup and the hyponatremia subgroup in each group. In addition, Δserum [Na+] was greater in the tolvaptan group, although the change was not clinically significant. In contrast, Δserum [Na+] did not show significant differences between the normo- and hyponatremia subgroups in each group. CONCLUSION Tolvaptan added to furosemide resulted in a greater diuretic effect than increased furosemide, even in normonatremia patients with CHF complicated by CKD stages G3b-5 in the very early treatment phase.
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Ivabradine.
Komajda, M
Handbook of experimental pharmacology. 2017;:167-175
Abstract
Ivabradine is a blocker of the funny current channels in the sinoatrial node cells. This results in pure heart rate reduction when elevated without direct effect on contractility or on the vessels. It was tested in a large outcome clinical trial in stable chronic heart failure (CHF) with low ejection fraction, in sinus rhythm, on a contemporary background therapy including betablockers (SHIFT Systolic Heart Failure Treatment with the If inhibitor Trial).The primary composite endpoint (cardiovascular mortality or heart failure hospitalization) was reduced by 18% whereas the first occurrence of heart failure hospitalizations was reduced by 26%. The effect was of greater magnitude in patients with baseline heart rate ≥75 beats per minute. Ivabradine improved also the quality of life and induced a reverse remodelling.The safety was overall good with an increase in (a)symptomatic bradycardia and visual side effects.The efficacy and tolerability were similar to those observed in the overall trial in subgroups with diabetes mellitus, low systolic blood pressure (SBP), renal dysfunction or chronic obstructive pulmonary disease (COPD).Ivabradine is indicated in CHF with systolic dysfunction, in patients in sinus rhythm with a heart rate ≥75 bpm in combination with standard therapy including betablocker therapy or when betablocker therapy is contraindicated or not tolerated (European Medicine Agency).