Tolerability of Highly Protein Bound Targeted Oral Oncolytic Drugs in Patients With Hypoalbuminemia: A Retrospective Analysis

Background: Hypoalbuminemia is commonly observed in cancer patients. Given the pharmacokinetic interactions between serum proteins and protein bound medications, administration of highly protein bound targeted oral oncolytic drugs may result in elevated unbound drug levels and decreased tolerability in those with hypoalbuminemia. Objective: To describe the impact of hypoalbuminemia on oral oncolytic drug tolerability. Methods: A retrospective study was conducted of adult patients receiving treatment with targeted oral oncolytic drugs with ≥95% protein binding. The primary end point of this study was to compare time to discontinuation resulting from documented toxicity in those with and without hypoalbuminemia. Results: The study included 143 patients receiving 16 targeted oral oncolytic drugs (42% with hypoalbuminemia, 58% without hypoalbuminemia). Adverse events were common, with similar incidence among patients with and without hypoalbuminemia (73% vs 76%, respectively; P = 0.727). Median time to therapy discontinuation resulting from documented toxicity was significantly shorter in those with hypoalbuminemia (22 months vs not reached; P = 0.003). Cox regression demonstrated that hypoalbuminemia was the only significant risk factor for shorter time to discontinuation resulting from documented adverse effects (hazard ratio = 3.0; 95% CI = 1.15-8.0; P = 0.025). Conclusion and Relevance: This represents the first report of the impact of hypoalbuminemia on tolerability of highly protein bound oral oncolytic drugs, demonstrating that patients with hypoalbuminemia may be at increased risk for early discontinuation resulting from toxicity. Given the importance of maintaining dose intensity in patients receiving oncolytic therapy, albumin levels should be monitored throughout treatment and supportive care maximized in those developing hypoalbuminemia.

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Television Viewing and Cognitive Dysfunction of Korean Older Adults

Healthcare ◽

10.3390/healthcare8040547 ◽

2020 ◽

Vol 8 (4) ◽

pp. 547

Author(s):

Mi Sook Jung ◽

Eunyoung Chung

Keyword(s):

Older Adults ◽

Cognitive Dysfunction ◽

Cognitive Aging ◽

Significant Risk ◽

Multivariate Logistic Regression Analysis ◽

Later Life ◽

Significant Risk Factor ◽

Tv Viewing ◽

Increased Risk ◽

The Impact

This study examined the association between television (TV) viewing and cognitive dysfunction in elderly Koreans. Among participants of the 2014 National Survey of Older Koreans, 9644 were considered in this study. To better identify the association between two factors, propensity score (PS) matching with exact method was used. Finally, 168 viewers and non-viewers each were selected based on estimated PS on key variables and eliminating double matches. Multivariate logistic regression analysis was performed when controlling for possible covariates. Viewers were more likely to have cognitive dysfunction than non-viewers, with significant differences in most covariates. After correcting confounding effects of these covariates with PS matching, TV viewing was found to be a significant risk factor of cognitive dysfunction, along with absence of diagnosed hypertension and non-participation in physical leisure activities. TV viewing might be associated with increased risk of cognitive dysfunction in later life. Appropriate education and strategies to minimize TV viewing among older adults should be established to contribute to attenuating cognitive aging. More interventional studies can help older adults, caregivers, and healthcare professionals explore the cognitively beneficial alternatives to TV use considering the impact of socioeconomic factors of selecting TV viewing as a preferred leisure activity.

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Age-Associated TET2 Mutations: Common Drivers of Myeloid Dysfunction, Cancer and Cardiovascular Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21020626 ◽

2020 ◽

Vol 21 (2) ◽

pp. 626 ◽

Cited By ~ 7

Author(s):

Christina K. Ferrone ◽

Mackenzie Blydt-Hansen ◽

Michael J. Rauh

Keyword(s):

Cardiovascular Disease ◽

Inflammatory Diseases ◽

Significant Risk ◽

Significant Risk Factor ◽

Hematopoietic Stem ◽

Increased Risk ◽

On Chip ◽

Developed World ◽

The Impact ◽

Inactivating Mutations

Acquired, inactivating mutations in Tet methylcytosine dioxygenase 2 (TET2) are detected in peripheral blood cells of a remarkable 5%–10% of adults greater than 65 years of age. They impart a hematopoietic stem cell advantage and resultant clonal hematopoiesis of indeterminate potential (CHIP) with skewed myelomonocytic differentiation. CHIP is associated with an overall increased risk of transformation to a hematological malignancy, especially myeloproliferative and myelodysplastic neoplasms (MPN, MDS) and acute myeloid leukemia (AML), of approximately 0.5% to 1% per year. However, it is becoming increasingly possible to identify individuals at greatest risk, based on CHIP mutational characteristics. CHIP, and particularly TET2-mutant CHIP, is also a novel, significant risk factor for cardiovascular diseases, related in part to hyper-inflammatory, progeny macrophages carrying TET2 mutations. Therefore, somatic TET2 mutations contribute to myeloid expansion and innate immune dysregulation with age and contribute to prevalent diseases in the developed world—cancer and cardiovascular disease. Herein, we describe the impact of detecting TET2 mutations in the clinical setting. We also present the rationale and promise for targeting TET2-mutant and other CHIP clones, and their inflammatory environment, as potential means of lessening risk of myeloid cancer development and dampening CHIP-comorbid inflammatory diseases.

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The Impact of Partner Stalking on Mental Health and Protective Order Outcomes Over Time

Violence and Victims ◽

10.1891/088667007782312168 ◽

2007 ◽

Vol 22 (5) ◽

pp. 546-562 ◽

Cited By ~ 18

Author(s):

TK Logan ◽

Jennifer Cole

Keyword(s):

Mental Health ◽

Partner Violence ◽

Significant Risk ◽

Significant Risk Factor ◽

Protective Order ◽

Increased Risk ◽

Women’S Perceptions ◽

Psychological Harm ◽

The Impact ◽

Over Time

The goals of this article are to examine stalking victimization over time among a large sample (n = 662) of women who received a protective order against a violent partner and to examine the impact of stalking on mental health and protective order outcomes. Findings suggest that stalking is a significant risk factor for other forms of partner violence (e.g., psychological, physical, and sexual violence) and that the experience of being stalked by a violent partner contributes uniquely to women’s perceptions of psychological distress, personal safety, and perceptions of protective order effectiveness. Both the criminal justice system and victim service representatives need to be vigilant in educating women about the increased risk of stalking to their safety and mental health. Further, study findings suggest that stalking must be addressed to prevent future physical and psychological harm in partner violence cases.

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Siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syndrome

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-214828 ◽

2019 ◽

Vol 78 (5) ◽

pp. 683-687 ◽

Cited By ~ 5

Author(s):

Helga Westerlind ◽

Marie Holmqvist ◽

Lotta Ljung ◽

Thomas Frisell ◽

Johan Askling

Keyword(s):

Rheumatoid Arthritis ◽

Risk Factors ◽

Acute Coronary Syndrome ◽

General Population ◽

Cox Regression ◽

Significant Risk ◽

Coronary Syndrome ◽

Risk Increase ◽

Increased Risk ◽

The Impact

ObjectivesTo investigate a potential shared susceptibility between rheumatoid arthritis (RA) and acute coronary syndrome (ACS) by estimation of the risk of ACS among full siblings of patients with RA.MethodsBy linking nation-wide Swedish registers, we identified a cohort of patients with new-onset RA 1996–2016, age- and sex-matched (5:1) general population comparator subjects, full siblings of RA and comparator subjects, and incident ACS events through 31 December 2016. We used Cox regression to estimate the HR of ACS among patients with RA and the siblings of patients with RA versus the general population, overall and stratified by RA serostatus. We explored the impact of traditional cardiovascular (CV) risk factors on the observed associations.ResultsWe identified 8109 patients with incident RA, and 11 562 full siblings of these. Compared with the general population, the HR of ACS in RA was 1.46 (95% CI 1.28 to 1.67) and 1.22 (95% CI 1.09 to 1.38) among their siblings. The increased risks seemed confined to seropositive RA (patients: 1.52 [1.30 to 1.79], their siblings: 1.27 [1.10 to 1.46]); no significant risk increase was observed among siblings of patients with seronegative RA (HR 1.13 [95% CI 0.92 to 1.39]). Adjustment for 19 traditional CV risk factors did not appreciably alter these associations.ConclusionSiblings of patients with RA are at increased risk of ACS, suggesting shared susceptibility between RA and ACS, indicating the need and potential for additional cardio-preventive measures in RA (and their siblings).

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Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽

10.1027/0227-5910/a000271 ◽

2014 ◽

Vol 35 (5) ◽

pp. 330-337 ◽

Cited By ~ 14

Author(s):

Cun-Xian Jia ◽

Lin-Lin Wang ◽

Ai-Qiang Xu ◽

Ai-Ying Dai ◽

Ping Qin

Keyword(s):

Risk Factor ◽

Family Income ◽

Rural China ◽

Significant Risk ◽

Significant Risk Factor ◽

Health Condition ◽

Physical Illness ◽

Rural Residents ◽

Increased Risk ◽

Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

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1487. Pneumonia due to Co-Infection in the ICU: Detection and Clinical Significance

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1668 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S745-S746

Author(s):

Casey S Zelus ◽

Michael Blaha ◽

Kaeli Samsom ◽

Jasmine R Marcelin ◽

Trevor C Van Schooneveld ◽

...

Keyword(s):

Clinical Significance ◽

Diagnostic Testing ◽

Significant Risk ◽

Significant Risk Factor ◽

Categorical Variables ◽

Chi Square ◽

Mechanically Ventilated ◽

Critical Care Units ◽

Outcomes Measures ◽

The Impact

Abstract Background Pneumonia is a significant cause of morbidity and mortality, with increasing interest in the detection and clinical significance of co-infection. However, the impact of methodology to obtain lower respiratory samples along with the utility of various microbiological diagnostic testing remains unclear. Methods A single-center retrospective analysis was performed on bronchoalveolar lavage (BAL) samples obtained from mechanically ventilated adults treated in critical care units from August 2012 to December 2017. BAL methodology (bronchoscopic vs blinded), microbiological diagnostic testing, and outcomes measures were obtained. Associations between categorical variables were assessed using Chi-Square or Fisher’s exact tests. Kruskal Wallace tests analyzed differences in distributions of measures between categories based on number of organism types detected. SAS software version 9.4 (SAS Institute Inc., Cary, NC). Results Analysis of the 803 samples that met inclusion criteria found a significant linear association between mortality and number of organism types detected by BAL, with 30 day mortality rates of 43.0%, 47.8%, and 58.3% among those with zero, one, and two or more organisms respectively (p = 0.003). Comparing BALs with at least one organism isolated, the detection of viruses specifically was associated with increased mortality, with the presence and absence of viral organisms corresponding to 56.3% and 46.5% mortality at thirty days (p = 0.03). No association was found between mortality and isolation of acid-fast bacilli, bacteria, or fungi. Co-infection was detected more frequently among bronchoscopic BALs than blinded BALs (26.3% vs 8.6%, p < 0.0001), with more viruses detected bronchoscopic BALs (41.9% vs 13.1%, p < 0.0001), and more bacteria in blinded BALs (41.8% vs 33.0%, p = 0.01). 30 Day Mortality vs Isolation of Specific Organism Types from BAL Number of Organism Types Isolated from BAL Compared to BAL Methodology BAL Methodology vs Isolation of Specific Organism Types Conclusion Co-infection in mechanically ventilated adult patients with pneumonia appears to be a significant risk factor for mortality, with the detection of viral organisms potentially playing an independent role. Within this population, bronchoscopic BALs may have a valuable diagnostic and prognostic methodology. Disclosures All Authors: No reported disclosures

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The impact of levothyroxine exposure on delivery outcome in hypothyroid pregnant women (PETAL study): A five-year retrospective cohort study

Obstetric Medicine ◽

10.1177/1753495x211064108 ◽

2021 ◽

pp. 1753495X2110641

Author(s):

Diana Oprea ◽

Nadine Sauvé ◽

Jean-Charles Pasquier

Keyword(s):

Cohort Study ◽

Pregnant Women ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Caesarean Delivery ◽

Significant Risk ◽

Significant Risk Factor ◽

Singleton Pregnancy ◽

Delivery Outcome ◽

The Impact

Background Hypothyroidism affects 3% of pregnant women, and to date, no studies have addressed the impact levothyroxine-treated hypothyroidism on delivery outcome. Methods This retrospective cohort study was conducted among 750 women with a singleton pregnancy who gave birth between 2015 and 2019. Delivery modes were compared between 250 hypothyroid women exposed to levothyroxine and 500 euthyroid control women. The aim of this study was to determine the impact of levothyroxine exposure on delivery outcome. Results Multiple logistic regression showed no significant association between exposure to levothyroxine and the overall rate of caesarean delivery (aOR 1.1; 95% CI 0.8 to 1.6). Mean TSH concentrations were significantly higher throughout the pregnancy in hypothyroid women despite levothyroxine treatment. Maternal and neonatal outcomes in both groups were not different. Conclusion Hypothyroidism treated with levothyroxine during pregnancy according to local guidelines is not a significant risk factor for caesarean delivery.

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Obesity Does Not Increase Mortality after Emergency Surgery

Journal of Obesity ◽

10.1155/2014/492127 ◽

2014 ◽

Vol 2014 ◽

pp. 1-3 ◽

Cited By ~ 5

Author(s):

Paula Ferrada ◽

Rahul J. Anand ◽

Ajai Malhotra ◽

Michel Aboutanos

Keyword(s):

Wound Infection ◽

Emergency Surgery ◽

Significant Risk ◽

Significant Risk Factor ◽

Patient Characteristics ◽

Obese Patients ◽

Exact Test ◽

Icu Admission ◽

Nonobese Patients ◽

The Impact

Objective.The aim of this study is to evaluate the impact of obesity on patient outcomes after emergency surgery.Methods.A list of all patients undergoing emergent general surgical procedures during the 12 months ending in July 2012 was obtained from the operating room log. A chart review was performed to obtain the following data: patient characteristics (age, gender, BMI, and preexisting comorbidities), indication for surgery, and outcomes (pulmonary embolus (PE), deep venous thrombosis (DVT), respiratory failure, ICU admission, wound infection, pneumonia, and mortality). Obesity was defined as a BMI over 25. Comparisons of outcomes between obese and nonobese patients were evaluated using Fischer’s exact test. Predictors of mortality were evaluated using logistic regression.Results.341 patients were identified during the study period. 202 (59%) were obese. Both groups were similar in age (48 for obese versus 47 for nonobese,P=0.42). Obese patients had an increased incidence of diabetes, (27% versus 7%,P<0.05), hypertension (52% versus 34%,P<0.05), and sleep apnea (0% versus 5%,P<0.05). There was a statistically significant increased incidence of postoperative wound infection (obese 9.9% versus nonobese 4.3%,P<0.05) and ICU admission (obese 58% versus nonobese 42%,P=0.01) among the obese patients. Obesity alone was not shown to be a significant risk factor for mortality.Conclusions.A higher BMI is not an independent predictor of mortality after emergency surgery. Obese patients are at a higher risk of developing wound infections and requiring ICU admission after emergent general surgical procedure.

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Abstract TP209: Effect of Chemotherapy on Stroke Risk in Cancer Patients

Stroke ◽

10.1161/str.51.suppl_1.tp209 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Takaya Kitano ◽

Tsutomu Sasaki ◽

Yasufumi Gon ◽

Kenichi Todo ◽

Shuhei Okazaki ◽

...

Keyword(s):

Cancer Patients ◽

Propensity Scores ◽

Stroke Risk ◽

Cox Regression ◽

Treatment Plan ◽

University Hospital ◽

Chemotherapy Group ◽

Kaplan Meier ◽

Increased Risk ◽

The Impact

Introduction: Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We aimed to clarify the impact of chemotherapy on stroke risk in cancer patients. Methods: We investigated 27,932 patients enrolled in a hospital-based cancer registry at Osaka University Hospital between 2007 and 2015. The registry collects clinical data, including cancer status (site and stage), on all patients treated for cancer. Of them, 19,006 patients with complete data were included. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression. Results: Of the 19,006 patients, 5,887 (31%) patients were in the chemotherapy group. Non-targeted chemotherapy was used in 5,371 patients. Stroke occurred in 44 patients (0.75%) in the chemotherapy group and 51 patients (0.39%) in the no-chemotherapy group. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than patients in the no-chemotherapy group (HR 1.84; 95% CI 1.23-2.75; Figure [A]). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91; Figure [B]). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03). These findings were consistent with analysis wherein the effect of chemotherapy was treated as a time-dependent covariate (HR 1.02; 95% CI 0.55-1.88). Conclusions: In this population, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.

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Relationship between hypoglycaemia, cardiovascular outcomes, and empagliflozin treatment in the EMPA-REG OUTCOME® trial

European Heart Journal ◽

10.1093/eurheartj/ehz621 ◽

2019 ◽

Vol 41 (2) ◽

pp. 209-217 ◽

Cited By ~ 11

Author(s):

David Fitchett ◽

Silvio E Inzucchi ◽

Christoph Wanner ◽

Michaela Mattheus ◽

Jyothis T George ◽

...

Keyword(s):

Cox Regression ◽

Severe Hypoglycaemia ◽

Glycated Haemoglobin ◽

Protective Effects ◽

Increased Risk ◽

Symptomatic Hypoglycaemia ◽

Post Hoc ◽

The Impact ◽

Time Varying Covariates

Abstract Aims Hypoglycaemia, in patients with Type 2 diabetes (T2D) is associated with an increased risk for cardiovascular (CV) events. In EMPA-REG OUTCOME, the sodium-glucose co-transporter-2 inhibitor empagliflozin reduced the risk of CV death by 38% and heart failure hospitalization (HHF) by 35%, while decreasing glycated haemoglobin (HbA1c) without increasing hypoglycaemia. We investigated CV outcomes in patients with hypoglycaemia during the trial and the impact of hypoglycaemia on the treatment effect of empagliflozin. Methods and results About 7020 patients with T2D (HbA1c 7–10%) were treated with empagliflozin 10 or 25 mg, or placebo and followed for median 3.1 years. The relationship between on-trial hypoglycaemia and CV outcomes, and effects of empagliflozin on outcomes by incident hypoglycaemia [HYPO-broad: symptomatic hypoglycaemia with plasma glucose (PG) ≤70 mg/dL, any hypoglycaemia with PG <54 mg/dL, or severe hypoglycaemia, and HYPO-strict: hypoglycaemia with PG <54 mg/dL, or severe hypoglycaemia] was investigated using adjusted Cox regression models with time-varying covariates for hypoglycaemia and interaction with treatment. HYPO-broad occurred in 28% in each group and HYPO-strict in 19%. In the placebo group, hypoglycaemia was associated with an increased risk of HHF for both HYPO-broad [hazard ratio (HR, 95% confidence interval, CI) 1.91 (1.25–2.93)] and HYPO-strict [1.72 (1.06–2.78)]. HYPO-broad (but not HYPO-strict) was associated with an increased risk of myocardial infarction (MI) [HR 1.56 (1.06–2.29)]. Empagliflozin improved CV outcomes, regardless of occurrence of hypoglycaemia (P-for interactions >0.05). Conclusion In this post hoc exploratory analysis, hypoglycaemia was associated with an increased risk of HHF and MI. Hypoglycaemia risk was not increased with empagliflozin and incident hypoglycaemia did not attenuate its cardio-protective effects.

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