Baseline Charlson Comorbidity Index Score Research Articles

Risk of adverse events in patients with bullous pemphigoid treated with oral corticosteroids in the United States

AbstractBackgroundThe potential association of long‐term oral corticosteroid (OCS) use with adverse events (AEs) in patients with bullous pemphigoid (BP) is not well characterized in a real‐world setting.ObjectivesTo evaluate the effect of OCS use and treatment duration on the incident AEs in patients with BP.MethodsThis retrospective cohort study used medical and pharmacy claims and patient enrollment data from IQVIA PharMetrics® Plus from 2006−2021. Eligible patients had a diagnosis of BP between 1 January 2006 and 30 June 2020 (≥2 claims for BP ≥ 30 days apart). Patients in the OCS cohort also had a claim for OCS use, ≥7.5 mg daily dose of prednisone or equivalent, and no claims for a nonoral systemic corticosteroid (CS) at any time during the study period. A control cohort of patients with BP not using OCS was also selected. Relative risk ratios were estimated between the incidence of AEs in OCS users with different exposure durations (short‐term, <30 days; medium‐term, 30−90 days; long‐term, >90 days) and nonusers by Poisson regression, after adjusting for age, sex, prior drug use, and baseline Charlson Comorbidity Index score within the follow‐up period.ResultsAt the 1‐year follow‐up, long‐term OCS users had a higher incidence of infections, cataract, osteoporosis, heart failure, depression or anxiety, and diabetes compared with OCS nonusers (p < 0.05). Furthermore, compared with nonusers, long‐term users had increased 1‐year risks (risk ratio; 95% confidence interval) for heart failure (2.27; 1.50−3.44), diabetes (2.05; 1.30−3.24), osteoporosis (1.72; 1.23−2.41), and infection (1.50; 1.13−1.99). Long‐term OCS users also had increased 1‐year risks for heart failure (2.00; 1.21−3.28) and osteoporosis (1.70; 1.16−2.50) compared with short‐term OCS users.ConclusionsLong‐term OCS use (≥7.5 mg) in patients with BP was associated with an increased risk of AEs. Study findings demonstrate a need for steroid‐sparing options with an improved safety profile.

Patient Characteristics, Treatment Patterns, and Health Outcomes in a Real-World Population of Patients with Myelofibrosis Treated with Fedratinib

Introduction: Myelofibrosis (MF) is a type of myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, progressive anemia, and debilitating constitutional symptoms. Fedratinib (FEDR) is a selective Janus kinase-2 inhibitor (JAK2i) approved for the treatment of adult patients with intermediate (int)-2 or high-risk primary or secondary MF. Patients with MF have a median overall survival of 5-7 years; however, prior to FEDR approval, ruxolitinib (RUX) was the only approved JAK2i for MF treatment, with the majority of patients discontinuing RUX within 3 years of treatment initiation (Harrison C, et al. Ann Hematol 2020;99:1177-1191). Given the current availability and use of FEDR, the primary study objective was to describe demographics, clinical characteristics, and treatment patterns of patients with MF receiving FEDR in real-world practice settings after prior RUX treatment. A secondary objective was to assess changes in MF-related symptoms and spleen size during FEDR treatment. Methods: We report interim data from a medical records review of adult patients with MF who received FEDR treatment after RUX discontinuation (due to treatment refractoriness, relapse, or intolerance) in Canada (CAN), Germany (GER), and the United Kingdom (UK). Data collection is ongoing, and we present data abstracted from March through May 2023. Patients were required to have an int-2 or high-risk MF diagnosis at FEDR initiation and to have initiated FEDR after date of first availability in each country (CAN: Sep 21, 2020, GER: Feb 9, 2021, UK: Nov 1, 2021) up to 6 months prior to data abstraction. Patients who received allogenic, hematopoietic cell transplantation after initial MF diagnosis or participated in a JAK2i trial were excluded. Spleen size evaluation through palpation at FEDR initiation and at least once within the first 6 months of FEDR use was required. Study outcomes measured were patient characteristics, treatment patterns, MF-related symptoms, and spleen size evaluations. Descriptive statistics are reported. Results: A total of 58 patients (CAN: 13, GER: 32, UK: 13) were included in the analysis. Median age at MF diagnosis and FEDR initiation was 67.9 and 71.8 years, respectively. 65.5% of patients were male, and 91.4% were White. Most patients were diagnosed with primary MF (60.3%) and had JAK2 V617F mutation (84.5%). Among patients who had a bone marrow biopsy (n = 51), 58.8% had grade 2 bone marrow fibrosis. Mean baseline Charlson Comorbidity Index score was 2.5. Median time from MF diagnosis and RUX treatment discontinuation to FEDR initiation was 34.0 months and 0.7 months, respectively. Most common reasons for FEDR initiation were splenomegaly (75.9%), RUX failure (67.2%), and to achieve symptom control (63.8%) (Table). Over a median follow-up of 12.1 months after FEDR initiation, 19 patients (32.7%) discontinued FEDR treatment with a median treatment duration of 7.7 months. Among the 39 patients taking FEDR at data abstraction, median treatment duration was 12.5 months. At FEDR initiation, 48.3% and 51.7% had int-2 risk and high-risk MF, respectively. The most common MF-related symptoms presented were fatigue (74.1%), abdominal discomfort (63.8%), and night sweats (46.6%) (Table). 62.1% of patients initiated FEDR treatment at the recommended therapeutic dose of 400 mg, and 74.1% were receiving 400 mg at end of follow-up/treatment discontinuation. Among patients with ≥ 1 FEDR dose change, titration to therapeutic dose (68.4%) was the most common reason for their first dose change. MF-related symptoms decreased in the first 6 months of FEDR treatment, including fatigue (74.1% [at FEDR initiation] reduced to 52.8% [at 6 months after FEDR initiation]), abdominal discomfort (63.8% reduced to 11.3%), and night sweats (46.6% reduced to 3.8%). The proportion of patients with severe (palpable spleen:> 20 cm) and moderate splenomegaly (palpable spleen: 11-20 cm) decreased from FEDR initiation to 6 months after initiation (severe splenomegaly: 32.8% to 7.5%, moderate splenomegaly: 55.2% to 15.1%) (Figure). Conclusion: Thepatients included in this study exhibited a significant level of illness . In this interim analysis, patients treated with FEDR following RUX treatment failure showed resolution of MF-related symptoms and a marked decrease in splenomegaly in the initial 6-month period, demonstrating the real-world effectiveness of FEDR treatment in patients with MF.

The Prevalence and Risk Factors of Acute Kidney Injury during Colistin Therapy: A Retrospective Cohort Study from Lebanon.

The current study aimed to determine the prevalence, risk factors, and stages of severity of acute kidney injury (AKI) caused by colistimethate sodium (CMS) treatment in patients diagnosed with systemic antibiotic-resistant Gram-negative bacterial infections. The predictors of all-cause mortality in this patient population were also examined. This retrospective cohort study included patients who were admitted to a university-affiliated hospital and acute tertiary care referral center in Beirut, Lebanon between January 2015 and December 2018 and underwent CMS treatment for a period of 48 h or more. The study sample included 298 adult patients, of which 46.3% (n = 138/298) developed AKI (assessed using the Kidney Disease Improving Global Outcomes (KDIGO) criteria). Of these, 37.7% (n = 51/138) were diagnosed with stage 1 AKI, 23.9% with stage 2 (n = 33/138), and 38.4% with stage 3 (n = 53/138). Nephrotoxicity was reversed in 87.5% of AKI patients who survived until hospital discharge. Independent risk factors for AKI included patient age ≥ 75 years (aOR = 1.854; 95% CI: 1.060-3.241; p-value = 0.03); underlying chronic kidney disease (aOR = 4.849; 95% CI: 2.618-9.264; p-value < 0.0001); and concomitant use of vasopressors (aOR = 4.305; 95% CI: 2.517-7.456; p-value < 0.0001). Multivariate analysis showed that the predictors of severe AKI (stage 2 or 3) included baseline hypoalbuminemia (aOR = 2.542; 95% CI: 1.000-6.564; p-value = 0.05); concomitant use of vasopressors (aOR = 6.396; 95% CI: 2.741-15.87; p-value < 0.0001); and CMS days of therapy (DOT) prior to development of AKI ≥ 7 days (aOR = 4.728; 95% CI: 2.069-11.60; p-value < 0.0001). All-cause mortality was recorded in 51.3% of patients (n = 153/298), and this was significantly higher in patients with AKI (76.8%; n = 106/138) compared to those without (29.4%; n = 47/160; OR = 7.964; 95% CI: 4.727-13.417; p-value < 0.0001). Independent predictors of all-cause mortality included a baseline Charlson comorbidity index score ≥5 (aOR = 4.514; 95% CI: 2.443-8.530; p-value < 0.0001); concomitant use of vasopressors (aOR = 7.76; 95% CI: 4.238-14.56; p-value < 0.0001); and CMS-induced AKI (aOR = 4.117; 95% CI: 2.231-7.695; p-value < 0.0001). The findings of this study suggest that old age, history of chronic kidney disease, and concomitant vasopressor treatment are all independent predictors of CMS-induced AKI. The risk of developing severe AKI significantly increases with CMS DOT. Understanding the risk factors of nephrotoxicity is essential for improving prognosis and treatment outcomes.

Abstract 3657: Mental health disorders among prostate cancer patients in a population-based cohort

Abstract Background. Prostate cancer is the most common malignancy among men in the United States. Few studies evaluate mental health disorders comprehensively among prostate cancer patients with long-term follow-up. The primary aim of our study is to assess the incidence of mental health disorders among prostate cancer patients compared to a general population cohort. A secondary aim is to investigate risk factors for mental health disorders among prostate cancer patients. Methods. Cohorts of 18,134 cancer patients with prostate adenocarcinomas diagnosed between 2004 and 2017 and 73,470 men without cancer matched by age, birth state and follow up time from the general population were identified. Mental health diagnoses were identified from electronic medical records and statewide healthcare facilities data. Cox proportional hazard models were used to estimate hazard ratios (HRs). Results. Prostate cancer patients had increased risks of mental illnesses for the first five years after cancer diagnosis (0-2 years: HR=1.81, 95%CI=1.75-1.87; 2-5 years: HR=1.05, 95%CI=1.01-1.08) compared to the general population, but not in the later follow up periods. Elevated risks of anxiety disorder among prostate cancer patients were observed during across follow-up periods (0-2 years: HR= 1.59, 95% CI= 1.49-1.70; 2-5 years: HR= 1.20, 95% CI= 1.12-1.28; 5-10 years: HR= 1.20, 95% CI= 1.12-1.29; 10- 16 years: HR= 1.29, 95% CI= 1.14-1.45). Likewise, mood disorders, including depressive disorders, among prostate cancer survivors were found for all follow-up periods (0-2 years: HR= 1.59, 95% CI= 1.50-1.69; 2-5 years: HR= 1.21, 95% CI= 1.14-1.29; 5-10 years: HR= 1.20, 95% CI= 1.13-1.28; 10-16 years: HR=1.25, 95% CI= 1.12-1.38).The risks of any mental illness were increased with PSA&amp;gt;20ng/ml, high Gleason score, high-level risk group (intermediate, high, and very high), higher AJCC staging, and androgen deprivation treatment (ADT) therapy within 10 years after prostate cancer diagnosis. Surgery, radiation, ADT and tumor characteristics were also important risk factors for depression at 0-2 years after prostate cancer diagnosis. A baseline Charlson Comorbidity Index score of 1+ and unmarried status were associated with increased risk of any mental illness and depression across all time periods. We also observed that increased risks of any mental illness were associated with Hispanic, black or multiple races, underweight or obese, and family history of prostate cancer for all time periods. Prostate cancer survivors had a 26% increased risk of death associated with a mental illness diagnosis and a 61% increased risk of death with a depression diagnosis. Conclusion. Prostate cancer diagnosis is associated with poor mental health, which was observed as long as 16 years after cancer diagnosis. Providing long-term mental health support may be potentially beneficial to increasing life expectancy for prostate cancer patients. Citation Format: Siqi Hu. Mental health disorders among prostate cancer patients in a population-based cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3657.

Risk of health status worsening in primary infertile men: A prospective 10‐year follow‐up study

A severe male infertility factor has been associated with both lower health status and increased mortality in infertile men. To investigate reproductive factors associated with health status impairment in infertile men over a 10-year time frame since the first clinical evaluation. Data from 899 infertile men were analysed at baseline between 2003 and 2010. Health-significant comorbidities were scored with the Charlson Comorbidity Index. Patients were followed up yearly recording any worsening in their health status until 2019. Cox regression models were used to estimate hazard ratios and 95% confidence intervals of Charlson Comorbidity Index score increase. At a median follow-up of 136 months (Interquartile range: 121, 156), 85 men (9.5%) depicted an increase of their baseline Charlson Comorbidity Index score of at least one point. The most frequent reason for Charlson Comorbidity Index upgrade was cancer (34%), cardiovascular diseases (29%) and diabetes mellitus (22%). Compared to patients without a Charlson Comorbidity Index increase, patients with a Charlson Comorbidity Index increase presented with higher body mass index and follicle-stimulating hormone values, a higher rate of baseline Charlson Comorbidity Index ≥ 1 (all p<0.01) and a greater proportion of non-obstructive azoospermia (p<0.001). In the Cox regression model, the patient's BMI (p<0.001), baseline Charlson Comorbidity Index ≥ 1 (p<0.01) and azoospermia status (p=0.001) were found to be independently associated with Charlson Comorbidity Index increases. Almost 10% of men presenting for primary infertility had a decrease of the overall health status already in the relatively short 10-year time frame after the first presentation. Non-obstructive azoospermic men showed the worst health status impairment and should be strictly followed-up regardless of their fertility status.

Testosterone in males with COVID-19: A 7-month cohort study.

BackgroundCirculating testosterone levels have been found to be reduced in men with severe acute respiratory syndrome coronavirus 2 infection, COVID‐19, with lower levels being associated with more severe clinical outcomes.ObjectivesWe aimed to assess total testosterone levels and the prevalence of total testosterone still suggesting for hypogonadism at 7‐month follow‐up in a cohort of 121 men who recovered from laboratory‐confirmed COVID‐19.Materials and methodsDemographic, clinical, and hormonal values were collected for all patients. Hypogonadism was defined as total testosterone ≤9.2 nmol/L. The Charlson Comorbidity Index was used to score health‐significant comorbidities. Descriptive statistics and multivariable linear and logistic regression models tested the association between clinical and laboratory variables and total testosterone levels at follow‐up assessment.ResultsCirculating total testosterone levels increased at 7‐month follow‐up compared to hospital admittance (p < 0.0001), while luteinizing hormone and 17β‐estradiol levels significantly decreased (all p ≤ 0.02). Overall, total testosterone levels increased in 106 (87.6%) patients, but further decreased in 12 (9.9%) patients at follow‐up, where a total testosterone level suggestive for hypogonadism was still observed in 66 (55%) patients. Baseline Charlson Comorbidity Index score (OR 0.36; p = 0.03 [0.14, 0.89]) was independently associated with total testosterone levels at 7‐month follow‐up, after adjusting for age, BMI, and IL‐6 at hospital admittance.ConclusionsAlthough total testosterone levels increased over time after COVID‐19, more than 50% of men who recovered from the disease still had circulating testosterone levels suggestive for a condition of hypogonadism at 7‐month follow‐up. In as many as 10% of cases, testosterone levels even further decreased. Of clinical relevance, the higher the burden of comorbid conditions at presentation, the lower the probability of testosterone levels recovery over time.

Clinical complications in patients with primary and recurrent Clostridioides difficile infection: A real-world data analysis.

Objective:Clostridioides difficile infection and recurrent C. difficile infection result in substantial economic burden and healthcare resource use. Sepsis and bowel surgery are known to be serious complications of C. difficile infection. This study evaluated clinical complications in patients with C. difficile infection and recurrent C. difficile infection during a 12-month period following the primary C. difficile infection.Methods:A retrospective analysis of commercial claims data from the IQVIA PharMetrics Plus™ database was conducted for patients aged 18–64 years with an index C. difficile infection episode requiring inpatient stay or an outpatient visit for C. difficile infection followed by a C. difficile infection treatment. Each C. difficile infection episode ended after a 14-day C. difficile infection-claim-free period was observed. Recurrent C. difficile infection was defined as a further C. difficile infection episode within an 8-week window following the claim-free period. Clinical complications were documented over 12 months of follow-up and stratified by the number of recurrent C. difficile infection episodes (0 rCDI, 1 rCDI, 2 rCDI, and 3+ rCDI).Results:In total, 46,571 patients with index C. difficile infection episode were included. During the 6-month pre-index, the mean (standard deviation) baseline Charlson comorbidity index score, by increasing the recurrent C. difficile infection group, was 1.2 (1.9), 1.5 (2.2), 1.8 (2.3), and 2.3 (2.5). During the 12-month follow-up, sepsis occurred in 16.5%, 27.3%, 33.1%, and 43.3% of patients, and subtotal colectomy or diverting loop ileostomy was performed in 4.6%, 7.3%, 8.9%, and 10.5% of patients, respectively, by increasing the recurrent C. difficile infection group.Conclusions:Reduction in recurrent C. difficile infection is an important step to reduce the burden of serious clinical complications, and new treatments are needed to reduce C. difficile infection recurrence.

Abstract 5797: Genitourinary disease risks among ovarian cancer survivors in a population-based cohort study

Abstract Background. While genitourinary complications during treatment for ovarian cancer are well known, long-term adverse outcomes in the growing population of ovarian cancer survivors have yet to be characterized. The aim of our study is to describe the incidence of genitourinary diseases among ovarian cancer survivors after ovarian cancer diagnosis, compared to the general female population. Methods. We identified a cohort of 1,270 ovarian cancer survivors diagnosed between 1996 and 2012 in the Utah Cancer Registry, and up to five cancer-free women were matched to ovarian cancer survivors on birth year and state from the Utah Population Database (N=5,286). Genitourinary disease diagnoses were identified with ICD-9 codes from electronic medical records and statewide healthcare facilities data. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI) for genitourinary outcomes at 1 to &amp;lt;5 years after cancer diagnosis and 5+ years after cancer diagnosis with adjustment for potential confounders (e.g., race, baseline body mass index (BMI), and baseline Charlson Comorbidity Index (CCI)). Results. Urinary system disorders were diagnosed more frequently in ovarian cancer survivors compared to women without cancer (34.6% vs 19.3%, p-value &amp;lt;0.001) in years 1-5 of follow up (HR: 2.53, 95% CI: 2.12-3.01). More than 5 years after cancer diagnosis, ovarian cancer survivors had a higher risk of hydronephrosis compared to the general population (HR: 9.10, 95% CI: 4.29-19.33). Genital organ disorders were also more common among ovarian cancer survivors (22.0%) compared to women in the general population (16.3%; HR: 1.89, 95% CI: 1.57-2.27). The risk of pelvic peritoneal adhesions was highest 1-5 years after cancer diagnosis (HR: 16.59, 95% CI: 7.00-39.34) and persisted 5+ years after cancer diagnosis (HR: 8.88, 95% CI: 1.88-41.91). A higher risk of urinary system disorders among ovarian cancer patients was associated with advanced cancer stage (HRadvanced vs. localized: 3.11, 95% CI: 2.18-4.45), older age at cancer diagnosis (HR80+ vs. 18-49: 2.85, 95% CI: 1.62-5.01), and higher baseline CCI score (HR2+ vs. 0: 2.71, 95% CI: 1.84-3.99). The associations remained when we restricted analyses to ovarian cancer survivors with high-grade serous ovarian cancer. Conclusions. In this population-based cohort study, ovarian cancer survivors experienced increased risks of various genitourinary diseases for many years after cancer diagnosis. Understanding the multimorbidity trajectory for ovarian cancer survivors after cancer treatment is needed to ultimately improve clinical care after cancer diagnosis. The present results point to the importance of monitoring for genitourinary diseases among ovarian cancer survivors. Citation Format: Chun-Pin Chang, Yuji Chen, Brenna Blackburn, Sarah Abdelaziz, Kerry Rowe, John Snyder, Mark Dodson, Vikrant Deshmukh, Michael Newman, Joseph B. Stanford, Christina A. Porucznik, Jennifer Ose, Alison Fraser, Ken Smith, Jennifer Doherty, David Gaffney, Mia Hashibe. Genitourinary disease risks among ovarian cancer survivors in a population-based cohort study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5797.

Incidence of Long-term Opioid Use Among Opioid-Naive Patients With Hidradenitis Suppurativa in the United States

Risk of long-term opioid use among patients with hidradenitis suppurativa (HS), who experience pain that substantially impairs quality of life, is unknown to date. To compare overall and subgroup incidence of long-term opioid use in a population of opioid-naive patients with HS and control patients. This retrospective cohort study was based on a demographically heterogeneous population-based sample of more than 56 million unique patients from January 1, 2008, through December 10, 2018. Patients with HS (n = 22 277) and controls (n = 828 832) were identified using electronic health records data. Data were analyzed from December 13, 2018, through January 28, 2019. The primary outcome was incident long-term opioid use. Among the 22 277 patients with HS, mean (SD) age was 40.8 (14.6) years, 16 912 (75.9%) were women, and 13 190 (59.2%) were white. Crude 1-year incidence of long-term opioid use among opioid-naive patients with HS was 0.33% (74 of 22 277), compared with 0.14% (1168 of 828 832) among controls (P < .001). In adjusted analysis, patients with HS had 1.53 (95% CI, 1.20-1.95; P < .001) times the odds of new long-term opioid use compared with controls. Among patients with HS, advancing age (odds ratio [OR], 1.02 per 1-year increase; 95% CI, 1.00-1.03; P = .05), ever smoking (OR, 3.64; 95% CI, 2.06-6.41; P < .001), history of depression (OR, 1.97; 95% CI, 1.21-3.19; P = .006), and baseline Charlson comorbidity index score (OR, 1.15 per 1-point increase; 95% CI, 1.03-1.29; P = .01) were associated with higher odds of long-term opioid use. Among patients with HS and long-term opioid use, 4 of 74 (5.4%) were diagnosed with opioid use disorder during the study period. The most frequent schedule II opioid prescriptions included oxycodone hydrochloride (55 of 74 patients [74.3%]), hydrocodone bitartrate (44 [59.5%]), hydromorphone hydrochloride (16 [21.6%]), morphine sulfate (13 [17.6%]), and fentanyl citrate (6 [8.1%]). Tramadol hydrochloride (32 [43.2%]) represented the most frequent non-schedule II prescription. Disciplines prescribing the most opioids to patients with HS included primary care (398 [72.8%]), anesthesiology/pain management (48 [8.8%]), gastroenterology (25 [4.6%]), surgery (23 [4.2%]), and emergency medicine (10 [1.8%]). In this study, patients with HS were at higher risk for long-term opioid use. These results suggest that periodic assessment of pain and screening for long-term opioid use may be warranted, particularly among patients who are older, who smoke tobacco, or who have depression and other medical comorbidities.

Incidence of Clostridioides difficile infections among young and middle-aged adults: Veterans Health Administration.

Clostridioides difficile infection (CDI) remains a significant public health concern, resulting in excess morbidity, mortality, and costs. Additional insight into the burden of CDI in adults aged &lt;65 years is needed. A 6-year retrospective cohort study was conducted using data extracted from United States Veterans Health Administration electronic medical records. Patients aged 18-64 years on January 1, 2011, were followed until incident CDI, death, loss-to-follow-up, or December 31, 2016. CDI was identified by a diagnosis code accompanied by metronidazole, vancomycin, or fidaxomicin therapy, or positive laboratory test. The clinical setting of CDI onset was defined according to 2017 SHEA-IDSA guidelines. Of 1,073,900 patients, 10,534 had a CDI during follow-up. The overall incidence rate was 177 CDIs per 100,000 person years, rising steadily from 164 per 100,000 person years in 2011 to 189 per 100,000 person years in 2016. Those with a CDI were slightly older (55 vs 51 years) and sicker, with a higher baseline Charlson comorbidity index score (1.4 vs 0.5) than those without an infection. Nearly half (48%) of all incident CDIs were community associated, and this proportion rose from 41% in 2011 to 56% in 2016. The findings from this large retrospective study indicate that CDI incidence, driven primarily by increasing community-associated infection, is rising among young and middle-aged adult Veterans with high service-related disability. The increasing burden of community associated CDI in this vulnerable population warrants attention. Future studies quantifying the economic and societal burden of CDI will inform decisions surrounding prevention strategies.

The impact of Charlson Comorbidity Index on survival outcomes in men with prostate cancer who underwent definitive prostate radiotherapy.

114 Background: Life expectancy is very essential in deciding treatment options in men with prostate cancer (PCa); however, the impact of comorbidities on outcomes is not well-established. We investigated the influence of Charlson Comorbidity Index (CCI) on survival endpoints in men with localized PCa who were treated with prostate radiotherapy (RT). Methods: Men with intermediate and high risk PCa who were treated with definitive RT between 1/2007 and 12/2012 were included. Groups were created according to their baseline CCI score at diagnosis into no, mild and severe comorbidity (CCI 0, 1 or 2+). The groups were then compared based on patients’ characteristics and prognostic factors. Kaplan-Meier curves and Uni/multivariate analyses (MVA) were used to examine the impact of CCI groups on overall (OS), disease specific (DSS), and biochemical relapse free (BRFS) survival. Results: 257 patients were identified after excluding low risk, metastatic cases and those with inadequate follow up. Median follow-up was 92 months (range: 2-135) and median age was 73 years (range: 48-85). 53% of the cases were black and 67% were of intermediate risk. Median RT dose was 76 Gy and 47% received androgen deprivation therapy. CCI groups 0, 1 and 2+ encompassed 76 (30%), 54 (21%) and 127 (49%) patients, respectively. Groups were generally well-balanced. 10 and 15 years OS was significantly different across CCI groups (76% &amp; 53%, 46% &amp; 31% and 55% &amp; 14%, for CCI-0, 1 and 2+ respectively; p &lt; 0.001). CCI-0 had better DSS than CCI-2+ ( p = 0.03) with no difference for CCI-0 vs 1 ( p = 0.1). BRFS was non-different among CCI groups ( p = 0.99). On MVA, increased CCI was deterministic for OS ( p &lt; 0.001) after adjusting for age, Gleason’s score and T-stage. For DSS, only age and T3 vs T1/2 were independently prognostic ( p &lt; 0.001); whereas CCI-1 vs 0 was only marginal ( p = 0.05). Conclusions: Higher CCI was a significant predictor of shorter OS in intermediate and high-risk PCa. Baseline comorbidities should be taken into consideration during patient counselling for treatment options and in designing prospective trials for men with localized prostate cancer.

Real World Treatment Patterns, Adverse Events and Healthcare Resource Utilization and Costs Among Chronic Lymphocytic Leukemia (CLL) Patients in the United States

Background: CLL is one of the most common types of leukemia among adults. Treatment options for CLL have expanded in recent years, but few studies provide contemporary real-world data on treatment patterns, treatment-related adverse events (AEs) and the economic burden associated with these agents. This study aimed to evaluate treatment-related AEs and the healthcare resource utilization (HCRU) and cost associated with the current treatment for chronic lymphocytic leukemia (CLL).Methods: This retrospective study used medical and pharmacy claims from the Optum Research Database, a large national US database, to identify adults (≥ 18 years old) commercially insured and Medicare Advantage (MA) enrollees. The study included patients with CLL (≥ 2 medical claims at least 7 days apart between July 1, 2012, through May 30, 2017), at least 1 claim for systemic CLL-directed therapy and continuous enrollment for 12 months prior to (baseline period) and ≥ 1 month after the first observed CLL-directed therapy (index date). Patients with systemic CLL-directed therapy during the baseline period or undergoing stem cell transplantation during the entire study period were excluded from analysis. Up to 3 line of therapy (LOT) periods were captured based on timing and receipt of systemic CLL-directed therapy. Cohorts based on the most common regimens received, regardless of LOT sequence, were created. Potential treatment-related AEs (prevalent and incident conditions) during regimen cohorts were identified by ICD-9 and ICD-10 diagnosis codes in position 1 or 2 on claims. All-cause and AE-related healthcare resource utilization and costs (per patient per month (PPPM)) were examined. All analyses were descriptive.Results: A total of 3292 patients with CLL met all study criteria; 65% were MA enrollees and 35% were commercially insured. Mean age (standard deviation, [SD]) was 71 years (SD 11) with a baseline Charlson comorbidity index score of 3.5 (SD 1.9). During the study period, 31% of patients had ≥ 2 LOTs and 10% had ≥ 3 LOTs. The most common regimens (excluding rituximab maintenance therapy) observed by LOT were; bendamustine + rituximab (23%) during LOT1, ibrutinib (22%) during LOT2 and ibrutinib (17%) during LOT3. Among the study patients, 4,509 LOT periods (LOT1-LOT3) were observed. Of these periods, 3177 accounted for the 5 most common treatment regimens observed: rituximab (excluding maintenance therapy) (30%); bendamustine + rituximab (28%); ibrutinib (20%); obinutuzumab ± chlorambucil (14%); and cyclophosphamide + fludarabine + rituximab (8%). The most common AEs associated with these treatment regimens are reported in the Table.Conclusions: The most common regimen during LOT1 was bendamustine + rituximab, and was ibrutinib during LOT2 and LOT3.This study provides evidence that occurrence of AEs among patients with CLL receiving systemic anti-cancer therapy in the real-world setting is substantial and associated with significant health care cost. The economic burden associated with increased AEs underscores the need for treatments with fewer AEs. DisclosuresKabadi:AstraZeneca: Employment. Le:Optum: Employment; Optum/United Health Group: Equity Ownership. Dacosta Byfield:Optum/United Health Group: Equity Ownership; Optum: Employment. Olufade:AstraZeneca: Employment; AstraZeneca: Equity Ownership.

Variations of the renal function parameters in rectal cancer patients with a defunctioning loop ileostomy.

The objective of this study is to investigate the impact of the temporary loop ileostomy on renal function and also to assess the factors associated with the change in renal function observed between the index surgery (the moment of the radical surgical procedure) and the closure of the ileostomy (the moment of the secondary surgical act of suppression of the ileostomy). A total of 69 rectal cancer patients from a single referral surgical unit who had a loop ileostomy during low anterior resection of the rectum were included in this study. Serum creatinine levels were evaluated, and estimated glomerular filtration rate (eGFR) was calculated prior to index surgery and closure of the ileostomy. During this time interval, there was a significant decrease in eGFR levels (mean difference - 4.5mL/min/1.73m2, 95% CI - 7.8 to - 1.3mL/min/1.73m2), and also a significant increase in the serum creatinine values (mean difference 0.07, 95% CI 0.02-0.12mg/dL). The eGFR decrease was more pronounced in diabetic patients, in those with a baseline Charlson Comorbidity Index score ≥ 1 or in those that received chemotherapy. In a multivariable regression analysis, the use of neoadjuvant chemotherapy was the only variable significantly associated with the change in eGFR levels between the two surgical interventions. Renal function impairment is an important event that the surgeon has to take into consideration when deciding upon opting for a loop ileostomy to temporarily defunction a colorectal anastomosis.

Impact of Charlson Comorbidity Index (CCI) and Refining the MIPI Index in Mantle Cell Lymphoma (MCL)

Impact of Charlson Comorbidity Index (CCI) and Refining the MIPI Index in Mantle Cell Lymphoma (MCL)

PCV51 - MEDICATION COST IMPLICATION FOR THE MANAGEMENT OF HYPERTENSION AND DIABETES IN NIGER DELTA: TERTIARY HOSPITAL BASED STUDY IN BAYELSA STATE, NIGERIA

Objectives: To assess the economic burden and health care resource utilization among patients in long-term care facilities who were diagnosed with stroke. MethOds: Patients diagnosed with stroke (International Classification of Diseases, 9th Revision, Clinical Modification diagnosis codes 433, 434 and 436) were identified using the Long Term Care Minimum Data Set (MDS) linked to 5% Medicare data from 01JAN2009 through 31DEC2010. The initial diagnosis date was designated as the index date. Patients without a stroke diagnosis (control cohort) were matched to stroke patients, and 1:1 propensity score matching (PSM) was used to control for age, region, gender and baseline Charlson Comorbidity Index score. The index date for the control cohort was randomly chosen to reduce selection bias. Patients in both cohorts were required to be age ≥ 65 years, have at least two consecutive quarterly assessments documented in MDS data 6 months prior to the index date and have continuous medical and pharmacy benefits 1 year before and after the index date. Results: Once PSM was applied, 1,014 patients were included in each cohort, and baseline characteristics were balanced. A higher percentage of stroke patients had inpatient admissions (40.34% vs. 23.37%, p< 0.0001), outpatient visits (92.31% vs. 89.45%, p= 0.0253), skilled nursing facility (SNF; 37.67% vs. 28.21%, p< 0.0001) and durable medical equipment (DME) claims (30.47% vs. 22.09%, p< 0.0001) than those in the control cohort. Stroke patients also incurred considerably higher inpatient ($7,068 vs. $3,418, p< 0.0001), outpatient ($3,545 vs. $2,539, p< 0.0001), SNF ($8,036 vs. $3,695, p< 0.0001), DME ($394 vs. $235, p= 0.0023) and carrier claim costs ($3,606 vs. $2,489, p< 0.0001) than those without a stroke diagnosis. cOnclusiOns: Patients diagnosed with stroke had considerably higher health care resource utilization and costs than those in the control cohort.

Discharge patterns, survival outcomes, and changes in clinical management of hospitalized adult patients with cancer with a do-not-resuscitate order.

Do-not-resuscitate (DNR) orders prevent medically futile attempts at resuscitation but are not always instituted in hospitalized patients with advanced cancer. One explanation for this underuse is the perception that DNR orders are inevitably associated with withdrawal of all medical interventions and inpatient death. To audit discharge and survival outcomes and changes in clinical management in hospitalized adult oncology patients with a DNR order, allowing an assessment of whether such orders lead to cessation of acute interventions and high rates of in-hospital death. Retrospective data were collected from 270 oncology inpatients at Austin Health, Melbourne, Australia, between February 1, 2012 and November 30, 2012. Mean and median time to institution of DNR orders after admission were 2.1 and 1.0 days, respectively (interquartile range, 0-2 days). Medical interventions continued in 80% or more of cases after DNR orders were placed included blood draws, intravenous antimicrobials, imaging, blood products, and radiotherapy. Two-thirds of patients survived hospitalization and were discharged alive. Survival at 30 days and 90 days after DNR orders were implemented was 63% and 33%, respectively. Baseline Charlson Comorbidity Index score of 5 or less and Eastern Cooperative Oncology Group performance status of 2 or less were associated with a higher probability of being discharged alive and longer overall survival. Most medical interventions were continued with high frequency in adult oncology inpatients after placement of DNR orders. A majority of patients survived hospitalization and remained alive at 30 days after DNR orders were documented. This study offers some reassurance that DNR orders do not inevitably lead to cessation of appropriate medical treatment.

PCV54 - Evaluation Of The Burden Of General Cardiovascular Disease Among United States Medicare Patients

To evaluate the economic burden and health care utilization of general cardiovascular disease (CVD) patients in the U.S. Medicare population. A retrospective database analysis was conducted using Medicare data (2008-2010). General CVD patients were identified using myocardial infarction (International Classification of Disease, 9th Revision, Clinical Modification [ICD-9-CM] codes 410.xx, 412.xx), unstable angina (411.1x, 411.81, 411.89), ischemic stroke (434.xx, 436.xx, 437.0x, 437.1x, 438.xx, 997.02), transient ischemic attack (435.xx), heart failure (428.xx) and percutaneous coronary intervention (ICD-9 procedure codes 00.66, 36.09). The first diagnosis date was designated as the index date. One-year continuous enrollment pre- and post-index date was required. Charlson Comorbidity Index (CCI) score and comorbid conditions were examined for the baseline period. Prescribed medications were evaluated within 60 days post-diagnosis. Health care utilization and costs were measured for the follow-up period. A total of 203,865 patients were identified for study (mean age 78.9 years). CVD patients were more often female (60.7%), Caucasian (86.0%) and resided in the Southern U.S. region. (39.5%). The baseline CCI score was 1.86, and the most frequently diagnosed comorbid conditions were diabetes (32.8%), tumor (31.0%) and chronic obstructive pulmonary disease (25.6%). Furosemide (13.6%) was most often prescribed within 60 days after diagnosis, followed by simvastatin (11.4%) and lisinopril (10.6%). Health care utilization including Medicare carrier (98.3%), Durable Medical Equipment (DME, 43.9%), Home Health Agency (HHA, 25.6%), outpatient visits (80.5%) and inpatient hospital (52.8%), Skilled Nursing Facility (SNF, 17.7%) and hospice admissions (8.4%) and prescription claims (54.4%) were observed for the follow-up period. CVD patients incurred higher Medicare carrier ($5,679), DME ($534), HHA ($1,506), outpatient ($16,455), inpatient ($12,230), SNF ($3,489), hospice ($822), pharmacy ($1,818) and total costs ($42,533). General CVD Medicare patients utilized a high percentage of Medicare carrier, outpatient and inpatient utilizations, and incurred high health care expenses.

DTIC and GM-CSF in the treatment of patients with metastatic melanoma.

e19045 Background: To describe patients with metastatic melanoma being treated with mono-therapy, dacarbazine (DTIC) or granulocyte-macrophage colony-stimulating factor (GM-CSF). Methods: Using a large U.S. medical claims database, patients were identified between 2005 and 2010 using ≥2 melanoma diagnoses (ICD-9-CM: 172.xx, V10.82) and ≥2 diagnoses for metastasis (ICD-9-CM: 197.xx, 198.xx). Patients who received mono-therapy with DTIC or GM-CSF as the first documented drug therapy after metastatic diagnosis were identified. Patient demographic and clinical characteristics and treatment duration were compared between patients treated with DTIC and those who received GM-CSF. Furthermore, comparisons were also made between the two treatment groups after 1-to-1 matching on age, gender, and baseline comorbidities. Results: A total of 81 patients with metastatic melanoma receiving first-line DTIC and 24 patients with metastatic melanoma receiving first-line GM-CSF were included in this analysis. On average, DTIC patients were 8.5 years older (p = 0.009) and had higher baseline Charlson Comorbidity Index scores (D0.43, p = 0.005) than GM-CSF patients. The mean duration of first line treatment was 94 days on DTIC and 135 days on GM-CSF. The mean length of follow-up from the start of first line was 257 days on DTIC and 451 days on GM-CSF. After each GM-CSF patient was matched with a DTIC patient on age, gender, and baseline Charlson Comorbidity Index score, the mean duration of first line treatment was 79 days on matched DTIC and 135 days on GM-CSF, and the mean length of follow-up from the start of first line was 317 days on matched DTIC and 451 days on GM-CSF. Conclusions: Patients with metastatic melanoma who received DTIC treatment were older and had higher comorbidity index scores but shorter treatment duration than those who received GM-CSF; the difference in treatment duration remained after DTIC patients were matched with GM-CSF patients on age, gender and comorbidity index scores.

Short-Acting Opioids Raise Fracture Risk

Bruce Jancin is with the Denver bureau of Elsevier Global Medical News. DENVER — Elderly patients who are placed on short-acting opioids for arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on long-acting opioids, according to a large study. The increased risk was particularly strong during the first 2 weeks of therapy, when it was almost sevenfold in patients on short-acting opioids, such as propoxyphene or oxycodone, as in patients started on nonsteroidal anti-inflammatory drugs (NSAID) or long-acting opioids, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk associated with short-acting opioid therapy dropped but remained about three times that with NSAID therapy, Matthew Miller, MD, ScD, reported at the annual meeting of the American Public Health Association. The fracture risk during the first 2 weeks on long-acting opioids didn't differ significantly from that in patients who were placed on NSAIDs. Over 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on long-acting opioids than in those on NSAIDs. In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on short-acting opioids, added Dr. Miller, associate director of the Harvard Injury Control Research Center, Boston. “Our findings indicate that opioids increase the risk of fractures among older patients with arthritis and suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed. These results have the potential to change clinical practice in the elderly, said Dr. Miller. At present, short-acting opioids are prescribed far more often than long-acting ones. <Our findings, if borne out in other databases, could help inform safer prescribing practices consonant with the latest American Geriatrics Society guidelines on the pharmacological management of pain in older persons, which recommend that all patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy,” he said. His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with opioid analgesics, and 4,874 who started on NSAIDs. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months. Not surprisingly, patients who were started on opioids tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on long-acting opioids, and 1.6 in the NSAID group. The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids. A dose effect was evident. Patients on low-doseoopioids hada 2.2 times the fracture risktofdihose onan NSAIDs, after adjustment for comorbid conditions and other potentially confounding variables. Patients on moderate-dose opioids had 4.6 times the-risk. And those on high-dose opioid therapy had a 5.1-foldinisk. Among high-dose opioid users, a patient who was placed on a short-acting opioid had an adjusted risk of fracture d.1 times that of someone on a high-dose, long-acting opioid. Asked why he thought short-acting opioids were prescribed 13 times as frequentlytas long-acting ones in the study population, Dr. Miller reid his impression is that many physicians believe that if they prescribe a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous. “It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream. Yet 90% of the drugs that we're prescribing when we're prescribing opioids in an elderly population are short-acting drugs, raising the question of whether we're putting people at unnecessary risk,” Dr. Miller said. The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use. Dr. Miller declared having no relevant financial interests.