Controlled decongestion by Reprieve therapy in acute heart failure: results of the TARGET-1 and TARGET-2 studies.

AIMS: Safe and effective decongestion is the main goal of therapy in acute heart failure (AHF). In the non-randomized, prospective TARGET-1 and TARGET-2 studies (NCT03897842), we investigated whether adding the Reprieve System® (which continuously monitors urine output and delivers a matched volume of hydration fluid sufficient to maintain the set fluid balance rate) to standard diuretic-based regimen improves decongestion in AHF. METHODS AND RESULTS: The population consisted of 19 patients hospitalized with AHF (mean age 67 ± 10 years, 18 male, ejection fraction 34 ± 15%, median N-terminal pro-B-type natriuretic peptide 4492 pg/mL). Patients served as their own controls: each patient underwent 24 h of standard diuretic therapy followed by 24 h of diuretics with Reprieve therapy (with normal saline used for matched volume replacement). The primary efficacy endpoint of actual fluid loss not exceeding the target fluid loss at the end of therapy was met in all 19 (100%) patients. The mean diuresis during Reprieve therapy was 6284 ± 2679 mL (vs. 1966 ± 1057 mL 24 h before therapy) and 2053 ± 888 mL (24 h after therapy) (both P < 0.0001). At the end of therapy, patient global assessment improved from 7.7 ± 1.1 to 3.0 ± 1.3 points (P < 0.001), central venous pressure decreased from 15.5 ± 5.3 mmHg to 12.8 ± 4.8 mmHg (P < 0.05) and the median urine sodium loss was 9.7 [3-13] mmol/h. The Reprieve therapy was safe, systolic blood pressure remained stable, mean creatinine dropped from 1.45 ± 0.4 mg/dL to 1.26 ± 0.4 mg/dL (P < 0.001) and biomarkers of renal injury did not change during treatment. CONCLUSIONS: The Reprieve System in conjunction with diuretic therapy supports safe and controlled decongestion in AHF.

Patient-centered management of complex patients can reduce costs without shortening life.

OBJECTIVE: To determine the effect of intensive patient-centered management (PCM) on service utilization and survival. STUDY DESIGN: Prospective cohort study of 756 patients in California who had a life-limiting diagnosis with multiple comorbid conditions (75% were oncology patients) and who were covered by a large commercial health maintenance organization from February 2003 through December 2004. METHODS: Group membership determined assignment to the PCM cohort versus the usual-management cohort after blindly screening for clinical complexity. Both cohorts accessed the same delivery system, utilization management practices, and benefits. Intervention was intensive PCM, involving education, home visits, frequent contact, and goal-oriented care plans. RESULTS: Roughly half (358) of the 756 patients received PCM. Fewer PCM oncology patients elected either chemotherapy or radiation (42% increase over usual-management oncology patients). PCM patients had reductions in inpatient diagnoses indicative of uncoordinated care: nausea (-44%), anemia (-33%), and dehydration (-17%). PCM patients had utilization reductions: -38% inpatient admissions (95% confidence interval [CI] = -37%, -38%), -36% inpatient hospital days (95% CI = -35%, -37%), and -30% emergency department visits (95% CI = -29%, -31%). PCM patients had utilization increases: 22% more home care days (95% CI = 20%, 23%) and 62% more hospice days (95% CI = 56%, 67%). Overall costs were reduced by 26% (95% CI = 25%, 27%). Patients' lives were not shortened (26% of PCM patients died vs 28% of patients who received usual management) (P = .80). CONCLUSION: Comprehensive PCM can sharply reduce utilization and costs over usual management without shortening life.

Sperm transport and storage and its relation to the annual sexual cycle of the female red-sided garter snake, Thamnophis sirtalis parietalis.

Female red-sided garter snakes (Thamnophis sirtalis parietalis) store sperm from both late-summer and spring matings. Before winter dormancy, sperm are stored in specialized furrows in the vaginal portion of the oviduct, 3-6 cm anterior to the vent. After 6 weeks in dormancy, the epithelial cells lining this vaginal region hypertrophy and stain strongly with periodic acid-Schiff (PAS). This PAS+ epithelial border sloughs and associates with sperm. These aggregations of PAS+ material, which will be referred to as carrier matrices, move anteriorly through the oviduct. After 20 weeks in dormancy, most sperm are found in specialized infundibular storage regions. Spring mating induces a rapid degeneration of winter-stored sperm. Stored sperm are evacuated from infundibular storage receptacles within 6 hours after mating. Yet sperm from the spring mating are not evident in the oviduct until 24 hours after mating. Carrier matrices begin to form at this time. At 48 hours after mating, sperm, often associated with carrier matrices, appear in the infundibulum. At 40 days after mating, most sperm have moved into infundibular storage receptacles. Evidence suggests that carrier matrices not only facilitate the transport of sperm anteriorly from vaginal to infundibular regions, but also function as nutritional stores.