Cardiovascular, Kidney Failure, and All-Cause Mortality Events in Patients with Focal Segmental Glomerulosclerosis in a U.S. Real-World Database.

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) leads to proteinuria and progressive decline in glomerular filtration rate which correlates with kidney failure and increased cardiovascular risk. The purpose of this study was to estimate the effects of proteinuria on kidney failure status/all-cause mortality and cardiovascular disease events/all-cause mortality, as well as the relationship between progression to kidney failure and occurrence of cardiovascular disease/mortality events among adult patients (≥18 years old) with FSGS. METHODS: This was an observational, retrospective cohort study utilizing Optum® de-identified Market Clarity Data and proprietary Natural Language Processing (NLP) data. The study period was from January 1, 2007 through March 31, 2021, with patients in the overall cohort being identified from July 1, 2007 through March 31, 2021. The index date was the first FSGS ICD-10 diagnosis code or FSGS-related NLP term within the identification period. RESULTS: Elevated proteinuria >1.5 g/g and ≥3.5 g/g increased risk for kidney failure/all-cause mortality (adjusted hazard ratio [95% CI]: 2.34 [1.99-2.74] and 2.44 [2.09-2.84], respectively) and cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 2.11 [1.38-3.22] and 2.27 [1.44-3.58], respectively). Progression to kidney failure was also associated with a higher risk of cardiovascular disease/all-cause mortality (adjusted hazard ratio [95% CI]: 3.04 [2.66-3.48]. CONCLUSIONS: A significant proportion of FSGS patients experience kidney failure and cardiovascular disease events. Elevated proteinuria and progression to kidney failure were associated with a higher risk of cardiovascular disease/all-cause mortality events, and, elevated pre-kidney failure proteinuria was associated with progression to kidney failure/all-cause mortality events. Treatments that meaningfully reduce proteinuria and slow the decline in glomerular filtration rate have the potential to reduce the risk of cardiovascular disease, kidney failure and early mortality in patients with FSGS.

Kidney Failure Attributed to Focal Segmental Glomerulosclerosis: A USRDS Retrospective Cohort Study of Epidemiology, Treatment Modalities, and Economic Burden.

Rationale & Objective: This study describes the epidemiology, characteristics, and clinical outcomes of patients with focal segmental glomerulosclerosis (FSGS)-attributed kidney failure in the US Renal Data System (USRDS) during 2008-2018, and health care resource utilization and costs among those with Medicare-linked data. Study Design: This was a retrospective cohort study. Setting & Population: Patients with FSGS-attributed kidney failure in the USRDS were enrolled in the study. Outcomes: The outcomes were as follows: Prevalence and incidence, clinical and demographic characteristics, time to kidney transplant or death, health care resource utilization, and direct health care costs. Analytical Approach: Patients with FSGS as the primary cause of kidney failure were followed from USRDS registration (index date) until death or data end. Prevalence and incidence were calculated per 1,000,000 US persons. Patient characteristics at index and treatment modalities during follow-up were described. Time to kidney transplant or death was assessed with Kaplan-Meier and competing risk analyses. Health care resource utilization and costs were reported among patients with 1 year Medicare Part A+B coverage postindex, including (Medicare Coverage subgroup) or excluding (1-year Medicare Coverage subgroup) those who died. Results: The FSGS cohort and Medicare Coverage and 1-year Medicare Coverage subgroups included 25,699, 6,340, and 5,575 patients, respectively. Mean annual period prevalence and incidence rates of FSGS-attributed kidney failure were 87.6 and 7.5 per 1,000,000 US persons, respectively. Initial treatment for most patients was in-center hemodialysis (72.1%), whereas 7.3% received kidney transplant. Accounting for competing risk of death, year 1 and 5 kidney transplant rates were 15% and 34%, respectively. In the Medicare Coverage and 1-year Medicare Coverage subgroups, 76.6% and 74.2% required inpatient admission, 69.9% and 67.3% visited the emergency room, and mean monthly health care costs were $6,752 and $5,575 in the year postindex, respectively. Limitations: Drug costs may be underestimated because Medicare Part D coverage was not required; kidney acquisition costs were not available. Conclusions: FSGS-attributed kidney failure is associated with substantial clinical and economic burden, prompting the need for novel therapies for FSGS to delay kidney failure.

This study of patients in the US Renal Data System observed increasing prevalence and fluctuating incidence of focal segmental glomerulosclerosis (FSGS)-attributed kidney failure from 2008 to 2018. Patients experienced a high clinical burden, including more than 3 years of treatment with dialysis, one-third receiving a kidney transplant, and one-third dying during follow-up. In the first year after US Renal Data System registration, three-quarters of patients with Medicare coverage required hospitalization, and more than two-thirds visited the emergency room. The total annual health care costs were >$68,000 per patient with FSGS-attributed kidney failure, underscoring the high economic burden of this disorder and the treatments required to sustain life. Novel therapies for FSGS are needed to delay or ideally prevent the need dialysis and transplantation after kidney failure.

Kidney Failure Attributed to Immunoglobulin A Nephropathy: A USRDS Retrospective Cohort Study of Epidemiology, Treatment Modalities, and Economic Burden.

Rationale & Objective: This study describes the epidemiology, characteristics, and outcomes of patients with immunoglobulin A nephropathy (IgAN)-attributed kidney failure in the US Renal Data System (USRDS) from 2008 to 2018, including health care resource utilization and costs among patients with Medicare-linked data. Study Design: Retrospective cohort study. Setting & Population: Patients with IgAN-attributed kidney failure in the USRDS. Outcomes: Prevalence/incidence, clinical/demographic characteristics, time to kidney transplant, and health care resource utilization and costs. Analytical Approach: Patients with IgAN as primary cause of kidney failure (IgAN cohort) were followed from USRDS registration (index date) until data end/death. Prevalence/incidence were calculated per 1,000,000 US persons. Demographic and clinical characteristics at index and treatment modality during follow-up were summarized. Time from index to kidney transplant was assessed using Kaplan-Meier and competing risk analyses. Health care resource utilization and health care costs were reported among patients with 1 year Medicare Part A+B coverage postindex, including or excluding those who died (Medicare Coverage and 1-year Medicare Coverage subgroups, respectively). Results: The IgAN cohort, Medicare Coverage, and 1-year Medicare Coverage subgroups included 10,101, 1,696, and 1,510 patients, respectively. Mean annual period prevalence and incidence of IgAN-attributed kidney failure were 39.3 and 2.9 per 1,000,000 US persons, respectively. Initial treatment was in-center hemodialysis (63.1%) or kidney transplant (15.1%). Year 1 and 5 kidney transplant rates were 5% and 17%, respectively, accounting for competing risk of death. In the Medicare Coverage and 1-year Medicare Coverage subgroups, 74.4% and 72.3%, respectively, required inpatient admission, 67.3% and 64.4%, respectively, visited the emergency room, and mean total health care costs were $6,293 (SD: $6,934) and $5,284 ($3,455), respectively, per-patient-per-month in the year postindex. Limitations: Drug costs may be underestimated as Medicare Part D coverage was not required; kidney acquisition costs were unavailable. Conclusions: IgAN-attributed kidney failure is associated with substantial clinical and economic burdens. Novel therapies for IgAN that delay kidney failure are needed.

This study of patients in the United States Renal Data System (USRDS) observed fluctuating incidence and increasing prevalence of immunoglobulin A nephropathy (IgAN)-attributed kidney failure from 2008 to 2018. Patients experienced a high clinical burden, with 63% receiving in-center dialysis and over 15% receiving transplantation as initial therapy. In the first year after USRDS registration, nearly three-quarters of patients with Medicare coverage required hospitalization, and around two-thirds visited the emergency room. The total annual health care costs were >$63,000 per patient with IgAN-attributed kidney failure, underscoring the high economic burden of this disorder and currently available treatments. Novel therapies for IgAN are needed to delay or prevent the need for costly dialysis and transplantation after kidney failure.

Treatment patterns for patients initiating novel acute migraine specific medications (nAMSMs) in the context of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway.

BACKGROUND: New acute and preventive migraine medications are available, but data on current treatment patterns are limited. This study describes migraine treatment patterns among patients initiating novel acute migraine specific medications (nAMSMs), overall and by prior use of anti-calcitonin gene-related peptide (CGRP) pathway monoclonal antibodies (mAbs). METHODS: In this retrospective cohort study using IQVIA open-source pharmacy and medical claims data, we identified patients with ≥ 1 claim for a nAMSM (ubrogepant, rimegepant, lasmiditan) between 01/01/2020 and 09/30/2020 (index period). Patients were indexed on their first nAMSM claim and stratified into 2 cohorts: patients with prior mAb use (≥ 1 claim for erenumab, fremanezumab, galcanezumab in the 6-month pre-index period) or patients without prior mAb use. Treatment patterns were assessed during the 6-month post-index period. RESULTS: Overall, 78,574 patients were identified (63% indexed on ubrogepant, 34% on rimegepant, and 3% on lasmiditan) with 26,656 patients (34%) having had prior mAb use. In the pre-index period, 79% of patients used non-mAb preventive medications and 75% of patients used acute medications. Following the index nAMSM claim, 65% of patients had ≥ 1 refill and 21% had ≥ 4 refills of their index nAMSM; 10% of patients switched to another nAMSM. Post-index mAb use was observed in 82% of patients with a prior mAb and 15% of patients without. Among patients with pre- and post-index use of acute medications, 38% discontinued ≥ 1 acute medication class in the post-index period. Among patients with concomitant use of traditional preventive medications at index, 30% discontinued ≥ 1 concomitant preventive anti-migraine medication in the post-index period. CONCLUSIONS: Most patients initiating nAMSMs had prior treatment with acute and preventive medications. Approximately one-third of patients had prior treatment with anti-CGRP pathway mAbs. After starting nAMSMs, more than one-third of patients discontinued at least one traditional acute medication and one-third of patients discontinued at least one traditional preventive medication. Despite nAMSM initiation, most patients with prior anti-CGRP pathway mAb use continued mAb use. Around 15% of patients without a prior mAb newly started a mAb. These results provide insight into how nAMSMs and mAbs have been integrated into clinical management of migraine in the real-world.

Impact of Proteinuria and Kidney Function Decline on Health Care Costs and Resource Utilization in Adults With IgA Nephropathy in the United States: A Retrospective Analysis.

Rationale & Objective: Among patients with IgA nephropathy (IgAN), proteinuria and decline in kidney function may be associated with increased economic burden. This study aimed to provide current information on the epidemiology and economic burden of IgAN in the United States. Study Design: Retrospective cohort study. Setting & Study Population: Overall, 9,984 patients in the Optum's Market Clarity database identified by the presence of at least 2 natural language processing-derived IgAN signs and disease and symptoms terms; 813 with linked claims data included in a health care resource utilization/cost subcohort. Predictor: High-risk proteinuria (≥1 g/d), chronic kidney disease (CKD) stage. Outcomes: Standardized prevalence, health care resource utilization, costs. Analytical Approach: Descriptive statistics for categorical and continuous variables. Direct standardization for prevalence estimation. Generalized linear models for health care resource utilization/costs, reported as per-patient-per-month (PPPM) costs in 2020 US dollars. Results: The estimated standardized US prevalence of IgAN (2016-2020) was 329.0 per 1,000,000 persons. High-risk proteinuria (≥1 vs <1 g/d) was associated with a higher mean PPPM number of outpatient visits (3.49 vs 1.74; P = 0.01) and pharmacy claims (3.79 vs 2.41; P = 0.01), contributing to higher mean total costs PPPM ($3,732 vs $1,457; P = 0.01). Furthermore, higher CKD stage was also associated with higher health care resource utilization (number of outpatient visits PPPM, number of pharmacy claims PPPM, proportion of patients with inpatient visits and emergency department visits; P < 0.001) and mean total cost PPPM (from $2,111 CKD stage 1 to $10,703 CKD stage 5/kidney failure; P < 0.001). Limitations: Generalizability outside of the catchment group for the database, missing data/errors inherent in retrospective database studies, relatively small sample size, use of Optum Market Clarity standardized pricing algorithms, exclusion of out-of-pocket costs. Conclusions: Health care resource utilization and costs were higher for IgAN patients with high-risk proteinuria and worsening kidney function. Treatments that reduce proteinuria and slow CKD disease progression may reduce the economic burden associated with IgAN. Plain-Language Summary: Immunoglobulin A nephropathy (IgAN) is a rare kidney disease. Over time, the kidneys may leak protein into the urine (proteinuria). IgAN can lead to kidney failure. Because IgAN is rare, it is hard to know how many people have it. This study used electronic health records to estimate the number of patients with IgAN in the United States, describe the characteristics of patients, and understand their treatments and the costs. The number of patients with IgAN increased between 2016 and 2020. The researchers think this is because doctors learned more about IgAN. Patients with severe disease used more health care resources and had higher costs. The authors believe treatments that slow kidney damage may reduce the cost of treating IgAN.

Humanistic and Economic Burden of IgA Nephropathy: Systematic Literature Reviews and Narrative Synthesis.

BACKGROUND: Immunoglobulin A nephropathy (IgAN) is a progressive inflammatory kidney disease requiring long-term treatment to reduce the risk of progression to kidney failure. Here, we present two systematic literature reviews (SLRs) to identify and summarize literature reporting the humanistic and economic burden of IgAN. METHODS: Electronic literature databases (Ovid Embase, PubMed, and Cochrane) were searched for relevant literature on 29 November 2021, supplemented with gray literature searches. Studies reporting any health-related quality of life (HRQoL) or health state utility outcomes in IgAN patients were included in the humanistic impact SLR, and studies reporting the costs and healthcare resource utilization associated with or economic models of IgAN disease management were included in the economic burden SLR. Narrative synthesis was used to discuss the heterogeneous studies included in the SLRs. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Cochrane guidelines were followed, and all included studies were assessed for risk of bias using the Center for Evidence-Based Management tool for Critical Appraisal of a Survey or the Drummond Checklist. RESULTS: A total of 876 and 1122 references were identified from electronic and gray literature searches for humanistic and economic burden, respectively. Three studies reporting humanistic impact and five studies reporting economic burden met criteria for inclusion in these SLRs. The included humanistic studies reported patient preferences in the USA and China, HRQoL for patients with IgAN in Poland, and impact of exercise on HRQoL for patients with IgAN in China. The five economic studies reported costs of IgAN treatment in Canada, Italy, and China, along with two economic models from Japan. DISCUSSION: Current literature suggests IgAN is associated with substantial humanistic and economic burdens. However, these SLRs demonstrate the paucity of research conducted to specifically describe the humanistic or economic burden of IgAN and highlight the need for further research.

United States Patients' Perspective of Living With Migraine: Country-Specific Results From the Global "My Migraine Voice" Survey.

BACKGROUND: Migraine is associated with debilitating symptoms that can affect daily functioning. "My Migraine Voice" was a large, cross-sectional, multi-country online survey aimed at understanding disease burden directly from people with migraine. OBJECTIVE: This study reports on the social and economic impacts of migraine, specifically the impact on activities of daily living and the costs of migraine, from the point of view of people with migraine in the United States. METHODS: The online survey was administered to adults with a self-reported diagnosis of migraine who experienced 4 or more monthly migraine days each month for the previous 3 months. Prespecified screening quotas were used so that 90% of respondents reported current or past use of preventive migraine medication, 80% of whom switched treatment (ie, changed their prescribed preventive medication at least once). The remaining 10% were preventive treatment naïve (ie, never used any prescribed preventive medication). Burden of migraine on activities of daily living and caregivers (eg, functional limitations, fear of next migraine attack, sleep problems) and economic burden (eg, out-of-pocket costs, impact on work productivity using the validated work productivity and activity impairment questionnaire) reported by respondents from the United States are presented. Results are stratified by employment status, migraine frequency (chronic vs episodic migraine), and history of preventive treatment. RESULTS: Thousand hundred and one individuals with migraine from the United States responded to the survey. Respondents reported limitations completing daily activities during all migraine phases, including during the premonitory/aura and postdrome phases. Most (761/1101 (69%)) relied on family, friends, or others for help with daily tasks and reported being helped a median of 9 days (25th percentile 5 days, 75th percentile 15 days) within the last 3 months. Respondents with chronic migraine reported being helped for more days (median 10 days, 25th percentile 5 days, 75th percentile 23 days) in the last 3 months. Almost all (962/1101 (87%)) experienced sleep difficulties and 41% (448/1101) (48% (336/697) of those with 2 or more preventive treatment failures) were very or extremely fearful of a next migraine attack. Median (25th percentile, 75th percentile) monthly out-of-pocket costs of $90.00 ($30.00, $144.00) in doctor's fees (n = 504), $124.00 ($60.00, $234.00) in health insurance (n = 450), $40.00 ($20.00, $100.00) for prescriptions (n = 630), and $50.00 ($0.00, $100.00) for complementary therapies (n = 255) were reported. Those with 2 or more preventive treatment failures reported higher monthly out-of-pocket doctor fees (median $99.00 ($30.00, $150.00), n = 388). Among employed respondents (n = 661), migraine resulted in 22% absenteeism, 60% presenteeism, 65% work productivity loss, and 64% activity impairment. CONCLUSIONS: Migraine impacts individuals' activities of daily living, work-life, and financial status, especially individuals with high needs, namely those with 4 or more monthly migraine days and prior treatment failures. People with migraine are impaired during all migraine phases, experience fear of their next migraine attack and sleep difficulties, and pay substantial monthly out-of-pocket costs for migraine. Burden is even greater among those who have had 2 or more preventive treatment failures. Impacts of migraine extend beyond probands to caregivers who help people with migraine with daily tasks, employers who are affected by employee absenteeism, presenteeism, and reduced productivity, and society which is burdened by lost and reduced economic productivity and healthcare costs.

Primary immune thrombocytopenia in US clinical practice: incidence and healthcare burden in first 12 months following diagnosis.

Introduction: Primary immune thrombocytopenia (ITP), an autoimmune disorder characterized by low platelet count, can lead to serious bleeding events. Little is known about the current epidemiology of ITP in the US, and even less is known about the current healthcare burden of ITP, especially in the 12-month period following ITP diagnosis.Method: We used a retrospective cohort design and data from two US private healthcare claims databases (2010-2016) to identify persons with evidence of newly diagnosed ITP. We weighted estimates of the annual incidence of ITP by age and sex to reflect the US population, and summarized healthcare utilization and expenditures (2016 US$) during the first 12 months after ITP diagnosis ("follow-up period").Results: Annual incidence of ITP in the US was 6.1 per 100,000 persons, higher among females versus males (6.7 vs. 5.5), and highest among children aged 0-4 years (8.1) and adults aged ≥65 years (13.7). Patients with ITP averaged 0.33 (95% CI: 0.32-0.35) hospitalizations and 15.3 (15.1-15.6) ambulatory encounters during the follow-up period; mean total healthcare expenditures during this period were $21,290 (20,502-22,031). Hospitalizations were more common during the first 3 months following diagnosis, and were twice as frequent among children versus adults; expenditures for ambulatory encounters were substantially higher for adults versus children aged 0-4 years.Conclusions: Our findings suggest that nearly 20,000 children and adults are newly diagnosed with ITP each year in the US, substantially higher than previously reported. Among patients requiring formal medical care, the economic burden during the first 12 months following diagnosis is high, with estimated US expenditures totaling over $400 million.

Febrile neutropenia-related care and associated costs in elderly patients with breast cancer, lung cancer, or non-Hodgkin lymphoma.

PURPOSE: Limited information is available regarding elderly patients experiencing febrile neutropenia (FN). This study evaluated FN-related care among elderly cancer patients who received high/intermediate FN-risk chemotherapy and experienced ≥ 1 FN episodes. METHODS: We used Medicare data to identify patients aged ≥ 66 years who initiated high/intermediate FN-risk chemotherapy between 1 January 2008 and 31 August 2015 to treat breast cancer (BC), lung cancer (LC), or non-Hodgkin lymphoma (NHL) and had ≥ 1 FN episodes. We identified within-cycle FN episodes for each chemotherapy cycle on Part A inpatient claims or outpatient or Part B claims. We described the FN-related care setting (inpatient hospital, outpatient emergency department [ED], or outpatient non-ED) and reported mean total cost of FN-related care per episode overall and by care setting (adjusted to 2015 US$). RESULTS: We identified 2138, 3521, and 2862 patients with BC, LC, and NHL, respectively, with ≥ 1 FN episodes (total episodes: 2407, 3840, 3587, respectively). Most FN episodes required inpatient care (BC, 88.1%; LC, 93.0%; NHL, 93.2%) with mean hospital length of stay (LOS) 6.2, 6.5, and 6.8 days, respectively. Intensive care unit admission was required for 20.4% of BC, 29.0% of LC, and 25.7% of NHL hospitalizations (mean LOS: 4.7, 4.7, 5.5 days, respectively). The mean total cost of FN care per episode was $11,959 BC, $14,388 LC, and $15,006 NHL, with inpatient admission the costliest care component ($11,826; $14,294; and $14,873; respectively). CONCLUSIONS: Among elderly patients with BC, LC, or NHL who experienced FN, most FN episodes required costly hospital care, highlighting the FN burden on healthcare systems.

Trends in the use of primary prophylactic colony-stimulating factors and neutropenia-related hospitalization in elderly cancer patients receiving myelosuppressive chemotherapy in the USA: 1995-2015.

PURPOSE: To assess changes in neutropenia-related hospitalization, myelosuppressive chemotherapy, and primary prophylactic colony-stimulating factor (PP-CSF) use in elderly cancer patients receiving myelosuppressive chemotherapy. METHODS: We identified annual cohorts of patients aged ≥ 66 years with breast cancer, lung cancer, or non-Hodgkin lymphoma (NHL) initiating myelosuppressive chemotherapy during 1995-2015 using Medicare 5% (1994-2008) and 20% (2007-2015) data. We described myelosuppressive chemotherapy changes by febrile neutropenia (FN) risk category (high, intermediate, unclassified), PP-CSF use, and, in the first cycle of myelosuppressive chemotherapy, neutropenia-related hospitalization (ICD-9-CM: 288.0X, first 5 positions). We evaluated hospitalization trends using a logistic regression model with spline curve of calendar year adjusting for baseline characteristics. RESULTS: Annual cohorts included 1451-2114 eligible patients for 1995-2007 and 5272-7603 for 2008-2015. Myelosuppressive chemotherapy use with high/intermediate FN risk increased from 31% in 1995 to 56% in 1999, stabilized through 2008 (range 56-61%), then decreased to 52% in 2015. PP-CSF use increased from 5.5% in 1995 to 52.7% in 2015, mainly due to pegfilgrastim introduction in 2002. Crude neutropenia-related hospitalization incidence decreased from 5.2% in 1995 to 2.7% in 2015; adjusted incidence decreased, on average, by 4.7% yearly before 2010 (p < 0.0001) and was flat from 2010 onward (p = 0.53). CONCLUSIONS: Among elderly patients with breast cancer, lung cancer, or NHL receiving myelosuppressive chemotherapy, PP-CSF use increased substantially after 2002. Neutropenia-related hospitalization incidence in the first cycle decreased yearly before 2010 and was flat afterward. Further studies are needed to understand overall decreasing neutropenia-related hospitalization trends and effects of changes in myelosuppressive chemotherapy and FN management.

Effects of calcimimetics on long-term outcomes in dialysis patients: literature review and Bayesian meta-analysis.

AIM: Randomized controlled trials (RCTs) with clinical outcomes are considered the gold standard for regulatory approval. However, by design they are only able to answer a small number of clinical questions. Other high-quality studies are required for clinical decision-making. The EVOLVE was the largest RCT, evaluating the effects of cinacalcet on clinical outcomes among adult patients receiving maintenance dialysis suffering from secondary hyperparathyroidism. While the EVOLVE trial did not reach its primary end point, imbalance in subjects' age at randomization and discontinuation rates are two of the reasons that the lack of mortality benefit is in question. We undertook a systematic literature review and Bayesian meta-analysis combining randomized and observational studies on the estimated effects of the oral calcimimetic cinacalcet on clinical outcomes including all-cause mortality, cardiovascular-related mortality, hospitalization for cardiovascular events, fracture and parathyroidectomy among patients on maintenance dialysis. METHODS: Data sources included MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials databases. RCTs and observational studies were included. Data extraction was completed by two authors independently and in duplicate determined the methodological quality of the studies and extracted data. RESULTS: Of 564 unique citations identified, 16 studies were included: six observational studies and ten RCTs. Four high-quality studies (two observational and two RCTs) were deemed suitable for meta-analysis. Results indicated a statistically significant reduction in the risk of death associated with cinacalcet (hazard ratio: 0.83; 95% credible interval: 0.78-0.89). CONCLUSION: The results of this meta-analysis indicate that treatment of secondary hyperparathyroidism with calcimimetic therapy may in fact reduce mortality among patients receiving maintenance dialysis. This finding provides justification for a well-designed and adequately powered randomized trial to definitively address the question.

Development and psychometric validation of the Nausea/Vomiting Symptom Assessment patient-reported outcome (PRO) instrument for adults with secondary hyperparathyroidism.

BACKGROUND: We developed the Nausea/Vomiting Symptom Assessment (NVSA©) patient-reported outcome (PRO) instrument to capture patients' experience with nausea and vomiting while on calcimimetic therapy to treat secondary hyperparathyroidism (SHPT) related to end-stage kidney disease. This report summarizes the content validity and psychometric validation of the NVSA©. METHODS: The two NVSA© items were drafted by two health outcomes researchers, one medical development lead, and one regulatory lead: it yields three scores: the number of days of vomiting or nausea per week, the number of vomiting episodes per week, and the mean severity of nausea. An eight-week prospective observational study was conducted at ten dialysis centers in the U.S. with 91 subjects. Criterion measures included in the study were the Functional Living Index-Emesis, Kidney Disease Quality of Life Instrument, EQ-5D-5 L, Static Patient Global Assessment, and Patient Global Rating of Change. Analyses included assessment of score distributions, convergent and known-groups validity, test-retest reliability, ability to detect change, and thresholds for meaningful change. RESULTS: Qualitative interviews verified that the NVSA© captures relevant aspects of nausea and vomiting. Patients understood the NVSA© instructions, items, and response scales. Correlations between the NVSA© and related and unrelated measures indicated strong convergent and discriminant validity, respectively. Mean differences between externally-defined vomiting/nausea groups supported known-groups validity. The scores were stable in subjects who reported no change on the Patient Global Rating of Change indicating sufficient test-retest reliability. The no-change group had mean differences and effect sizes close to zero; mean differences were mostly positive for a worsening group and mostly negative for the improvement group with predominantly medium or large effect sizes. Preliminary thresholds for meaningful worsening were 0.90 days for number of days of vomiting or nausea per week, 1.20 for number of episodes of vomiting per week, and 0.40 for mean severity of nausea. CONCLUSIONS: The NVSA© instrument demonstrated content validity, convergent and known-groups validity, test-retest reliability, and the ability to detect change. Preliminary thresholds for minimally important change should be further refined with additional interventional research. The NVSA© may be used to support study endpoints in clinical trials comparing the nausea/vomiting profile of novel SHPT therapies.

Performance Goals for an Adjunct Diagnostic Test to Reduce Unnecessary Biopsies After Screening Mammography: Analysis of Costs, Benefits, and Consequences.

PURPOSE: Because benign biopsies resulting from false-positive mammographic findings are a known harm of breast cancer screening, physicians and test manufacturers are searching for ways to reduce their frequency. The aim of this study was to estimate potential costs and consequences associated with using an adjunct diagnostic test for triaging women with suspicious mammographic findings before biopsy. METHODS: A decision model was developed to compare the use of an adjunct test before biopsy to the current standard of care for suspicious mammographic findings. The decision analysis was performed from the perspective of a national health payer, with a 1-year time horizon among women representative of the US screening population aged 40 to 79 years. Three primary outcomes were assessed: (1) incremental costs, (2) number of benign biopsies avoided, and (3) number of missed opportunities for diagnosing cancer per million women screened. Input parameters were obtained from the medical literature and expert opinion. Sensitivity analyses were performed to evaluate the effects of uncertainty in parameter estimates. RESULTS: The base-case analysis demonstrated that the use of an adjunct diagnostic test with 95% sensitivity, 75% specificity, and a cost of $1,000 would eliminate 8,127 unnecessary breast biopsies per million women screened. However, this would cost the US health care system an additional $6,462,977 and result in 255 missed opportunities for diagnosing cancer per million women screened. CONCLUSIONS: The addition of an adjunct test for triaging women for breast biopsy after abnormal findings on screening mammography would likely eliminate many unnecessary biopsies but also increase overall health care costs. This exploratory analysis highlights the fact that mammography remains a relatively inexpensive and effective breast cancer screening and diagnostic modality.

The association between cinacalcet use and missed in-center hemodialysis treatment rate.

PURPOSE: Missed in-center hemodialysis treatments (MHT) are a general indicator of health status in hemodialysis patients. This analysis was conducted to estimate the association between cinacalcet use and MHT rate. METHODS: We studied patients receiving hemodialysis and prescription benefits services from a large dialysis organization. Incident cinacalcet users were propensity score matched to controls on 31 demographic, clinical, and laboratory variables. We applied inverse probability (IP) of censoring and crossover weights to account for informative censoring. Weighted negative binomial modeling was used to estimate MHT rates and pooled logistics models were used to estimate the association between cinacalcet use and MHT. RESULTS: Baseline demographic and clinical variables included serum calcium, phosphorus, parathyroid hormone, and vitamin D use, and were balanced between 15,474 new cinacalcet users and 15,474 matched controls. In an analysis based on intention-to-treat principles, 40.8% of cinacalcet users and 46.5% of nonusers were censored. MHT rate was 13% lower among cinacalcet initiators versus controls: IP of censoring weighted incidence rate ratio was 0.87 (95% confidence interval [CI]: 0.84-0.90 p < 0.001). In analyses based on as-treated principles, 72.8% and 61.5% of cinacalcet users and nonusers, respectively, crossed over or were censored. MHT rate was 15% lower among cinacalcet initiators versus controls: IP of censoring/crossover weighted incidence rate ratio was 0.85 (95%CI: 0.82-0.87 p < 0.001). CONCLUSIONS: After controlling for indication and differential censoring, cinacalcet treatment was associated with lower MHT rates, which may reflect better health status. Copyright © 2016 John Wiley & Sons, Ltd.

The effectiveness of telemedicine for paediatric retrieval consultations: rationale and study design for a pragmatic multicentre randomised controlled trial.

BACKGROUND: In many health systems, specialist services for critically ill children are typically regionalised or centralised. Studies have shown that high-risk paediatric patients have improved survival when managed in specialist centres and that volume of cases is a predictor of care quality. In acute cases where distance and time impede access to specialist care, clinical advice may be provided remotely by telephone. Emergency retrieval services, attended by medical and nursing staff may be used to transport patients to specialist centres. Even with the best quality retrieval services, stabilisation of the patient and transport logistics may delay evacuation to definitive care. Several studies have examined the use of telemedicine for providing specialist consultations for critically ill children. However, no studies have yet formally examined the clinical effectiveness and economic implications of using telemedicine in the context of paediatric patient retrieval. METHODS/DESIGN: The study is a pragmatic, multicentre randomised controlled trial running over 24 months which will compare the use of telemedicine with the use of the telephone for paediatric retrieval consultations between four referring hospitals and a tertiary paediatric intensive care unit. We aim to recruit 160 children for whom a specialist retrieval consultation is required. The primary outcome measure is stabilisation time (time spent on site at the referring hospital by the retrieval team) adjusted for initial risk. Secondary outcome measures are change in patient's physiological status (repeated measure, two time points) scored using the Children's Emergency Warning Tool; change in diagnosis (repeated measure taken at three time points); change in destination of retrieved patients at the tertiary hospital (general ward or paediatric intensive care unit); retrieval decision, and length of stay in the Paediatric Intensive Care Unit for retrieved patients. The trial has been approved by the Human Research Ethics Committees of Children's Health Services Queensland and The University of Queensland, Australia. DISCUSSION: Health services are adopting telemedicine, however formal evidence to support its use in paediatric acute care is limited. Generalisable evidence is required to inform clinical use and health system policy relating to the effectiveness and economic implications of the use in telemedicine in paediatric retrieval. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12612000156886 .

Economic evaluation of diagnostic localization following biochemical prostate cancer recurrence.

OBJECTIVES: The aim of this study was to assess potential cost-effectiveness of using a prostate cancer specific functional imaging technology capable of identifying residual localized disease versus small volume metastatic disease for asymptomatic men with low but detectable prostate specific antigen (PSA) elevation following radical prostatectomy. METHODS: Markov modeling was used to estimate the incremental impact on healthcare system costs (2012 USD) and quality-adjusted life-years (QALYs) of two alternative strategies: (i) using the new diagnostic to guide therapy versus (ii) current usual care-using a combination of computed tomography, magnetic resonance imaging, and bone scan to guide therapy. Costs were based on estimates from literature and Medicare reimbursement. Prostate cancer progression, survival, utilities, and background risk of all-cause mortality were obtained from literature. Base-case diagnostic sensitivity (75 percent), specificity (90 percent), and cost (USD 2,500) were provided by our industry partner GE Healthcare. RESULTS: The new diagnostic strategy provided an average gain of 1.83 (95 percent uncertainty interval [UI]: 1.24-2.64) QALYs with added costs of USD 15,595 (95 percent UI: USD -6,330-44,402) over 35 years. The resulting incremental cost-effectiveness ratio was USD 8,516/QALY (95 percent UI: USD -2,947-22,372). RESULTS were most influenced by the utility discounting rate and test performance characteristics; however, the new diagnostic provided clinical benefits over a wide range of sensitivity and specificity. CONCLUSION: This analysis suggests a diagnostic technology capable of identifying whether men with biochemical recurrence after radical prostatectomy have localized versus metastatic disease would be a cost-effective alternative to current standard work-up. The results support additional investment in development and validation of such a diagnostic.

Design of a cost-effectiveness analysis alongside a randomized trial of transplantation using umbilical cord blood versus HLA-haploidentical related bone marrow in advanced hematologic cancer.

BACKGROUND: BMT CTN 1101 is a Phase III randomized controlled trial evaluating the comparative effectiveness of double unrelated umbilical cord blood (dUCB) versus HLA-haploidentical related donor bone marrow (haplo-BM) donor cell sources for blood or bone marrow transplantation (BMT) in patients with hematologic malignancies. Herein, we present the rationale, design and methods of the first cost-effectiveness analysis to be conducted alongside a BMT trial. METHODS: Consenting patients will provide health insurance information to allow calculation of direct medical costs from reimbursement records, and will provide out-of-pocket costs, time costs and health-related quality of life measures through an online survey. These outcomes will inform a cost-effectiveness analysis comparing dUCB and haplo-BM donor cell sources from patient, payer and societal perspectives. CONCLUSION: Novel approaches may significantly change the cost, outcomes or availability of BMT. The results of this analysis will be the first to provide a comprehensive evaluation of the comparative effectiveness of these approaches from multiple perspectives.

Costs and outcomes evaluation of patient navigation after abnormal cancer screening: evidence from the Patient Navigation Research Program.

BACKGROUND: Navigators can facilitate timely access to cancer services, but to the authors' knowledge there are little data available regarding their economic impact. METHODS: The authors conducted a cost-consequence analysis of navigation versus usual care among 10,521 individuals with abnormal breast, cervical, colorectal, or prostate cancer screening results who enrolled in the Patient Navigation Research Program study from January 1, 2006 to March 31, 2010. Navigation costs included diagnostic evaluation, patient and staff time, materials, and overhead. Consequences or outcomes were time to diagnostic resolution and probability of resolution. Differences in costs and outcomes were evaluated using multilevel, mixed-effects regression modeling adjusting for age, race/ethnicity, language, marital status, insurance status, cancer, and site clustering. RESULTS: The majority of individuals were members of a minority (70.7%) and uninsured or publically insured (72.7%). Diagnostic resolution was higher for navigation versus usual care at 180 days (56.2% vs 53.8%; P = .008) and 270 days (70.0% vs 68.2%; P < .001). Although there were no differences in the average number of days to resolution between the 2 groups (110 days vs 109 days; P = .63), the probability of ever having diagnostic resolution was higher for the navigation group versus the usual-care group (84.5% vs 79.6%; P < .001). The added cost of navigation versus usual care was $275 per patient (95% confidence interval, $260-$290; P < .001). There was no significant difference in stage distribution among the 12.4% of patients in the navigation group vs 11% of the usual-care patients diagnosed with cancer. CONCLUSIONS: Navigation adds costs and modestly increases the probability of diagnostic resolution among patients with abnormal screening test results. Navigation is only likely to be cost-effective if improved resolution translates into an earlier cancer stage at the time of diagnosis.

Access to the Indian health service care system is not associated with early enrollment in medicaid for American Indian and Alaska Natives with cancer.

BACKGROUND: For uninsured American Indians and Alaskan Natives (AIAN) diagnosed with cancer, prompt enrollment in Medicaid may speed access to treatment and improve survival. We hypothesized that AIANs who were eligible for the Indian Health Service Care System (IHSCS) at cancer diagnosis may be enrolled in Medicaid sooner than other AIANs. METHODS: Using Washington, Oregon, and California State Cancer Registries, we identified AIANs with a primary diagnosis of lung, breast, colorectal, cervical, ovarian, stomach, or prostate cancer between 2001 and 2007. Among AIANs enrolled in Medicaid within 365 days of a cancer diagnosis, we linked cancer registry records with Medicaid enrollment data and used a multivariate logistic regression model to compare the odds of delayed Medicaid enrollment between those with (n = 223) and without (n = 177) IHSCS eligibility. RESULTS: Among AIANs who enrolled in Medicaid during the year following their cancer diagnosis, approximately 32% enrolled >1 month following diagnosis. Comparing those without IHSCS eligibility to those with IHSCS eligibility, the adjusted odds ratio (OR) for moderately late Medicaid enrollment (between 1 and 6 months after diagnosis) relative to early Medicaid enrollment (≤1 month after diagnosis) was 1.10 [95% confidence interval (CI), 0.62-1.95] and for very late Medicaid enrollment (>6 months to 12 months after diagnosis), OR was 1.14 (CI, 0.54-2.43). CONCLUSION: IHSCS eligibility at the time of diagnosis does not seem to facilitate early Medicaid enrollment. IMPACT: Because cancer survival rates in AIANs are among the lowest of any racial group, additional research is needed to identify factors that improve access to care in AIANs.