Current Status of Fallopian Tube Transplantation

Experience in both animals and humans has shown that it is technically feasible to transplant the vascularized oviduct alone, without the ethically complicating ovary, using a procedure compatible with a concurrent standard hysterectomy in the donor. But although the operation is well within the capability of many gynecologic surgeons, immunologic barriers still stand in the way of its widespread clinical utilization.     

Experience with Tolvaptan for Euvolemic and Hypervolemic Hyponatremia in the Acute Care Setting

Background:

Hyponatremia is a common electrolyte disorder and is associated with multiple comorbidities. Management strategies are varied and etiology-dependent. The use of tolvaptan, a vasopressin antagonist, outside of clinical trials has not been well characterized.

Objectives:

To quantify tolvaptan compliance with institutional guidelines and make recommendations concerning reasonable expectations for its role in hyponatremia management.

Methods:

This was a retrospective observational study in a 125-bed community hospital. Patients admitted in 2013 who received at least one dose of tolvaptan were included.

Results:

Thirty-seven patient encounters were evaluated. Tolvaptan was prescribed with 83.7% adherence to the institutional order set. Mean age was 71 ± 16.4 years with 20 (54%) females. Hyponatremia was a contributory cause of admission in 15 (40.5%) patients and offending medications were discontinued in 7 (19%). Causes of hyponatremia included syndrome of inappropriate antidiuretic hormone (SIADH), heart failure, and cirrhosis in 78.3%, 8.2%, and 13.5% of participants, respectively. Management included fluid restriction in 19 (51%) and furosemide in 5 (13.5%), with tolvaptan administration on average 3.2 days after admission. Most patients (78.4%) required ≤2 doses. Sodium concentration was elevated 8 mEq/L by the end of hospitalization. Discharge to palliative care or death occurred in 8 (21.6%). Postdischarge review revealed 3 (8%) maintained sodium concentration ≥130 mEq/dL.

Conclusion:

Tolvaptan was initiated after other interventions and with limited duration per institutional guidelines. This cohort had complicating underlying chronic diseases. These results will be used to refine recommendations with pharmacist input for risk/benefit stratification based on reasonable expectations.     

Tolvaptan for Volume Management in Heart Failure

Volume management in acute decompensated and chronic heart failure (HF) remains a significant challenge. Although progress has been made in the development of mortality-reducing neurohormonal regimens in the reduced ejection fraction population, no clinical trial has yet demonstrated anything more than symptomatic relief or biomarker reduction with pharmacotherapeutic volume-based interventions made in the acutely decompensated individual or those with evolving outpatient congestion. As the number of patients with HF continues to grow, in addition to HF-related hospitalizations, identifying therapies that have the potential to aid in diuresis more safely and efficaciously is paramount to decreasing inpatient length of stay and preventing unnecessary admissions. More recently, a significant amount of research has been dedicated to the use of vasopressin antagonists, specifically tolvaptan, as adjunctive therapy to loop and thiazide diuretics. Although these agents do not seem to have a pervasive role in fluid management in the acute decompensated and chronic HF populations, they are effective tools to have available for specific clinical situations. This review summarizes the literature surrounding the use of tolvaptan for volume management in congestive HF, as well as offering practical guidance for use of this agent.     

EVEREST study: Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan

Acute heart failure syndromes are a common cause of emergency department visits and hospitalization in North America and Europe. Although in-hospital mortality is relatively low, the postdischarge mortality and rehospitalization rates can be as high as 10–15 and 30%, respectively, within 60–90 days following discharge. It appears that the main reason for admission and readmission for heart failure is related to congestion manifested by dyspnea, jugular venous distension and edema. Often, congestion is associated with dilutional hyponatremia that is difficult to treat. Hyponatremia is an important predictor of increased mortality and the available therapies to treat congestion and/or hyponatremia are often ineffective and/or unsafe. Accordingly, there is an unmet need to develop a new agent that effectively relieves congestion due to high filling pressure without worsening renal function and improving or normalizing serum sodium in hyponatremic patients. This paper provides an overview of a new compound, tolvaptan, an oral selective V₂-vasopressin antagonist in light of the recently published Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. The biochemical and pharmacological properties are discussed in conjunction with its clinical efficacy and safety, exploring the potential role of tolvaptan in the management of acute heart failure syndromes presenting with or without hyponatremia.     

Cost-effectiveness of Tolvaptan for Euvolemic or Hypervolemic Hyponatremia

Purpose

Tolvaptan is clinically effective in increasing serum sodium concentrations for patients with euvolemic or hypervolemic hyponatremia. Appropriate treatment of hyponatremia may reduce the risk of death, hospital resource utilization, and economic burden. The aim of this study was to estimate the cost-effectiveness of tolvaptan treatment in patients who need to be hospitalized for treatment and monitoring of euvolemic or hypervolemic hyponatremia.

Methods

A decision-analytic model was constructed to assess the clinical and economic impact of tolvaptan compared with placebo during a 1-month treatment period. The probabilities, utility weights, resource utilization, and costs in the model were derived from clinical trials, survey research, and the Korean National Health Insurance database. Cost analysis was performed from the perspective of the South Korean health care setting in 2012 Korean won (KRW). The model outcome was the incremental cost per quality-adjusted life-year gained. In addition, subgroup analysis was performed to identify the cost-effectiveness in case of tolvaptan treatment only for patients with marked hyponatremia. Deterministic and probabilistic sensitivity analyses were performed on key model parameters and assumptions.

Findings

The total cost per patient was KRW 1,826,771 for tolvaptan treatment and KRW 2,281,926 for placebo. The quality-adjusted life-years for treatment with and without tolvaptan were 0.0481 and 0.0446, respectively. The base-case analysis revealed that tolvaptan was a more effective and less expensive strategy compared with placebo. In the subgroup analysis, this trend was more apparent in case of tolvaptan treatment only for patients with marked hyponatremia. The robustness of the results was confirmed by using deterministic and probabilistic sensitivity analyses.

Implications

This cost-effectiveness analysis found that the use of tolvaptan was less expensive and more effective than treatment without tolvaptan in patients with euvolemic or hypervolemic hyponatremia.     

托伐普坦固体分散体的制备及体外溶出特性考察

目的 采用固体分散技术提高难溶性药物托伐普坦的体外溶出度。方法 选用聚维酮K_29/32为载体材料,以溶剂蒸发法制备托伐普坦固体分散体。采用差示扫描量热法(DSC)、X-射线粉末衍射法(XRPD)对所得固体分散体进行鉴定, 并进行溶解度、体外溶出实验。结果 固体分散体的DSC 图谱及X-射线粉末衍射确定了托伐普坦以无定形态分散在载体中, 体外溶解实验表明其溶出较原料药、物理混合物均有明显提高。结论 将托伐普坦与PVP K_29/32制成固体分散体,其分散状态发生了改变,溶出性能明显提高。