***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : In most cases of hyponatremia , arginine vasopressin secretion is inappropriately high . This placebo-controlled , r and omized , double-blind multicenter study evaluated the efficacy and safety of oral conivaptan , a V1A/V2-receptor antagonist , in patients with euvolemic or hypervolemic hyponatremia . Methods : Eighty-three patients with serum [ Na+ ] less than 130 mEq/L were stratified by volume status and r and omly assigned to placebo or conivaptan 40 or 80 mg/d for 5 days . Results : Conivaptan increased the baseline-adjusted area under the serum [Na+]-time curve significantly more than placebo ( P = 0.0001 ) . Patients given either dose of conivaptan demonstrated a serum [ Na+ ] of 4 mEq/L or greater above baseline significantly faster than those given placebo ( P < 0.001 ) and maintained that increase for a greater total time ( P = 0.0001 ) . The least squares mean change in serum [ Na+ ] from baseline to end of treatment was also significantly greater with conivaptan 40 and 80 mg/d ( 6.8 and 8.8 mEq/L , respectively ) ( P = 0.0001 ) than that with placebo ( 1.2 mEq/L ) . The percentage of patients who obtained an increase from baseline in serum [ Na+ ] of 6 mEq/L or greater or normal serum [ Na+ ] was significantly higher among patients given conivaptan 40 and 80 mg/d ( 67 % and 88 % , respectively ) than among those given placebo ( 20 % ; P < 0.001 ) . Conivaptan was well tolerated ; the most frequent adverse events were urinary tract infection , anemia , pyrexia , cardiac failure , hypotension , and hypokalemia . Conclusion : Oral conivaptan was effective in increasing serum [ Na+ ] in patients with euvolemic or hypervolemic hyponatremia and had a favorable safety profile Hyponatremia is the most common electrolyte disorder in clinical practice . Its incidence increases with age and it is associated with increased morbidity and mortality . Recently , the vaptans , antagonists of the arginine vasopressin pathway , have shown promise for safe treatment of hyponatremia . Here we evaluated the efficacy , safety , and tolerability of oral lixivaptan , a selective vasopressin V2-receptor antagonist , for treatment of nonhospitalized individuals with euvolemic hyponatremia ( sodium less than 135 mmol/l ) in a multicenter , r and omized , double-blind ,  placebo-controlled  , phase III study . About half of the 206 patients were elderly in a chronic care setting . Of these patients , 52 were given a placebo  and 154 were given 25 - 100 mg per day lixivaptan , titrated based on the daily serum sodium measurements . Compared with placebo ( 0.8 mmol/l ) , the serum sodium concentration significantly increased by 3.2 mmol/l from baseline to day 7 ( primary efficacy endpoint ) with lixivaptan treatment . A significantly greater proportion of patients that received lixivaptan achieved normal serum sodium ( 39.4 % ) by day 7 relative to placebo ( 12.2 % ) . Overall , lixivaptan was considered safe and well-tolerated . Thus , oral lixivaptan can be safely initiated in the outpatient setting and effectively increases serum sodium concentrations in out patients with euvolemic hyponatremia Purpose Tolvaptan may reduce the signs of volume overload in heart failure ( HF ) patients who experience volume overload despite using conventional diuretics . In this study , we evaluated the dose-response effects of tolvaptan on weight loss , urine volume and electrolyte excretion in furosemide-treated Japanese HF patients exhibiting volume overload . Methods In the study , 117 HF patients with volume overload on stable doses of furosemide ( ≥40 mg/day ) were treated with tolvaptan ( 15 , 30 or 45 mg ) or placebo once-daily for 7 days . Results The decrease in body weight from baseline to the day after the final dose with 15 , 30 or 45 mg tolvaptan ( –1.62 ± 1.55 , –1.35 ± 1.54 and –1.85 ± 1.10 kg , respectively ) , was significantly greater compared with that in the placebo group ( –0.53 ± 0.96 kg ) ( p < 0.05 ) . However , the decrease in body weight  with tolvaptan was not significantly dose-dependent . Signs of volume overload improved at all doses of tolvaptan . Tolvaptan elicited a dose-dependent increase in urine volume and a decrease in urine osmolality , but did not affect urinary sodium or potassium excretion . Adverse reactions associated with diuresis were most frequently observed at the higher doses of tolvaptan . Conclusions Once-daily tolvaptan ( 15 , 30 or 45 mg ) was effective and tolerable as an add-on treatment to furosemide therapy in Japanese HF patients with volume overload OBJECTIVES Hyponatremia ( serum sodium [ Na+ ] concentration < 136 mmol/L ) is a prevalent and potentially life-threatening medical comorbidity for schizophrenic patients . No definitive pharmacological treatments have been established . Tolvaptan ( OPC-41061 ) , an oral non-peptide V2-receptor antagonist , was recently shown to correct hyponatremia in a diverse population of 448 hyponatremic patients .  Efficacy in a sub-set of 19 schizophrenic patients with idiopathic hyponatremia included in that sample is specifically examined . METHODS Nineteen subjects were r and omly assigned to receive placebo ( n = 12 ) or tolvaptan ( n = 7 ) once daily for 30 days . Dosage adjustment was based on serum Na+ changes , initially 15 mg , titratable to 30 or 60 mg . The average daily area under the curve ( AUC ) changes in serum Na+ from baseline to Day 4 and Day 30 were co- primary end points . RESULTS Increases in serum Na+ concentrations were significantly greater with tolvaptan than placebo at Day 4 ( p = .0055 ) and at Day 30 ( p < .0001 ) . Two subjects receiving tolvaptan ( 28.6 % ) became dehydrated and experienced hypotension , and five subjects receiving placebo ( 41.7 % ) experienced symptoms associated with dilutional hyponatremia . CONCLUSIONS These results suggest that tolvaptan effectively normalizes idiopathic hyponatremia  in schizophrenic patients . Clinicians are advised to carefully monitor fluid status especially at the beginning of treatment to prevent dehydration The rate of hyponatremia is higher in hospitalized cancer patients than in hospitalized patients without cancer and is associated with poor clinical outcomes . The availability of V2 receptor antagonists has been a major breakthrough in the management of hyponatremia , but its efficacy and safety in treating hyponatremia in patients with cancer is not known Hyponatremia is common and is associated with a poor prognosis . Traditional management with fluid restriction is difficult to maintain , and it is often ineffective . The objective of this study was to determine the effect of tolvaptan versus fluid restriction on serum sodium concentration . The study was a prospect i ve , multicenter , r and omized , active-controlled , open-label trial . Twenty-eight hospitalized subjects with serum sodium < 135 mmol/L were enrolled in the study . After a 2-day run-in period , subjects were r and omized 2:1 to tolvaptan alone ( n = 17 ) or fluid restriction ( 1,200 ml/day ) plus placebo ( n = 11 ) . Oral tolvaptan was started at 10 mg/day and increased to 60 mg/day as needed . Treatment was continued for up to 27 days , and follow-up continued for up to 65 days . The primary end point was the normalization of serum sodium , defined as > 135 mmol/L or a > or = 10 % increase from baseline . At the last inpatient visit , serum sodium had increased by 5.7 + /- 3.2 mmol/L in the tolvaptan group and 1.0 + /- 4.7 mmol/L in the fluid restriction group ( p = 0.0065 ) . No differences in adverse events were observed between the groups . In conclusion , tolvaptan appears to be more effective than fluid restriction at correcting hyponatremia in hospitalized subjects , without an increase in adverse events OBJECTIVE Tolvaptan , an oral antagonist of the vasopressin V(2 ) receptor , has been found to improve hyponatremia in patients with mixed etiologies . This study analyzed a subgroup of patients with the syndrome of inappropriate antidiuretic hormone secretion ( SIADH ) to evaluate the efficacy and safety of tolvaptan in this group . DESIGN AND PATIENTS Hyponatremic patients in the SALT-1 and SALT-2 studies with a diagnosis of SIADH were identified based on clinical diagnosis by individual study investigators . Subjects were r and omized to receive oral placebo ( n=52 ) or tolvaptan 15 mg daily , with further titration to 30 and 60 mg daily , if necessary , based on the response of serum [ Na(+ ) ] ( n=58 ) . RESULTS In patients with SIADH , improvement in serum [ Na(+ ) ] was significantly greater ( P<0.0001 ) with tolvaptan than placebo over the first 4 days of therapy as well as the entire 30-day study , with minimal side effects of increased thirst , dry mouth , and urination . Only 5.9 % of tolvaptan-treated patients had overly rapid correction of hyponatremia as defined by current guidelines . After discontinuation of tolvaptan , serum [ Na(+ ) ] declined to values similar to placebo . A significant positive treatment effect favoring tolvaptan on the physical component , and a near-significant trend on the mental component , was found using the SF-12 Health Survey . Tolvaptan was associated with a significantly reduced incidence of fluid restriction . CONCLUSIONS Results for the SIADH subgroup were analogous to those of the combined SALT population regarding efficacy and safety but demonstrated a greater improvement in the physical component of the SF-12 Health Survey than in the full mixed etiology SALT patient group Water retention and dilutional hyponatremia , mainly attributable to an impairment of free water excretion and increased vasopressin activity , are well-documented complications in cirrhotic patients with ascites .  VPA-985 is a selective , nonpeptide , orally active , vasopressin-2-receptor antagonist . The aim of this study was to determine the pharmacodynamics , safety , and pharmacokinetics of ascending single doses ( 25 , 50 , 100 , 200 , and 300 mg ) in cirrhotic patients with ascites in a r and omized , double-blind , placebo-controlled trial . Each dose level was studied in 5 patients ( 4 active and 1 placebo ) . After an overnight fast and fluid restriction ( continued for 4 hours after dose administration ) , all patients were given placebo on baseline day and an oral suspension of VPA or placebo on the following day . VPA produced a significant dose-related increase in daily urine output ( 1,454 + /- 858 mL to 4,568 + /- 4,385 mL with VPA 300 mg ) and a dose-related decrease in urine osmolality . The free water clearance reached greater than 3 mL/min for doses 100 mg or greater . Simultaneously , significant increases in serum osmolality , sodium , and vasopressin levels were found . There was a significant increase in sodium urine excretion .  VPA was rapidly absorbed and maximum serum concentrations were achieved within 1 hour after administration . Elimination half-life ranged from 9.0 hours after 100 mg to 22.6 hours after 200 mg . In conclusion , VPA induced a dose-related aquaretic response , suggesting a therapeutic potential in managing water retention in patients with liver cirrhosis with ascites PURPOSE The effect of serum sodium concentration and tolvaptan treatment on length of stay ( LOS ) in patients hospitalized with heart failure ( HF ) was evaluated . METHODS Data for this study were derived from a large , international , Phase III trial of patients hospitalized for HF . Two distinct post hoc analyses were performed , analyzing the association between serum sodium concentration and index hospitalization LOS in normonatremic patients and hyponatremic patients treated with placebo plus st and ard of care versus tolvaptan .  Analysis of covariance models were constructed to adjust for potential variation in care delivery and adjusted for hyponatremia status or treatment . RESULTS Patients with a baseline serum sodium concentration of < 135 meq/L who received placebo had an adjusted mean LOS that was 3.06 days longer than did normonatremic patients ( p < 0.001 ) . More severely hyponatremic patients had an adjusted mean LOS 5.18 days longer than did normonatremic patients ( p < 0. 
    Output:
    
Effects were generally consistent across the different agents , suggesting class effect .
In people with chronic hyponatraemia  , vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3 % increased risk of it being rapid .
To date there is very low certainty evidence for patient-important outcomes ; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm ; there does not appear to be an important effect on cognitive function , but hospital stay may be slightly shorter , although available data are limited .