Investigation into the Cost-Effectiveness of Extended Posttraumatic Thromboprophylaxis.

BACKGROUND: Severely injured patients are at particularly high risk for venous thromboembolism (VTE). Although thromboprophylaxis (PPX) is employed during the inpatient period, patients may continue to be at high risk after discharge. Comparative evidence from surgical subspecialities (eg oncology) reveals benefits of postdischarge (ie extended) PPX. We hypothesized that an extended, postinjury oral thromboprophylaxis regimen would be cost-effective. STUDY DESIGN: A cost-utility model compared no PPX with a 30-day course of apixaban, dabigatran, enoxaparin, fondaparinux, or rivaroxaban in trauma patients. Immediate events including deep venous thrombosis, pulmonary embolus, or bleeding within 30 days of injury were modeled in a decision tree with patients entering a Markov process to account for sequelae of VTE, including postthrombotic syndrome and chronic thromboembolic pulmonary hypertension. Effectiveness was measured in quality-adjusted life years. One-way and probabilistic sensitivity analyses were performed to identify conditions under which the preferred PPX strategy changed. RESULTS: Rivaroxaban was the dominant strategy (ie less costly and more effective) compared with no PPX or alternative regimens, delivering 30.21 quality-adjusted life years for $404,546.38. One-way sensitivity analyses demonstrated robust preference for rivaroxaban. When examining only patients with moderate-high or high VTE Risk Assessment Profile scores, rivaroxaban remained the preferred strategy. Probabilistic sensitivity analysis demonstrated a preference for rivaroxaban in 100% of cases at a standard willingness-to-pay threshold of $100,000/quality-adjusted life year. CONCLUSIONS: A 30-day course of rivaroxaban is a cost-effective extended thromboprophylaxis strategy in trauma patients in this theoretical study. Prospective studies of postdischarge thromboprophylaxis to prevent postinjury VTE are warranted.

A comparative cost-utility analysis of postoperative calcium supplementation strategies used in the current management of hypocalcemia.

BACKGROUND: Symptomatic hypocalcemia is a common complication of total thyroidectomy. Management strategies include responsive treatment initiation for symptoms or prevention by routine or parathyroid hormone-directed calcium supplementation. The comparative cost-effectiveness of even the most often utilized strategies is unclear. METHODS: A Markov cohort model was created to compare routine supplementation with calcium alone (RS), postoperative parathyroid hormone-based selective supplementation with calcium and calcitriol (SS), and no supplementation (NS) in asymptomatic patients. Patients could remain asymptomatic or develop symptomatic hypocalcemia, managed with outpatient oral supplementation or intravenous calcium infusion and administered either inpatient or outpatient. Effectiveness was measured in quality-adjusted life years. Sensitivity analyses were performed to test model parameter assumptions. RESULTS: RS was the preferred strategy, costing $329/patient and resulting in 0.497 quality-adjusted life years, which was only marginally better compared to SS ($373 for 0.495 quality-adjusted life years). NS was most costly at $4,955 for 0.491 quality-adjusted life years. Preference for RS over SS was sensitive to the probability of developing symptoms and the probability of symptom treatment with intravenous supplementation. On probabilistic sensitivity analysis, RS was preferred in 75.4% of scenarios. CONCLUSION: After total thyroidectomy, a preventative calcium supplementation strategy should be strongly considered. In this data-driven theoretical model, RS was the least costly option and resulted in an incremental gain in quality-adjusted life years.

Factors associated with late recurrence after parathyroidectomy for primary hyperparathyroidism.

BACKGROUND: A recent study with unusually lengthy follow-up after surgery for primary hyperparathyroidism reported higher recurrence rates than previously appreciated. We sought to identify specific factors associated with late recurrence after seemingly curative parathyroidectomy. METHODS: Prospectively collected data were retrieved for patients who had surgical treatment of sporadic primary hyperparathyroidism with ≥ 3-year follow-up (3-17.6 years). Recurrence was defined by 6 months of eucalcemia with subsequent hypercalcemia and a high or unsuppressed parathyroid hormone. Recurrent patients were compared with cured patients (defined by consistent eucalcemia). RESULTS: Among 261 patients, 28 (10.7%) had recurrence and 233 (89.3%) were cured. The mean time to recurrence was 77 months (range 13-170). The mean final intraoperative parathyroid hormone (49.0 pg/mL vs 37.5 pg/mL, P < .01), 6-month calcium levels (9.6 mg/dL vs 9.2 mg/dL, P = .02) and mean 6-month parathyroid hormone levels (86.5 pg/mL vs 59.6 pg/mL, P = .04) were higher for recurrence. By multivariable analysis, 6-month calcium ≥ 9.7 and eucalcemic elevation of the parathyroid hormone at 6 months were independently associated with recurrent primary hyperparathyroidism. CONCLUSION: Long-term follow-up after apparent curative surgery for primary hyperparathyroidism identified a high late recurrence rate (10.7%), up to 17 years later. A 6-month calcium >9.7 mg/dL and eucalcemic parathyroid hormone elevation at 6 months may be associated with recurrence, and such findings may help guide management.

Comparative characteristics of primary hyperparathyroidism in pediatric and young adult patients.

BACKGROUND: Primary hyperparathyroidism is rare in pediatric patients. Our study aim was to compare primary hyperparathyroidism in pediatric (<19 years) and young adult (19-29 years) patients. METHODS: A prospectively collected database from a single, high-volume institution was queried for all patients age <30 years who had initial parathyroidectomy for primary hyperparathyroidism yielding 126/4,546 (2.7%) primary hyperparathyroidism patients representing 39 pediatric and 87 young adult patients. Presenting symptoms, operative data, and postoperative course were compared for patients age 0-19 years and 20-29 years. RESULTS: Sporadic primary hyperparathyroidism was present in 81.7% and occurred less often in pediatric patients than young adult patients (74.4% vs 86.2%, P = .12). Among patients with hereditary primary hyperparathyroidism, multiple endocrine neoplasia type 1 was the most common type. Multiglandular disease was common in both pediatric (30.7%) and young adult (21.8%) patients. Following parathyroidectomy, 3 (2.3%) patients had permanent hypoparathyroidism and none had permanent recurrent laryngeal nerve paralysis. Biochemical cure at 6 months was equally likely in pediatric and young adult patients (97.1% vs 93.6%, P = .44) with comparable follow-up (78.4 months vs 69.1 months, P = .66) and rates of recurrent disease (5.9% vs 10.3%, P = .46). Recurrence was due to multiple endocrine neoplasia 1-related primary hyperparathyroidism in all cases. CONCLUSION: Although primary hyperparathyroidism is sporadic in most patients <19 years, they are more likely to have multiple endocrine neoplasia type 1-associated primary hyperparathyroidism (23%). Parathyroidectomy for primary hyperparathyroidism can be performed safely in pediatric patients with a high rate of cure. Follow-up for patients with hereditary disease is necessary.

Tumor genotype determines phenotype and disease-related outcomes in thyroid cancer: a study of 1510 patients.

OBJECTIVES: To correlate thyroid cancer genotype with histology and outcomes. BACKGROUND: The prognostic significance of molecular signature in thyroid cancer (TC) is undefined but can potentially change surgical management. METHODS: We reviewed a consecutive series of 1510 patients who had initial thyroidectomy for TC with routine testing for BRAF, RAS, RET/PTC, and PAX8/PPARG alterations. Histologic metastatic or recurrent TC was tracked for 6 or more months after oncologic thyroidectomy. RESULTS: Papillary thyroid cancer (PTC) was diagnosed in 97% of patients and poorly differentiated/anaplastic TC in 1.1%. Genetic alterations were detected in 1039 (70%); the most common mutations were BRAFV600E (644/1039, 62%), and RAS isoforms (323/1039, 31%). BRAFV600E-positive PTC was often conventional or tall cell variant (58%), with frequent extrathyroidal extension (51%) and lymph node metastasis (46%). Conversely, RAS-positive PTC was commonly follicular variant (87%), with infrequent extrathyroidal extension (4.6%) and lymph node metastasis (5.6%). BRAFV600E and RET/PTC-positive PTCs were histologically similar. Analogously, RAS and PAX8/PPARG-positive PTCs were histologically similar. Compared with RAS or PAX8/PPARG-positive TCs, BRAFV600E or RET/PTC-positive TCs were more often associated with stage III/IV disease (40% vs 15%, P < 0.001) and recurrence (10% vs 0.7%, P < 0.001; mean follow-up 33 ± 21 mo). Distant metastasis was highest in patients with RET/PTC-positive TC (10.8%, P = 0.02). CONCLUSIONS: In this large study of prospective mutation testing in unselected patients with TC, molecular signature was associated with distinctive phenotypes including cancers, with higher risks of both distant metastasis and early recurrence. Preoperative genotype provides valuable prognostic data to appropriately inform surgery.