Burden of illness in not adequately controlled chronic hypoparathyroidism: Findings from a 13-country patient and caregiver survey.

OBJECTIVE: To address knowledge gaps regarding burdens associated with not adequately controlled chronic hypoparathyroidism. DESIGN: Global patient and caregiver survey. STUDY POPULATIONS: Patients with chronic hypoparathyroidism not adequately controlled on conventional therapy and their caregivers. MEASUREMENTS: Health-related quality of life (HRQoL) and health status were evaluated using the 36-item Short Form version 2 (SF-36 v2.0) and Five-Level EuroQoL 5 Dimensions (EQ-5D-5L) instruments, respectively. Hypoparathyroidism-associated symptoms were assessed by a disease-specific Hypoparathyroidism Symptom Diary and caregiver burden via the Modified Caregiver Strain Index (MCSI). RESULTS: Data were obtained from 398 patients and 207 caregivers. Patients' self-rated hypoparathyroidism-related symptom severity was none (3%), mild (32%), moderate (53%) or severe (12%). Per the Hypoparathyroidism Symptom Diary, patients reported moderate, severe or very severe symptoms of physical fatigue (73%), muscle cramps (55%), heaviness in limbs (55%) and tingling (51%) over a 7-day recall period. Impacts (rated 'somewhat' or 'very much') were reported by 84% of patients for ability to exercise, 78% for sleep, 75% for ability to work and 63% for family relationships. Inverse relationships were observed between patient self-rated overall symptom severity and HRQoL and health status assessment scores-the greater the symptom severity, the lower the SF-36 and EQ-5D-5L scores. Caregiver burden increased with patient self-rated symptom severity: none, 1.7 MCSI; mild, 5.4 MCSI; moderate, 9.5 MCSI; and severe, 12.5 MCSI. CONCLUSION: Patients with not adequately controlled hypoparathyroidism reported substantial symptoms and impacts. Greater patient symptom severity was associated with decreased patient HRQoL and health status assessments and increased caregiver burden.

Patients with bone metastases from solid tumors initiating treatment with a bone-targeted agent in 2011: a descriptive analysis using oncology clinic data in the US.

PURPOSE: Three bone-targeted agents (BTAs) are approved in the USA for prevention of bone complications among solid tumor patients with bone metastases: two intravenous bisphosphonates (IV BP) (pamidronate and zoledronic acid), and one subcutaneous receptor activator of nuclear factor-kappaB (RANK) ligand inhibitor (denosumab). Using electronic medical record data from outpatient community and hospital-affiliated oncology clinics, we examined the characteristics of patients who initiated treatment with a BTA in 2011 and followed them for a maximum of 12 months. METHODS: Adult patients with bone metastasis secondary to solid tumors newly treated with a BTA during 2011 were identified from the Oncology Services Comprehensive Electronic Records (OSCER) database. We examined patient characteristics at BTA initiation, treatment patterns, and compliance during a 12-month period. Sensitivity analyses were performed in a subgroup of patients who had confirmed 12 months of follow-up data. RESULTS: Denosumab patients (N = 1,594) were older (65 % ≥65 years vs. 60 % ≥65 years), further along in their disease progression (time since bone metastasis diagnosis: 16 % ≥2 years vs. 10 % ≥2 years), less likely to switch BTA (overall: 6 vs. 14 %; subgroup: 8 vs. 19 %), and more compliant with treatment (overall: median doses of 7 vs. 4; subgroup: 11 vs. 8) compared to IV BP patients (N = 1,975). Findings were consistent across gender, age, tumor type, naïve, and transition strata. CONCLUSIONS: Patients receiving denosumab and IV BPs may differ. Despite higher age and more advanced disease, patients treated with denosumab are more likely to stay on treatment and have better compliance.

The cost-effectiveness of initial treatment of multiple myeloma in the U.S. with bortezomib plus melphalan and prednisone versus thalidomide plus melphalan and prednisone or lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance treatment.

The outlook for transplant-ineligible multiple myeloma patients has improved enormously over recent years with the incorporation of new agents into standard regimens. Novel regimens combine melphalan and prednisone (MP) with bortezomib (VMP), with thalidomide (MPT), and with lenalidomide with (MPR-R) and without (MPR) lenalidomide maintenance. The efficacy, safety, and cost-effectiveness of these regimens have not yet been compared; therefore, we conducted a pharmacoeconomic analysis using data from randomized controlled trials versus MP. Using a Markov model developed from a U.S. payer's perspective, we compared VMP with MPT and MPR-R over a lifetime horizon. MPT and MPR-R were chosen because, like VMP, they are superior to MP in response and outcomes. Data from the Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA; VMP), Intergroupe Francophone du Myelome (IFM) 99-06 (MPT), and MM-015 (MPR-R) trials were used. The IFM 99-06 study was selected because of the superior activity in this study compared with other MPT studies. Using patient-level (VMP) and published (MPT, MPR-R) data, we estimated the health-state transition and adverse event probabilities for each regimen, related costs, and state-specific utility estimates. Costs (in 2010 U.S. dollars) and health outcomes were discounted at 3%. Discounted lifetime direct medical costs were lowest with VMP at $119,102. MPT cost $142,452 whereas MPR-R cost $248,358. Incremental cost-effectiveness ratio calculations projected that VMP would confer cost savings and better health outcomes relative to MPT and MPR-R. We conclude that VMP is highly likely to be cost-effective compared with MP, MPT, and MPR-R.

Association of Serum Calcium and Phosphate With Incident Cardiovascular Disease in Patients With Hypoparathyroidism.

The pathophysiological basis for the increased incidence of cardiovascular disease in patients with chronic hypoparathyroidism is poorly understood. To evaluate associations between levels of albumin-corrected serum calcium, serum phosphate, and calcium-phosphate product with the odds of developing cardiovascular events in patients with chronic hypoparathyroidism with ≥1 calcitriol prescription, we conducted a retrospective nested case-control study of patients who developed a cardiovascular event and matched controls without an event. The primary outcome was the instance of cardiovascular events. An electronic medical record database was used to identify 528 patients for the albumin-corrected serum calcium analysis and 200 patients for the serum phosphate and calcium-phosphate product analyses. Patients with ≥67% of albumin-corrected serum calcium measurements outside the study-defined 2.00 to 2.25 mmol/L (8.0 to 9.0 mg/100 ml) range had 1.9-fold higher odds of a cardiovascular event (adjusted odds ratio, 95% confidence interval 1.89, 1.10 to 3.25) compared with patients with <33% of calcium measurements outside the range. Likewise, patients with any serum phosphate measurements above 0.81 to 1.45 mmol/L (2.5 to 4.5 mg/100 ml) had 3.3-fold higher odds (3.26; 1.24 to 8.58), and those with any calcium-phosphate product measurements above 4.40 mmol2/L2 (55 mg2/dL2) had 4.8-fold higher odds of a cardiovascular event (95% confidence interval 1.36 to 16.81) compared with patients with no measurements above these ranges. In adult patients with chronic hypoparathyroidism, a cardiovascular event was more likely in those with a higher proportion of albumin-corrected serum calcium measurements outside 2.00 to 2.25 mmol/L (8.0 to 9.0 mg/100 ml) or any serum phosphate and any calcium-phosphate product measurements above the normal population range.

Impact on caregivers of adult patients receiving parenteral support for short-bowel syndrome with intestinal failure: A multinational, cross-sectional survey.

BACKGROUND: Patients with short-bowel syndrome and intestinal failure (SBS-IF) require parenteral support (PS) and may need long-term home-care support. This survey assessed the impact of care provision on adult caregivers of adult patients receiving PS for SBS-IF. METHODS: An online, cross-sectional survey of caregivers of adults with a self-reported physician diagnosis of SBS-IF was conducted in France, Germany, Italy, the UK, and USA. Impact on caregivers was evaluated using the 18-item Caregiver Strain Index (CSI), the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP), and self-reporting impact questionnaires. RESULTS: Caregivers (N = 121; aged 51 ± 13.7 years; 59% women) provided assistance for a mean of 9.9 ± 12.53 years; 77% were providing care 7 days per week. Patients (51 ± 16.4 years; 56% women) of caregivers were typically family members: spouse/partner (61%), adult son/daughter (19%), or parent (10%). Caregivers reported experiencing some strain (CSI score 4 ± 3.4). Among 71 of 73 employed caregivers, the WPAI:SHP assessment showed that caregivers missed 7% ± 12.7% of work hours in the preceding week and were present but not productive at work 37% ± 23.1% of the time; 28% of caregivers reported a reduced number of working hours because of caregiving. Many caregivers reported limitations in recreational activities (53%), and ≥30% had difficulty spending time with family and friends. Caregivers (87%) also reported worrying about the patient's health. CONCLUSIONS: Caregivers of adult patients with SBS-IF experience negative daily personal impacts and loss of productivity arising from their caregiving responsibilities.

Association of Calcium and Phosphate Levels with Incident Chronic Kidney Disease in Patients with Hypoparathyroidism: A Retrospective Case-Control Study.

Objective: Reasons for the increased incidence of chronic kidney disease (CKD) in patients with chronic hypoparathyroidism are poorly understood. This study evaluated associations between levels of albumin-corrected serum calcium, serum phosphate, and calcium-phosphate product and the odds of CKD development in patients with chronic hypoparathyroidism. Design: A retrospective nested case-control study of adult patients with chronic hypoparathyroidism who had ≥1 prescription for calcitriol who developed CKD and matched controls who did not develop CKD were selected from the IBM® Explorys electronic medical record database. Patients. The study included a cohort of 300 patients for the albumin-corrected serum calcium analysis and 80 patients for the serum phosphate and calcium-phosphate product analyses. Measurements. We examined associations between albumin-corrected serum calcium, serum phosphate and calcium-phosphate product levels, and the risk of devloping CKD (defined as ≥2 outpatient estimated glomerular filtration values <60 mL/min/1.73 m2 occuring ≥3 months apart or ≥1 diagnostic code for CKD stages 3-5). Results: Individuals who had ≥67% of albumin-corrected serum calcium measurements outside, above, or below the study-defined range (2.00-2.25 mmol/L [8.0-9.0 mg/dL]) had 3.5-, 2.9-, and 2.7-fold higher odds of developing CKD (adjusted odds ratios [95% CI]: 3.46 [1.82-6.56], 2.85 [1.30-6.28], and 2.68 [1.16-6.15]), respectively, compared with patients who had <33% of albumin-corrected calcium measurements in those ranges. There was no association between developing CKD and having any serum phosphate measurements or any calcium-phosphate product measurements above normal population ranges. Conclusion: In adult patients with chronic hypoparathyroidism, a higher proportion of albumin-corrected calcium measurements outside of the 2.00-2.25 mmol/L (8.0-9.0 mg/dL) range was associated with higher odds of developing CKD.

Safety and treatment patterns of multikinase inhibitors in patients with metastatic renal cell carcinoma at a tertiary oncology center in Italy.

BACKGROUND: Multikinase inhibitors (MKIs) sunitinib and sorafenib have become a standard of care for metastatic renal cell carcinoma (mRCC). This study assessed safety and treatment patterns for these agents in a real-world clinical practice setting in Italy. METHODS: A retrospective medical record review was performed at a tertiary oncology center in Italy. The study included MKI-naïve non-trial patients ≥18 years old, with a histological diagnosis of mRCC, and who received sunitinib or sorafenib as first MKI during 9/2005-7/2008. Data were collected on adverse events (AEs), treatment modifications (discontinuations, interruptions, dose changes), and reasons for these modifications. RESULTS: 145 patients were included; 85 received sunitinib and 60 received sorafenib as first-line MKI. Median treatment duration was 6.6 (sunitinib) and 5.8 (sorafenib) months. 97.6% and 70.0% of patients receiving sunitinib and sorafenib, respectively, experienced ≥1 AE; 27.1% and 31.7% had ≥1 grade 3/4 AE. The most common any grade AE for sunitinib was fatigue/asthenia (81.2%), followed by mucositis/stomatitis (58.8%) and decreased taste sensation (42.4%), while for sorafenib this was fatigue/asthenia (43.3%) followed by hand-foot syndrome (38.3%) and diarrhea (31.7%). Treatment discontinuation, interruption, and dose reduction due to AEs occurred in 11.8%, 23.5%, and 30.6%, respectively, of patients receiving sunitinib, and 5.0%, 23.3%, and 36.7%, respectively, of patients receiving sorafenib. CONCLUSIONS: In this retrospective study, most patients experienced ≥1 AE during first-line MKI treatment. AEs were reported frequently and resulted in treatment modifications in 40% of patients receiving sunitinib and 45% of patients receiving sorafenib. These results suggest a need for additional effective and more tolerable treatments for mRCC.

Risk of Cardiovascular Conditions in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study.

INTRODUCTION: In patients with chronic hypoparathyroidism disordered calcium homeostasis has been associated with risk of cardiovascular diseases, including cardiomyopathy, congestive heart failure, and arrhythmia; however, larger-scale studies are needed to examine these risks. This study evaluated the risk of cardiovascular conditions among patients with chronic hypoparathyroidism. METHODS: Adults with and without chronic hypoparathyroidism were selected from a medical insurance claims database in the USA from January 2007 to June 2017, and were followed for up to 5 years. Associations between chronic hypoparathyroidism and incident atrial fibrillation (AF), tachyarrhythmia, myocardial infarction (MI), coronary artery disease (CAD), heart failure (HF), stroke, cerebrovascular disease, peripheral vascular disease (PVD), and a combined cardiovascular endpoint of cerebrovascular disease, CAD, HF, and PVD were compared between cohorts using Kaplan-Meier analyses and unadjusted and adjusted Cox proportional hazards models. RESULTS: In 8097 patients with chronic hypoparathyroidism compared with 40,485 patients without, respectively, mean ± SD ages were 58.6 ± 16.3 and 47.3 ± 18.0 years, 76.2% and 54.4% were female, and 19.4% and 9.5% had the combination of cardiovascular findings at baseline. In adjusted analyses, patients with chronic hypoparathyroidism had significantly higher risk (adjusted hazard ratio and 95% confidence interval) of incident AF (1.72; 1.51-1.97), tachyarrhythmia (1.68; 1.32-2.14), MI (1.18; 1.01-1.38), CAD (1.39; 1.26-1.54), HF (1.64; 1.46-1.84), stroke (1.45; 1.31-1.62), cerebrovascular disease (1.48; 1.34-1.62), PVD (1.66; 1.51-1.81), and combined cardiovascular endpoint (1.63; 1.52-1.75), all P < 0.001 except P = 0.036 for MI, compared with patients without chronic hypoparathyroidism. CONCLUSIONS: This large retrospective cohort study showed that chronic hypoparathyroidism was associated with increased risk of incident cardiovascular conditions and arrhythmias. Results should be evaluated in light of limitations inherent to claims database analyses. Further studies are warranted to investigate reasons for these risks and to develop strategies for reducing cardiovascular conditions in patients with chronic hypoparathyroidism.

Predictors and timing of response to teduglutide in patients with short bowel syndrome dependent on parenteral support.

BACKGROUND AND AIMS: This study aimed to identify predictors and estimate time to teduglutide response among adult patients with short bowel syndrome with intestinal failure (SBS-IF) dependent on parenteral support (PS). METHODS: Post-hoc analysis was performed on individual patient data from teduglutide-treated patients in the phase III teduglutide trial STEPS and the STEPS-2 extension. Response was defined as ≥20% PS volume reduction from baseline for two consecutive visits. Early responders experienced the reduction at 20 and 24 weeks during STEPS while late responders experienced the reduction during STEPS-2. Timing and predictors for response were assessed among the treated population using Cox proportional hazard model. Time to response was compared in aetiological subgroups using Kaplan-Meier analysis. Patient characteristics and time to response were compared between early vs. late responders. RESULTS: A total of 34 patients were included in this analysis; overall median time to response was 4.3 months. The presence of stoma predicted a positive response to teduglutide (hazard ratio [HR]: 5.6; 95% confidence interval [CI]: 1.4-21.9; p = 0.013). Vascular disease (vs. inflammatory bowel disease [IBD]) as cause of major intestinal resection (HR: 0.2; 95% CI: 0.0-0.8; p = 0.015), presence of ileocecal valve (HR: 0.1; 95% CI: 0.0-0.8; p = 0.047), and female sex (HR: 0.3; 95% CI: 0.1-1.0; p = 0.026) are negatively associated with response. In subgroup analyses, patients with IBD (vs. vascular disease), with (vs. without) a stoma, and without (vs. with) colon-in-continuity had a shorter time to response (all p < 0.05). The mean times to response were 3.6 (standard deviation (SD): 1.1) months for early responders (n = 27) and 10.0 (SD: 6.1) months for late responders (n = 7). Fewer early responders had colon-in-continuity (51.9%) and ileocecal valve (0.0%) compared to late responders (100% and 28.6%, respectively; both p < 0.05). Early responders had a lower mean percentage of colon remaining compared to late responders (24.6% vs. 57.1%, respectively; p = 0.016). CONCLUSIONS: Time to response to teduglutide depends on bowel anatomy and SBS-IF aetiology. IBD, presence of a stoma, and absence of ileocecal valve were associated with earlier response to teduglutide. These findings may enhance management of patients with SBS-IF; however, due to sample size limitations, additional studies are needed to confirm these findings.

Risk of Nephrolithiasis and Nephrocalcinosis in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study.

INTRODUCTION: Chronic hypoparathyroidism managed with conventional treatment, comprising oral administration of calcium and active vitamin D, has been associated with renal complications, including nephrolithiasis and nephrocalcinosis. Further larger-scale studies are needed to examine these risks. This study evaluated the risk of nephrolithiasis and nephrocalcinosis in patients with chronic hypoparathyroidism. METHODS: A retrospective cohort study using a managed care claims database in the United States from January 2007 to June 2017. Included patients were those with chronic hypoparathyroidism (excluding those receiving parathyroid hormone) and randomly selected patients without hypoparathyroidism over a maximum of 5-year follow-up. The main outcome measures were nephrolithiasis, identified by diagnosis codes or procedure codes for removing kidney stones, and nephrocalcinosis, identified by diagnosis codes. RESULTS: The nephrolithiasis analyses included 8097 adult patients with hypoparathyroidism and 40,485 adult patients without hypoparathyroidism. After excluding patients with a diagnosis of nephrocalcinosis at baseline, nephrocalcinosis analyses included 8051 patients with hypoparathyroidism and 40,466 patients without hypoparathyroidism. During 5 years of follow-up, patients with chronic hypoparathyroidism had significantly increased risk of nephrolithiasis and nephrocalcinosis in Kaplan-Meier analysis compared with patients without hypoparathyroidism (both P < 0.001). In the adjusted analyses, chronic hypoparathyroidism was associated with higher risks of nephrolithiasis (hazard ratio [HR], 1.81; 95% confidence interval [CI] 1.60-2.04) and nephrocalcinosis (HR, 6.94; 95% CI 4.41-10.92). A sensitivity analysis restricted to patients with at least one kidney imaging examination showed that 2.6% of patients (n = 59) with hypoparathyroidism and 0.5% of patients (n = 20) without hypoparathyroidism (ratio, 5.5; P < 0.001) developed nephrocalcinosis. CONCLUSIONS: This large retrospective cohort study showed a statistically significant and clinically meaningful increased risk of nephrolithiasis and nephrocalcinosis in patients who have chronic hypoparathyroidism compared with those who do not have chronic hypoparathyroidism.

Risk of Chronic Kidney Disease and Estimated Glomerular Filtration Rate Decline in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study.

INTRODUCTION: Chronic hypoparathyroidism, treated with conventional therapy of oral calcium supplements and active vitamin D, may increase the risk of kidney complications. This study examined risks of development and progression of chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) decline in patients with chronic hypoparathyroidism. METHODS: A retrospective cohort study using a managed care claims database in the United States from January 2007 to June 2017 included patients with chronic hypoparathyroidism (excluding those receiving parathyroid hormone) and randomly selected patients without hypoparathyroidism followed for up to 5 years. Main outcome measures were (1) development of CKD, defined as new diagnosis of CKD stage 3 and higher or ≥ 2 eGFR measurements < 60 ml/min/1.73 m2 ≥ 3 months apart, (2) progression of CKD, defined as increase in baseline CKD stage, (3) progression to end-stage kidney disease (ESKD), and (4) eGFR decline ≥ 30% from baseline. Time-to-event analyses included Kaplan-Meier analyses with log-rank tests, and both unadjusted and adjusted Cox proportional hazards models were used to compare outcomes between cohorts. RESULTS: The study included 8097 adults with and 40,485 without chronic hypoparathyroidism. In Kaplan-Meier analyses, patients with chronic hypoparathyroidism had higher risk of developing CKD and CKD progression and higher rates of eGFR decline (all P < 0.001). In multivariable Cox models adjusted for baseline characteristics, hazard ratios (95% confidence intervals [CIs]) were 2.91 (2.61-3.25) for developing CKD, 1.58 (1.23-2.01) for CKD stage progression, 2.14 (1.51-3.04) for progression to ESKD, and 2.56 (1.62-4.03) for eGFR decline (all P < 0.001) among patients with chronic hypoparathyroidism compared with those without hypoparathyroidism. CONCLUSION: Patients with chronic hypoparathyroidism have increased risk of development and progression of CKD and eGFR decline compared with those without hypoparathyroidism. Further studies are warranted to understand underlying mechanisms for the associations between chronic hypoparathyroidism and kidney disease.

Understanding celiac disease monitoring patterns and outcomes after diagnosis: A multinational, retrospective chart review study.

BACKGROUND: Long-term outcomes and monitoring patterns in real-world practice are largely unknown among patients with celiac disease. AIM: To understand patterns of follow-up and management of patients with celiac disease, and to characterize symptoms and villous atrophy after diagnosis. METHODS: A retrospective chart review study was performed using medical chart data of patients diagnosed with celiac disease. Three gastroenterology referral centers, with substantial expertise in celiac disease, participated in the United Kingdom, United States, and Norway. Demographic and clinical data were collected from medical charts. Descriptive analyses were conducted on patients with biopsy-confirmed celiac disease, diagnosed between 2008 and 2012, with at least one follow-up visit before December 31, 2017. Patient demographic and clinical characteristics, biopsy/serology tests and results, symptoms, and comorbidities were captured at diagnosis and for each clinic visit occurring within the study period (i.e., before the study end date of December 31, 2017). RESULTS: A total of 300 patients were included in this study [72% female; mean age at diagnosis: 38.9 years, standard deviation (SD) 17.2]. Patients were followed-up for a mean of 29.9 mo (SD 22.1) and there were, on average, three follow-up visits per patient during the study period. Over two-thirds (68.4%) of patients were recorded as having ongoing gastrointestinal symptoms and 11.0% had ongoing symptoms and enteropathy during follow-up. Approximately 80% of patients were referred to a dietician at least once during the follow-up period. Half (50.0%) of the patients underwent at least one follow-up duodenal biopsy and 36.6% had continued villous atrophy. Patterns of monitoring varied between sites. Biopsies were conducted more frequently in Norway and patients in the United States had a longer follow-up duration. CONCLUSION: This real-world study demonstrates variable follow-up of patients with celiac disease despite most patients continuing to have abnormal histology and symptoms after diagnosis.

Angiogenesis inhibitor therapies for metastatic renal cell carcinoma: effectiveness, safety and treatment patterns in clinical practice-based on medical chart review.

OBJECTIVE: To assess the effectiveness, safety, and treatment patterns of anti-angiogenic agents in metastatic renal cell carcinoma (mRCC) in tertiary clinical practice settings. PATIENTS AND METHODS: We retrospectively reviewed the medical records in two tertiary oncology centres in the USA for all patients treated while off clinical trials from April 2003 to June 2008 who met the entry criteria and received one or more prescriptions for sunitinib or sorafenib, or one or more intravenous administrations of bevacizumab (off-label) as first-line anti-angiogenic treatment. The objective response rate (ORR) reviewed by independent physicians, adverse events (AEs), and treatment modifications were assessed. RESULTS: Among 144 patients receiving sunitinib (57), sorafenib (62) and bevacizumab (25), the median treatment duration was 10.5, 8.1 and 7.9 months, and the ORR was 37%, 9% and 13%, respectively. The ORR was lower for patients with metastases to bone, brain, lungs or lymph nodes. Common AEs (all grades) for sunitinib were fatigue (53%), diarrhoea (37%); for sorafenib, diarrhoea (50%), fatigue (40%); for bevacizumab, fatigue (40%), nausea (24%). In all, 34 (60%), 51 (82%) and 20 (80%) patients receiving sunitinib, sorafenib and bevacizumab, respectively, discontinued treatment; 10 (18%), 11 (18%) and four (16%) discontinued due to AEs; 21%, 40% and 12% had a dose interruption, and 30%, 35% and 0% had a dose reduction. CONCLUSIONS: Currently available anti-angiogenic agents had considerable effectiveness in clinical practice. However, the response rates appeared to be low in certain subgroups, but sample sizes were small. Patients had significant rates of AEs, many of which led to treatment modifications. The findings from this retrospective study suggest that there is a need for better-tolerated therapies for mRCC.

Good research practices for measuring drug costs in cost-effectiveness analyses: a managed care perspective: the ISPOR Drug Cost Task Force report--Part III.

OBJECTIVES: The objective of this report is to provide guidance and recommendations on how drug costs should be measured for cost-effectiveness analyses conducted from the perspective of a managed care organization (MCO). METHODS: The International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force on Good Research Practices-Use of Drug Costs for Cost Effectiveness Analysis (DCTF) was appointed by the ISPOR Board of Directors. Members were experienced developers or users of CEA models. The DCTF met to develop core assumptions and an outline before preparing a draft report. They solicited comments on drafts from external reviewers and from the ISPOR membership at ISPOR meetings and via the ISPOR Web site. RESULTS: The cost of a drug to an MCO equals the amount it pays to the dispenser for the drug's ingredient cost and dispensing fee minus the patient copay and any rebates paid by the drug's manufacturer. The amount that an MCO reimburses for each of these components can differ substantially across a number of factors that include type of drug (single vs. multisource), dispensing site (retail vs. mail order), and site of administration (self-administered vs. physician's office). Accurately estimating the value of cost components is difficult because they are determined by proprietary and confidential contracts. CONCLUSION: Estimates of drug cost from the MCO perspective should include amounts paid for medication ingredients and dispensing fees, and net out copays, rebates, and other drug price reductions. Because of the evolving nature of drug pricing, ISPOR should publish a Web site where current DCTF costing recommendations are updated as new information becomes available.

Impact of Teduglutide on Quality of Life Among Patients With Short Bowel Syndrome and Intestinal Failure.

BACKGROUND: Teduglutide reduces or eliminates parenteral support (PS) dependency in patients with short bowel syndrome (SBS). Recent post hoc analyses demonstrated that effects are correlated with baseline PS volume. We assessed the SBS-related quality-of-life (QoL) impact of teduglutide, particularly whether improvements are greater among subgroups achieving more PS volume reduction. METHODS: Using phase 3 trial data of teduglutide in patients with SBS (NCT00798967), change in Short Bowel Syndrome-Quality of Life (SBS-QoL) scores from baseline were compared between teduglutide vs placebo in the overall population and subgroups classified by baseline PS volume requirement, disease etiology, and bowel anatomy. Generalized estimating equation models were fitted to assess impact of teduglutide on SBS-related QoL using data from all visits, adjusted for baseline characteristics. RESULTS: Of 86 patients, 43 each were randomized to teduglutide or placebo (mean age: 51 vs 50 years, respectively). In adjusted analyses, teduglutide had a nonsignificant reduction (improvement) of -8.6 points (95% CI: 2.6 to -19.8) in SBS-QoL sum score from baseline to Week-24 vs placebo. The impact of teduglutide varied by subgroup. Patients treated with teduglutide experienced significantly greater reductions in SBS-QoL sum score at Week-24 vs placebo in 2 subgroups, ie, the third (highest) tertile baseline PS volume (-27.3, 95% CI: -50.8 to -3.7) and inflammatory bowel disease (IBD; -29.6, 95% CI: -46.3 to -12.9). Results were similar for SBS-QoL subscale and item scores. CONCLUSIONS: The impact of teduglutide treatment on SBS-related QoL vs placebo varied among subgroups and was significant and most pronounced among patients with highest baseline PS volume requirement or IBD.

Five-year Estimated Glomerular Filtration Rate in Patients With Hypoparathyroidism Treated With and Without rhPTH(1-84).

CONTEXT: Chronic hypoparathyroidism (HypoPT) is conventionally managed with oral calcium and active vitamin D. Recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) is a therapy targeting the pathophysiology of HypoPT by replacing parathyroid hormone. OBJECTIVE: To compare changes in the estimated glomerular filtration rate (eGFR) in patients with chronic HypoPT receiving or not receiving rhPTH(1-84) during a 5-year period. DESIGN/SETTING: A retrospective analysis of patients with chronic HypoPT treated with or without rhPTH(1-84). PATIENTS: Sixty-nine patients with chronic HypoPT from 4 open-label, long-term trials (NCT00732615, NCT01268098, NCT01297309, and NCT02910466) composed the rhPTH(1-84) cohort and 53 patients with chronic HypoPT not receiving rhPTH(1-84) from the Geisinger Healthcare Database (01/2004-06/2016) composed the historical control cohort. INTERVENTIONS: The rhPTH(1-84) cohort (N = 69) received rhPTH(1-84) therapy; the historical control cohort (N = 53) did not receive rhPTH(1-84). MAIN OUTCOME MEASURES: Changes in eGFR from baseline during a 5-year follow-up were examined in multivariate regression analyses. RESULTS: At baseline, demographic characteristics and eGFR were similar between cohorts, though the proportions with diabetes and cardiac disorders were lower in the rhPTH(1-84) cohort. At the end of follow-up, mean eGFR increased by 2.8 mL/min/1.73 m2 in the rhPTH(1-84) cohort, while mean eGFR fell by 8.0 mL/min/1.73 m2 in the control cohort. In the adjusted model, the difference in the annual eGFR change between the rhPTH(1-84) cohort and the control cohort was 1.7 mL/min/1.73 m2 per year (P = 0.009). CONCLUSIONS: Estimated glomerular filtration rate was preserved for over 5 years among patients with chronic HypoPT receiving rhPTH(1-84) treatment, contrasting with an eGFR decline among those not receiving rhPTH(1-84).

[Oral care practice and procedures in intubated patients: an observational study].

BACKGROUND: Effective oral care improves patient comfort and prevents oral infection. While common in general nursing practice, administering oral care to intubated patients is particularly challenging. PURPOSE: This study investigated practices and factors associated with oral care of intubated patients in intensive care units (ICUs). METHODS: This study used a cross-sectional design and recruited nurses using purposive sampling. Data were collected with a structured observational checklist between January and April 2008 at a medical center in northern Taiwan. Observational data reflected oral care procedures performed by thirty-one ICU nurses on intubated patients in six ICUs. RESULTS: Cotton and foam swabs were found to be the main oral care cleaning instruments used with intubated patients, with dilute mouthwash the primary cleaning solution. Nearly three-quarters (72.4%) of participants were found to employ proper oral care procedures. Participants selected different cleaning equipment, cleaning solutions, cleaning solution usage methods and oral endotracheal tube securement methods based on differing conditions. ICU nurse age was positively associated oral care completeness. The level of oral care completeness achieved by participants in medical ICUs was significantly higher those assigned to surgical ICUs. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Study findings showed that ICU nurses did not follow procedures and steps recommended by current evidence-based practice (e.g., brushing the teeth and gums; positioning patients in a side or semi- / high-fowlers position when providing oral care to intubated patients). ICUs must establish policies and procedures for oral care of intubated patients that reflect patient characteristics. Furthermore, ICUs should provide oral care related on-the-job training and education in order to improve the quality of oral care administered to critical care patients.

Clinical burden and healthcare resource utilization among patients with chronic hypoparathyroidism, overall and by adequately vs not adequately controlled disease: a multi-country chart review.

Aims: To assess the real-world clinical burden and healthcare resource utilization (HRU) among patients with chronic hypoparathyroidism, overall and by adequately controlled (AC) vs not adequately controlled (NAC) disease, informed by guideline-recommended clinical management targets, including biochemistry and symptoms. Materials and methods: In this retrospective online chart review, endocrinologists in the US, Canada, the UK, France, Germany, Italy, and Spain were randomly selected to review the medical charts of adult patients with chronic hypoparathyroidism receiving calcium and activated vitamin D. Patients' demographics, disease characteristics, symptoms, comorbidities, and hypoparathyroidism-related HRU during the 1 year before the review date were assessed. Clinical burden and HRU were compared between patients with NAC and AC hypoparathyroidism. Results: Of 614 patients with hypoparathyroidism (AC, N = 442; NAC, N = 172), the mean age was 43.6 years, and the majority were female (61.6%), Caucasian (78.8%), and had post-surgical hypoparathyroidism (74.4%). Mean duration of hypoparathyroidism was 46.0 months. Hypoparathyroidism-related symptoms and comorbidities were reported in 59.4% and 46.7% of patients, respectively; 90.7% of patients had ≥1 hypoparathyroidism-related HRU event. More patients with NAC (57.6%) vs AC (42.5%) hypoparathyroidism experienced ≥1 comorbidity including calcium/phosphate imbalances, and brain, cardiovascular, metabolic, and renal disorders (all p < 0.01). More patients with NAC vs AC hypoparathyroidism incurred ≥1 hypoparathyroidism-related hospitalization (27.9% vs 16.3%) and emergency room visits (47.7% vs 38.5%), and patients with NAC vs AC hypoparathyroidism had a higher number of outpatient visits (3.6 vs 2.6; all p < 0.05), in the 1-year observation period. Limitations and conclusions: Limitations of this online chart review include possible under-estimation of disease burden, limited sample size, and the inability to rule out selection bias. Findings indicate that patients with chronic hypoparathyroidism experience substantial symptomatic and comorbid burdens resulting in frequent HRU, suggesting an unmet need, particularly in NAC disease.

Development of a Patient-Reported Outcome Measure for Chronic Hypoparathyroidism.

INTRODUCTION: A patient-reported outcome (PRO) measure specific to chronic hypoparathyroidism is lacking to facilitate the evaluation of treatment. A PRO measure that followed the recommendations of the US Food and Drug Administration (FDA) PRO guidance was created to address key hypoparathyroidism symptoms. METHODS: A literature review was conducted to identify symptoms of hypoparathyroidism and any existing PRO measures appropriate for evaluating these symptoms, followed by concept elicitation interviews involving six individuals with hypoparathyroidism. On the basis of the results of the literature review and interviews, a draft item pool was developed and refined through two sets of cognitive debriefing interviews with six additional patients. A translatability assessment was also conducted to evaluate concepts, phrases, or components of the items that could be problematic in future translations and to identify culturally specific phrasing. RESULTS: No PRO measures appropriate to address hypoparathyroidism symptoms documented in the literature were identified. Qualitative research participants included 11 women and one man, with an average age of 49 years; the majority (10) of these participants were white. Concept elicitation interview results were generally consistent with the results of the literature review; the most commonly reported symptoms included issues with cognition, often described as "brain fog" (n = 6), muscle cramping (n = 5), tingling (n = 5), and muscle spasms or twitching (n = 4). The initial draft item pool included 20 items; based upon participant feedback, the final Hypoparathyroidism Symptom Diary comprised 13 items and was found to be easily understood and relevant to the participants. No significant issues were identified by the translatability assessment. CONCLUSION: The Hypoparathyroidism Symptom Diary was developed following the recommendations of the FDA's PRO guidance. The measure addresses a comprehensive set of symptoms, as well as key impacts of hypoparathyroidism deemed important by patients. FUNDING: Shire Human Genetic Therapies, Inc., Lexington, MA, USA, a member of the Takeda group of companies.

Psychometric evaluation of the hypoparathyroidism symptom diary.

PURPOSE: To conduct an initial psychometric evaluation of the reliability and validity of the Hypoparathyroidism Symptom Diary (HPT-SD). PATIENTS AND METHODS: Data were collected during a cross-sectional, observational study. Participants with self-reported hypoparathyroidism (HPT) completed the HPT-SD, the Functional Assessment in Cancer Therapy-Cognitive Function (FACT-Cog), the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), and the Hospital Anxiety and Depression Scale (HADS) measures. Item- and scale-level internal consistency reliability, known-groups validity, and construct validity were evaluated. Subscales were identified and preliminary scoring algorithms were developed. RESULTS: The study included 52 participants (mean age, 51 years). Overall, the measurement properties of the HPT-SD were very good. Item-level response frequency distributions showed evidence of possible floor effects for four muscle-related symptom items. Inter-item correlations revealed a pattern of relationships among symptom items (r=0.3-0.8) and among impact items (r=0.5-0.7) and provided evidence for two HPT-SD subscales: Symptoms and Impacts. Construct validity correlations supported a priori convergent validity hypotheses (|r|≥0.4) between HPT-SD subscales and the FACT-Cog, FACIT-Fatigue, and HADS. Mean HPT-SD Symptom and Impact scores were in the expected direction and significantly different between subgroups of patients with high and low HPT disease severity. CONCLUSION: Results indicate that the HPT-SD is an appropriate measure of HPT-related symptoms and impacts. Floor effects may be attributed to the observational study design: participants manage symptoms with calcium and active vitamin D supplements prior to an escalation in severity. Future studies should assess the HPT-SD measurement properties using longitudinal study designs.