Major clinical events and healthcare resource use among patients with long-chain fatty acid oxidation disorders in the United States: Results from LC-FAOD Odyssey program.

Major clinical events (MCEs) related to long-chain fatty acid oxidation disorders (LC-FAOD) in triheptanoin clinical trials include inpatient or emergency room (ER) visits for three major clinical manifestations: rhabdomyolysis, hypoglycemia, and cardiomyopathy. However, outcomes data outside of LC-FAOD clinical trials are limited. The non-interventional cohort LC-FAOD Odyssey study examines data derived from US medical records and patient reported outcomes to quantify LC-FAOD burden according to management strategy including MCE frequency and healthcare resource utilization (HRU). Thirty-four patients were analyzed of which 21 and 29 patients had received triheptanoin and/or medium chain triglycerides (MCT), respectively. 36% experienced MCEs while receiving triheptanoin versus 54% on MCT. Total mean annualized MCE rates on triheptanoin and MCT were 0.1 and 0.7, respectively. Annualized disease-related inpatient and ER events were lower on triheptanoin (0.2, 0.3, respectively) than MCT (1.2, 1.0, respectively). Patients were managed more in an outpatient setting on triheptanoin (8.9 annualized outpatient visits) vs MCT (7.9). Overall, this shows that those with LC-FAOD in the Odyssey program experienced fewer MCEs and less HRU in inpatient and ER settings during triheptanoin-treated periods compared with the MCT-treated periods. The MCE rate was lower after initiation of triheptanoin, consistent with clinical trials.

Health-related quality of life (QoL) in patients with advanced melanoma receiving immunotherapies in real-world clinical practice settings.

BACKGROUND: Pembrolizumab (PEMBRO) and ipilimumab + nivolumab (IPI + NIVO) are approved advanced melanoma (AM) immunotherapies. To address limited health-related quality of life (QoL) real-world evidence with immunotherapies in AM, we compared QoL in AM patients receiving either treatment in clinical practice. METHODS: A prospective US observational study enrolled adult AM patients initiating first-line PEMBRO or IPI + NIVO between June 2017 and March 2018. Endpoints included the QLQ-C30 global health score (GHS) and EuroQol visual analog scale (EQ-VAS) scores. Mean changes were compared using repeated measures mixed-effects models and are presented covariate adjusted. RESULTS: 225 PEMBRO and 187 IPI + NIVO patients were enrolled. From baseline through week 24, PEMBRO was associated with 3.2 mean GHS score increase (95% CI 0.5, 5.9; p = .02), while no change was observed with IPI + NIVO; 0.2 (95% CI - 2.6, 3.0; p = 0.87). Among objective treatment-responders, GHS scores associated with PEMBRO increased 6.0 (95% CI 3.1, 8.8; p < .0001); IPI + NIVO patients increased 3.8 (95% CI 0.8, 6.9; p = .01). In treatment non-responders, IPI + NIVO was associated with GHS/QoL deterioration of - 3.7 (95% CI - 6.8, - 0.6; p = .02), PEMBRO non-responders demonstrated no change; 0.7 (95% CI - 2.3, 3.7; p = 0.6). Between treatments, PEMBRO patients increased 2.6 greater in EQ-VAS (95% CI 0.6, 4.5; p = .01) vs IPI + NIVO at 24 weeks. CONCLUSIONS: PEMBRO was associated with better 24-week QoL compared to IPI + NIVO in actual clinical practice settings. Real-world data has known limitations, but with further confirmation these results may have implications for treatment selection.

Effect of a patient decision aid (PDA) for type 2 diabetes on knowledge, decisional self-efficacy, and decisional conflict.

BACKGROUND: Patients with type 2 diabetes (T2DM) often have poor glycemic control on first-line pharmacologic therapy and require treatment intensification. Intensification decisions can be difficult because of many available options and their many benefits and risks. The American Diabetes Association recommends patient-centered, evidence-based tools supporting shared decision-making between patients and clinicians. We developed a patient decision aid (PDA) targeting decisions about treatment intensification for T2DM. Our objective was to determine the effectiveness of this PDA for patients with T2DM on metformin who require treatment intensification. METHODS: This study was a pragmatic randomized controlled trial conducted in 27 US primary care and endocrinology clinics. Subjects were English-speaking adults with T2DM receiving metformin with persistent hyperglycemia who were recommended to consider medication intensification. Subjects were randomized to receive either the PDA or usual care (UC). Main outcome measures were change in knowledge, decisional self-efficacy, and decisional conflict. RESULTS: Of 225 subjects enrolled, 114 were randomized to the PDA and 111 to UC. Mean [SD] age was 52 [1] years, time since T2DM diagnosis was 6 [+/-6] years, 45.3% were male, and most (55.5%) were non-Caucasian. Compared to UC, PDA users had significantly larger knowledge gains (35.0% [22.3] vs 9.9% [22.2]; P < 0.0001) and larger improvements in self-efficacy (3.7 [16.7] vs-3.9 [19.2]; P < 0.0001) and decisional conflict (-22.2 [20.6] vs-7.5 [16.6]; P < 0.0001). CONCLUSIONS: The PDA resulted in substantial and significant improvements in knowledge, decisional conflict and decisional self-efficacy. Decisional conflict scores after PDA use were within the range that correlates with effective decision-making. This PDA has the potential to facilitate shared-decision-making for patients with T2DM. TRIAL REGISTRATION: NCT02110979.

Economic burden of patients with post-surgical chronic and transient hypoparathyroidism in the United States examined using insurance claims data.

BACKGROUND: Hypoparathyroidism (HP) is a rare endocrine disease commonly caused by the removal or damage of parathyroid glands during surgery and resulting in transient (tHP) or chronic (cHP) disease. cHP is associated with multiple complications and comorbid conditions; however, the economic burden has not been well characterized. The objective of this study was to evaluate the healthcare resource utilization (HCRU) and costs associated with post-surgical cHP, using tHP as a reference. METHODS: This analysis of a US claims database included patients with both an insurance claim for HP and thyroid/neck surgery between October 2014 and December 2019. cHP was defined as an HP claim ≥ 6 months following surgery and tHP was defined as only one HP claim < 6 months following surgery. The cHP index date was the first HP diagnosis claim following their qualifying surgery claim, whereas the tHP index date was the last HP diagnosis claim following the qualifying surgery claim. Patients were continuously enrolled at least 1 year pre- and post-index. Patients' demographic and clinical characteristics, all-cause HCRU, and costs were descriptively analyzed. Total all-cause costs were calculated as the sum of payments for hospitalizations, emergency department, office/clinic visits, and pharmacy. RESULTS: A total of 1,406 cHP and 773 tHP patients met inclusion criteria. The average age (52.1 years cHP, 53.5 years tHP) and representation of females (83.2% cHP, 81.2% tHP) were similar for both groups. Neck dissection surgery was more prevalent in cHP patients (23.6%) than tHP patients (5.3%). During the 1-2 year follow-up period, cHP patients had a higher prevalence of inpatient admissions (17.4%), and emergency visits (26.0%) than the reference group -tHP patients (14.4% and 21.4% respectively). Among those with a hospitalization, the average number of hospitalizations was 1.5-fold higher for cHP patients. cHP patients also saw more specialists, including endocrinologists (28.7% cHP, 15.8% tHP), cardiologists (16.7% cHP, 9.7% tHP), and nephrologists (4.6% cHP, 3.3% tHP). CONCLUSION: This study demonstrates the increased healthcare burden of cHP on the healthcare system in contrast to patients with tHP. Effective treatment options are needed to minimize the additional resources utilized by patients whose HP becomes chronic.

Bleeding-associated outcomes with preoperative clopidogrel use in on- and off-pump coronary artery bypass.

Clopidogrel use prior to coronary artery bypass graft surgery in patients presenting with acute coronary syndromes is associated with a greater incidence of procedural related morbidity. We studied the impact of clopidogrel pre-treatment in patients undergoing off-pump versus on-pump coronary revascularization. This report describes a post hoc analysis of 431 on-pump and 165 off-pump cases from a retrospective multicenter study of the impact of preoperative (within 5 days) clopidogrel use on bleeding related outcomes and surgical reintervention. Logistic regression was used to analyze the outcomes with respect to surgery type and clopidogrel exposure while using a propensity score risk adjustment for off-pump surgery. The hospital length of stay (9.3 ± 5.4 days vs. 8.9 ± 5.3 days, p = 0.35), major bleeding (21% vs. 20%, p = 0.74) and reoperation (3.7% vs. 4.8%, p = 0.53) were similar between on-pump and off-pump, respectively. In both surgical cohorts, recent clopidogrel use was associated with a greater incidence of major bleeding, reoperation, and transfusion. After multivariable adjustment, the odds ratio of major bleeding (1.76, 95% confidence interval 0.88-3.52 on-pump; 2.37, 95% confidence interval 1.06-5.30 off-pump) and reoperation (4.52, 95% confidence interval 0.58-36.6 in on-pump; 7.05, 95% confidence interval 0.82-60.5 in off-pump) was increased in clopidogrel-treated patients compared to no clopidogrel. Major bleeding and reoperation did not differ significantly between patients undergoing on- or off-pump surgery. Clopidogrel treatment within 5 days prior to surgery increased the risk of bleeding and reoperation in all CABG patients irrespective of whether surgery was performed on- or off-pump.

Real-world Clinical Outcomes of First-Line Ibrutinib or Chemoimmunotherapy in Patients with Chronic Lymphocytic Leukemia by Risk Status.

INTRODUCTION: Certain genetic features in chronic lymphocytic leukemia (CLL) are associated with inferior outcomes after chemoimmunotherapy (CIT). This retrospective study evaluated treatment patterns and clinical outcomes of patients with CLL, stratified into high-risk and non-high-risk groups, who received first-line ibrutinib or CIT therapy. METHODS: High-risk group included confirmed presence of del(17p), del(11q), unmutated IGHV, TP53 mutations, or complex karyotype. Weighted high-risk ibrutinib and CIT groups were compared for treatment effects using inverse probability of treatment weighting. Hazard ratios [95% CI] (HR) for time to next treatment (TTNT) were analyzed using Kaplan-Meier curves. RESULTS: Bendamustine/rituximab was the most common CIT regimen initiated for high-risk patients. During the available follow-up (median 34-35 months), 74.7% of the weighted high-risk ibrutinib group received only one line of treatment, compared with 47.2% of the weighted high-risk CIT group. The most common second-line treatment was ibrutinib for those in the CIT groups and venetoclax for the ibrutinib groups. The weighted high-risk ibrutinib group had a significantly longer TTNT (median not reached) than the weighted high-risk CIT group (median 34.4 months) and was 54% less likely to start a new treatment (HR 0.5 [0.3-0.6], P < 0.010). Among CIT-treated groups, high-risk patients had significantly shorter median TTNT than non-high-risk patients (P < 0.010). However, within the ibrutinib-treated groups, the median TTNT was similar between high-risk and non-high-risk patients (HR 2.2 [1.0-5.0]; P = 0.060). CONCLUSION: This study found that first-line single-agent ibrutinib therapy was associated with significantly longer TTNT than CIT regimens in real-world patients with high-risk CLL. The results support the use of ibrutinib in high-risk patients. INFOGRAPHIC.

Health-related quality of life and treatment satisfaction in Chronic Lymphocytic Leukemia (CLL) patients on ibrutinib compared to other CLL treatments in a real-world US cross sectional study.

The objective of this study was to describe real-world health-related quality of life (HRQoL) and treatment satisfaction of ibrutinib-treated patients with CLL compared to a reference group. This study was completed in two parts. The first portion (Norming Study) was a US online survey conducted to serve as a reference population. The Norming Study included a total of 139 patients with CLL, excluding those treated with ibrutinib: 64 were treatment naive (Tx naive), 36 were 1st line (1L), and 38 were in or had completed ≥2 lines (2L+) patients with CLL. The second portion (CLL Ibrutinib Study) included 1L and 2L+ ibrutinib patients with CLL treated for ≥6 months in which 118 patients (1L n = 88 and 2L+ n = 30) completed the study. Respondents completed demographic and clinical information and the following HRQoL surveys: (Short Form-12v2® Health Survey [SF-12v2], Functional Assessment of Cancer Therapy-General [FACT-G], FACT-Leukemia [FACT-Leu] Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, and Cancer Therapy Satisfaction Questionnaire [CTSQ]). Higher scores indicate better HRQoL/treatment satisfaction. Differences in effect sizes between the two samples at the group level were calculated using Hedges' g. Medium to large positive effects were seen in the CLL Ibrutinib group on several measures compared to the Reference Study groups. The FACT-G total score was 89.2±11.1 for CLL Ibrutinib Study patients compared to 75.8±22.6 CLL Norming Tx naïve patients, 61.3±21.8 in 1L, and 61.7±20.7 in 2L+. Similar trends were seen with FACT-Leu total score and FACIT-Fatigue. CLL Ibrutinib Study patients scored higher on all CTSQ domain scores compared to the CLL Norming patients treated with other CLL therapies. We found that Ibrutinib-treatment had better HRQoL and treatment satisfaction compared to patients receiving other therapies, irrespective of line of therapy.

HIV-associated wasting prevalence in the era of modern antiretroviral therapy.

OBJECTIVE: To understand the prevalence of HIV-associated wasting (HIVAW) in the United States. DESIGN: Medical and pharmacy claims study using IBM MarketScan Commercial, Medicare Supplemental and Medicaid Databases. METHODS: Study period: July 2012-September 2018 (first HIV diagnosis claim = HIV index date). People with HIV (PWH) were excluded if they were aged less than 18 years, had any malignancy claim or had less than 6 months of enrollment data pre or post-HIV index date. HIVAW was defined by proxy using claims for weight loss-related diagnoses, appetite stimulant/nontestosterone anabolic agents or enteral/parenteral nutrition. Prevalence was reported cumulatively, by insurance type and antiretroviral therapy (ART) pharmacy claims (defined as ≥1 pharmacy claim of any ART within 12 months post-HIV index date). Statistical analysis assessed factors potentially associated with HIVAW. RESULTS: The study population comprised 42 587 PWH (64.6% male, mean age 44 years, 67.5% on Medicaid, 63.9% on ART). Cumulative HIVAW prevalence (2012-2018) was 18.3% (n = 7804) for all PWH (17.9% on ART, 19.1% not on ART). HIVAW prevalence by payer was 7.5% for Commercial and Medicare Supplemental and 23.5% for Medicaid. The strongest associations with the likelihood of meeting the definition of HIVAW were for individuals with Medicaid and hospitalization(s) post-HIV index date; race and ART status were not associated. CONCLUSIONS: Findings suggest HIVAW remains prevalent in PWH. ART use was not found to be associated with HIVAW. HIVAW was highest among those with Medicaid coverage or any hospitalization(s). Further research is needed to better understand additional factors associated with and contributing to HIVAW.

The economic burden of HIV-associated wasting in the era of modern antiretroviral therapy.

BACKGROUND: HIV-associated wasting (HIVAW) is associated with increased morbidity and mortality in people living with HIV (PWH). Evaluating health care resource utilization and cost predictors of HIVAW is important in understanding the overall economic burden of the disease. OBJECTIVE: To evaluate the economic burden and cost predictors associated with HIVAW. METHODS: This analysis of the IBM MarketScan Commercial, Medicare Supplemental, and Medicaid databases included members with a claim for HIV (using International Classification of Diseases, Ninth Revision and Tenth Revision, Clinical Modification codes) between July 2012 and September 2018, with the HIV index date defined as the first HIV diagnosis claim in the dataset. PWH were excluded if they were aged less than 18 years, had any malignancy claim, or had less than 6 months of enrollment data pre-HIV or post-HIV index date. Members were defined as having HIVAW using an algorithm of claims for weight loss-related diagnoses, appetite stimulant or nontestosterone anabolic agents, or enteral/parenteral nutrition at any time post-HIV index. Taking antiretroviral therapy (ART) was defined as having at least 1 pharmacy claim of any ART 12 months post-HIV index. Total all-cause costs were calculated as the sum of payments for hospitalizations, emergency department visits, outpatient visits, and pharmacy use. A multivariate generalized linear model with log-link and γ distribution was used to estimate the impact of HIVAW predictors of total all-cause costs. RESULTS: Among 42,587 members with HIV included in the study (64.6% male; mean age: 44 years; 67.5% insured with Medicaid; and 63.9% taking ART), the overall prevalence of HIVAW was 18.3% during the study period. HIVAW prevalence was 17.9% for those taking ART and 19.1% for those not taking ART. Prevalence by payer type was 7.5% for Commercial ± Medicare Supplemental and 23.5% for Medicaid. Members with HIVAW had more comorbidities and opportunistic infections compared with members without HIVAW. Members with HIVAW were also more than twice as likely to be hospitalized (71.1% vs 32.1%) and had 5 times the number of hospitalizations (1.0 vs 0.2) and twice the number of emergency department visits (3.0 vs 1.3) per year post-index compared with members without HIVAW (P < 0.01). HIVAW was associated with 1.3-times-higher mean annualized total all-cause costs per member (95% CI = 1.26-1.36). CONCLUSIONS: HIVAW remains prevalent despite advances in ART and is associated with additional health care resource utilization and costs. Further research is needed to better understand the relationship between HIVAW and comorbidity burden and ART utilization and payer types. DISCLOSURES: This study was sponsored by EMD Serono, Inc., Rockland, MA, USA (CrossRef Funder ID: 10.13039/100004755). Dr Siddiqui has received consulting and speaking fees from AbbVie, BioFire, Cumberland, EMD Serono, Inc., Rockland, MA, USA, and Merck. Dr Samuel, Ms Hayward, Ms Wirka, Dr Phillips, and Dr Harbour are employees of EMD Serono, Inc., Rockland, MA, USA. Drs Deering and Harshaw are employees of EPI-Q, Inc., which received payment from EMD Serono, Inc., Rockland, MA, USA, for the development and execution of this study.

Correction to: Real-World Recurrence Rates and Economic Burden in Patients with Resected Early-Stage Melanoma.

The presentation of the numbers of patients in Tables 1 and 3 was adjusted.

Real-World Recurrence Rates and Economic Burden in Patients with Resected Early-Stage Melanoma.

INTRODUCTION: Real-world data on recurrence and economic burden in patients with resected early-stage melanoma are limited. The objective of this study was to assess real-world recurrence rates, risk factors for recurrence, and costs of recurrence in patients with resected stage IIB, IIC, or IIIA melanoma in the USA. METHODS: This retrospective analysis included patients with resected stage IIB, IIC, or IIIA melanoma (American Joint Committee on Cancer staging manual, seventh edition) in the Surveillance, Epidemiology, and End Results (SEER) program-Medicare database of the National Cancer Institute. Recurrence rates and healthcare costs (2018 USD) after recurrence were assessed. RESULTS: Two-year recurrence rates for stages IIB, IIC, and IIIA melanoma were 29, 44, and 46%, respectively. In patients with stage IIB or IIC disease, the odds of recurrence were significantly higher in those aged > 75 years [odds ratio (OR) 1.853, 95% confidence interval (CI) 1.416, 2.425], with ulceration (OR 1.771; 95% CI 1.293, 2.425), or with a higher Charlson Comorbidity Index (OR 1.244; 95% CI 1.129, 1.372); however, the odds of recurrence were significantly lower in those with T3 staging (OR 0.522; 95% CI 0.393, 0.695). In those with stage IIIA melanoma, superficial spreading was associated with significantly lower odds of recurrence (OR 0.178; 95% CI 0.053, 0.601). Following recurrence, mean healthcare costs at 1 year were $31,870 for patients with stage IIB or IIC melanoma and $29,224 for those with stage IIIA melanoma. CONCLUSION: The SEER data show that a substantial proportion of adults with early-stage melanoma experience a recurrence within 2 years following resection, resulting in a significant economic burden to the US healthcare system. Dermatologists can distinguish patients with resected early-stage melanoma who are at a high risk for recurrence and consider referrals to medical oncologists for approved adjuvant therapy or enrollment in clinical trials after surgical resection to reduce the recurrence of melanoma.

Hospitalization and emergency department utilization in patients with advanced melanoma receiving pembrolizumab versus ipilimumab plus nivolumab in US academic centers.

Background: Both pembrolizumab (PEMBRO) and ipilimumab + nivolumab (IPI + NIVO) are FDA-approved immunotherapy regimens for advanced melanoma (AM). Each regimen has different toxicity profiles potentially impacting healthcare resource utilization (HCRU). This study compared real-world hospitalization and emergency department (ED) utilization within 12 months of therapy initiation of each regimen.Methods: A retrospective cohort study was conducted in AM patients ≥18 years old initiating PEMBRO or IPI + NIVO between January 1, 2016-December 30, 2017. Patients were identified from 12 US-based academic and satellite centers. All-cause hospitalization ED visits were identified. These events were used to calculate rates per 1,000 patient months. Utilization between groups was compared using multivariate logistic regression.Results: In total, 400 patients were included (200 PEMBRO, 200 IPI + NIVO). PEMBRO vs IPI + NIVO patients had poorer Eastern Cooperative Group (ECOG) performance status, 29% 2-4, vs 12% (p < .001); more diabetes, 21% vs 13% (p = .045); were more often PD-L1 expression positive, 77% vs 63% (p = .011); and less likely BRAF mutant, 35% vs 50% (p = .003). The proportion with more than one hospitalization over 12 months was 17% PEMBRO vs 24% IPI + NIVO. Less than 2% had more than one admission and none had more than two. Unadjusted mean (SD) hospitalizations per 1,000 patient-months were 16 (37) and 20 (38), PEMBRO and IPI + NIVO, respectively. Adjusted odds ratio for hospitalization was 0.6 (95% CI = 0.3-0.9; p = .027) for PEMBRO vs IPI + NIVO. ED visits occurred in 18% vs 21%, PEMBRO and IPI + NIVO, respectively, 0.7 (p = .186).Conclusions: PEMBRO patients had a significantly lower probability of hospitalization through 12 months vs IPI + NIVO. The probability of ED visits did not differ.

Factors associated with immunotherapy selection in patients with advanced melanoma.

AIM: To explore factors associated with pembrolizumab (PEMBRO) versus ipilimumab + nivolumab (IPI+NIVO) selection in advanced melanoma. MATERIALS & METHODS: Total of 12 academic and satellite clinics contributed to this study. Descriptive and logistic regression analyses were conducted to explore associations between clinical characteristics and treatment choice.  Results: Total of 400 patients were included: 200 PEMBRO and 200 IPI+NIVO. Patients were significantly more likely to receive PEMBRO versus IPI+NIVO if they had poorer Eastern Cooperative Oncology Group score, 2-4 versus 0-1 (odds ratio [OR]: 6.6; 95% CI: 3.0-14.7), if they were PD-L1 positive (OR: 4.5; 95% CI: 1.9-10.4) or had BRAF wild-type tumor (OR: 2.2; 95% CI: 1.4-3.6). CONCLUSION: Patient factors are significantly associated with treatment selection in advanced melanoma. Outcomes comparisons should take this into consideration.

Changing Patients' Treatment Preferences and Values with a Decision Aid for Type 2 Diabetes Mellitus: Results from the Treatment Arm of a Randomized Controlled Trial.

INTRODUCTION: Failure to intensify treatment for type 2 diabetes mellitus (T2DM) when indicated, or clinical inertia, is a major obstacle to achieving optimal glucose control. This study investigates the impact of a values-focused patient decision aid (PDA) for T2DM antihyperglycemic agent intensification on patient values related to domains important in decision-making and preferred treatments. METHODS: Patients with poorly controlled T2DM who were taking a metformin-containing regimen were recruited through physicians to access a PDA presenting evidence-based information on T2DM and antihyperglycemic agent class options. Participants' preferences for treatment, decision-making, and the relative importance they placed on various values related to treatment options (e.g., dosing, weight gain, side effects) were assessed before and after interacting with the PDA. Changes from baseline were calculated (post-PDA minus pre-PDA difference) and assessed in univariate generalized linear models exploring associations with patients' personal values. RESULTS: Analyses included 114 diverse patients from 27 clinics across the US. The importance of avoiding injections, concern about hypoglycemia, and taking medications only once a day significantly decreased after interacting with the PDA [- 1.1 (p = 0.002), - 1.3 (p < 0.001), - 1.1 (p = 0.004), respectively], while the importance of taking medications that avoided weight gain increased [0.8 (p = 0.004)]. Prior to viewing the PDA, most patients (58.8%) had not begun thinking about the decision of adding a medication, and few (12.3%) indicated that they had already made a decision. Post-PDA, 46.5% could state a medication preference. CONCLUSION: The values-focused PDA for T2DM medication intensification prepared patients to make a shared decision with their clinician and changed patients' values regarding what was important in making that decision. Helping patients understand their options and underlying values can promote shared decision-making and may reduce clinical inertia delaying treatment intensification. FUNDING: Janssen Scientific Affairs, LLC.

Impact of breakthrough pain on community-dwelling cancer patients: results from the National Breakthrough Pain Study.

OBJECTIVE: To characterize cancer-related breakthrough pain (BTcP) among community-dwelling patients with cancer. METHODS: Data from the National Breakthrough Pain Study, a cross-sectional observational survey describing breakthrough pain (BTP) in the community, were analyzed for a subset of patients with BTcP. Eligible patients were community-dwelling adults with commercial insurance and insurance claims consistent with cancer and chronic pain who consented to a structured telephone interview. Assessments included the Brief Pain Inventory-Short Form (BPI), the Short Form 12 Health Survey, the Sheehan Disability Scale, the Work Performance Questionnaire, Generalized Anxiety Disorder-7 Screener, and Patient Health Questionnaire-2. RESULTS: In total, 112 patients with cancer pain also experienced BTcP; 83.3% were in remission. Most patients reported experiencing ≥2 BTcP episodes per day, a median time to BTcP peak of 15 minutes, and a median duration of BTcP of 30 minutes. Mild pain at onset that gradually worsened was reported by 54.5% of patients, and incidental pain triggered by physical activity was reported by 58.0%. Most patients who reported using a medication to manage BTcP received an oral immediate-release opioid, such as oxycodone or hydrocodone, and only 1 received a rapid-onset opioid; few (24.1%) reported that pharmacologic treatment for BTcP worked every time. Patients reported mean (standard deviation) BPI scores of 4.2 (1.75) and 5.7 (1.98) for average and worst pain intensity during the preceding 24 hours, respectively, and high interference with activity, mood, ability to walk and work, social relations, sleep, and enjoyment of life. CONCLUSION: Results indicate that BTcP among community-dwelling patients with cancer continues to be a health burden and reveals opportunities to improve its management.

National Breakthrough Pain Study: prevalence, characteristics, and associations with health outcomes.

The National Breakthrough Pain Study is a large observational study that assessed breakthrough pain (BTP) in a population of commercially insured community-dwelling patients with opioid-treated chronic pain. Eligible patients were identified from an administrative claims database, and consenting patients were asked to complete a structured telephone interview and several validated questionnaires. Questionnaires assessed pain interference with function (Brief Pain Inventory-Short Form), health status (Short Form 12 [SF-12] Health Survey), disability (Sheehan Disability Scale), work performance (World Health Organization Health and Work Performance Questionnaire), and mood (Generalized Anxiety Disorder-7 Screener [GAD-7] and Patient Health Questionnaire-2 [PHQ-2]). Of 2198 patients interviewed, 1278 patients had persistent pain controlled with opioid therapy; 1023 (80%) of these patients reported BTP. Patients had a median of 2.0 episodes of BTP per day (range, 1-50) and a median duration of BTP of 45 minutes (range, 1-720). Compared with patients without BTP, patients with BTP had more pain-related interference in function (Brief Pain Inventory, mean ± SD: 34.2 ± 15.6 vs 25.0 ± 15.7 [P < 0.001]), worse physical health (SF-12 physical component score: 29.9 ± 9.6 vs 35.1 ± 10.4 [P < 0.001]) and mental health (SF-12 mental component score: 47.4 ± 11.3 vs 49.3 ± 10.4 [P < 0.001]), more disability (Sheehan Disability Scale global impairment score: 15.1 ± 9.1 vs 10.6 ± 8.5; World Health Organization Health and Work Performance Questionnaire absolute absenteeism: 12.4 ± 59.9 vs 7.7 ± 44.9 hours [both P < 0.001]), and worse mood (GAD-7 score: 7.4 ± 5.9 vs 5.9 ± 5.4; PHQ-2 anhedonia score: 1.2 ± 1.1 vs 0.9 ± 1.0 [both P < 0.001]). In this population of community-dwelling patients with opioid-treated chronic pain, BTP was highly prevalent and associated with negative outcomes. This burden of illness suggests the need for specific treatment plans.

Impact of worsening renal function during hospital admission on resource utilization in patients with heart failure.

Renal impairment frequently accompanies heart failure (HF) and is a recognized independent risk factor for morbidity and mortality. Few data are available assessing the impact of worsening renal function (WRF) during hospitalization on health care resource use in patients with HF. Health Insurance Portability and Accountability Act-compliant, de-identified, clinical, laboratory, and economic data for patients admitted to a tertiary care medical center with a primary diagnosis of HF were extracted by MedMining and reviewed retrospectively by the authors. Patients were excluded if they had no previous HF or were admitted for acute coronary syndrome or coronary artery bypass grafting within 30 days of index hospitalization. WRF was defined as ≥ 0.3 mg/dl increase in serum creatinine from baseline at any time during hospitalization. Of 5,803 hospitalized patients with primary HF diagnosis, 827 patients (14%) fulfilled all prespecified inclusion and exclusion criteria (74 ± 14 years of age, 43% men, 98% white, admission serum creatinine 1.4 ± 0.9 mg/dl, estimated glomerular filtration rate < 90 ml/min/1.73 m(2) at admission in 83%). During index hospitalization, WRF was identified in nearly 33%. Compared to patients without WRF, those with WRF had greater prevalence of diabetes (54% vs 43%), lower estimated glomerular filtration rate (44 ± 30 vs 62 ± 35 ml/min/1.73 m(2)), higher serum potassium (4.3 ± 0.7 vs 4.2 ± 0.7 mEq/L), and higher B-type natriuretic peptide (845 ± 821 vs 795 ± 947 pg/ml) at baseline (all p values < 0.05). Patients developing WRF incurred higher total inpatient costs ($10,977, range 671 to 212,819, vs $7,820, range 697 to 269,797, p < 0.001) and longer hospital stay (8.2 ± 6.8 vs 5.7 ± 5.5 days, p < 0.001). In conclusion, occurrence of WRF during HF-related hospitalization is associated with higher hospitalization costs and longer hospital stay.

Consensus and discordance in the management of growth hormone-treated patients: results of a knowledge, attitudes, beliefs, and practices survey.

Our purpose was to determine pediatric endocrinologists' knowledge, attitudes, beliefs, and practices (KABPs) regarding recombinant human growth hormone (rhGH) treatment, examine care-related attitude consensus or discordance, and identify evidence-based practice gaps. We developed a survey for National Cooperative Growth Study (NCGS) investigators (N = 711) to elicit their KABPs regarding GH stimulation testing as a diagnostic tool, IGF-1 monitoring for safety and dosing guidance, and pubertal dosing. Responses were compared with NCGS data from the last 20 years. Comparison between survey responses and NCGS data revealed potential discrepancies between expressed opinions and actual practice. In conclusion, this KABP survey, combined with NCGS data, suggests changes over time in diagnostic and rhGH-related therapeutic practices. Variability and inconsistency exist between the survey responses and practice trends over time as reflected in the NCGS database. Further study is necessary to provide evidence to guide rhGH treatment decisions.

Comparing outcomes associated with dose manipulations of enteric-coated mycophenolate sodium versus mycophenolate mofetil in renal transplant recipients.

BACKGROUND: This study assessed the incidence of reported gastrointestinal (GI) complications in patients treated with enteric-coated mycophenolate sodium (EC-MPS) versus mycophenolate mofetil (MMF) and to examine the impact of dose manipulations on biopsy-proven acute rejection (BPAR). METHODS: A retrospective study was conducted in 379 renal transplant recipients initiated on EC-MPS or MMF through 3-months posttransplant between the years of 2001 to 2007. Descriptive univariate analyses were used for comparisons of baseline characteristics and outcome measures between the cohorts. A Cox proportional hazards model was used to evaluate the time to a first BPAR event. RESULTS: GI complications occurred at an incidence of 52.8% and 48.9% in the EC-MPS and MMF cohorts, respectively (NS). Patients requiring dose manipulations due to GI complications were 19.7% with EC-MPS and 25.3% with MMF (NS). The mean equimolar dose reduction below 2000 mg was 930+/-292.13 mg with EC-MPS and 933+/-173.95 mg with MMF (NS). Patients treated with EC-MPS experienced significantly fewer BPAR episodes than those treated with MMF (14% EC-MPS vs. 23.1% MMF; P =0.0221). CONCLUSIONS: In this study, EC-MPS had a similar incidence of GI complications and dose manipulations compared with MMF. Despite similar GI complication rates and dose manipulations, treatment with EC-MPS seemed to result in a lower incidence of BPAR. Based on these observations, more studies need to be conducted to evaluate risks for BPAR relating to mycophenolic acid product.

Impact of clopidogrel in patients with acute coronary syndromes requiring coronary artery bypass surgery: a multicenter analysis.

OBJECTIVES: The purpose of our multicenter study was to examine the impact of pre-operative administration of clopidogrel on reoperation rates, incidence of life-threatening bleeding, inpatient length of stay, and other bleeding-related outcomes in acute coronary syndrome (ACS) patients requiring cardiopulmonary bypass (coronary artery bypass graft surgery [CABG]) in a broad cross section of U.S. hospitals. BACKGROUND: There is relative uncertainty about the relationship between clopidogrel and CABG-associated outcomes in the setting of ACS. METHODS: A retrospective cohort analysis was performed of randomly selected ACS patients requiring CABG in 14 hospitals across the U.S. Patients exposed to clopidogrel were compared with those not exposed to clopidogrel within 5 days prior to surgery. RESULTS: Of the 596 patients enrolled in the study, 298 had been exposed to clopidogrel within 5 days (Group A). Patients in Group A were more than 3-fold more likely to require reoperation for assessment of bleeding than patients not exposed to clopidogrel (6.4% vs. 1.7% Group B, p = 0.004). Major bleeding occurred in 35% of Group A patients versus 26% of Group B patients (p = 0.049). Length of stay was greater in Group A compared with Group B (9.7 +/- 6.0 days vs. 8.6 +/- 4.7 days, unadjusted p = 0.016). After logistic regression analysis, clopidogrel exposure within 5 days of CABG was the strongest predictor of reoperation (odds ratio [OR]: 4.60, 95% confidence interval [CI]: 1.45 to 14.55) and major bleeding (OR: 1.824, 95% CI: 1.106 to 3.008). CONCLUSIONS: After ACS, patients who undergo CABG within 5 days of receiving clopidogrel are at increased risk for reoperation, major bleeding, and increased length of stay. These risks must be balanced by the clinical benefits of clopidogrel use demonstrated in randomized clinical trials.