Assessing Heterogeneity of Treatment Effect in Real-World Data.

Increasing availability of real-world data (RWD) generated from patient care enables the generation of evidence to inform clinical decisions for subpopulations of patients and perhaps even individuals. There is growing opportunity to identify important heterogeneity of treatment effects (HTE) in these subgroups Thus, HTE is relevant to all with interest in patients' responses to interventions, including regulators who must make decisions about products when signals of harms arise postapproval and payers who make coverage decisions based on expected net benefit to their beneficiaries. Prior work discussed HTE in randomized studies.

Comparative Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin Among Adults With Cancer and Atrial Fibrillation.

Background: While clinical guidelines recommend direct-acting oral anticoagulants (DOAC) over warfarin to treat isolated nonvalvular atrial fibrillation, guidelines are silent regarding nonvalvular atrial fibrillation treatment among individuals with cancer, reflecting the paucity of evidence in this setting. We quantified relative risk of ischemic stroke or systemic embolism and major bleeding (primary outcomes), and all-cause and cardiovascular death (secondary outcomes) among older individuals with cancer and nonvalvular atrial fibrillation comparing DOACs and warfarin.

Methods: This retrospective cohort study used Surveillance, Epidemiology, and End Results cancer registry and linked US Medicare data from 2010 through 2016, and included individuals diagnosed with cancer and nonvalvular atrial fibrillation who newly initiated DOAC or warfarin.

Safety and effectiveness of apixaban versus warfarin for acute venous thromboembolism in patients with end-stage kidney disease: A national cohort study.

Background: Patients with end-stage kidney disease (ESKD) are at significantly increased risk for both thrombosis and bleeding relative to those with normal renal function. The optimal therapy of venous thromboembolism (VTE) in patients with ESKD is unknown.

Objective: To compare the safety and effectiveness of apixaban relative to warfarin in patients with ESKD and acute VTE.

Associations of Nutritional, Environmental, and Metabolic Biomarkers with Diabetes-Related Mortality in U.S. Adults: The Third National Health and Nutrition Examination Surveys between 1988-1994 and 2016.

Background: Nutritional, environmental, and metabolic status may play a role in affecting the progression and prognosis of type 2 diabetes. However, results in identifying prognostic biomarkers among diabetic patients have been inconsistent and inconclusive. We aimed to evaluate the associations of nutritional, environmental, and metabolic status with disease progression and prognosis among diabetic patients.

Use of oral anticoagulants among individuals with cancer and atrial fibrillation in the United States, 2010-2016.

Background: Anticoagulation among patients with cancer and atrial fibrillation is challenging due to elevated risk of bleeding and stroke. We characterized use of oral anticoagulants among patients with cancer and non-valvular atrial fibrillation (NVAF).

Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data and included patients with cancer aged ≥66 years with an incident diagnosis of NVAF from 2010 to 2016.

Use of Medications for Treating Anxiety or Depression among Testicular Cancer Survivors: A Multi-Institutional Study.

Background: This study examined sociodemographic factors, cisplatin-related adverse health outcomes (AHO), and cumulative burden of morbidity (CBM) scores associated with medication use for anxiety and/or depression in testicular cancer survivors (TCS).

Methods: A total of 1,802 TCS who completed cisplatin-based chemotherapy ≥12 months previously completed questionnaires regarding sociodemographic features and cisplatin-related AHOs [hearing impairment, tinnitus, peripheral sensory neuropathy (PSN), and kidney disease]. A CBM score encompassed the number and severity of cisplatin-related AHOs.

Clinical and Genome-Wide Analysis of Serum Platinum Levels after Cisplatin-Based Chemotherapy.

Purpose: Serum platinum is measurable for years after completion of cisplatin-based chemotherapy (CBC). We report the largest investigation of serum platinum levels to date of 1,010 testicular cancer survivors (TCS) assessed 1-35 years after CBC and evaluate genetic contributions to these levels.

Experimental Design: Eligible TCS given 300 or 400 (±15) mg/m cisplatin underwent extensive audiometric testing, clinical examination, completed questionnaires, and had crude serum platinum levels measured.

Adverse Health Outcomes in Relationship to Hypogonadism After Chemotherapy: A Multicenter Study of Testicular Cancer Survivors.

Background: This study examined the prevalence of hypogonadism, its clinical and genetic risk factors, and its relationship to adverse health outcomes (AHOs) in North American testicular cancer survivors (TCS) after modern platinum-based chemotherapy.

Patients And Methods: Eligible TCS were <55 years of age at diagnosis and treated with first-line platinum-based chemotherapy. Participants underwent physical examinations and completed questionnaires regarding 15 AHOs and health behaviors.

Clinical and Genome-wide Analysis of Cisplatin-induced Tinnitus Implicates Novel Ototoxic Mechanisms.

Purpose: Cisplatin, a commonly used chemotherapeutic, results in tinnitus, the phantom perception of sound. Our purpose was to identify the clinical and genetic determinants of tinnitus among testicular cancer survivors (TCS) following cisplatin-based chemotherapy.

Experimental Design: TCS ( = 762) were dichotomized to cases (moderate/severe tinnitus; = 154) and controls (none; = 608).

Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors.

Testicular cancer has become the paradigm of adult-onset cancer survivorship, due to the young age at diagnosis and 10-year relative survival of 95%. This clinical review presents the current status of various treatment-related complications experienced by long-term testicular cancer survivors (TCS) free of disease for 5 or more years after primary treatment. Cardiovascular disease and second malignant neoplasms represent the most common potentially life-threatening late effects.

Cumulative Burden of Morbidity Among Testicular Cancer Survivors After Standard Cisplatin-Based Chemotherapy: A Multi-Institutional Study.

Purpose In this multicenter study, we evaluated the cumulative burden of morbidity (CBM) among > 1,200 testicular cancer survivors and applied factor analysis to determine the co-occurrence of adverse health outcomes (AHOs). Patients and Methods Participants were ≤ 55 years of age at diagnosis, finished first-line chemotherapy ≥ 1 year previously, completed a comprehensive questionnaire, and underwent physical examination. Treatment data were abstracted from medical records.

Predicting Cardiovascular Disease Among Testicular Cancer Survivors After Modern Cisplatin-based Chemotherapy: Application of the Framingham Risk Score.

Background: Testicular cancer survivors (TCSs) are at increased risk of cardiovascular disease (CVD) after cisplatin-based chemotherapy (CBCT). Identifying at-risk survivors would allow early intervention, but risk prediction tools such as the Framingham Risk Score (FRS) have not been applied to TCSs given modern chemotherapy.

Methods: TCSs > 1 year post-CBCT were evaluated.

Clinical and Genetic Risk Factors for Adverse Metabolic Outcomes in North American Testicular Cancer Survivors.

Testicular cancer survivors (TCS) are at significantly increased risk for cardiovascular disease (CVD), with metabolic syndrome (MetS) an established risk factor. No study has addressed clinical and genetic MetS risk factors in North American TCS. TCS were aged <55 years at diagnosis and received first-line chemotherapy.

Clinical and Genome-Wide Analysis of Cisplatin-Induced Peripheral Neuropathy in Survivors of Adult-Onset Cancer.

Our purpose was to characterize the clinical influences, genetic risk factors, and gene mechanisms contributing to persistent cisplatin-induced peripheral neuropathy (CisIPN) in testicular cancer survivors (TCSs). TCS given cisplatin-based therapy completed the validated EORTC QLQ-CIPN20 questionnaire. An ordinal CisIPN phenotype was derived, and associations with age, smoking, excess drinking, hypertension, body mass index, diabetes, hypercholesterolemia, cumulative cisplatin dose, and self-reported health were examined for 680 TCS.

Multi-Institutional Assessment of Adverse Health Outcomes Among North American Testicular Cancer Survivors After Modern Cisplatin-Based Chemotherapy.

Purpose To provide new information on adverse health outcomes (AHOs) in testicular cancer survivors (TCSs) after four cycles of etoposide and cisplatin (EPX4) or three or four cycles of bleomycin, etoposide, cisplatin (BEPX3/BEPX4). Methods Nine hundred fifty-two TCSs > 1 year postchemotherapy underwent physical examination and completed a questionnaire. Multinomial logistic regression estimated AHOs odds ratios (ORs) in relation to age, cumulative cisplatin and/or bleomycin dose, time since chemotherapy, sociodemographic factors, and health behaviors.

Residual Platinum Concentrations in Post-Cancer Chemotherapy and Healthy Control Populations Using an Automated, 96-Well Plate Method and Inductively Coupled Plasma Mass Spectrometry.

Background: Platinating agents are among the most commonly used cytotoxic drugs worldwide. It is recognized that Pt concentration can remain significantly increased in serum up to 20 years after completion of chemotherapy, with levels related to late treatment effects.

Methods: A Freedom EVO® Tecan liquid handler was used for aliquoting 50 μL serum at 10-fold dilution into 96-well plates.

Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer.

Purpose: Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer.

Patients And Methods: Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.

The impact of renin-angiotensin system, angiotensin І converting enzyme (insertion/deletion), and angiotensin ІІ type 1 receptor (A1166C) polymorphisms on breast cancer survival in Iran.

Introduction: Several proteins of renin-angiotensin system (RAS) have been implicated in the process of growth promotion or inhibition of breast tissue and cancer cells. This study aimed to investigate the association between angiotensin I converting enzyme (ACE) insertion/deletion (I/D) and angiotensin receptor-1 (AGTR1) A1166C polymorphisms and survival of 110 women with breast cancer.

Materials And Methods: The I/D and A1166C polymorphisms were evaluated by using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) in 110 breast cancer patients who had been treated between 2007 and 2009.

Lack of association of genetic polymorphisms of angiotensin converting enzyme 1 and angiotensin II type 1 receptor with breast cancer risk in Iranian population.

We aimed to investigate the association of insertion/deletion (I/D) and A1166C polymorphisms of angiotensin I converting enzyme 1 and angiotensin II type 1 receptor genes, respectively and their combination on breast cancer risk in an Iranian population. A case-control study (70 cases, 70 controls) was performed on an Iranian population. The I/D and A1166C polymorphisms were analyzed by polymerase chain reaction (PCR) and restriction fragment length polymorphism PCR, respectively.

The effect of renin angiotensin system on tamoxifen resistance.

Breast cancer is one of the most common forms of cancer observed in women and endogenous estrogens are thought to play a major role in its development. Tamoxifen is a selective estrogen receptor (ER) modulator which is widely used to treat and prevent breast cancer. Tamoxifen is an ER antagonist in the breast but an ER agonist in cardiovascular system (CVS) and some other tissues.

Association of angiotensin I converting enzyme (insertion/deletion) and angiotensin II type 1 receptor (A1166C) polymorphisms with breast cancer prognostic factors in Iranian population.

It has been indicated that renin-angiotensin system (RAS) has role in various steps of cancer progression. The presence of RAS components has been shown in normal and breast cancer tissue. insertion/deletion (I/D) is one of angiotensin I converting enzyme (ACE) polymorphisms and A1166C is one of angiotensin II type-1 receptor (AT1R) polymorphisms which have been associated with various diseases such as cardiovascular diseases.