Effect of Delayed Parathyroidectomy on Risk of Future Cardiovascular and Nephrolithiasis Interventions in Adults with Primary Hyperparathyroidism [Original Study].

OBJECTIVE: To determine whether the timing of parathyroid surgery impacts the risk of renal stone retreatment and cardiovascular interventions. SUMMARY BACKGROUND DATA: Long-term, untreated primary hyperparathyroidism is associated with significant morbidity including nephrolithiasis and cardiovascular disease. METHODS: We conducted a Population-based Cohort study of New York and California state-wide data from 2000-2020. Adult patients who underwent renal stone treatment and subsequently diagnosed with primary hyperparathyroidism (pHPT) and underwent parathyroidectomy (PTX) were included. Patients were excluded if PTX was prior to index stone procedure, they underwent second stone treatment within 6 months, with stage V CKD, with secondary or tertiary hyperparathyroidism, with prior kidney transplant or hemodialysis, or with prior cancer diagnosis. Rate of renal stone retreatment and cardiovascular interventions after PTX in pHPT patients with nephrolithiasis who underwent parathyroid surgery at ≤ 2 years and >2 years after index stone procedure was measured. RESULTS: We identified 2,093 patients who underwent first-time stone treatment and subsequent PTX. The median time to PTX was 560 days (IQR 187-1477) and follow-up was 7.4 years (IQR 4.5-13.1). Delaying PTX for more than 2 years increased the risk of renal stone retreatment by 59% (HR 1.59; P<0.001), increased the risk of experiencing coronary disease or associated interventions by 118% (HR=2.18; P=0.01), and increased the risk of experiencing an overall cardiovascular event by 52% (HR 1.52; P<0.01). CONCLUSIONS AND RELEVANCE: In symptomatic pHPT, delaying PTX significantly increases the risk of requiring future stone retreatment and cardiac/vascular surgical interventions. This highlights the importance of early surgical referral and multidisciplinary approaches to optimize outcomes and resource utilization in pHPT.

Machine learning-derived clinical decision algorithm for the diagnosis of hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism.

PURPOSE: To train and validate machine learning-derived clinical decision algorithm (MLCDA) for the diagnosis of hyperfunctioning parathyroid glands using preoperative variables to facilitate surgical planning. METHODS: This retrospective study included 458 consecutive primary hyperparathyroidism (PHPT) patients who underwent combined 4D-CT and sestamibi SPECT/CT (MIBI) with subsequent parathyroidectomy from February 2013 to September 2016. The study cohort was divided into training (first 400 patients) and validation sets (remaining 58 patients). Sixteen clinical, laboratory, and imaging variables were evaluated. A random forest algorithm selected the best predictor variables and generated a clinical decision algorithm with the highest performance (MLCDA). The MLCDA was trained to predict the probability of a hyperfunctioning vs normal gland for each of the four parathyroid glands in a patient. The reference standard was a four-quadrant location on operative reports and pathology. The accuracy of MLCDA was prospectively validated. RESULTS: Of 16 variables, the algorithm selected 3 variables for optimal prediction: combined 4D-CT and MIBI using (1) sensitive reading, (2) specific reading, and (3) cross-product of serum calcium and parathyroid hormone levels and outputted an MLCDA using five probability categories for hyperfunctioning glands. The MLCDA demonstrated excellent accuracy for correct classification in the training (4D-CT + MIBI: 0.91 [95% CI: 0.89-0.92]) and validation sets (4D-CT + MIBI: 0.90 [95% CI: 0.86-0.94]. CONCLUSION: Machine learning generated a clinical decision algorithm that accurately diagnosed hyperfunctioning parathyroid glands through classification into probability categories, which can be implemented for improved preoperative planning and convey diagnostic certainty. KEY POINTS: Question Can an MLCDA use preoperative variables for the diagnosis of hyperfunctioning parathyroid glands to facilitate surgical planning? Findings The developed MLCDA demonstrated excellent accuracy for correct classification in the training (0.91 [95% CI: 0.89-0.92]) and validation sets (0.90 [95% CI: 0.86-0.94]). Clinical relevance Using standard preoperative variables, an MLCDA for diagnosing hyperfunctioning parathyroid glands can be implemented to improve preoperative parathyroid localization and included in radiology reports for surgical planning.

Assessing Impact of Nutrition Care by Registered Dietitian Nutritionists on Patient Medical and Treatment Outcomes in Outpatient Cancer Clinics: A Cohort Feasibility Study.

More information is needed about the impact of outpatient nutrition care from a registered dietitian nutritionist (RDN) on patient outcomes. This study aimed to assess the feasibility of a cohort study design to evaluate impact of RDN nutrition care on patient outcomes, describe clinic malnutrition screening practices, and estimate statistical parameters for a larger study. Seventy-seven patients with lung, esophageal, colon, rectal, or pancreatic cancer from six facilities were included (41 received RDN care and 36 did not). RDN nutrition care was prospectively documented for six months and documented emergency room visits, unplanned hospitalizations and treatment changes were retrospectively abstracted from medical records. Most facilities used the Malnutrition Screening Tool (MST) to determine malnutrition risk. Patients receiving RDN care had, on average, five, half hour visits and had more severe disease and higher initial malnutrition risk, although this varied across sites. Documented medical and treatment outcomes were relatively rare and similar between groups. Estimated sample size requirements varied from 113 to 5856, depending on tumor type and outcome, and intracluster correlation coefficients (ICCs) ranged from 0 to 0.47. Overall, the methods used in this study are feasible but an interventional or implementation design might be advantageous for a larger study.

Use and Misuse of Opioids After Endocrine Surgery Operations.

OBJECTIVE: To examine the rate of new and persistent opioid use after endocrine surgery operations. SUMMARY OF BACKGROUND DATA: A global epidemic of opioid misuse and abuse has been evolving over the past 2 decades with opioid use among surgical patients being a particularly difficult problem. Minimal data exists regarding opioid misuse after endocrine surgical operations. METHODS: A retrospective cohort study using the MarketScan identified adult patients who underwent thyroidectomy, parathyroidectomy, neck dissections for thyroid malignancy, and adrenalectomy from 2008 to 2017. Persistent opioid use was defined as receipt of ≥1 opioid prescription 90-180 days postop with no intervening procedures or anesthesia. Multivariable models were used to examine associations between clinical characteristics and any use and new persistent use of opioids. RESULTS: A total of 259,115 patients were identified; 54.6% of opioid naïve patients received a perioperative opioid prescription. Fulfillment of this prescription was associated with malignant disease, greater extent of surgery, younger age, residence outside of the Northeast, and history of depression or substance abuse. The rate of new persistent opioid use was 7.4%. A lateral neck dissection conferred the highest risk for persistent opioid use (P < 0.01). Persistent opioid use was also associated with older age, Medicaid coverage, residency outside of the Northeast, increased medical co-morbidities, a history of depression, anxiety, substance use disorder, and chronic pain (all P < 0.01). Importantly, the risk for persistent opioid use increased with higher doses of total amount of opioids prescribed. CONCLUSIONS: The rate of new, persistent opioid use after endocrine surgery operations is substantial but may be mitigated by decreasing the number of postoperative opioids prescribed.

Trends and Outcomes of Surgical Management of Primary Papillary Carcinoma in the Pediatric Population.

BACKGROUND: Childhood papillary thyroid cancer is more aggressive than carcinomas in adults. Current American Thyroid Association pediatric guidelines recommend a total or near-total thyroidectomy for all pediatric patients without gross evidence of lymph node metastases. Our objective is to analyze trends in the surgical management of pediatric papillary thyroid cancer and assess how well the guidelines are implemented. METHODS: A retrospective cohort study of pediatric patients (ages 19 y and under) who underwent a thyroidectomy was conducted using the Surveillance, Epidemiology, and End Results database 2006-2017. Procedure type was classified as lobectomy or less and subtotal or total thyroidectomy. Descriptive statistics to illustrate patient and tumor characteristics as well as chi-square analysis to evaluate frequency of treatment with total thyroidectomies versus lobectomy or less were performed. Logistic regression analysis controlling for age, sex, size of tumor, rural versus urban institutions, and surgery year was conducted to identify factors predictive of procedure type. RESULTS: A total of 2271 children underwent surgical management of papillary thyroid cancer between 2006 and 2017. Most patients received a subtotal or total thyroidectomy as surgical management (n = 2,085, 91.8%). One hundred eighty-six patients (8.2%) received a lobectomy or less. The number of lobectomies or less increased with time, with 41 (6.6%) patients between 2006 and 2009, 98 (8.0%) between 2009 and 2015, and 47 (11.1%) between 2016 and 2017 (P = 0.03). Mortality rates were low (n = 15, 0.7%). On logistic regression analysis, later stages, larger sizes, and earlier operative years were predictive of a near-total or total thyroidectomy. CONCLUSIONS: Despite the American Thyroid Association Guidelines recommending a total thyroidectomy for pediatric well-differentiated thyroid cancer, the results of this study demonstrate that thyroid lobectomies are being performed in increasing frequency for smaller tumors in earlier stages of disease. Further investigation of whether this trend actually affects the outcomes in this patient cohort is needed.

The Evolving Practice Patterns of Academic Endocrine Surgeons: A Cross-sectional Analysis of the Faculty Practice Solutions Center Database 2014 to 2017.

OBJECTIVE: To examine the evolution of an academic endocrine surgeon's practice over time. SUMMARY BACKGROUND: Amid growing recognition that surgical volume and specialization are linked to better outcomes, endocrine surgery is one of the youngest fields to develop its own formal fellowship training program. However, 3 decades after the emergence of endocrine surgery as a distinct specialty, the medical community and public still have a limited understanding of endocrine surgeons and what they do. METHODS: We performed a cross-sectional analysis of endocrine surgeons identified in the Faculty Practice Solutions Center Database from 2014 to 2017. Trends in annual number of endocrine surgeries performed, number of all surgeries performed, total work relative value units generated, and patient payer mix stratified by years of practice were evaluated. RESULTS: One hundred thirty-nine endocrine surgeons practicing in 103 institutions over 4 years were analyzed. The proportion of endocrine-specific operations increases over time. A typical academic endocrine surgeon meets the high-volume threshold for thyroidectomies early in their career, but does not reach the thresholds for parathyroidectomies or adrenalectomies until after 4 years. Increased productivity as reflected by adjusted work relative value units does increase over the first 15 years of practice, but also decreases as the proportion of endocrine-specific practice increases. The greatest proportion of endocrine surgeons' patients are insured by commercial plans (46%-50%), and payer mix is stable across all levels of practice. CONCLUSIONS: Although endocrine surgeons perform a high-volume of endocrine-specific operations, practice patterns are heterogeneous and suggest that most surgeons have to grow their endocrine-specific practice over time.

A Multidisciplinary Head-to-Head Comparison of American College of Radiology Thyroid Imaging and Reporting Data System and American Thyroid Association Ultrasound Risk Stratification Systems.

BACKGROUND: Ultrasound plays a critical role in evaluating thyroid nodules. We compared the performance of the two most popular ultrasound malignancy risk stratification systems, the 2015 American Thyroid Association (ATA) guidelines and the American College of Radiology Thyroid Imaging and Reporting Data System (ACR TI-RADS). MATERIALS AND METHODS: We retrospectively identified 250 thyroid nodules that were surgically removed from 137 patients. Their ultrasound images were independently rated using both ATA and ACR TI-RADS by six raters with expertise in ultrasound interpretation. For each system, we generated a receiver operating characteristic curve and calculated the area under the curve (AUC). RESULTS: Sixty-five (26%) nodules were malignant. There was "fair agreement" among raters for both ATA and ACR TI-RADS. Our observed malignancy risks for ATA and ACR TI-RADS categories were similar to expected risk thresholds with a few notable exceptions including the intermediate ATA risk category and the three highest risk categories for ACR TI-RADS. Biopsy of 226 of the 250 nodules would be indicated by ATA guidelines based on nodule size and mean ATA rating. One hundred forty-six nodules would be biopsied based on ACR TI-RADS. The sensitivity, specificity, and negative and positive predictive values were 92%, 10%, 79%, and 27%, respectively, for ATA and 74%, 47%, 84%, and 33%, respectively, for ACR TI-RADS. The AUC for ATA was 0.734 and for ACR TI-RADS was 0.718. CONCLUSION: Although both systems demonstrated good diagnostic performance, ATA guidelines resulted in a greater number of thyroid biopsies and exhibited more consistent malignancy risk prediction for higher risk categories. IMPLICATIONS FOR PRACTICE: With the rising incidence of thyroid nodules, the need for accurate detection of malignancy is important to avoid the overtreatment of benign nodules. Ultrasonography is one of the key tools for the evaluation of thyroid nodules, although the use of many different ultrasound risk stratification systems is a hindrance to clinical collaboration in everyday practice and the comparison of data in research. The first step toward the development of a universal thyroid nodule ultrasound malignancy risk stratification system is to better understand the strengths and weaknesses of the current systems in use.

Periadrenal Volume is a Better Predictor of Prolonged Operative Time in Laparoscopic Retroperitoneal Adrenalectomy than BMI.

BACKGROUND: Retroperitoneal laparoscopic adrenalectomy is gaining traction as a minimally invasive technique. One of the purported relative contraindications is BMI given the smaller working space. We hypothesize that other anthropometric measurements may be better predictors of operative time. METHODS: An IRB-approved, single-institution, retrospective study of 83 patients who underwent laparoscopic retroperitoneal adrenalectomy evaluated the association of anthropometric measurements taken from cross-sectional imaging and the primary outcome of operative time. Descriptive statistics were performed with Wilcoxon rank-sum test for continuous variables (median; IQR) and Chi-square (n; %) for categorical variables. A linear random effects model was used to model operative time. RESULTS: The majority of the patients were white (40; 48.2%) women (46; 55.4%) with a median age of 54 with interquartile range (IQR) of 43-63 and a median BMI of 27.8 (IQR 21.2-38.6). On univariable analysis, factors that led to longer operative time included right-sided operation (p = 0.04), male gender (p < 0.01), clinical diagnosis (p < 0.01), waist area (p < 0.01), waist/hip ratio (p < 0.01), periadrenal volume (p < 0.01), posterior adiposity index (PAI) (p < 0.01) and BMI (p < 0.01). Only side, order of operation, and periadrenal fat volume (p < 0.01, p = 0.02 and p < 0.01, respectively) remained independent predictors of increased operative time on multivariable analysis. CONCLUSION: This study demonstrates that anthropometric measurements, specifically periadrenal fat volume, and side of operation, are better predictors for increased operative time in laparoscopic retroperitoneal adrenalectomies than BMI. This information can help facilitate appropriate patient selection for this operative approach.

Biochemical Profile Affects IOPTH Kinetics and Cure Rate in Primary Hyperparathyroidism.

BACKGROUND: Recently, normocalcemic (NC) and normohormonal (NH) variants of primary hyperparathyroidism (pHPT) have been described, with distinct biochemical profiles from the typical high serum calcium and parathyroid hormone (PTH) levels. Here, we investigate whether biochemical profile affects cure rate, as well as the kinetics of intraoperative PTH (IOPTH). METHODS: This is a single-center, retrospective study of pHPT patients undergoing parathyroidectomy. Patients were grouped based on preoperative calcium and PTH levels into typical, NC (normal calcium, elevated PTH, no evidence of secondary hyperparathyroidism), and NH (elevated calcium, unsuppressed PTH) biochemical profiles. All patients had IOPTH monitoring and ≥6-month post-op serum studies to confirm surgical cure. Patient variables were analyzed with Kruskal-Wallis test and Chi-square analysis. IOPTH kinetic curves were analyzed using a linear mixed model. RESULTS: From June 2006 to October 2014, 646 patients met inclusion criteria. Biochemical profile was typical in 460 patients (71%), NC in 101 (16%), and NH in 85 (13%). IOPTH levels were higher at all time points in typical patients, p < 0.001. Surgical cure rates were significantly lower for NC patients (90.1%) than for typical (98.5%) or NH patients (97.7%), p < 0.001, although a stricter criteria for cure was used in this group (normal calcium AND normal PTH). In a multivariable linear mixed model, NC patients had a significantly slower rate of IOPTH decline (p < 0.001 at 10 min). CONCLUSIONS: Here, we better characterize the atypical variants of pHPT. Using a stricter definition of cure in the NC variant, these patients have a lower surgical cure rate than typical or NH variants in pHPT. The IOPTH curve is affected by biochemical profile, with both NC and NH patients having lower absolute values and NC patients having a slower decline.

Racial and Socioeconomic Disparities in Access and Utilization of Adrenal Metastasectomy.

BACKGROUND: There is substantial evidence that resecting adrenal metastases can be safely accomplished and extend overall survival in select patients. However, patient access to this operation has not been studied at the population level. The purpose of this study was to determine differences in utilization rates of adrenal metastasectomy (ADMX) across patient populations. METHODS: The Healthcare Utilization Project National Inpatient Sample was used to identify patients who had adrenal metastases (ADM) and who underwent ADMX from 2007 to 2011. Patients were identified by ICD-9-CM diagnosis and procedure codes. Predictor variables included sex, race, median household income, and primary insurance payer. Primary outcomes included receiving an ADMX and same hospitalization mortality. Secondary outcomes included length of stay, infection, cardiac, pulmonary, and renal complications. Univariable and multivariable logistic regression models were used to identify statistical associations. RESULTS: 32,331 ADM and 1070 ADMX patients identified in the database. Despite similar comorbidities, Black patients had 0.30 (95% CI 0.21-0.41) lower odds to receive an ADMX compared to White patients. Medicaid patients had 0.38 (0.28-0.52) less odds and Private Insurance patients 1.18 (1.00-1.39) more odds to receive an ADMX compared to Medicare patients. Women had a 1.39 (1.22-1.58) higher odds ratio of undergoing ADMX compared to men. Of the ADMX cohort, there was no difference in same hospitalization mortality or surgical complications. CONCLUSIONS: Black and Medicaid patients underwent fewer adrenal metastasectomies despite similar comorbidities and postoperative outcomes. This suggests a potential disparity in access to this treatment that disproportionately affects Black and low-income patients, and prompts further study, outreach attempts, as well as, research into improving access.

Diagnostic Performance of 4D CT and Sestamibi SPECT/CT in Localizing Parathyroid Adenomas in Primary Hyperparathyroidism.

Background There currently is no consensus on the optimal localization procedure and imaging protocol for parathyroid adenoma. Parathyroid four-dimensional (4D) CT has emerged as a promising method for preoperative localization. Purpose To evaluate the diagnostic performance of parathyroid 4D CT and technetium 99m-sestamibi (hereafter, referred to as sestamibi) SPECT/CT in preoperative localization in patients with primary hyperparathyroidism. Materials and Methods This was a single-institution retrospective study of patients with primary hyperparathyroidism who underwent a combined imaging protocol of sestamibi SPECT/CT and 4D CT (noncontrast, contrast agent-enhanced, arterial, and delayed venous phases) acquired in a single setting from February 2013 to May 2016, with subsequent parathyroidectomy within 6 months. Reference standard for correct localization was on the basis of location denoted on operative reports, with pathologic confirmation of parathyroid adenoma or hyperplasia. By using a four-quadrant analysis, sensitivity, specificity, and area under the curve (AUC) for localization of the hyperfunctioning parathyroid gland or glands at sestamibi SPECT/CT and 4D CT were compared, per modality and in combination. Results Four hundred patients (319 women, 81 men; mean age, 61 years ± 14 [standard deviation]) were evaluated. Similar diagnostic performance was found in both combined 4D CT with sestamibi SPECT/CT and 4D CT alone (area under the curve [AUC], 0.88 [95% CI: 0.86, 0.90] and 0.87 [95% CI: 0.85, 0.90], respectively; P = .82). Both modalities outperformed sestamibi SPECT/CT (AUC, 0.78; 95% CI: 0.76, 0.81; P < .001). Four-dimensional CT showed higher sensitivity than did sestamibi SPECT/CT (sensitivity, 79.3% [414 of 522] vs 58.0% [303 of 522], respectively; P < .001). In a subset analysis, 4D CT had higher sensitivity than sestamibi SPECT/CT in patients with single-gland disease (sensitivity, 92.5% [297 of 321] vs 75.1% [241 of 321], respectively; P < .001) and with multigland disease (sensitivity, 58.2% [117 of 201] vs 30.8% [62 of 201], respectively; P < .001). Conclusion Four-dimensional CT provided superior preoperative localization compared with sestamibi SPECT/CT in patients with single and multigland disease. The combination of the two modalities did not improve diagnostic performance compared with four-dimensional CT alone. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Sinha and Oates in this issue.

Vitamin D Does Not Affect Intraoperative Parathyroid Hormone Kinetics: A Mixed Linear Model Analysis.

BACKGROUND: Intraoperative parathyroid hormone (ioPTH) monitoring is used to confirm completeness of resection in patients undergoing parathyroidectomy for primary hyperparathyroidism (pHPT). Though there is an inverse relationship between vitamin D and parathyroid hormone (PTH), previous studies have suggested that 25-hydroxyvitamin D (25OHD) level does not affect the likelihood of meeting the Miami criterion. Here, we further investigate whether preoperative 25OHD level affects ioPTH kinetics. METHODS: This is a retrospective case-control study of patients undergoing parathyroidectomy for pHPT at a tertiary referral center. Patients were categorized based on preoperative 25OHD level as vitamin D deficient (≤ 20 ng/mL), insufficient (21-30 ng/mL), or sufficient (>30 ng/mL). Differences in baseline characteristics were analyzed with Kruskal-Wallis H test or chi-square analysis. ioPTH kinetic curves were analyzed using a log-transformed mixed linear model with subject-level random effects. Significance was set at P < 0.05. RESULTS: Among 630 patients who met inclusion criteria, there was a significant difference in ioPTH between groups at baseline (P < 0.001), but not at any other time point. As a continuous variable, as well as a categorical variable, in a mixed linear model, vitamin D had no significant effect on ioPTH kinetics. CONCLUSIONS: Despite a difference in preoperative and baseline PTH levels, preoperative 25OHD had no significant effect on ioPTH kinetics. Therefore, ioPTH assays can be used and interpreted uniformly, regardless of patients' vitamin D status.

Cost Effectiveness of Routine Laryngoscopy in the Surgical Treatment of Differentiated Thyroid Cancer.

BACKGROUND: Some surgeons perform flexible fiberoptic laryngoscopy (FFL) in all patients prior to thyroid cancer operations. Given the low likelihood of recurrent laryngeal nerve (RLN) or aerodigestive invasion in clinically low-risk thyroid cancers, the value of routine FFL in this group is controversial. We hypothesized that routine preoperative FFL would not be cost effective in low-risk differentiated thyroid cancer (DTC). METHODS: A decision model was constructed comparing preoperative FFL versus surgery without FFL in a clinical stage T2 N0 DTC patient without voice symptoms. Total thyroidectomy and definitive hemithyroidectomy were both modeled as possible initial surgical approaches. Outcome probabilities and their corresponding utilities were estimated via literature review, and costs were estimated using Medicare reimbursement data. Sensitivity analysis was conducted to examine the uncertainty of cost, probability, and utility estimates in the model. RESULTS: When the initial surgical strategy was total thyroidectomy, routine preoperative FFL produced an incremental cost of $183 and an incremental effectiveness of 0.000126 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) for routine FFL prior to total thyroidectomy was $1.45 million/QALY, exceeding the $100,000/QALY threshold for cost effectiveness. Routine FFL became cost effective if the preoperative probability of asymptomatic vocal cord paralysis increased from 1.0% to 4.9%, or if the cost of preoperative FFL decreased from $128 to $27. Changing the extent of initial surgery to hemithyroidectomy produced a higher ICER for routine FFL of $1.7 million/QALY. CONCLUSION: Routine preoperative FFL is not cost effective in asymptomatic patients with sonographically low-risk DTC, regardless of the initial planned extent of surgery.

Occult urolithiasis in asymptomatic primary hyperparathyroidism.

OBJECTIVE: Recent international guidelines suggest renal imaging to detect occult urolithiasis in all patients with asymptomatic primary hyperparathyroidism (PHPT), but data regarding their prevalence and associated risk factors are limited. We evaluated the prevalence and risk factors for occult urolithiasis. METHODS: Cross-sectional analysis of 96 asymptomatic PHPT patients from a university hospital in the United States with and without occult nephrolithiasis. RESULTS: Occult urolithiasis was identified in 21% of patients. Stone formers had 47% higher 24-hour urinary calcium excretion (p = 0.002). Although available in only a subset of patients (n = 28), activated vitamin D [1,25(OH)2D] was 29% higher (p = 0.02) in stone formers. There was no difference in demographics, BMI, calcium or vitamin D intake, other biochemistries, renal function, BMD, or fractures. Receiver operating characteristic curves indicated that urinary calcium excretion and 1,25(OH)2D had an area under the curve of 0.724 (p = 0.003) and 0.750 (p = 0.04), respectively. A urinary calcium threshold of >211mg/day provided a sensitivity of 84.2% and a specificity of 55.3% while a 1,25(OH)2D threshold of >91pg/mL provided a sensitivity and specificity of 62.5% and 90.0% respectively for the presence of stones. CONCLUSION: Occult urolithiasis is present in about one-fifth of patients with asymptomatic PHPT and is associated with higher urinary calcium and 1,25(OH)2D. Given that most patients will not have occult urolithiasis, targeted imaging in those most likely to have occult stones rather than screening all asymptomatic PHPT patients may be useful. The higher sensitivity of urinary calcium versus 1,25(OH)2D suggests screening those with higher urinary calcium may be an appropriate approach.

Probing Competitive and Co-operative Hydroxyl and Ammonium Hydrogen-Bonding Directed Epoxidations.

The diastereoselectivities and rates of epoxidation (upon treatment with Cl3CCO2H then m-CPBA) of a range of cis- and trans-4-aminocycloalk-2-en-1-ol derivatives (containing five-, six-, and seven-membered rings) have been investigated. In all cases where the two potential directing groups can promote epoxidation on opposite faces of the ring scaffold, evidence of competitive epoxidation pathways, promoted by hydrogen-bonding to either the in situ formed ammonium moiety or the hydroxyl group, was observed. In contrast to the relative directing group abilities already established for the six-membered ring system (NHBn ≫ OH > NBn2), an N,N-dibenzylammonium moiety appeared more proficient than a hydroxyl group at directing the stereochemical course of the epoxidation reaction in a five- or seven-membered system. In the former case, this was rationalized by the drive to minimize torsional strain in the transition state being coupled with assistance from hydrogen-bonding to the ammonium moiety. In the latter case, this was ascribed to the steric bulk of the ammonium moiety disfavoring conformations in which hydrogen-bonding to the hydroxyl group results in direction of the epoxidation to the syn face. In cases where the two potential directing groups can promote epoxidation on the same face of the ring scaffold, an enhancement of epoxidation diastereoselectivity was not observed, while introduction of a second, allylic heteroatom to the substrate results in diminishment of the rate of epoxidation in all cases. Presumably, reduction of the nucleophilicity of the olefin by the second, inductively electron-withdrawing heteroatom is the dominant factor, and any assistance to the epoxidation reaction by the potential to form hydrogen-bonds to two directing groups rather than one is clearly unable to overwhelm it.

Cancer care cost trends in the United States: 1998 to 2012.

BACKGROUND: The authors examine trends in spending on cancer from 1998 through 2012, including cancer care costs, prevalence, and cases by payer, and discuss the results within the context of a prior analysis and recent health policy and programmatic changes. METHODS: Condition-specific distribution of expenditures from the Medical Expenditure Panel Survey, supplemented with results from the National Nursing Home Survey and other data sources, was used as the basis for allocating the Personal Health Care components of the National Health Expenditure Accounts among conditions. RESULTS: Cancer care expenditures grew at an annualized rate of 2.9% from 1998 to 2012. The share of expenditures for hospital-based care declined to a low of 48% during 2007 through 2009. Professional and clinical services' shares declined substantially between 2007 to 2009 and 2010 to 2012 when the hospital share increased. Treated prevalence decreased for all payers between the first and last study periods with the exception of private payers (11.2% increase). Out-of-pocket expenditures declined to 4.7%, whereas Medicare's share increased slightly. Medication expenditures increased, notably within retail and mail order settings. CONCLUSIONS: The previous rapid growth of cancer prevalence and expenditures has now slowed, most remarkably since the 2007 recession. Out-of-pocket expenses for cancer treatment continue to decline, most recently reaching the lowest point in 25 years. In addition, the early effects of Affordable Care Act expansion can be observed in the decline of treated prevalence in the Medicaid population as the demographics of Medicaid enrollees change.