Days Of Initial Diagnosis Research Articles

ALK testing patterns in early-stage non-small cell lung cancer: A real-world evidence study.

8074 Background: Comprehensive biomarker testing in advanced non-small cell lung cancer (aNSCLC) is standard of care, but disparities exist. As new clinical data emerge in early disease (eNSCLC), the set of actionable lung driver mutations (LDMs) and therefore the testing landscape in that setting will change. In particular, following the results of the ALINA trial, therapies that target ALK fusions are anticipated to become part of routine treatment of eNSCLC in 2024.This study thus sought to identify the factors associated with receipt of timely ALK testing in eNSCLC, prior to this shift. Methods: We retrospectively analyzed patients with resected stage I-IIIa NSCLC diagnosed between 2018-2023 using the expanded nationwide (US-based) de-identified Flatiron Health EHR-derived database; data were consolidated from approximately 280 US cancer clinics (≅800 sites of care), using natural language processing with machine learning (ML) to extract patient characteristics. The primary endpoint was ALK testing results (by any modality) within 90 days of initial diagnosis. We used multivariable logistic regression to assess the association between clinico-demographic characteristics and likelihood of testing. Results: The sample contained 21,982 stage I-IIIa patients. Of these, 6,685 (30%) were tested within 90 days, and 15,297 (70%) were not. Patients were more likely to be tested within 90 days if they were diagnosed in more recent years (2023 vs. 2018 odds ratio (OR) 2.12); had no history of smoking (OR 1.21); had highest socioeconomic status (SES) quintile (OR vs. lowest SES 1.14); had more advanced disease (stage IIIa vs. stage I OR 2.43); or were treated in a community setting (OR vs. academic 1.13), all p < 0.05. Patients with Medicare insurance (OR vs. commercial insurance 0.89, p = 0.014) or squamous histology (OR vs. non-squamous 0.46, p < 0.01) were less likely to be tested. There were no significant differences between black and white patients (OR 0.91, p = 013). Conclusions: In this real-world analysis of patients diagnosed between 2018-2023 most patients did not have testing within 90 days of diagnosis. Our data show variation in the baseline probability of testing with respect to clinico-demographic factors. Given that barriers to testing persist in aNSCLC, this suggests that once ALK inhibitors become part of routine care in eNSCLC, some groups might be less likely to be tested and therefore to receive efficacious targeted treatment. Preemptive measures such as education of patients, providers, payers, and policy makers could help prevent disparities from emerging.

SPOP Mutations as a Predictive Biomarker for Androgen Receptor Axis-Targeted Therapy in De Novo Metastatic Castration-Sensitive Prostate Cancer.

Intensification of androgen deprivation therapy (ADT) with either docetaxel or androgen receptor axis-targeted therapies (ARAT) are the current standard of care for patients with metastatic castration-sensitive prostate cancer (mCSPC). However, biomarkers guiding treatment selection are lacking. We hypothesized that ADT intensification with ARAT, but not with docetaxel, would be associated with improved outcomes in patients with de novo (dn)-mCSPC harboring SPOP mutations. Patient-level data from a deidentified nationwide (U.S.-based) prostate cancer clinico-genomic database between January 2011 and December 2021 were extracted. Eligibility criteria: diagnosis of metastatic disease within 30 days of original prostate cancer diagnosis, genomic profiling of a tissue biopsy collected within 90 days of original diagnosis, and initiation of ARAT or docetaxel within 120 days of initial diagnosis. The log-rank test and Cox proportional hazards models were used to compare time to castration-resistant prostate cancer (TTCRPC) and overall survival (OS) for patients with and without SPOP mutations undergoing ADT intensification with ARAT or docetaxel. In the ARAT cohort, presence of SPOP mutation compared with wild-type was associated with more favorable TTCRPC [not reached (NR) vs. 16.7 months; adjusted HR (aHR), 0.20; 95% confidence interval (CI), 0.06-0.63; P = 0.006] and OS (NR vs. 27.2 months; aHR, 0.19; 95% CI, 0.05-0.79; P = 0.022). In contrast, SPOP mutation status was not associated with TTCRPC or OS in docetaxel-treated cohort. In real-world settings, SPOP mutations were associated with improved outcomes to ADT plus ARAT (but not ADT plus docetaxel) in patients with dn-mCSPC. This may serve as a predictive biomarker to guide treatment selection for patients with mCSPC.

COVID-19 disease severity in US Veterans infected during Omicron and Delta variant predominant periods

The SARS-CoV-2 Omicron variant is thought to cause less severe disease among the general population, but disease severity among at-risk populations is unknown. We performed a retrospective analysis using a matched cohort of United States veterans to compare the disease severity of subjects infected during Omicron and Delta predominant periods within 14 days of initial diagnosis. We identified 22,841 matched pairs for both periods. During the Omicron period, 20,681 (90.5%) veterans had mild, 1308 (5.7%) moderate, and 852 (3.7%) severe disease. During the Delta predominant period, 19,356 (84.7%) had mild, 1467 (6.4%) moderate, and 2018 (8.8%) severe disease. Moderate or severe disease was less likely during the Omicron period and more common among older subjects and those with more comorbidities. Here we show that infection with the Omicron variant is associated with less severe disease than the Delta variant in a high-risk older veteran population, and vaccinations provide protection against severe or critical disease.

Time interval between diagnostic excision-biopsy of a primary melanoma and sentinel node biopsy: effects on the sentinel node positivity rate and survival outcomes

IntroductionThe optimal time interval between diagnostic excision of a primary cutaneous melanoma and sentinel node (SN) biopsy is unknown. The current study sought to determine whether this interval influenced the SN-positivity rate, recurrence or survival. MethodsData collected from 2004 to 2014 for a Dutch population-based cohort of patients with melanoma who underwent SN biopsy (SNB) within 100 days of initial diagnosis (n = 7660) and for a similarly specified cohort from a large Australian melanoma treatment centre (n = 3478) were analysed. Time to SNB was analysed continuously (in weeks) and categorically (per month). The effects of SNB timing on SN-positivity were assessed using multivariable logistic regression, and its effects on recurrence-free survival (RFS) and overall survival (OS) were assessed using Cox proportional hazard regression analyses. Advanced modelling using a multivariable Cox model with penalised splines for modelling the continuous effects of time to SNB on RFS and OS was also performed. ResultsIn neither the Dutch nor the Australian cohort was there a significant association between time to SNB and SN-positivity in either cohort, nor was there an impact of time to SNB on RFS or OS in either cohort. The spline-based HR curves for RFS and OS confirmed these findings. ConclusionsThe time interval between diagnostic excision of a primary melanoma and SNB did not influence the SN-positivity rate or survival outcomes. This provides reassurance that neither early nor delayed definitive wide excision and SNB will adversely affect prognosis.

IMPACT OF TIMING OF INITIATION OF INFLIXIMAB ON THE RISK OF IBD-RELATED SURGERY AND COMPLICATIONS

Abstract BACKGROUND Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal system. Approximately 20% of new diagnoses are pediatric patients. Treatment for pediatric IBD has changed in recent years, focusing on decreased steroid use, and shifting to early initiation of biologics, especially in those at risk for complicated disease. Infliximab (IFX) is used for induction and maintenance. Clinical trials have shown that IFX improves clinical remission rates, and decreases hospitalizations and surgery rates. However, there is conflicting long-term data on whether infliximab has changed the natural course of IBD and decreased surgical risk. OBJECTIVE The objective of our study was to evaluate factors associated with increased risk of surgery in pediatric CD and UC patients using a large national health claims network database. METHODS We used TriNetX database and identified patients up to age 18 years, with a diagnosis of CD or UC (using ICD 9 and 10 codes) and treated with infliximab from January 1, 2006 to October 1, 2020. For each patient, we collected data on demographics profile, medication use, IBD related surgeries, and complications. Patients were then categorized into “early treatment” and “late treatment” groups, with early treatment being those who initiated infliximab therapy within 90 days of IBD diagnosis. The primary outcome was the need for surgery (partial or total colectomy, small intestinal resection and stricturoplasty). Secondary outcome was any IBD related complications (intraabdominal abscess, fistula formation, perianal abscess, fistuloectomy and fistulotomy). RESULTS A total of 7,954 IBD patients met inclusion criteria, of which 5,756 patients had CD, and 2,198 patients had UC. There were 2366 patients who were started on infliximab therapy within 90 days of initial diagnosis and the remaining 5,558 patients were in the late treatment group. A total of 169 (2.1%) patients underwent a major surgery and 560 (7%) patients experienced an IBD-related complication. Multivariate regression analysis did not reveal any significant association between timing of initiation of infliximab therapy and risk of surgery for both CD (OR: 1.12; 95% CI: 0.72 to 1.69, P=0.60) and UC (OR:1.57 ;95% CI: 0.91, 2.67, P=0.09). However, among CD patients, TPN use (OR: 5.45; 95% CI: 1.15 to 18.76, P = 0.014), fistulizing CD (OR: 4.59; 95% CI: 2.73 to 7.49; P <0.0001) and malnutrition (OR: 1.62; 95% CI: 1.02 to 2.47, P = 0.03), were more likely to develop IBD-related complications. There were no significant risk factors associated with greater odds of surgery or IBD-related complications in UC patients. CONCLUSION Late initiation of infliximab therapy was not associated with increased risk of surgery or IBD-related complication compared to early therapy. Prospective studies are needed to further evaluate these findings.

Comparison of the rate of delayed/nonunion in fifth metatarsal fractures receiving anti-inflammatory medications

PurposeControversy exists regarding the acute effect of non-steroidal anti-inflammatory drugs (NSAIDs) on early fracture healing. The purpose of this study was to analyze the rate of nonunion or delayed union in patients with fifth metatarsal (5th MT) fractures. We hypothesize that the use of NSAIDs would increase the rate of nonunion/delayed union in 5th MT fractures.MethodsUsing PearlDiver, a national insurance database was analyzed. ICD codes were used to identify patients diagnosed with 5th MT fracture from 2007-2018. Patients were grouped by initial management (nonoperative vs. open reduction and internal fixation (ORIF) or non/malunion repair within 60 days) and sub-grouped by whether they had been prescribed at least one pre-defined NSAID. Subsequent ORIF or nonunion/malunion repair operative intervention was used as a surrogate for fracture nonunion/delayed union.ResultsOf the 10,991 subjects with a diagnosis of 5th MT, 10,626 (96.7%) underwent initial nonoperative treatment, 1,409 of which (13.3%) received prescription NSAIDS within 60 days of diagnosis. 16/1,409 (1.14%) subjects who received anti-inflammatory prescriptions underwent ORIF or repair of non/malunion at least 60 days after diagnosis while 46/9,217 (0.50%; P=0.003483) subjects who did not receive anti-inflammatory prescriptions underwent ORIF or repair of non/malunion at least 60 days after diagnosis. In the 365 subjects who underwent early repair/ORIF (within 60 days), there was no significant difference in the rate of nonunion/delayed union.ConclusionThe rate of nonunion/delayed union of 5th MT fractures was significantly higher in subjects receiving NSAIDs within 60 days of initial diagnosis in patients managed non-operatively.Level of evidenceLevel III

Physical Therapy and Health Care Utilization for Older Adults With Lumbar Spinal Stenosis.

Lumbar spinal stenosis (LSS) is associated with high health care utilization for older adults. Physical therapy (PT) offers low medical risk and reduced cost burden with functional outcomes that appear to be equivalent to higher risk interventions such as surgery. However, it is unknown whether receipt of PT following incident LSS diagnosis is associated with reduced health care utilization. The objectives of this study were to: (1) compare health characteristics for Medicare beneficiaries who received outpatient PT within 30 days of incident LSS diagnosis to those who did not; (2) compare the 1-year utilization rates for specific health care services for these 2 groups; and (3) quantify the likelihood of progression to specific health services based on the receipt of PT. This was a retrospective cohort study using nationally representative claims data for Medicare Part B beneficiaries between 2007 and 2010. Lumbar spinal stenosis was determined using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Beneficiaries 65 years and older were classified into 2 groups (PT and no PT) based on receipt of PT within 30 days of initial diagnosis. Baseline characteristics were identified at incident diagnosis. Hazard ratios (HRs) were estimated for the risk of receiving health services outcomes including spinal surgery, spinal injections, chiropractic care, advanced imaging, spinal radiographs, opioid medication, nonopioid analgesics, and hospitalizations beginning on day 31 up to 1 year following incident LSS diagnosis. Among 60 646 Medicare beneficiaries with incident LSS who met the inclusion criteria, 1124 were classified in the PT group and 59 522 in the no PT group. Compared with the PT group, beneficiaries in the no PT group had a greater risk of having hospitalizations (HR = 1.40), opioid medications (HR = 1.29), spinal surgery (HR = 1.29), and spinal radiographs (HR = 1.19) within 1 year. Fewer than 2% of Medicare beneficiaries received PT within 30 days of initial LSS diagnosis. Receipt of PT was associated with less utilization of higher risk and costly health services for 1 year. These results may inform practitioners when making early decisions about rehabilitative care for older adults with LSS.

Is time-to-treatment associated with higher mortality in Korean elderly lung cancer patients?

Lung cancer is a leading cause of cancer-related deaths in many countries, including South Korea. As treatment delays after diagnosis may correlate with survival, this study aimed to investigate the association between time-to-treatment and one-and five-year overall mortality in patients aged 60 years or above. Survival analysis using the Cox proportional hazard model were conducted after controlling for all independent variables. Of a total of 1,535 individuals who received surgical treatment due to lung cancer, 837 patients received treatment within 30 days and 698 after 30 days of initial diagnosis. Individuals who received surgical treatment after 30 days of diagnosis were more likely to die within 1-year (Hazard Ratio, HR: 1.15, 95% Confidence Interval, CI: 1.01-1.32) and 5-year (HR: 1.16, 95% CI: 1.02-1.33) compared to those who received treatment within 30 days. The increase in mortality risk with time delay persisted when applying other cut-off times, including standards at 2, 3, and 6 months. We also found that the mortality rate of lung cancer patients differs depending on age (74 years or younger), household income (<80 percentile), patient severity, and the residing region. Our findings show that time delay is an important factor that can influence the outcome of lung cancer patients, highlighting the importance of monitoring and providing appropriate and timely treatment.

Factors Associated With Breast Cancer Surgery Delay Within a Coordinated Multihospital Community Health System: When Does Surgical Delay Impact Outcome?

BackgroundMultiple factors influence the time elapsed between diagnosis of breast cancer and surgical extirpation of the primary tumor. The disease-free interval between resection of primary breast cancer and first evidence of recurrence is predictive of mortality. We aimed to determine patient, disease, and treatment factors associated with a delay in time to surgery (TTS) and identify the point when prolonged TTS negatively impacts disease-free survival. Patients and MethodsCancer registry and electronic medical record data for patients with breast cancer who underwent surgery as first course of treatment during 2006–2016 were retrospectively reviewed. Patients undergoing surgery in ≤30 vs. 31–60 vs. >60 days of initial diagnosis were compared. Kaplan–Meier survival analyses with Cox proportional hazards were performed to evaluate impact of time from breast cancer diagnosis to definitive therapeutic surgery on breast cancer recurrence or death (all-cause). ResultsOverall, 4462 patients were analyzed, 43.4% of whom underwent surgery beyond 30 days. The following factors were associated with TTS >30 days: age <50, non-Hispanic White race/ethnicity, commercial or health exchange/Medicaid insurance, diagnosis of noninvasive disease (i.e., ductal carcinoma in situ), had breast magnetic resonance imaging before definitive surgery, underwent total mastectomy (especially if immediate reconstruction, particularly if autologous, was performed), and did not receive adjuvant therapies (P < .001 for all). After adjusting for relevant variables, significant predictors of recurrence/death included a TTS >60 days, increased patient age, higher breast cancer stage, and triple-negative biomarker expression. ConclusionRisk of recurrence or death is not compromised until TTS exceeds 60 days after initial breast cancer diagnosis.

Early-onset colorectal cancer in younger patients: A population-based study.

124 Background: In the US, the incidence of colorectal cancer (CRC) is increasing in patients younger than 50 years who may present with advanced stage, high grade, left-sided colon or rectal cancers with signet ring cell histopathology, aggressive clinical course, and reduced overall survival. Understanding the characteristics of this population could inform screening, early detection, and optimal treatment. In this study, we describe the attributes of adults who are 50 years and younger with a first diagnosis of CRC and ascertain molecular testing rates and time to surgery by using data from a commercially insured cohort in the U.S. Methods: This retrospective study of patients ages 50 and younger with a first diagnosis of CRC utilizes the IBM MarketScan database, and focuses on claims from January 2013 to December 2018. Included patients had continuous insurance enrollment of 12 months before and 6 months after diagnosis. We determined rates of tumor testing for microsatellite instability (MSI) or immunohistochemistry (IHC) for mismatch repair (MMR) proteins and referral to genetic services in all patients, as well as mutational analysis of KRAS, NRAS, and BRAF in metastatic CRC patients. Time to surgical resection of primary tumor (TTS) in non-metastatic colon cancer patients was measured. Results: During the 5-year period, 10,577 patients ages 18 to 50 years had a first diagnosis of CRC, which was 15.6% of the 67,921 adults of all ages with CRC. Claims for MSI or IHC for MMR proteins within 120 days of initial diagnosis were done in 4,429 (41.9%) patients and referral to genetics services/counseling within 1 year of initial diagnosis were done in 443 (4.1%) patients. Among metastatic CRC patients, KRAS, NRAS, or BRAF tumor mutational analyses within 120 days of initial diagnosis were documented in 323 (31.5%). The median TTS ranged from 7 to 15 days with no statistically significant differences based on geographic region or health insurance plan type. Conclusions: Younger patients with early onset CRC had low rates of referral to genetics services, tumor MSI or IHC for MMR proteins testing, and KRAS, NRAS, and BRAF mutational analysis. There were no geographic or insurance type trends in TTS in non-metastatic colon cancer patients. Although underreporting is possible in our study, the findings of low utilization of genetic services and tumor genomic testing in these younger patients with early onset CRC should alert the oncology community to critical management gaps in the care of this population.

Epidemiological characteristics of imported malaria cases in Fujian Province from 2014 to 2018

To analyze the epidemiological characteristics of imported malaria cases in Fujian Province from 2014 to 2018, so as to provide scientific basis for the development of the control strategy for imported malaria. The epidemiological data of malaria cases in Fujian Province from 2014 to 2018 were retrieved from the Notifiable Disease Reporting System and Parasitic Disease Information Reporting System of Chinese Center for Disease Control and Prevention, and the classification, origin of infections, temporal distribution, spatial distribution, population distribution, reporting institutions and diagnosis were analyzed. A total of 540 overseas imported malaria cases were reported in Fujian Province from 2014 to 2018, and all cases were laboratory-confirmed, including 398 cases with falciparum malaria, 88 cases with vivax malaria, 38 cases with ovale malaria, 14 cases with malariae malaria and 2 cases with mixed infections. There were 90.56% (489/540) of the imported malaria cases with infections in 27 African countries, 5.92% (32/540) with infections in 5 Asian countries and 3.52% (19/540) with infections in one Oceania country. There was no significant seasonal distribution of the cases, and the imported malaria cases were predominantly detected in Fuzhou City (80.00%, 432/540) and at ages of 20 to 49 years (81.48%, 440/540). Initial diagnosis was predominantly at the city-level medical institutions, and 77.96% (421/540) were diagnosed as malaria at the initial diagnosis institutions. The median duration from onset to initial diagnosis was 2 days and 70.19% (379/540) were diagnosed within 3 days of onset. The interval between initial diagnosis and definitive diagnosis was 0 day, with 85.37% (461/540) definitively diagnosed within 3 days of initial diagnosis. Overseas imported malaria is a continuous problem challenging the malaria elimination programme of Fujian Province. Improving the healthcare-seeking awareness and the diagnostic capability of healthcare workers, and intensifying the monitoring and management of malaria among overseas labors are strongly recommended.

EP1.12-06 New Treatment Option for ES-SCLC: Patient Characteristics and Use of an Atezolizumab Regimen in the Real-World Setting

Results from the Phase III IMpower133 study (NCT02763579) were previously made public. Based on improvements in overall survival in patients with extensive-stage small cell lung cancer (ES-SCLC) who received atezolizumab plus carboplatin and etoposide (IMpower133 regimen) vs chemotherapy administered in the 1L setting, the NCCN added this regimen to its guidelines (category 1, preferred) on October 10, 2018. Accordingly, some providers began implementing this regimen in their clinical practice, creating a unique opportunity to characterise its early and broad use in a real-world setting. Patients with ES-SCLC who started treatment within 90 days of initial diagnosis and had a confirmed administration of atezolizumab with carboplatin or cisplatin and etoposide (atezo regimen) on or after September 25, 2018, were included from the de-identified Flatiron Health electronic health records–derived database, representing > 280 US cancer clinics (≈ 800 sites of care). Treatment data were analysed through April 30, 2019. Broad use was defined as treatment with the atezo regimen outside of several main clinical trial restrictions (ECOG PS ≥ 2, abnormal laboratory values, cisplatin use or as 2L treatment). Frequencies and percentages are reported. Monthly uptake was defined as the percentage of ES-SCLC patients starting 1L therapy each month who were treated with the atezo regimen. Uptake of the atezo regimen increased from 10% in October 2018 to 46% in February 2019 (before FDA approval on March 18, 2019) and 66% in April 2019 (after FDA approval); 143 patients were identified, 92% of whom had ES-SCLC at initial diagnosis (Table). The atezo regimen was used broadly among 46% of patients (18% with ECOG PS ≥ 2, 18% with an abnormal laboratory value, 1% on cisplatin, 17% as 2L ES-SCLC treatment). The median time from ES-SCLC diagnosis to start of the atezo regimen was 16 days for 1L patients and 78 days for 2L patients. Patients treated with the atezo regimen in the 1L were administered atezolizumab at a median of 8 days after start of chemotherapy; those treated in the 2L were typically administered atezolizumab immediately at the start of the line. This real-world analysis demonstrates the broad use of the atezo regimen, with nearly half of patients treated outside of several main IMpower133 trial restrictions. Further, a rapid uptake of the regimen even before FDA approval underscores its impact on changing clinical practice and the high unmet need of this patient population.TableCharacteristics of Patients Treated With the Atezolizumab Plus Carboplatin/Cisplatin and Etoposide Regimen in Routine Clinical CarePatients, n143Treated prior to FDA approval (March 18, 2019), n (%)101 (71)Median age at ES-SCLC diagnosis (IQR), years67 (61, 73)Aged ≥ 65 years at ES-SCLC diagnosis, n (%)90 (63)Female, n (%)71 (50)White, n (%)100 (70)Smoking history, n (%)137 (96)Stage at initial diagnosis, n (%)LS7 (5)ES132 (92)Unknown4 (3)ECOG PS, n (%)a0 or 176 (53)2+26 (18)Unknown41 (29)Radiation therapy, n (%)b14 (10)LS setting, n7ES setting, n7Regimen, n (%)Atezolizumab, carboplatin, etoposide141 (99)Atezolizumab, cisplatin, etoposide2 (1)Line of therapy of atezo regimen in ES setting, n (%)1L119 (83)2L24 (17)Median time from ES-SCLC diagnosis to start of line of therapy containing atezo regimen (IQR), days1L16 (11, 26)2L78 (59, 98)Median time from ES-SCLC diagnosis to first administration of atezo within line (IQR), days1L24 (14, 27)2L78 (59, 98)Abnormal baseline laboratory value, n (%)c26 (18)1L, first line; 2L, second line; atezo, atezolizumab; ECOG, Eastern Cooperative Oncology Group; FDA, US Food and Drug Administration; IQR, interquartile range; LS, limited stage; PS, performance status. a ECOG PS value closest to within −30 to +7 days of treatment start. b Includes radiation therapy to chest following initial diagnosis of SCLC, including concurrent radiation therapy with systemic chemotherapy, chemotherapy followed by radiation therapy, up-front palliative radiation therapy to the chest or for superior vena cava syndrome. c Abnormal values defined as those not meeting the following definitions: absolute lymphocyte count ≥ 500/μL, lymphocyte count ≥ 500/μL, absolute neutrophil count ≥ 1500 cells/μL, platelet count ≥ 100,000/μL, hemoglobin ≥ 9.0 g/dL, aspartate aminotransferase ≤ 5 × upper limit of normal (ULN), alanine aminotransferase ≤ 5 × ULN, alkaline phosphatase ≤ 5 × ULN, serum bilirubin ≤ 1.25 × ULN, serum creatinine ≤ 1.5 × ULN, serum calcium ≤ 12 mg/dL. Open table in a new tab

A Case of Humoral Hypercalcemia of Malignancy Secondary to Hepatocellular Carcinoma with Fulminant Clinical Course

Hepatocellular carcinoma is one of the most common liver malignancies in the United States. Poor prognosis is associated with paraneoplastic syndromes such as hypercalcemia, hypercholesterolemia, or hypoglycemia. Hypercalcemia as a paraneoplastic syndrome of hepatocellular carcinoma has been rarely reported. We report a mortality case of incidentally diagnosed hepatocellular carcinoma associated with humoral hypercalcemia of malignancy. The patient demonstrated a fulminant disease course with an unexpected fatal outcome within 40 days of initial diagnosis. Our case can suggest importance of early definitive treatment of hepatocellular carcinoma, extremely close monitoring, and aggressive medical treatment when it is associated with humoral hypercalcemia of malignancy.

Risk of Pulmonary Embolism in Patients With Isolated Great Saphenous Vein Thrombus.

Risks associated with isolated great saphenous vein (GSV) thrombosis remain controversial. The purpose of this study is to identify the risk of pulmonary embolism (PE) in patients with isolated GSV thrombosis, particularly those with thrombus within 3 cm of the sapheno-femoral junction. A retrospective chart review of color flow Doppler lower extremity venous ultrasound examinations from an academic hospital from 2011 to 2016 was conducted. Seventy-eight patients were identified as having acute thrombus in their GSV and were then further stratified based on the presence or absence of concomitant deep venous thrombosis (DVT). A control group of 49 patients who presented with leg swelling and were found to have a normal color flow Doppler examination was also identified. Patients without thrombus (n = 49), patients with isolated GSV thrombus (n = 29), and patients with GSV thrombus with concomitant DVT (n = 49) underwent full chart review to determine whether any patients developed PE. This was diagnosed specifically by computed tomography angiogram or ventilation/perfusion scan, within 60 days of initial diagnosis of lower extremity thrombus. In our analysis, there was no significant difference in the risk of PE in patients with isolated GSV thrombus compared with a control group of normal patients (3.5% vs 2.0%, P = 0.38). However, patients with GSV thrombus and concomitant DVT had a significantly increased risk of PE compared with patients with isolated GSV thrombus (26.5% vs 3.5%, P = 0.01). We found that the risk of PE in patients with isolated GSV thrombus is not significantly increased compared with a normal cohort.

Outcome on Reinstitution of Anticoagulation Following Intracranial Hemorrhage: A Single Institutional Analysis

Introduction: Arterial and venous thromboembolic events, including stroke and myocardial infarction, are a leading cause of morbidity and mortality in the United States. Anticoagulation therapies including but not limited to vitamin K anticoagulant (VKA) and direct oral anticoagulants (DOACs) are critical in preventing such morbidity and/or mortality. Adversely, studies have shown an increased risk of bleeding associated with anticoagulation. For instance, there is a two-fivefold increase risk of intracranial hemorrhage (ICH) with warfarin use. On the other hand, 6.5% to 19.6% of all strokes result in ICH which increases mortality. For patients who were on anticoagulation prior to ICH, there seems to be no consensus on the appropriate timing to resume anticoagulation if at all. Most reported observational studies reveal that the decision on whether and when to resume anticoagulation is based on several clinical factors, such as the size and location of the ICH, the recurrence rate of the particular type of ICH, the underlying indication for anticoagulation and social factors. We performed a single institutional analysis on the correlation of anticoagulation resumption with subsequent risk of ICH recurrence and/or thromboembolismMethod: We retrospectively reviewed medical records of 600 adults [mean age 69 (22-79)] at Beaumont Hospital, an academic community center from May 2015 to May 2016 with confirmed ICH, of which 125 patients were on prior anticoagulation. Our aim was to determine whether there is correlation between timing of re-institution of anticoagulant post ICH and eventual outcome with regards to recurrent ICH and/or thrombosis. We also compared outcome in patients on VKA to those on DOACs. Statistical analysis was performed by an independent investigator.Results: Demographic distribution of studied patients were 97(77.6%) white, 10 (8.0%) African Americans and 18 (14.4%) others. Among these patients, 75 (60.0%) were on VKA, 18 (14.4%) on Enoxaparin, 26(20.8%) were on one of the DOACs, and 6(4.8%) were on unknown anticoagulant prior to intracranial hemorrhage (ICH) (Table 1). Although anticoagulation was not reinstituted in 71(56.8%) patients following ICH; 5 (4.0%) patients had anticoagulant restarted within 7 days of diagnosis of ICH; 27 (21.6%) patients were restarted between 7-30days and 18 (14.4%) patients were restarted after 30 days. All patients restarted within 7 days of diagnosis were on warfarin due to severe cardiac dysfunction requiring mechanical valves. Using SAS System for Windows version 9.3, statistical analysis was performed on 32 (25.6%) patients who restarted on anticoagulation within 30 days of initial diagnosis to determine the risk of recurrent ICH or thromboembolism. Results showed that 11 (37.5%) patients had recurrent ICH when anticoagulation was restarted within 14 days from initial diagnosis. Of these, 2 (6.25%) patients were on DOACs (specifically, rivaroxaban) while 9 (28.1%) patients were on VKA. Within 30 days of initial ICH diagnosis, 19 (15.2%) patients developed thrombosis. Of those, 16 (12.8%) patients were restarted more than twenty-one days from initial diagnosis; 3 (2.4%) were restarted between fourteen and twenty-one days post diagnosis. Subgroup analysis of the thrombosis arm revealed that 2 (10.5%) were restarted on rivaroxaban while 17 (89.5%) were restarted on VKA. Forty-one (32.8%) patients were alive within the studied time period and the outcome of 28 (22.4%) patients could not be ascertained from our database.Conclusion: Given the rising national trend on the use of anticoagulants for various medical necessities, it is imperative that a safe and efficient process be devised on reinstitution of anticoagulation post ICH. Although our study represents a single institutional analysis, it concurs with recent studies that early resumption of anticoagulant following stable ICH is associated with lower thromboembolic events and similar risk of ICH recurrence. Our study further reveals that the risk of recurrent ICH and/or thromboembolism may be less in patients on DOACs. Nonetheless, randomized clinical trials are needed to evaluate the true risk-benefit profile of anticoagulation resumption after ICH. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Antibiotic Prescription Fills for Acute Conjunctivitis among Enrollees in a Large United States Managed Care Network

Antibiotics are seldom necessary to treat acute conjunctivitis. We assessed how frequently patients with newly diagnosed acute conjunctivitis fill prescriptions for topical antibiotics and factors associated with antibiotic prescription fills. Retrospective, observational cohort study. A total of 340 372 enrollees in a large nationwide United States managed care network with newly diagnosed acute conjunctivitis, from 2001 through2014. We identified all enrollees newly diagnosed with acute conjunctivitis, calculating the proportion filling 1 or more topical antibiotic prescription within 14 days of initial diagnosis. Multivariate logistic regression assessed sociodemographic, medical, and other factors associated with antibiotic prescription fills for acute conjunctivitis. Geographic variation in prescription fills also was studied. Odds ratios (ORs) with 95% confidence intervals (CIs) for filling an antibiotic prescription for acute conjunctivitis. Among 340 372 enrollees with acute conjunctivitis, 198 462 (58%) filled ≥1 topical antibiotic prescriptions; 38 774 filled prescriptions for antibiotic-corticosteroid combination products. Compared with whites, blacks (OR, 0.89; 95% CI, 0.86-0.92) and Latinos (OR, 0.83; 95% CI, 0.81-0.86) had lower odds of filling antibiotic prescriptions. More affluent and educated enrollees had higher odds of filling antibiotic prescriptions compared with those with lesser affluence and education (P < 0.01 for all). Compared with persons initially diagnosed with acute conjunctivitis by ophthalmologists, enrollees had considerably higher odds of antibiotic prescription fills if first diagnosed by an optometrist (OR, 1.26; 95% CI, 1.21-1.31), urgent care physician (OR, 3.29; 95% CI, 3.17-3.41), internist (OR, 2.79; 95% CI, 2.69-2.90), pediatrician (OR, 2.27; 95% CI, 2.13-2.43), or family practitioner (OR, 2.46; 95% CI, 2.37-2.55). Antibiotic prescription fills did not differ for persons with versus without risk factors for development of serious infections, such as contact lens wearers (P= 0.21) or patients with human immunodeficiency virus infection or AIDS (P= 0.60). Nearly 60% of enrollees in this managed care network filled antibiotic prescriptions for acute conjunctivitis, and 1 of every 5 antibiotic users filled prescriptions for antibiotic-corticosteroids, which are contraindicated for acute conjunctivitis. These potentially harmful practices may prolong infection duration, maypromote antibiotic resistance, and increase costs. Filling antibiotic prescriptions seems to be driven more by sociodemographic factors and type of provider diagnosing the enrollee than by medical indication.

Coronavirus Infection in Hematopoietic Stem Cell Transplant Recipients

BackgroundHematopoietic stem cell transplants (HSCT) recipients are at increased risk of respiratory viral infections and their associated complications. Although the epidemiology of many respiratory viruses has been well characterized in this population, little is known about the epidemiology of human coronavirus (HoCV) infection.MethodsWe identified HSCT recipients with symptoms of a respiratory tract infection who tested positive for HoCV by nasopharyngeal (NP) swab from January 2013 to December 2016 at our hospital. NP swabs were analyzed by the FilmArray® Respiratory Panel, which detects 17 respiratory viruses, including 4 coronavirus serotypes. We reviewed the demographics, transplant type, comorbidities, smoking status, respiratory symptoms, co-pathogens, and radiographic findings of infected patients. We then assessed the incidence of developing a lower respiratory tract infection (LRTI), defined as new pulmonary infiltrates or detection of HoCV in bronchoalveolar lavage fluid, within 30 days of initial diagnosis.ResultsWe identified 58 HSCT recipients who tested positive for HoCV. The median patient age was 54 years, 29 (50%) were men, and 24 (41%) were current or prior smokers. Fifty (86%) patients had received an allogeneic HSCT and 8 (14%) had received an autologous HSCT. The coronavirus serotypes were: OC43 (n = 19, 33%), NL63 (n = 18, 31%), HKU1 (n = 16, 28%), and 229E (n = 5, 9%). The median time from transplant until detection of HoCV infection was 135 days (IQR=256). Seventeen (29%) patients were lymphopenic at the time of diagnosis and 17 (29%) were receiving corticosteroids. The most common initial symptoms were cough (n = 41, 71%), rhinorrhea (n = 31, 53%), and dyspnea (n = 17, 29%), and 19 (33%) and 16 (28%) patients had fever and hypoxia, respectively. Seventeen patients (29%) developed a LRTI within 30 days of diagnosis and 43% harbored a co-pathogen in the blood or respiratory tract. Three patients (5%) were intubated for respiratory failure and 1 (2%) died within 30 days.ConclusionHoCV infection is common in HSCT recipients and is caused by multiple serotypes. Nearly one-third of patients have fever and hypoxia upon initial diagnosis or progress to LRTI. Further research is needed to identify risk factors for HoCV LRTI in this population.Disclosures All authors: No reported disclosures.

Oncology patients in the health care safety net: Is it too late for early palliative care?

128 Background: Studies have suggested that uninsured and Medicaid patients are more likely to present with late-stage cancer than Medicare patients, and may be more likely to be admitted urgently or emergently. However, studies of palliative care interventions for cancer patients suggest that the greatest impact can be achieved if these services begin “early” (≥ 90 days prior to death). In our urban public hospital, we examined where patients receive their initial cancer diagnosis, and at what stage they are diagnosed, in order to determine how to best implement community-based palliative care services. Methods: Retrospective cohort analysis of cancer patients diagnosed over a five year period. Hospital tumor registry data were used to determine the location of diagnosis (inpatient vs. outpatient), stage and type of cancer at diagnosis, and patient status at the end of the study period (alive vs. deceased). Results: Of the 2,928 patients diagnosed with cancer, 26% of patients (n = 759) were diagnosed while hospitalized. Patients who received their diagnosis while hospitalized were more likely to be diagnosed with stage 3-4 disease (49%, n = 372), vs. stage 0-1 (21%, n = 163). 25% of patients who received their diagnosis in the inpatient setting died within 90 days of initial diagnosis. Patients diagnosed in the outpatient setting were more likely to be diagnosed with stage 0-1 (40%, n = 865), vs. stage 3-4 (32%, n = 688). Patients diagnosed while hospitalized were 2.9 times more likely to be diagnosed with late stage disease, compared to those diagnosed as outpatients (95% CI 2.3-3.5, p &lt; 0.0001). Conclusions: A large minority of patients received their cancer diagnosis while hospitalized, and were more likely to be diagnosed with late-stage disease. Additionally, a significant proportion of these patients died within 90 days of their initial diagnosis. In order to provide "early" palliative care for cancer patients in public hospitals, palliative care programs may need to offer initial consultation visits while patients are hospitalized, and then connect them with prompt outpatient follow-up. Safety net programs with palliative care services for cancer patients should emphasize continuity across inpatient and outpatient settings.

MP75-15 THE CONSEQUENCES OF DELAYING STONE TREATMENT

You have accessJournal of UrologyStone Disease: Evaluation I1 Apr 2015MP75-15 THE CONSEQUENCES OF DELAYING STONE TREATMENT Justin Friedlander, Nicholas Kavoussi, Shuvro De, Asim Ozayar, Nabeel Shakir, Jodi Antonelli, and Margaret Pearle Justin FriedlanderJustin Friedlander More articles by this author , Nicholas KavoussiNicholas Kavoussi More articles by this author , Shuvro DeShuvro De More articles by this author , Asim OzayarAsim Ozayar More articles by this author , Nabeel ShakirNabeel Shakir More articles by this author , Jodi AntonelliJodi Antonelli More articles by this author , and Margaret PearleMargaret Pearle More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2712AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES As the prevalence of nephrolithiasis has increased, so has the need for surgery to treat stones. This is particularly relevant at publically-funded hospitals with limited resources, including operative time, leading to potential delays in care for patients with stones. Consequently, drainage procedures to stabilize the patient and protect renal function may be necessary until definitive treatment can be offered. We sought to evaluate the impact of time to stone treatment on patient morbidity and healthcare resource utilization. METHODS Using billing records, we identified consecutive patients undergoing surgical stone procedures (shock wave lithotripsy, ureteroscopy, percutaneous nephrolithotomy) performed at our county hospital between January 2011 and December 2013 and reviewed their charts from the time of initial presentation with their stone to the time of definitive surgical intervention. We recorded clinical outcomes, including need for temporizing drainage procedures and unplanned hospital encounters, from diagnosis to treatment. RESULTS During the study period, a total of 795 patients underwent definitive surgical treatment for stones. The median time from diagnosis to surgery was 79 days (range 0-1147 days). A total of 199 patients underwent temporizing drainage with a stent (n=125) or a nephrostomy tube (n=74) and 52 of these patients required at least one or more tube changes before treatment. A total of 714 unplanned encounters (emergency department (ED) or clinic visits) were required for 432 patients (54.3%), including 89 patients (11.2%) who required hospital admission. Multivariate adjusted analysis revealed that patients treated > 45 days after diagnosis were 15.2 times (95% CI 8.4-30.6, p<0.0001) more likely to have an unplanned clinic visit; 3.6 times (95% CI 2.6-5.2, p<0.0001) more likely to have an unplanned ED visit; 5.7 times (95% CI 3.9-8.4, p<0.0001) more likely to have additional imaging studies performed and 5.4 times (95% CI 3.2-9.4, p<0.0001) more likely to have a positive urine culture requiring antibiotics than patients treated within 45 days of initial diagnosis. CONCLUSIONS Longer time interval between diagnosis and treatment of stones is associated with increased patient morbidity and more frequent use of imaging studies and antibiotics. The use of temporizing drainage procedures may provide the false impression that treatment can be safely deferred. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byLee W, Chen A, Kalil R, Cohen T, Berg W, Waltzer W, Kim J and Adler H (2017) Medicaid Patients Experience Longer Wait Times at Academic Urology Clinics Compared to Patients with MedicareUrology Practice, VOL. 5, NO. 5, (360-366), Online publication date: 1-Sep-2018. Volume 193Issue 4SApril 2015Page: e953 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Justin Friedlander More articles by this author Nicholas Kavoussi More articles by this author Shuvro De More articles by this author Asim Ozayar More articles by this author Nabeel Shakir More articles by this author Jodi Antonelli More articles by this author Margaret Pearle More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Risk of Bleeding With Dabigatran in Atrial Fibrillation

ImportanceIt remains unclear whether dabigatran etexilate mesylate is associated with higher risk of bleeding than warfarin sodium in real-world clinical practice.ObjectiveTo compare the risk of bleeding associated with dabigatran and warfarin using Medicare data.Design, Setting, and ParticipantsIn this retrospective cohort study, we used pharmacy and medical claims in 2010 to 2011 from a 5% random sample of Medicare beneficiaries. We identified participants as those newly diagnosed as having atrial fibrillation from October 1, 2010, through October 31, 2011, and who initiated dabigatran or warfarin treatment within 60 days of initial diagnosis. We followed up patients until discontinued use or switch of anticoagulants, death, or December 31, 2011.ExposuresDabigatran users (n = 1302) and warfarin users (n = 8102).Main Outcomes and MeasuresWe identified any bleeding events and categorized them as major and minor bleeding by anatomical site. Major bleeding events included intracranial hemorrhage, hemoperitoneum, and inpatient or emergency department stays for hematuria, gastrointestinal, or other hemorrhage. We used a propensity score weighting mechanism to balance patient characteristics between 2 groups and Cox proportional hazards regression models to evaluate the risk of bleeding. We further examined the risk of bleeding for 4 subgroups of high-risk patients: those 75 years or older, African Americans, those with chronic kidney disease, and those with more than 7 concomitant comorbidities.ResultsDabigatran was associated with a higher risk of bleeding relative to warfarin, with hazard ratios of 1.30 (95% CI, 1.20-1.41) for any bleeding event, 1.58 (95% CI, 1.36-1.83) for major bleeding, and 1.85 (95% CI, 1.64-2.07) for gastrointestinal bleeding. The risk of intracranial hemorrhage was higher among warfarin users, with a hazard ratio of 0.32 (95% CI, 0.20-0.50) for dabigatran compared with warfarin. Dabigatran was consistently associated with an increased risk of major bleeding and gastrointestinal hemorrhage for all subgroups analyzed. The risk of major bleeding among dabigatran users was especially high for African Americans and patients with chronic kidney disease.Conclusions and RelevanceDabigatran was associated with a higher incidence of major bleeding (regardless of the anatomical site), a higher risk of gastrointestinal bleeding, but a lower risk of intracranial hemorrhage. Thus, dabigatran should be prescribed with caution, especially among high-risk patients.