Development of cavitation while on bevacizumab (BV) therapy in patients (pts) with non-small cell lung cancer (NSCLC): Results from ARIES—A bevacizumab (BV) treatment observational cohort study (OCS)

e19045 Background: BV (Avastin), an anti-VEGF monoclonal antibody, prolongs progression-free and overall survival in advanced NSCLC pts. Severe (≥grade 3) pulmonary hemorrhage (sPH) is a rare but serious event that has been associated with BV-based therapy in phase 3 trials (rate of 2–4%). Potential risk factors include squamous histology, prior history of hemoptysis, and presence of tumor cavitation. Rates of baseline (BL) cavitation in NSCLC pts and development of cavitation on BV therapy are unknown. Pts in ARIES, an OCS of approximately 2,000 pts with NSCLC, had BL scans assessed for tumor cavitation. A substudy of approximately 250 pts also had follow-up scans to analyze the likelihood of developing cavitation on BV therapy. For the entire ARIES population, any pt developing sPH is assessed for tumor cavitation. Methods: Pts at specified ARIES sites submitted on-treatment CT scans to an independent review facility (IRF), in addition to BL scans. Evaluable pts had measurable disease at BL and at least one-post-BL scan. Correlations between cavitation (pre-existing or developing on-study) and clinical, tumor and treatment characteristics are evaluated using a chi-squared test or t-test. Incidence of sPH based on cavitation status will be assessed using Fisher's exact test. Results: As of 9/15/08, 210 pts had a post-BL CT scan reviewed by the IRF. Of these pts, 171 had measurable tumors at BL. For the 171 pt cohort: median F/U is 9.2 m; 99% have ≥1 quarterly update. Key BL characteristics for the substudy and overall cohorts, respectively, include: 44% vs 51% ≥65 yrs; 67% vs 67% adenocarcinoma; 6% vs 5% therapeutic AC. BL radiographic features: 41% vs 39% presence of central tumor; 13% vs 15% presence of cavitation. In substudy pts, there is 1 sPH to date in a pt without baseline cavitation. Conclusions: sPH is a rare, potentially serious event in pts with NSCLC receiving BV. Whether cavitation (BL or developing on-treatment) is associated with an increased risk of sPH has not been defined. The final analysis of an ARIES Lung substudy assessing on-study development of cavitation and association with sPH will be presented at the meeting. [Table: see text]

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Abstract 14: The Influence of Provider Specialty on Anticoagulation Prescription Fills and Stroke Risk in Atrial Fibrillation Patients With History of Cancer

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.11.suppl_1.14 ◽

2018 ◽

Vol 11 (suppl_1) ◽

Author(s):

Wesley T O’Neal ◽

J’Neka Claxton ◽

Richard MacLehose ◽

Lin Chen ◽

Lindsay G Bengtson ◽

...

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulant ◽

Cox Regression ◽

Prior History ◽

Cancer Type ◽

Patients With Cancer ◽

Increased Risk ◽

History Of ◽

Reduced Risk ◽

History Of Cancer

Background: Early cardiology involvement within 90 days of atrial fibrillation (AF) diagnosis is associated with greater likelihood of oral anticoagulant use and a reduced risk of stroke. Due to variation in cardiovascular care for patients with cancer, it is possible that a similar association does not exist for AF patients with cancer. Methods: We examined the association of early cardiology involvement with oral anticoagulation use among non-valvular AF patients with history of cancer (past or active), using data from 388,045 patients (mean age=68±15 years; 59% male) from the MarketScan database (2009-2014). ICD-9 codes in any position were used to identify cancer diagnosis prior to AF diagnosis. Provider specialty and filled anticoagulant prescriptions 3 months prior to and 6 months after AF diagnosis were obtained. Poisson regression models were used to compute the probability of an oral anticoagulant prescription fill and Cox regression was used to estimate the risk of stroke and major bleeding. Results: A total of 64,016 (17%) AF patients had a prior history of cancer. Cardiology involvement was less likely to occur among patients with history of cancer than those without (relative risk=0.92, 95% confidence interval (0.91, 0.93)). Similar differences were observed for cancers of the colon (0.90 (0.88, 0.92)), lung (0.76 (0.74, 0.78)), pancreas (0.74 (0.69, 0.80)), and hematologic system (0.88 (0.87, 0.90)), while no differences were observed for breast or prostate cancers. Patients with cancer were less likely to fill prescriptions for anticoagulants (0.89 (0.88, 0.90)) than those without cancer, and similar results were observed for cancers of the colon, lung, prostate, pancreas, and hematologic system. However, patients with cancer were more likely to fill prescriptions for anticoagulants (1.48 (1.45, 1.52)) if seen by a cardiology provider, regardless of cancer type. A reduced risk of stroke (hazard ratio=0.89 (0.81, 0.99)) was observed among all cancer patients who were seen by a cardiology provider than among those who were not, without an increased risk of bleeding (1.04 (0.95, 1.13)). Conclusion: AF patients with cancer were less likely to see a cardiologist, and less likely to fill an anticoagulant prescription than AF patients without cancer. However, cardiology involvement was associated with increased anticoagulant prescription fills and reduced risk of stroke, suggesting a beneficial role for cardiology providers to improve outcomes in AF patients with history of cancer.

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Abstract 27: Statin use and risk of hemorrhagic stroke in a community-based cohort of aging women: The Women’s Health Initiative

Circulation ◽

10.1161/circ.129.suppl_1.27 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Elena Salmoirago-Blotcher ◽

Kathleen M Hovey ◽

Judith K Ockene ◽

Chris A Andrews ◽

Jennifer Robinson ◽

...

Keyword(s):

Risk Factors ◽

Women's Health ◽

Hemorrhagic Stroke ◽

Extension Study ◽

Prior History ◽

Health Initiative ◽

Increased Risk ◽

History Of ◽

Statin Use ◽

The Women’S Health Initiative

Background: Statin therapy is recommended for treatment of hypercholesterolemia and prevention of cardiovascular events. Concerns have been raised about a potentially higher risk of hemorrhagic stroke in statin users; however, there is limited information in women and in older populations. We evaluated whether statin treatment was associated with increased risk of hemorrhagic stroke among women enrolled in the Women’s Health Initiative (WHI). Methods: This secondary data analysis was conducted among 68,132 women enrolled in the WHI Clinical Trials (CTs). Participants were 50 to 79 yrs old; postmenopausal; and were followed through 2005 (parent study) and for an additional 5 yrs (through September 30, 2010) in the WHI extension study. Statin use was assessed at baseline and at follow-up (FU) visits at 1, 3, 6, and 9 years. Women brought all medications in original containers for inventory. Strokes were self-reported annually and adjudicated by medical record review. Risk of hemorrhagic stroke by statin use (modeled as a time-varying covariate, with the “no use” category as the referent) was estimated from Cox proportional hazard regression models adjusted for age (model 1); risk factors for hemorrhagic stroke (model 2); and possible confounders by indication (model 3). All models adjusted for enrollment in the different CTs and in the extension study. Participants were censored at the date of last contact or loss to FU. Pre-specified subgroup analyses were conducted according to use or non-use of antiplatelet medications (including aspirin) or anticoagulants, and prior history of stroke. Results: Final models included 67,882 women (mean age at baseline 63 ± 7 yrs). Over a mean FU of 12 yrs, incidence rates of hemorrhagic stroke were 6.4/10,000 person-years among women on statins and 5.0/10,000 person-years among women not taking statins. The unadjusted risk of hemorrhagic stroke in statin users vs. non-users was 1.21 (CI: 0.96, 1.53). The HR was attenuated to 0.98 (CI: 0.76, 1.26) after adjusting for age, hypertension, and other risk factors for hemorrhagic stroke. Planned subgroups analyses showed that women taking both statins and antiplatelet agents had a higher risk of hemorrhagic stroke than women taking antiplatelet medications without statins (HR: 1.59; CI: 1.02, 2.46), whereas women not taking antiplatelet medications had no risk elevation with statins (HR=0.79; CI: 0.58-1.08); P for interaction = .01. No significant interactions were found for anticoagulant use or prior history of stroke, but the statistical power for these analyses was low. Conclusion: Statin use was not associated with an overall increased risk of hemorrhagic stroke among older community-dwelling women. However, women taking statins in conjunction with antiplatelet medications had elevated risk; a finding that warrants further study and potential incorporation into clinical decision making.

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Real World Analysis of the Incidence and Impact of Hypertension and Cardiac Toxicity Associated with Carfilzomib for Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2018-99-113832 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3255-3255

Author(s):

Selina J Chavda ◽

Rachael Pocock ◽

Simon Cheesman ◽

Emma Dowling ◽

Puneet Verma ◽

...

Keyword(s):

Nitric Oxide ◽

Cumulative Dose ◽

Real World ◽

Cardiac Toxicity ◽

Cardiac Complications ◽

Prior History ◽

Chi Squared ◽

History Of ◽

Median Cumulative Dose ◽

Number Of Cycles

Abstract Background: Carfilzomib (CFZ) is a potent, irreversible proteasome inhibitor (PI) licenced in patients with multiple myeloma (MM) demonstrating improved progression free and overall survival (OS) to standard of care therapies. However, CFZ is also associated with hypertension (HTN) and rarely cardiac toxicity. The exact mechanism is unclear but may be due to a disturbance of endothelial nitric oxide synthase and nitric oxide. Incidence of HTN in a pooled analysis of CFZ trials (Chari et al, Blood 2018, n=2044) showed all grade (G): 18.5%, ≥G3 5.9%. There is less data in the real world setting. Methods: This was a single centre retrospective analysis of all patients treated with CFZ between 2015-2018. BP was recorded in routine nursing records prior to each CFZ infusion in triplicate at each visit 10 minutes apart and the median recorded. HTN was graded by CTCAE criteria V4 (note: G1=pre-HTN (120-139/ 80-89)) and pulmonary hypertension as mean pulmonary arterial pressure (mPAsp) >25mmHg (American College of Cardiology criteria). Baseline demographics were obtained from medical records. OS was estimated using Kaplan Meier Curves and correlative analysis by Cox regression models. Results: 86 patients and 1976 consecutive BP recordings were evaluated with a mean of 23 BP assessments per patient (1-74). Demographics are shown in Table 1. 32 patients (37.2%) had prior history of HTN and 14 (16.3%) had prior cardiac co-morbidity (ischaemic heart disease, dysrhythmias and cardiac amyloidosis). Initial dosing of CFZ was 20mg/m2, increasing to 27mg/m2 (n=30 (34.9%)), 36mg/m2 (n=18 (20.9%)), 45mg/m2 (n=2 (2.3%)), 56mg/m2 (n=35 (40.7%)), 70mg/m2 weekly (n=1(1.2%)). Median time on therapy was 5.3 months (0-26) with a median of 6 (1-27) cycles. The overall incidence of all grade HTN was 60 (69.8%), predominantly G1-2 and was similar in those with and without pre-existing HTN (Chi squared test p=0.4) (Table 2). 11(13%) required intervention with anti-HTN medications for ≥G2 HTN which then returned the BP to baseline. Those treated at ≥45mg/m2 of CFZ had more episodes of HTN compared to those treated at 27-36mg/m2 (OR 3.65, 95% CI: 1.39-9.21, p<0.01) despite similar co-morbidities per group. Age >65 years was not associated with increased risk of HTN (OR 1.32, 95% CI 0.45-3.73, p=0.63) nor was ethnicity (Chi squared test p=0.1). 25 patients required treatment interruption for any cause, of which 12 were due to HTN (median 7 days (1-23)).13 patients required dose reduction for any cause, and 9(10%) required reductions due to HTN, mainly at 56mg/m2 (27 n=1(1.2%), 36 n=2(2.3%), 56 n=7(8.1%)). The planned median cumulative dose for the number of cycles received was 1264mg/m2 overall (36-5772) however, the actual median cumulative dose delivered was 784 mg/m2 (36-3248). The difference was the greatest with higher carfilzomib doses (≥56mg/m2 vs 27-45mg/m2 (Chi squared test, p<0.01)). Planned vs actual dose delivered for number of cycles of CFZ received was: 27mg/m2, 634 vs 472; 36mg/m2, 1219 vs 722; 45mg/m2, 785 vs 744; 56mg/m2, 2514 vs 1282; 70mg/m2, 1210 vs 770. 15(17%) patients developed cardiac complications including pulmonary HTN n=10(12%) and cardiac failure n=8(9%). Unlike HTN, cardiac complications were not associated with CFZ dose (<36mg/m2 vs ≥36mg/m2 OR 1.2, 95% CI 0.42-3.51, p=0.75) and were not related to development of HTN (OR 2.40, 95% CI 0.80-6.60, p=0.12) or prior history of HTN (OR 1.79, 95%CI 0.53-5.50, p=0.35). 1(1.2%) death was observed in a patient due to cardiac failure and progressive disease. OS was unaffected by HTN, cardiac toxicity, pulmonary HTN or HTN related treatment delays (median OS not reached regardless of developing cardiovascular adverse events, HR 1.45 95% CI 0.39-5.37, p=0.57; median follow up 17 vs 31 months respectively). Conclusions: This real world data demonstrated a higher incidence of HTN compared to clinical trials, however most were low grade toxicities. This may be partly due to under-reporting of G1 events which may not be clinically significant. Dose reductions were more frequent at CFZ doses ≥45, leading to a reduction in total cumulative dose received. Close monitoring and early intervention for HTN is therefore required to prevent further complications and to maintain cumulative dosing. In this dataset, cardiac complications did not appear to be related to HTN. Disclosures Cheesman: Celltrion: Other: Speaker Fee; Roche: Other: Advisory board. Wechalekar:Janssen: Honoraria. Rabin:Janssen: Consultancy, Other: Travel support, Speakers Bureau; Takeda: Consultancy, Other: Travel support , Speakers Bureau; Celgene: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau. Yong:Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria; Takeda: Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau. Popat:Amgen: Honoraria.

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Abstract 18516: Regional Dysfunction of Left Atrial Appendage and its Association with Stroke in Atrial Fibrillation

Circulation ◽

10.1161/circ.130.suppl_2.18516 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Abdullah A Alissa ◽

Yuko Inoue ◽

Jochen Cammin ◽

Qiulin Tang ◽

Elliot Fishman ◽

...

Keyword(s):

Atrial Fibrillation ◽

Left Atrial ◽

Left Atrial Appendage ◽

Atrial Appendage ◽

Control Group ◽

Prior History ◽

Area Change ◽

Increased Risk ◽

History Of ◽

Regional Dysfunction

Background: Atrial Fibrillation (AF) is associated with an increased risk of cardioembolic stroke. Previous studies demonstrate that the Left atrial appendage (LAA) is the most common site of intracardiac thrombus, and the LAA morphology alone may determine the risk of stroke. We aimed to determine the association between LAA regional dysfunction using novel, noninvasive, image-based motion-estimation CT (iME) and prior history of stroke in patients with AF. Methods: Among the patients with history of AF referred for ablation who underwent pre-ablation CT with retrospective ECG gating, we identified 18 patients with a prior history of stroke or TIA, and 18 age- and gender-matched controls. The patients in AF at the time of CT were excluded. Four-dimensional motion vector field was estimated from reconstructed CT images using iME at every 5% RR interval. To assess myocardial deformation, area change ratio and area change rate were calculated over the endocardial surface of the LA and LAA. Univariate and multivariate comparisons were made by using binary logistic regression model. Results: A total of 36 patients (mean age 67.6 ± 8.1 years, 66.7% male, 16.7% persistent AF) were included in the study. Univariate analysis showed that the LA pre-atrial contraction area change ratio and LAA maximum area change ratio were significantly lower (P= 0.02 and 0.04, respectively) in the stroke/TIA group compared to the control group. These changes remained statistically significant in multivariate analysis (P=0.03 and 0.04, respectively) after adjusting for age, sex, body mass index, LV ejection fraction, type of AF, and CHADS score. Conclusions: LAA regional dysfunction is associated with stroke/TIA in patients with AF. LAA regional dysfunction detected by iME could represent a marker for stroke and a possible therapeutic target.

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Abstract 16083: Risk of Preserved versus Reduced Ejection Fraction in Women With and Without History of Breast Cancer: The Pathways Heart Study

Circulation ◽

10.1161/circ.142.suppl_3.16083 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Jamal S Rana ◽

Heather Greenlee ◽

Richard Cheng ◽

Cecile A Laurent ◽

Hanjie Shen ◽

...

Keyword(s):

Breast Cancer ◽

Radiation Therapy ◽

Ejection Fraction ◽

Endocrine Therapy ◽

White Women ◽

Cox Regression ◽

Prior History ◽

Reduced Ejection Fraction ◽

Increased Risk ◽

History Of

Introduction: Incidence of heart failure (HF), specifically with preserved ejection fraction (HFpEF), is rising in the general population, yet is understudied. To provide a population-based estimate of HF in breast cancer (BC) survivors, we compared risk of HF in women with and without BC history in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records. All invasive BC cases diagnosed from 2005-2013 were identified and matched 1:5 with non-BC controls on birth year, race/ethnicity, and KPNC membership at BC diagnosis. Cox regression models assessed the hazard of HF by EF status: HFpEF (EF ≥ 45%), HF with reduced EF (HFrEF; EF < 45%), and unknown EF. Women with prior history of HF were excluded. Models were adjusted for factors known to affect BC risk or CVD and for prevalent CVD at BC diagnosis. We also examined case subgroups who received cardiotoxic chemotherapy, left-sided radiation therapy, and/or endocrine therapy, versus their controls. Results: A total of 14,804 women diagnosed with invasive BC and with no history of HF were identified and matched to 74,034 women without BC history. Women were on average 61 years at BC diagnosis and 65% white. Women with HFpEF were older and more likely to have hypertension (p<0.05). Among all cases vs. controls, there was increased risk of HFrEF (HR: 1.5, 95% CI: 1.18, 1.98) but not HFpEF or unknown EF (figure). Compared to their controls, women treated with chemotherapy were more than 3-times likely to develop HFrEF (HR: 3.26, 95% CI: 2.2, 4.8) and more than 1.5-times likely to develop HFpEF (HR=1.61, 95% CI: 1.15, 2.24). Women who received left-sided radiation therapy had nearly double the risk of developing HFrEF (HR=1.85, 95% CI: 1.20, 2.84). No associations were found among women who received endocrine therapy. Conclusions: Increased surveillance is warranted for women with BC receiving cardiotoxic chemotherapy for development of both HFrEF and HFpEF.

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Long-Lasting Increased Risk of Human Papillomavirus–Related Carcinomas and Premalignancies After Cervical Intraepithelial Neoplasia Grade 3: A Population-Based Cohort Study

Journal of Clinical Oncology ◽

10.1200/jco.2016.71.4543 ◽

2017 ◽

Vol 35 (22) ◽

pp. 2542-2550 ◽

Cited By ~ 38

Author(s):

Renée M.F. Ebisch ◽

Dominiek W.E. Rutten ◽

Joanna IntHout ◽

Willem J.G. Melchers ◽

Leon F.A.G. Massuger ◽

...

Keyword(s):

Human Papillomavirus ◽

Cervical Intraepithelial Neoplasia ◽

Incidence Rate ◽

Intraepithelial Neoplasia ◽

Population Based ◽

Cervical Intraepithelial Neoplasia Grade ◽

Increased Risk ◽

History Of ◽

Grade 3 ◽

Rate Ratios

Purpose The aim of this study was to determine the risk of human papillomavirus (HPV)–related carcinomas and premalignancies in women diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3). Knowledge of this risk is important to preventing the development and progression of other HPV-related premalignancies and carcinomas, by considering prophylactic HPV vaccination and/or by paying increased attention to other HPV-related carcinomas and premalignancies when CIN3 is identified. Methods Women diagnosed with a CIN3 between 1990 and 2010 were identified from the Dutch nationwide registry of histopathology and cytopathology (PALGA) and matched with a control group of women without CIN3. Subsequently, all cases of high-risk (hr) HPV–associated high-grade lesions and carcinomas in the anogenital region and oropharynx between 1990 and 2015 were extracted. Incidence rate ratios were estimated for carcinomas and premalignancies of the vulva, vagina, anus, and oropharynx. Results A total of 178,036 women were identified: 89,018 with a previous diagnosis of CIN3 and 89,018 matched control subjects without a history of CIN3. Women with a history of CIN3 showed increased risk of HPV-related carcinomas and premalignancies, with incidence rate ratios of 3.85 (95% CI, 2.32 to 6.37) for anal cancer, 6.68 (95% CI, 3.64 to 12.25) for anal intraepithelial neoplasia grade 3, 4.97 (95% CI, 3.26 to 7.57) for vulvar cancer, 13.66 (93% CI, 9.69 to 19.25) for vulvar intraepithelial neoplasia grade 3, 86.08 (95% CI, 11.98 to 618.08) for vaginal cancer, 25.65 (95% CI, 10.50 to 62.69) for vaginal intraepithelial neoplasia grade 3, and 5.51 (95% CI, 1.22 to 24.84) for oropharyngeal cancer. This risk remained significantly increased, even after long-term follow-up of up to 20 years. Conclusion This population-based study shows a long-lasting increased risk for HPV-related carcinomas and premalignancies of the anogenital and oropharyngeal region after a CIN3 diagnosis. Studies that investigate methods to prevent this increased risk in this group of patients, such as intensified screening or vaccination, are warranted.

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Induction of labor in patients with an unfavorable cervix after a cesarean using an osmotic dilator versus vaginal prostaglandin

Journal of Perinatal Medicine ◽

10.1515/jpm-2017-0029 ◽

2018 ◽

Vol 46 (3) ◽

pp. 299-307 ◽

Cited By ~ 2

Author(s):

Josefine T. Maier ◽

Melanie Metz ◽

Nina Watermann ◽

Linna Li ◽

Elisabeth Schalinski ◽

...

Keyword(s):

Birth Rate ◽

Induction Of Labor ◽

Cervical Ripening ◽

Exact Test ◽

Safe Delivery ◽

Trial Of Labor ◽

Increased Risk ◽

Chi Squared ◽

Maternal And Neonatal Outcomes ◽

Unfavorable Cervix

Abstract Background: Trial of labor after cesarean (TOLAC) is a viable option for safe delivery. In some cases cervical ripening and subsequent labor induction is necessary. However, the commonly used prostaglandins are not licensed in this subgroup of patients and are associated with an increased risk of uterine rupture. Methods: This cohort study compares maternal and neonatal outcomes of TOLAC in women (n=82) requiring cervical ripening agents (osmotic dilator vs. prostaglandins). The initial Bishop scores (BSs) were 2 (0–5) and 3 (0–5) (osmotic dilator and prostaglandin group, respectively). In this retrospective analysis, Fisher’s exact test, the Kruskal-Wallis rank sum test and Pearson’s chi-squared test were utilized. Results: Vaginal birth rate (including operative delivery) was 55% (18/33) in the osmotic dilator group vs. 51% (25/49) in the dinoprostone group (P 0.886). Between 97% and 92% (32/33 and 45/49) (100%, 100%) of neonates had an Apgar score of >8 after 1 min (5, 10 min, respectively). The time between administration of the agent and onset of labor was 36 and 17.1 h (mean, Dilapan-S® group, dinoprostone group, respectively). Time from onset of labor to delivery was similar in both groups with 4.4 and 4.9 h (mean, Dilapan-S® group, dinoprostone group, respectively). Patients receiving cervical ripening with Dilapan-S® required oxytocin in 97% (32/33) of cases. Some patients presented with spontaneous onset of labor, mostly in the dinoprostone group (24/49, 49%). Amniotomy was performed in 64% and 49% (21/33 and 24/49) of cases (Dilapan-S® group and dinoprostone group, respectively). Conclusions: This pilot study examines the application of an osmotic dilator for cervical ripening to promote vaginal delivery in women who previously delivered via cesarean section. In our experience, the osmotic dilator gives obstetricians a chance to perform induction of labor in these women.

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General medical disorders with psychiatric implications

10.1093/med/9780199360574.003.0038 ◽

2015 ◽

Author(s):

Erik J. Garcia ◽

Warren J. Ferguson

Keyword(s):

Mental Illness ◽

Psychiatric Symptoms ◽

The United States ◽

Prior History ◽

Medical Illness ◽

Medical Conditions ◽

Presenting Symptoms ◽

Medical Disorders ◽

Increased Risk ◽

History Of

Traditionally the domain of consultation/ liaison psychiatry, the challenge of recognizing and then appropriately treating the psychiatric complications of general medical disorders requires thoughtful planning and attention in corrections. Medical conditions that have psychiatric symptoms represent a significant diagnostic dilemma, particularly in the correctional health setting. Over half of the inmates in the United States have symptoms of a major mental illness, but the pervasiveness of substance use disorders, the increasing prevalence of elderly inmates, and limited access to a patient’s past medical and psychiatric records all contribute to the challenge of discerning when a psychiatric presentation results from an underlying medical condition. One early study underscored this challenge, noting that 46% of the patients admitted to community psychiatric wards had an unrecognized medical illness that either caused or exacerbated their psychiatric illness. A more recent study observed that 2.8% of admissions to inpatient psychiatry were due to unrecognized medical conditions. Emergency room medical clearance of patients presenting for psychiatric admission has revealed an increased risk for such underlying medical conditions among patients with any of five characteristics: elderly, a history of substance abuse, no prior history of mental illness, lower socioeconomic status, or significant preexisting medical illnesses. This chapter examines several of these risk groups and focuses on the presenting symptoms of delirium, mood disorders, and psychosis and the underlying medical conditions that can mimic or exacerbate them.

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Rapidly Shifting Concepts Regarding Androgens and Prostate Cancer

The Scientific World JOURNAL ◽

10.1100/tsw.2009.80 ◽

2009 ◽

Vol 9 ◽

pp. 685-690 ◽

Cited By ~ 8

Author(s):

Abraham Morgentaler

Keyword(s):

Prostate Cancer ◽

Cancer Recurrence ◽

Serum Testosterone ◽

High Serum ◽

Prior History ◽

Minimal Risk ◽

Increased Risk ◽

History Of ◽

Dramatic Shift ◽

Risk Of Cancer

There has been a recent dramatic shift in our understanding of the relationship between androgens and prostate cancer (PCa). Whereas for several decades it had been assumed that higher serum testosterone (T) concentrations would lead to ever-greater PCa growth, current literature indicates that PCa growth is unaffected by changes in serum T throughout most of the naturally occurring range. A Saturation Model has been proposed to explain how prostate tissue can be exquisitely sensitive to changes in serum T at the very low end of the concentration range, but appears indifferent to such changes above the near-castrate range. This has special applicability to T-deficient men, since this means that T therapy may not be nearly as risky as once assumed. Indeed, one of the more interesting changes over the last several years has been the growing acceptance of the use of T therapy in men with a prior history of PCa, with early data indicating minimal risk of cancer recurrence or progression. Provocative new evidence suggests that it is not high serum T that is problematic for PCa, butlowserum T that is associated with worrisome cancer features and outcomes, such as high Gleason score, advanced stage of presentation, and increased risk of biochemical recurrence after surgery. It will be interesting to see what changes will occur in this rapidly changing field over the next several years.

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Analysis of Second Primary Malignancies in Lenalidomide-Treated Patients with IPSS Low- or Int-1-Risk Myelodysplastic Syndromes

Blood ◽

10.1182/blood.v118.21.1704.1704 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1704-1704 ◽

Cited By ~ 2

Author(s):

Aristoteles Giagounidis ◽

Azra Raza ◽

Alan F. List ◽

Pierre Fenaux ◽

Bouchra Benettaib ◽

...

Keyword(s):

Research Funding ◽

Prior History ◽

Second Primary ◽

Employment Equity ◽

Phase 3 ◽

Advisory Committees ◽

Increased Risk ◽

History Of ◽

Equity Ownership ◽

Rbc Transfusion

Abstract Abstract 1704 Background: Lenalidomide (LEN) is approved in the US for the treatment of RBC transfusion-dependent patients with IPSS Low- or Int-1-risk myelodysplastic syndromes (MDS) with del(5q), with or without other cytogenetic abnormalities. In a phase 3 trial, treatment with LEN 5 mg and 10 mg resulted in RBC transfusion independence (TI) for ≥ 26 weeks in 43% and 56% of such patients, cytogenetic response in 25% and 50%, and a significant improvement of health-related quality of life (p <.05 for both 5 mg and 10 mg). Achievement of RBC-TI ≥ 8 weeks was associated with a significantly reduced risk of AML progression and death (p <.05 for both) (Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). In newly diagnosed multiple myeloma patients, results of phase 3 trials showed a numerical imbalance in the occurrence of second primary malignancies (SPMs) between patients treated with LEN (in combination with melphalan or immediately after high-dose melphalan therapy and stem cell transplantation) and control cohorts. SPMs were analyzed in clinical trials of LEN across indications, including MDS. Methods: This was a single arm analysis of SPM data retrieved from RBC transfusion-dependent patients with IPSS Low- or Int-1-risk MDS with or without del(5q) who received LEN as monotherapy in 5 studies (MDS-001, -002, -003, -004, and -007). The cutoff date was February 28, 2011. SPMs were defined using MedDRA (Medical Dictionary for Regulatory Activities) categories of invasive SPMs (hematologic malignancies and solid tumors) and non-melanoma skin cancers (NMSC). Acute myeloid leukemia (AML) is considered part of the natural history of disease progression in MDS. Although further follow-up is needed, results of a phase 3 study showed no obvious evidence for an increased risk of AML progression in LEN-treated RBC transfusion-dependent patients with IPSS Low- or Int-1-risk MDS and del(5q) (Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). AML was not included in the present analysis. The overall number of SPMs (invasive malignancies and NMSC), and the number and incidence rate (IR) of all invasive SPMs were evaluated, with IR defined as the number of new events per 100 person-years (pys). The IR of invasive SPMs was compared with the IR of new events of invasive cancer as reported from the SEER (Surveillance, Epidemiology, and End Results) cancer registry (2.1/100 pys for persons aged ≥ 65 years) (Howalder N et al. National Cancer Institute, 2011). Results: The combined population of all 5 studies comprised 557 LEN-treated patients. The median age was 71 years (range 27–95 years) and 72% of patients were aged ≥ 65 years. 88 patients (15.8%) had a prior history of cancer including malignant melanoma, meningioma, breast cancer, lung cancer, squamous cell carcinoma, and basal cell carcinoma. A total of 28 patients (5.0%) developed ≥ 1 SPM, including 17 (3.1%) with an invasive SPM and 12 (2.2%) with NMSC; 1 patient had both an invasive malignancy and a NMSC. Two of the 17 patients with invasive SPMs had a B-cell malignancy and 15 had solid tumors of heterogeneous type. Of the 28 patients with SPMs in total, 5 patients had a prior history of cancer. The IR of invasive SPMs was 2.60/100 pys (95% confidence interval 1.56–4.07), which is consistent with the IR reported in the SEER database among patients in this age group (2.1/100 pys for persons aged ≥ 65 years). The median time to onset of SPMs was 13.5 months (range 0.3–48.6 months). Conclusion: There was no clear evidence to associate LEN treatment with an increased risk of developing SPMs in patients with Low- or Int-1-risk MDS with or without del(5q). The IR of invasive SPMs among these LEN-treated patients is what would be expected from population-based estimates of invasive cancer incidence among persons in this age group. The collection of data on SPMs in LEN-treated patients including post-marketing information is ongoing. Disclosures: Giagounidis: Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. List:Celgene Corporation: Consultancy, Honoraria, Research Funding. Fenaux:Merck: Honoraria; Johnson & Johnson: Honoraria; Amgen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Cephalon: Honoraria; Novartis: Honoraria. Benettaib:Celgene Corporation: Employment, Equity Ownership. Brown:Celgene Corporation: Employment, Equity Ownership. Zhong:Celgene Corporation: Employment, Equity Ownership. Brandenburg:Celgene Corporation: Employment, Equity Ownership. Mufti:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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