Diagnosis Index Date Research Articles

Duration of Treatment of Multiple Myeloma Regimens in Patients with Relapsed or Refractory Multiple Myeloma: Findings in US Clinical Practice Settings

Introduction: Many new treatments and combinations have emerged over the last decade to treat relapsed or refractory multiple myeloma (RRMM). Treatment strategies include doublet and/or triplet combinations from the following classes of agents: immunomodulatory drugs, proteasome inhibitors, and recently approved immuno-oncology agents. Combinations with new agents like pomalidomide, carfilzomib, ixazomib, elotuzumab, and daratumumab have demonstrated improved survival in RRMM in clinical trials, specifically with continued treatment until disease progression, with an acceptable safety profile (Lonial S et al. N Engl J Med 2015; Dimopoulos M et al. N Engl J Med 2016; Palumbo A et al. N Engl J Med 2016; Moreau P et al. N Engl J Med 2016; Stewart AK et al. N Engl J Med 2015; Dimopoulos M et al. Blood 2012). Median duration of treatment (DoT) was described in the literature as 12.4 wk for pomalidomide plus low-dose dexamethasone, 68 wk for ixazomib plus lenalidomide/dexamethasone, 74 wk for elotuzumab plus lenalidomide/dexamethasone, and 88 wk for carfilzomib plus lenalidomide/dexamethasone (Lonial S et al. N Engl J Med 2015; Moreau P et al. N Engl J Med 2016; Stewart AK et al. N Engl J Med 2015; Dimopoulos M et al. Blood 2012). The actual DoT of these agents in clinical practice settings is not known and it is unclear if DoT is affected by safety concerns and/or might have an impact on patient (pt) outcomes. Here we provide real-world evidence of DoT and time to next therapy (TTNT) with each of these agents in an attempt to understand their potential for durability of response and tolerability.Methods: Analysis was conducted using the Explorys electronic medical records US database. Pts aged ≥18 y with ≥1 medical record with a diagnosis of MM (International Classification of Diseases [ICD], Ninth Revision, Clinical Modification diagnosis codes: 203.0x; ICD-10 codes: C90.0x) any time from January 1, 2010, preceded by ≥12 mo (baseline period) without a diagnosis of MM, were identified and followed longitudinally from their index diagnosis date (index date) through the course of available follow-up. A line of therapy (LoT) was defined as a drug/drug combination taken within a 28-d period from initiation of treatment course and ended upon cessation of those drugs, or at initiation of a drug not part of the current LoT. Pts with RRMM were identified as those who had ≥1 prior LoT. Demographic and baseline characteristics were analyzed using descriptive statistics. Distribution of treatment regimens in each LoT are reported; treatment cohorts are not mutually exclusive and LoTs containing multiple drugs are included in respective cohorts. Median DoT in each LoT and TTNT were estimated using descriptive and Kaplan-Meier analyses.Results: 1745 LoTs were identified for 854 pts with RRMM (median age 66 y; 51% male; 37% had hypertension; 10% had chronic pulmonary disease at baseline). LoTs comprised pomalidomide (n=567 [32%]), carfilzomib (n=609 [35%]), ixazomib (n=172 [10%]), elotuzumab (n=76 [4%]), and daratumumab (n=321 [18%]). These agents were mostly used in later LoTs (mean number of prior LoTs, 3.7). Median (IQR) follow-up from index date was 39.4 mo (25.5-56.4) for these pts. Baseline characteristics were similar across treatment cohorts, although pts receiving ixazomib and carfilzomib presented with higher rates of hypertension and chronic pulmonary disease at baseline (Table). Mean/median DoT for pts with a second line (2L) of treatment and pts with ≥2L was longest for elotuzumab (8.7/4.4 mo and 5.3/2.7 mo, respectively). Kaplan-Meier estimates supported these findings (Table). Mean/median TTNT for pts with 2L or ≥2L was longest for elotuzumab (2L: 9.6/6.5 mo; ≥2L: 6.1/3.7 mo) and carfilzomib (2L: 8.7/6.2 mo; ≥2L: 7.3/4.7 mo).Conclusions: Real-world evidence indicates that the new agents for RRMM-pomalidomide, carfilzomib, ixazomib, elotuzumab, and daratumumab-are used in later LoTs. DoT in clinical practice may be shorter than that reported in clinical trials. Rates of remaining on treatment were highest among pts treated with elotuzumab, suggesting that the longest durability of response observed with this immuno-oncology agent may be accompanied by acceptable tolerability despite longer exposure to treatment. Additional analyses and follow-up will determine whether longer DoT improves clinical outcomes.Study support: Bristol-Myers Squibb. [Display omitted] DisclosuresPotluri:SmartAnalyst Inc.: Employment; Janssen: Consultancy, Research Funding. Kanakamedala:SmartAnalyst Inc.: Employment. Chen:Bristol-Myers Squibb: Employment. Yasenchak:Bristol-Myers Squibb: Consultancy; Seattle Genetics: Consultancy. Ranjan:SmartAnalyst India Pvt. Ltd: Employment. Papademetriou:SmartAnalyst Inc.: Employment. Bhandari:SmartAnalyst India Pvt. Ltd: Employment. Mann:SmartAnalyst India Pvt. Ltd: Employment. Davis:Bristol-Myers Squibb: Employment.

Exposure to anesthesia is not associated with development of α-synucleinopathies: A nested case-control study

IntroductionPreclinical studies suggest that inhalational anesthetics may induce neuropathology changes in the nigrostriatal system, leading to development of α-synucleinopathies. We explored the role of general anesthesia in the development of Parkinson disease (PD) and other α-synucleinopathies. MethodsAll α-synucleinopathy cases in Olmsted County, Minnesota, from January 1991, to December 2010, were identified from diagnostic codes, and then reviewed for type and index date of diagnosis. Cases were matched by sex and age (±1 year) to a referent control, a resident living in Olmsted County, and free of α-synucleinopathies before the index date (year of onset of the α-synucleinopathy). Medical records of both cases and controls were reviewed for lifetime exposure to anesthesia prior to the index date. ResultsA total of 431 cases with clinically defined α-synucleinopathies were identified. Of these, 321 (74%) underwent 1,069 procedures under anesthesia before the diagnosis date, and in the control group, 341 (79%) underwent 986 procedures. When assessed as a dichotomous variable, anesthetic exposure was not significantly associated with α-synucleinopathies (odds ratio [OR], 0.75; 95% CI, 0.54-1.05; P=.094). No association was observed when anesthetic exposure was quantified by the number of exposures (OR, 0.64, 0.89, and 0.74, for 1, 2–3, and ≥4 exposures, respectively, compared to no exposure as the reference; P=.137) or quantified by the cumulative duration of exposure assessed as a continuous variable (OR, 1.00; 95% CI, 0.97-1.02 per 1-h increase of anesthetic exposure; P=.776). ConclusionsWe did not observe a significant association between exposure to general anesthesia and risk for the development of α-synucleinopathies.

Use of anti-TNF-α therapy in Crohn's disease is associated with increased incidence of multiple sclerosis

ObjectiveWe investigated if anti-tumor necrosis factor-α (anti-TNF-α) drugs used in the treatment of inflammatory bowel disease (IBD) alter the incidence of MS and if so, to understand the magnitude of such an effect. MethodsThis is a retrospective cohort study of data from Truven Health Market Scan administrative claims database. The patients included in the study had to be ≥ 18 years of age. The presence of IBD was based on at least 2 claims of International Classification of Diseases (ICD-9 or 10) diagnosis codes. The IBD diagnosis index date had to precede the MS diagnosis index date for inclusion in the study. The diagnosis of multiple sclerosis (MS) was defined as having at least 2 claims for the disease (ICD 9, 340 and ICD 10 codes, G35) and at least one prescription claim for any of the drugs that were defined as MS therapy. ResultsPatients with IBD had 1.32 times the risk of MS incidence compared to healthy controls (adjusted incidence rate ratio (IRR): 1.32; 95% CI: 1.03 – 1.71; p = .0312). Patients with IBD exposed to anti-TNF-α therapies had a 43% increase in the incidence of MS compared to those with IBD without exposure (adjusted incidence rate: 1.43; 95% CI: .062 – 3.32; p = .3989). Among CD patients treated anti-TNF-α medications an increase in the incidence of MS, compared to CD patients not exposed to such medications was observed (IRR = 2.62; 95% CI: 1.00 to 6.83; p = 0.049), statistically significant. After adjusting for age/gender, patients with CD using anti-TNF-α agents had an increase of incidence in MS (adjusted IRR: 2.24; 95% CI: 0.85 – 5.94; p = .1035) but it was not statistically significant. ConclusionsUse of anti-TNF-α drugs in CD was associated with a statistically significant increase in the incidence of MS but this effect was lost when controlled for age/gender.

Roles of Postdiagnosis Accumulation of Morbidities and Lifestyle Changes in Excess Total and Cause-Specific Mortality Risk in Rheumatoid Arthritis.

To elucidate how postdiagnosis multimorbidity and lifestyle changes contribute to the excess mortality of rheumatoid arthritis (RA). We performed a matched cohort study among women in the Nurses' Health Study (1976-2018). We identified women with incident RA and matched each by age and year to 10 non-RA comparators at the RA diagnosis index date. Specific causes of death were ascertained via death certificates and medical record review. Lifestyle and morbidity factors were reported biennially; 61 chronic conditions were combined into the Multimorbidity Weighted Index (MWI). After adjusting for baseline confounders, we used inverse probability weighting analysis to examine the mediating influence of postindex MWI scores and lifestyle factors on total, cardiovascular, and respiratory mortality, comparing women with RA to their matched comparators. We identified 1,007 patients with incident RA and matched them to 10,070 non-RA comparators. After adjusting for preindex confounders, we found that hazard ratios (HRs) and 95% confidence intervals (95% CIs) were higher for total mortality (HR 1.46 [95% CI 1.32, 1.62]), as well as cardiovascular (HR 1.54 [95% CI 1.22, 1.94]) and respiratory (HR 2.75 [95% CI 2.05, 3.71]) mortality in patients with RA compared to non-RA comparators. Adjusting for postindex lifestyle factors (physical activity, body mass index, diet, smoking) attenuated but did not substantially account for this excess RA mortality. After additional adjustment for postindex MWI scores, patients with RA had HRs of 1.18 (95% CI 1.05, 1.32) for total, 1.19 (95% CI 0.94, 1.51) for cardiovascular, and 1.93 (95% CI 1.42, 2.62) for respiratory mortality. We found that MWI scores substantially accounted for the excess total and cardiovascular mortality among women with RA. This finding underscores the importance of monitoring for the total disease burden as a whole in monitoring patients with RA.

Real-World Treatment Patterns in Patients with Light Chain (AL) Amyloidosis: Analysis of the Optum US Electronic Health Records and Commercial Claims Database

Real-World Treatment Patterns in Patients with Light Chain (AL) Amyloidosis: Analysis of the Optum US Electronic Health Records and Commercial Claims Database

A Longitudinal Population Level Analysis of Healthcare Resource Utilization, Comorbidity, and Survival in Idiopathic Multicentric Castleman Disease Patients

BACKGROUND: Human herpesvirus-8-negative/idiopathic multicentric Castleman disease (iMCD) is a heterogenous group of diseases characterized by proinflammatory hypercytokinemic state with a wide range of systemic manifestations ranging from generalized lymphadenopathy to death in severe cases. Limited data has shown an increased prevalence of organ dysfunction and cancers in iMCD patients either as a result of underlying disease pathophysiology or treatment received. The objective of this study was to assess the healthcare resource utilization, patterns of iMCD-related comorbidities, and survival of iMCD patients in a real-world setting. METHODS: We performed a retrospective analysis of administrative claims data for >30 million United States patients continuously enrolled over a three-year study period from January 1, 2017 and December 31, 2019. Patients were identified as iMCD if they had an ICD-10 diagnosis code for Castleman disease (D47.Z2) and ≥2 diagnostic codes corresponding to the minor criteria from the international evidence-based consensus diagnostic criteria for iMCD. Exclusion criteria included history of HIV, HHV-8, lymphoma, myeloma, lupus, or rheumatoid arthritis within one year of diagnosis of Castleman disease. Index diagnosis date (IDD) was defined as the first time a patient received a diagnosis for Castleman disease using the new ICD-10 code (D47.Z2) or the general code for lymphadenopathy (785.6) in ICD-9 that included Castleman disease, whichever was diagnosed first between 2006 and 2019. Included patients were followed for up to 5 years from IDD and evaluated for post-diagnosis hospitalizations, emergency room visits, hematologic malignancies, non-hematologic malignancies, thromboses, and organ dysfunction. Estimated average survival was calculated based on estimated incidence and prevalence rates for the iMCD patient population, assuming a stable incidence. RESULTS: We identified 191 iMCD patients including 109 women (57%) and 82 men (43%) with a mean age of 51 years (range: 6 - 90). The average post-diagnosis follow up was 3.2 years after IDD (range: 0.3 - 14.1). Within the first year of iMCD diagnosis, 58.9% of patients required inpatient hospitalization and 53.4% had at least one emergency room visit. Among the patients who remained enrolled after the first year, an average of 25.1% were hospitalized and 36.1% visited the emergency room during each subsequent year (Table 1). The annual rate of hospitalizations and emergency room visits for the entire database of >30 million patients was 9.0% and 20.6%, respectively. As shown in Table 2, the annual prevalence of iMCD-related comorbidities in this cohort was 18.2% for non-hematologic malignancies, 6.3% for hematologic malignancies (including lymphomas and myelomas from second year follow up onwards), 5.8% for thromboses, 5.7% for renal failure, and 5.2% for respiratory failure. Based on an average annual incidence of 2.45 (95% CI, 0.85 - 8.60) per million and average prevalence of 6.31 (95% CI, 3.25 - 13.05) per million, we estimated an average survival of 2.57 (95% CI, 1.59 - 4.25) years after diagnosis in this study time period. DISCUSSION: Using a large nationally representative health claims database, we identified a cohort of iMCD patients and found a high rate of hospitalizations and emergency room visits in the first five years following diagnosis. The annual prevalence of iMCD-related organ failure was approximately 5-6% primarily involving renal and respiratory systems. This study provides further evidence to support the previously reported increase in frequency of subsequent hematologic and non-hematologic malignancies in iMCD patients. In the five-year follow up period, the average estimated survival of iMCD patients was 2.57 (95% CI, 1.59 - 4.25) years after diagnosis, which is shorter than previously published average survival durations based on academic medical centers. The worse survival in this cohort may represent iMCD survival outside of academic medical centers or may reflect inaccuracies in estimated incidence and prevalence which were used to estimate average survival. Further studies are needed to compare outcomes to age-matched controls and to determine whether these adverse outcomes are broadly seen across iMCD patients or instead attributable to a smaller subset of more severe cases. Disclosures Mukherjee: Bristol Myers Squib: Honoraria; Partnership for Health Analytic Research, LLC (PHAR, LLC): Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Aplastic Anemia and MDS International Foundation: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; EUSA Pharma: Consultancy; Celgene/Acceleron: Membership on an entity's Board of Directors or advisory committees. Martin:EUSA Pharma: Current Employment. Sande:EUSA Pharma: Current Employment. Glen:HVH Precision Analytics: Current Employment. Paige:HVH Precision Analytics: Consultancy. Yarlagadda:HVH Precision Analytics: Current Employment. Fajgenbaum:EUSA Pharma: Research Funding; Janssen Pharmaceuticals: Research Funding.

Increased socioeconomic burden in patients with primary progressive multiple sclerosis: A Danish nationwide population-based study

BackgroundPrimary progressive multiple sclerosis (PPMS) is characterized by development of more chronic neurological manifestations from disease onset compared with relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) but the following socioeconomic consequences have never been described in a nation-wide patient population. ObjectiveTo determine if socioeconomic burden of PPMS is increased compared with RRMS and SPMS. MethodsWe included patients from The Danish Multiple Sclerosis Registry diagnosed between 1998 and 2015. Yearly average health costs, public transfers and earned income was calculated from the index diagnosis date, and each year in a five-year period before and after index diagnosis date, for the three patient groups. A regression model estimating the odds ratio (OR) with PPMS as the comparator, was used to analyze the differences between PPMS vs. RRMS and PPMS vs. SPMS controlling for age and sex. ResultsIn total, 9563 MS patients were identified (1998–2015), with a characteristic distribution between different disease courses: 7012 patients with RRMS (73%), 1099 patients with PPMS (11%) and 1452 patients with SPMS (15%). Total health costs were lower in RRMS vs. PPMS (OR 0.76; 95% CI 0.74–0.78; p<0.0001) but not in SPMS vs. PPMS (OR 1.06; 95% CI 1.03–1.09; p<0.0001). Especially homecare costs were lower in RRMS vs. PPMS (OR 0.17; 95% CI 0.17–0.18; p<0.0001), less pronounced in SPMS vs. PPMS (OR 0.93; 95% CI 0.90–0.97; p = 0.0001). OR for health costs before and after diagnosis was significantly lower in RRMS vs. PPMS regarding most variables, less pronounced in SPMS vs. PPMS. ConclusionThis nation-wide population-based study show that socioeconomic burden is significantly higher in PPMS relative to RRMS, but less pronounced compared with SPMS.

Hospitalization costs and risk of mortality in adults with nonalcoholic steatohepatitis: Analysis of a French national hospital database.

BackgroundNonalcoholic fatty liver disease (NAFLD) has reached high prevalence, paralleling the obesity pandemic. The aggressive form of the disease, nonalcoholic steatohepatitis (NASH), is characterized by fatty infiltration and inflammation of the liver, can progress to compensated cirrhosis (CC) and end-stage liver disease (ESLD: decompensated cirrhosis [DCC] and hepatocellular carcinoma [HCC]), and may ultimately require liver transplantation (LT). Real-world data on the burden of NAFLD/NASH are limited. This study aimed to evaluate the clinical and economic burden of NAFLD/NASH to the French hospital system.MethodsThis retrospective cohort study used data from the French PMSI-MCO database. Adults with NAFLD/NASH diagnosis identified between 2009 and 2015 were categorized into disease severity cohorts (NAFLD/NASH, CC, DCC, HCC, and LT). Demographic and clinical data were assessed at the index (diagnosis) date. Hospitalization resource utilization and costs were assessed in the pre- and post-index periods. Rates of liver disease progression and death were evaluated for each cohort.FindingsDuring the median follow-up of 34.8 months, of the 131,656 patients included, 1491 patients developed CC (1.1%), 7846 developed DCC (5.9%), 1144 developed HCC (0.9%), and 52 required LT (0.04%). The diagnosis of NAFLD/NASH was associated with increasing annual costs: €7736 vs €5076 before the diagnosis. Rates of comorbidities, hospitalization resource utilization, and costs increased with disease progression. The rate of death at seven-year follow-up was 7.9% in NAFLD/NASH, CC: 18.0%, DCC: 34.9%, and HCC: 48.8%.InterpretationNAFLD/NASH is associated with high economic burden and imparts substantial risk of negative clinical outcomes and mortality at all stages of disease.

Associations between Medication Assisted Therapy Services Delivery and Mortality in a National Cohort of Veterans with Posttraumatic Stress Disorder and Opioid Use Disorder

Objective: Opioid use disorder (OUD) is a notable concern in the United States (US) and strongly associated with mortality. There is a high prevalence of OUD in patients with posttraumatic stress disorder (PTSD) and the mortality associated with OUD may be exacerbated in patients with PTSD. Medication-assisted treatment (MAT) for OUD has become standard of care for OUD and has been shown to reduce mortality. However, there has been little study of MAT and mortality in patients with PTSD and OUD. Methods: We conducted a retrospective cohort study in U.S. veterans who had newly engaged in PTSD treatment, were diagnosed with OUD and were provided MAT for at least one day between 2004 and 2013. We assessed mortality for one year following the index diagnosis date. We calculated all-cause mortality as well as death by external cause, overdose plus suicide, overdose, and suicide rates per 100,000. We used hazard ratios (HR) and 95% confidence intervals (CI) to compare death rates between patients with high versus low adherence to MAT. We evaluated the impact of high versus low exposure to general substance abuse care. We considered a confidence interval that did not cross one to be significant. Results: A total of 5,901 patients met inclusion criteria. Most patients were men and the average age was 43.3 years (SD = 13.8). The all-cause mortality rate was 1,370 per 100,000 patients. High adherence to MAT resulted in a non-significant, decreased risk for death due to all-cause (HR = 0.73, 95% CI [0.47, 1.13]), external cause (HR = 0.71, 95% CI [0.38, 1.35]), and overdose or suicide (HR = 0.66, 95% CI [0.33, 1.35]). Patients with high exposure (≥ 60 days) to general substance abuse care were significantly less likely to die due to external cause (HR = 0.39, 95% CI [0.18, 0.85]) and overdose or suicide (HR = 0.31, 95% CI [0.12, 0.77]). Conclusions: In patients with PTSD and OUD, improved adherence to MAT and greater exposure to general substance abuse care may result in lower mortality. Studies with longer follow-up and larger sample sizes to assess the impact of MAT on suicide are needed to confirm our findings.

Survival, Chemotherapy Treatments, and Health Care Utilization Among Patients with Advanced Small Cell Lung Cancer: An Observational Study.

Most cases of small cell lung cancer (SCLC) are diagnosed at an advanced stage. The objective of this study was to investigate patient characteristics, survival, chemotherapy treatments, and health care use after a diagnosis of advanced SCLC in subjects enrolled in a health system network. This was a retrospective cohort study of patients aged ≥ 18years who either were diagnosed with stage III/IV SCLC or who progressed to advanced SCLC during the study period (2005-2015). Patients identified from the Indiana State Cancer Registry and the Indiana Network for Patient Care were followed from their advanced diagnosis index date until the earliest date of the last visit, death, or the end of the study period. Patient characteristics, survival, chemotherapy regimens, associated health care visits, and durations of treatment were reported. Time-to-event analyses were performed using the Kaplan-Meier method. A total of 498 patients with advanced SCLC were identified, of whom 429 were newly diagnosed with advanced disease and 69 progressed to advanced disease during the study period. Median survival from the index diagnosis date was 13.2months. First-line (1L) chemotherapy was received by 464 (93.2%) patients, most commonly carboplatin/etoposide, received by 213 (45.9%) patients, followed by cisplatin/etoposide (20.7%). Ninety-five (20.5%) patients progressed to second-line (2L) chemotherapy, where topotecan monotherapy (20.0%) was the most common regimen, followed by carboplatin/etoposide (14.7%). Median survival was 10.1months from 1L initiation and 7.7months from 2L initiation. Patients in a regional health system network diagnosed with advanced SCLC were treated with chemotherapy regimens similar to those in earlier reports based on SEER-Medicare data. Survival of patients with advanced SCLC was poor, illustrating the lack of progress over several decades in the treatment of this lethal disease and highlighting the need for improved treatments.

Frequency of Thrombosis Is Higher in MPN Patients Who Develop Second Cancer Than in Controls

Frequency of Thrombosis Is Higher in MPN Patients Who Develop Second Cancer Than in Controls

Guideline Discordance and Patient Cost Responsibility in Medicare Beneficiaries With Metastatic Breast Cancer.

Treatment for metastatic breast cancer (MBC) that is not concordant with the NCCN Guidelines for Breast Cancer has been associated with higher healthcare utilization and payer costs. However, a significant knowledge gap exists regarding the impact of guideline-discordant care on patient cost responsibility. This study examined this question among patients with MBC in the year postdiagnosis. This retrospective cohort study used data from the SEER-Medicare linked database from 2000 through 2013. Guideline discordance, defined by year-specific NCCN Guidelines, was assessed for first-line antineoplastic treatment and grouped into discrete categories. Patient cost responsibility (deductibles, coinsurance, copayments) in women with MBC were summed for all medical care received in the year postdiagnosis. The difference in patient cost responsibility by guideline discordance status was estimated using linear mixed-effect models. Of 3,709 patients with MBC surviving at least 1 year postdiagnosis, 17.6% (n=651) received guideline-discordant treatment. Median cost responsibility in the year postdiagnosis for patients receiving guideline-discordant treatment was $7,421 (interquartile range [IQR], $4,359-$12,983) versus $5,171 (IQR, $3,006-$8,483) for those receiving guideline-concordant care. In adjusted models, guideline-discordant treatment was significantly associated with $1,841 higher patient costs in the first year from index diagnosis date (95% CI, $1,280-$2,401) compared with guideline-concordant care. Patient cost responsibility differed by category of guideline discordance, with those receiving nonapproved bevacizumab having the highest cost responsibility (β=$3,330; 95% CI, $1,711-$4,948). Deviations from current treatment guidelines may have implications on patient healthcare cost responsibility. Additional research is needed to fully understand the mechanisms underlying how guideline deviation leads to greater costs for patients with MBC.

The risk of incident extrahepatic cancers is higher in non-alcoholic fatty liver disease than obesity – A longitudinal cohort study

Cancer is a major cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Obesity is a risk factor for cancers; however, the role of NAFLD in this association is unknown. We investigated the effect of NAFLD versus obesity on incident cancers. We identified all incident cases of NAFLD in a US population between 1997-2016. Individuals with NAFLD were matched by age and sex to referent individuals from the same population (1:3) on the index diagnosis date. We ascertained the incidence of cancer after index date until death, loss to follow-up or study end. NAFLD and cancer were defined using a code-based algorithm with high validity and tested by medical record review. The association between NAFLD or obesity and cancer risk was examined using Poisson regression. A total of 4,722 individuals with NAFLD (median age 54, 46% male) and 14,441 age- and sex-matched referent individuals were followed for a median of 8 (range 1-21) years, during which 2,224 incident cancers occurred. NAFLD was associated with 90% higher risk of malignancy: incidence rate ratio (IRR) = 1.9 (95% CI 1.3-2.7). The highest risk increase was noted in liver cancer, IRR = 2.8 (95% CI 1.6-5.1), followed by uterine IRR = 2.3 (95% CI 1.4-4.1), stomach IRR = 2.3 (95% CI 1.3-4.1), pancreas IRR = 2.0 (95% CI 1.2-3.3) and colon cancer IRR = 1.8 (95% CI 1.1-2.8). In reference to non-obese controls, NAFLD was associated with a higher risk of incident cancers (IRR = 2.0, 95% CI 1.5-2.9), while obesity alone was not (IRR = 1.0, 95% CI 0.8-1.4). NAFLD was associated with increased cancer risk, particularity of gastrointestinal types. In the absence of NAFLD, the association between obesity and cancer risk is small, suggesting that NAFLD may be a mediator of the obesity-cancer association. We studied the incidence of malignancies in a community cohort of adults with non-alcoholic fatty liver disease (NAFLD) in reference to age- and sex-matched adults without NAFLD. After 21 years of longitudinal follow-up, NAFLD was associated with a nearly 2-fold increase in the risk of developing cancers, predominantly of the liver, gastrointestinal tract and uterus. The association with increased cancer risk was stronger in NAFLD than obesity.

The usefulness of symptoms alone or combined for general practitioners in considering the diagnosis of a brain tumour: a case-control study using the clinical practice research database (CPRD) (2000-2014)

ObjectivesTo evaluate the utility of different symptoms, alone or combined, presented to primary care for an adult brain tumour diagnosis.Design and settingMatched case-control study, using the data from Clinical Practice...

Bidirectional association between migraine and fibromyalgia: retrospective cohort analyses of two populations

ObjectiveFibromyalgia (FM) and migraine are common pain disorders that tend to coexist. This study determined whether these two conditions exhibited any mutual influences.SettingCohort study.ParticipantsA retrospective, longitudinal cohort study was conducted...

Mean treatment cost of incident cases of penile cancer for privately insured patients in the United States

PurposeThe aims of this study were to estimate the short-term cost of treating newly diagnosed penile cancer and determine the correlates of penile cancer treatment cost in the United States. MethodsThe Truven MarketScan database was used to identify commercially insured patients with penile cancer newly diagnosed during 2011 to 2014. A control group without HPV-related cancer diagnosis was selected by matching to the case group by the propensity score method. Total healthcare costs in the 2 years after the cancer diagnosis index date were measured for each patient. The mean difference between case and control groups was considered the cancer-related cost. For patients without complete 2-year data, a generalized linear regression was performed to predict cost for censored months and identify predictors associated with monthly cost. ResultsA total of 250 patients with newly diagnosed penile cancer and 250 matched controls were included in the study. The adjusted mean differential healthcare cost for penile cancer was $76,404 in the first 2 years. For the penile cancer group, cost peaked in month 1 at $10,202 and dropped substantially each month thereafter until month 7, when the cost was $4,295. After month 7, the monthly cost remained steady at $2,700 to $4,200. ConclusionsThe estimated average cost of penile cancer for insured patients in the United States was about $76,000 in the first 2 years after diagnosis. Monthly cost was directly related to age, length of follow-up, comorbidity score, and prediagnosis cost.

Validating Self-reported Chronic Conditions in Alberta’s Tomorrow Project Cohort: Data Linkage to Administrative Healthcare Data

IntroductionAlberta’s Tomorrow Project (ATP) is a province-wide cohort study of cancer and chronic diseases in Canada. Approximately 55,000 Albertans aged 35-69 years with no history of cancer, other than non-melanoma skin cancer, had joined the ATP. Nearly all (&gt;96%) ATP participants consented to data linkage to administrative healthcare databases.&#x0D; Objectives and ApproachTo validate chronic conditions self-reported by the ATP participants, individual-level data of a total of 52,851 ATP participants were linked to Alberta Health (AH) administrative datasets using Personal Health Number. Cases of chronic conditions, including diabetes, cardiovascular diseases and gastrointestinal disorders, were identified by algorithms for disease diagnosis using International Classification of Diseases (ICD) codes in administrative healthcare data. Cases were identified as “prevalent” if the index date of diagnosis was before or within 6 months of ATP enrollment date. Self-reported chronic conditions were validated by the cases identified as “prevalent” using the linked AH datasets.&#x0D; ResultsAmong the ATP cohort, 804 participants self-reported ever being diagnosed with myocardial infarction (MI), 451 with stroke, 2,907 with diabetes, 566 with ulcerative colitis, 362 with Crohn’s disease and 112 with liver cirrhosis before or at the time of ATP enrollment. Using the linked AH administrative data, 339 participants were identified as prevalent cases with MI, 200 with stroke, 2,702 with diabetes, 208 with ulcerative colitis, 283 with Crohn’s disease and 55 with liver cirrhosis. The sensitivity and specificity of self-reporting having chronic conditions by the ATP participants were 71.1% and 97.0% for MI, 44.4% and 99.3% for stroke, 78.1% and 98.4% for diabetes, 73.6% and 99.2% for ulcerative colitis, 65.7% and 99.7% for Crohn’s disease and 50.9% and 99.8% for liver cirrhosis.&#x0D; Conclusion/ImplicationsBy linking with administrative healthcare data, we were able to validate the accuracy of self-reporting chronic conditions in ATP participants. The sensitivity of self-reporting was acceptable for MI, diabetes, ulcerative colitis and Crohn’s disease, but low for stroke and liver cirrhosis. The specificity was high for all chronic conditions.

Cardiovascular hazards of insufficient treatment of depression among patients with known cardiovascular disease: a propensity score adjusted analysis.

The association between depression care adequacy and the risk of subsequent adverse cardiovascular disease (CVD) outcomes among patients with a previous diagnosis of myocardial infarction (MI) or stroke is not well defined. This retrospective cohort study used commercial claims data (2010-2015) and included adults with newly diagnosed and treated major depressive disorder (MDD) following an initial MI or stroke diagnosis. Depression care adequacy was assessed during the 3-month period following the MDD diagnosis index date using two measures: antidepressant dosage adequacy and duration adequacy. Cox models adjusted for the propensity of receiving adequate depression care were used to compare the risk of a composite CVD outcome (MI, stroke, congestive heart failure, and angina) as well as each individual CVD event between patients receiving adequate vs. inadequate depression care. A total of 1568 patients were included in the final cohort. Of these, 937 (59.8%) were categorized as receiving inadequate depression care based on at least one of the two treatment adequacy criteria. Propensity score adjusted Cox models showed that depression care inadequacy was associated with a significantly higher risk of the composite CVD endpoint [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.04-1.39], stroke (HR 1.20, 95% CI 1.02-1.42), and angina (HR 1.95, 95% CI 1.21-3.16) with no significant interaction based on cohort included (MI vs. stroke) or the definition of inadequate depression (dose vs. duration inadequacy) (Pinteraction > 0.05). Inadequate MDD care was associated with a higher risk of adverse CVD events. These findings reveal a significant unmet clinical need in patients with post-MI or post-stroke MDD that may impact CVD outcomes.

Abstract 1191: Differences in time to second primary malignancies: Development among patients with head and neck squamous cell carcinoma

Abstract Purpose: Second primary malignancies (SPMs) are the leading cause of death in survivors of head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC are at increased risk of SPM. This is concerning since the number of survivors among these patients has been increasing. The human papillomavirus (HPV) has emerged as a distinct risk factor for oropharyngeal squamous cell carcinoma, which has different prognosis from classic tobacco/alcohol-associated HNSCC. We assessed the time to development of SPM in a large U.S. cohort of patients with an index HNSCC, comparing potentially-HPV-associated and non-HPV-associated HNSCC. Methods: This was a population-based cohort study of 109,512 patients with HNSCC in the Surveillance, Epidemiology, and End Results registry (2000-2014). HNSCC included were for invasive squamous cell carcinoma per the International Classification of Diseases for Oncology, third edition codes. SPM was defined as the first subsequent primary cancer occurring at least 2 months after first cancer diagnosis. Time to SPM development was calculated as the date of diagnosis of SPM minus 2 months after the index diagnosis date. The main exposure was HPV-relatedness, based on whether patients' first HNSCC was potentially-HPV-associated or non-HPV-associated. Adjusted Cox proportional hazards regression model was used to evaluate the differences in the time to development of SPM and HPV-relatedness, adjusting for age at diagnosis, sex, race, marital status, year of diagnosis of first cancer, stage, grade, and treatment. Results: Among the 109,512 patients with an index HNSCC, 12.3% developed SPM. Median time to SPM development overall was 31 months, for an index potentially-HPV-associated HNSCC patients was 32 months, and for an index non-HPV-associated HNSCC patients was 30 months. Patients diagnosed with an index non-HPV-associated HNSCC had a 36% higher risk of developing SPM (aHR=1.36; 95% CI: 1.38-2.53) compared with those with an index potentially-HPV-associated HNSCC. When sites were broken down further, compared to patients with oropharynx cancer, patients with hypopharynx (aHR=1.63; 95% CI: 1.50-1.77) had the higher risk of developing SPM, followed by oral cavity (aHR=1.40; 95% CI: 1.33-1.47), and larynx (aHR=1.27; 95% CI: 1.21-1.33) cancers. Patients had higher risk of developing SPM if they were 60-69 (aHR=2.49; 95% CI: 2.34-2.66) or ≥70 (aHR=2.82; 95% CI: 2.64-3.02) vs. 18-49 years, male (aHR=1.08; 95% CI: 1.04-1.13), black (aHR=1.23; 95% CI: 1.16-1.30) vs. white, and distant (aHR=1.15; 95% CI: 1.09-1.23) vs. localized tumor. Conclusion: Patients with an index non-HPV-associated-HNSCC were more likely to develop SPM compared to those with potentially-HPV-associated-HNSCC. Health care professionals may consider this during follow-up of patients with HNSCC. Citation Format: Eric Adjei Boakye, Paula Buchanan, Leslie Hinyard, Nosayaba Osazuwa-Peters, Mario Schootman, Jay F. Piccirillo. Differences in time to second primary malignancies: Development among patients with head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1191.

Young-Adult Polycystic Kidney Disease is Associated with Major Cardiovascular Complications.

Background: Patients with polycystic kidney disease (PKD) might have a risk of cardiovascular diseases because several cardiovascular risk factors are occasionally associated with PKD patients. Data on the association between PKD and the risk of cardiovascular events, including acute coronary syndrome (ACS), stroke, and congestive heart failure (CHF), are scant. Methods: Patients aged ≥20 years who were newly diagnosed with PKD (International Classification of Diseases, Ninth Revision, Clinical Modification codes 753.12 and 753.13) between 2000 and 2011 were selected as a PKD cohort (N = 5157). The association between PKD and cardiovascular events was analyzed. Results: We randomly selected a comparison cohort of people without PKD, who were frequency-matched by sex, age, and index date of diagnosis. At the end of 2011, the PKD cohort had a 1.40-fold greater incidence of ACS compared with the comparison cohort (8.59 vs. 6.17 per 1000 person-years), in addition to a 1.40-fold greater incidence of stroke, a 1.49-fold greater incidence of CHF, and a 1.64-fold greater incidence of mortality. Conclusions: This retrospective cohort study shows that patients with PKD have an increased risk of cardiovascular events including ACS, stroke, and CHF as well as mortality, particularly in younger patients. Early identification is necessary to attenuate the risk of cardiovascular complications in patients with PKD.