scholarly journals OP0133 THE PREVALENCE AND RISK FACTORS OF RETINAL TOXICITY ASSOCIATED WITH LONG-TERM HYDROXYCHLOROQUINE USE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 77-78
Author(s):  
S. Do ◽  
J. H. Du ◽  
J. X. An ◽  
J. Wang ◽  
A. Lin

Background:Hydroxychloroquine (HCQ) is commonly used for the treatment of various autoimmune diseases. The medication is generally well-tolerated. However, long-term use after 5 years may increase the risk of retinopathy. One study in 2014 has demonstrated the risk can be as high as 7.5%. Optical Coherence Tomography (OCT) has become a major modality in screening retinopathy.Objectives:To evaluate the prevalence of retinal toxicity among patients using hydroxychloroquine and to determine various risk factors associated with hydroxychloroquine-associated retinal toxicity.Methods:We performed a retrospective chart review on a cohort of adult patients with long-term use (≥ 5 years cumulative) of HCQ between January 1st, 2011 to December 31st, 2018 from the Kaiser Permanente San Bernardino County and Riverside medical center areas in Southern California, USA. Patients were excluded if they had previously been diagnosed with retinopathy prior to hydroxychloroquine use, were deceased, or had incomplete OCT exam. Our primary endpoint was the prevalence of patients who developed retinal toxicity detected by OCT, and later confirmed by retinal specialist. Potential risk factors (age, duration of therapy, daily consumption per actual body weight, cumulative dose, confounding diseases and medication) for developing retinopathy were also evaluated. Univariable and multivariable logistic regression analyses were used to determine risk factors associated with retinal toxicity.Results:Among 676 patients exposed to more than 5 years of HCQ, the overall prevalence of retinal toxicity was 6.8%, and ranged from 2.5% to 22.2% depending on the age, weight-based dosing, duration of use and cumulative dose. Duration of therapy for 10 years or more increased risk of retinopathy by approximately 5 to 19 folds. Similarly, weight-based dose of 7 mg/kg/day or greater was assciated with increased risk of retinopathy by approximately 5 times. Patients with cumulative dose of 2000 grams or more had greater than 15 times higher risk of developing retinopathy. Duration of use for10 years or more (odd ratio 4.32, 95% CI 1.99 – 12.49), age (odd ratio 1.04; 95% CI 1.01 - 1.08), cumulative dose of more than 1500 g (odd ratio 7.4; 95% CI 1.40 – 39.04) and atherosclerosis of the aorta (odd ratio 2.59; 95% CI, 1.24 – 5.41) correlated with higher risk of retinal toxicity.Conclusion:The overall prevalence of retinopathy was 6.8%. Regular OCT screening, especially in patients with hydroxychloroquine use for more than 10 years, daily intake > 7 mg/kg, or cumulative dose > 1500 grams is important in detecting hydroxychloroquine-associated retinal toxicityReferences:[1]Hobbs HE. Sorsby A, & Freedman A. Retinopathy Following Chloroquine Therapy. The Lancet. 1959; 2(7101): 478-480.[2]Levy, G. D., Munz, S. J., Paschal, J., Cohen, H. B., Pince, K. J., & Peterson, T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis & Rheumatism: 1997; 40(8): 1482-1486.[3]Ding, H. J., Denniston, A. K., Rao, V. K., & Gordon, C. Hydroxychloroquine-related retinal toxicity. Rheumatology. 2016; 55(6): 957-967.[4]Stelton, C. R., Connors, D. B., Walia, S. S., & Walia, H. S. Hydrochloroquine retinopathy: characteristic presentation with review of screening. Clinical rheumatology. 2013; 32(6): 895-898.[5]Marmor, M. F., Kellner, U., Lai, T. Y., Melles, R. B., & Mieler, W. F. Recommendations on screening for chloroquine and hydroxychloroquine retinopathy (2016 revision). Ophthalmology. 2016; 123(6): 1386-1394.[6]Melles, R. B., & Marmor, M. F. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA ophthalmology. 2014; 132(12): 1453-1460.Disclosure of Interests:None declared

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jee Hee Yoon ◽  
Seo-Yeon Ahn ◽  
Sung-Hoon Jung ◽  
Je-Jung Lee ◽  
Wonsuk Choi ◽  
...  

Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18  μg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid ( odds   ratio   OR = 0.99 , 95% confidence interval (CI) 0.98–0.99; P = 0.020 ) and megestrol acetate use ( OR = 2.63 , 95% CI 1.48–4.67; P = 0.001 ) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI ( OR = 2.54 , 95% CI 1.41–4.60; P = 0.002 ). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S576-S577
Author(s):  
Thomas Holowka ◽  
Harry Cheung ◽  
Maricar F Malinis ◽  
Sarah Perreault ◽  
Iris Isufi ◽  
...  

Abstract Background Ibrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib. Methods We performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection. Results A total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p &lt; 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p &lt; 0.001), neutropenia (OR 3.6, p &lt; 0.01), lymphopenia (OR 2.4, p &lt; 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p &lt; 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments. Conclusion The incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib. Disclosures All Authors: No reported disclosures


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Weber ◽  
D.W Biery ◽  
A Singh ◽  
S Divakaran ◽  
A.N Berman ◽  
...  

Abstract Background Autoimmune systemic inflammatory diseases are associated with an increased risk of cardiovascular disease, particularly myocardial infarction (MI). However, there are limited data on the prevalence and effects of inflammatory disease among U.S. adults who experience an MI at a young age. Purpose We sought to determine the prevalence and prognostic value of inflammatory disease in U.S. adults who experience an MI at a young age. Methods The YOUNG-MI registry is a retrospective cohort study of consecutive patients who experienced a Type 1 MI at or below the age of 50 years from 2000 to 2016 at two large medical centers. A diagnosis of rheumatoid arthritis (RA), psoriasis (PsO), systemic lupus erythematosus (SLE), or inflammatory arthritis was determined through physician review of electronic medical records (EMR). Demographic information, presence of cardiovascular (CV) risk-factors, medical procedures, and medications upon discharge were also ascertained from the EMR. Incidence of death was determined using a combination of EMR and national databases. Cox proportional hazard modeling was performed on a sub-sample following Mahalanobis Distance matching on age, sex, and CV risk factors. Results The cohort consisted of 2097 individuals (median age 45 years, 19% female, 53% ST-elevation MI). Among these, 53 (2.5%) individuals possessed a diagnosis of systemic inflammatory disease at or before their index MI (23% SLE, 9% RA, 64% PsO, 4% inflammatory arthritis). When compared to the remainder of the cohort, patients with a diagnosis of systemic inflammatory disease were more likely to be female (36% vs 19%, p=0.004) and be diagnosed with hypertension (62% vs 46%, p=0.025). There was, however, no significant difference in the prevalence of other CV risk factors – diabetes, smoking, dyslipidemia – or a family history of premature coronary artery disease. Despite these similarities, patients with inflammatory disease were less likely to be prescribed aspirin (88% vs 95%, p=0.049) or a statin (76% vs 89%, p=0.008) upon discharge. Over a median follow-up of 11.2 years, patients with inflammatory disease experienced an increased risk of all-cause mortality when compared with the full-cohort (Figure). Compared to the matched sample (n=138), patients with systemic inflammatory disease exhibited an increased risk of all-cause mortality (HR=2.68, CI [1.18 to 6.07], p=0.018), which remained significant after multivariable adjustment for length of stay and GFR (HR=2.38, CI [1.02 to 5.54], p=0.045). Conclusions Among individuals who experienced an MI at a young age, approximately 2.5% had evidence of a systemic inflammatory disease at or before their MI. When compared with a population of individuals with similar cardiovascular risk profiles, those with inflammatory disease had higher rates of all-cause mortality. Our findings suggest that the presence of a systemic inflammatory disorder is independently associated with worse long-term outcomes. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. 5T32 HL094301 NIH T32 Training Grant, “Noninvasive Cardiovascular Imaging Research Training Program”


2021 ◽  
Vol 11 (3) ◽  
pp. 484-493
Author(s):  
Jukapun Yoodee ◽  
Aumkhae Sookprasert ◽  
Phitjira Sanguanboonyaphong ◽  
Suthan Chanthawong ◽  
Manit Seateaw ◽  
...  

Anthracycline-based regimens with or without anti-human epidermal growth factor receptor (HER) 2 agents such as trastuzumab are effective in breast cancer treatment. Nevertheless, heart failure (HF) has become a significant side effect of these regimens. This study aimed to investigate the incidence and factors associated with HF in breast cancer patients treated with anthracyclines with or without trastuzumab. A retrospective cohort study was performed in patients with breast cancer who were treated with anthracyclines with or without trastuzumab between 1 January 2014 and 31 December 2018. The primary outcome was the incidence of HF. The secondary outcome was the risk factors associated with HF by using the univariable and multivariable cox-proportional hazard model. A total of 475 breast cancer patients were enrolled with a median follow-up time of 2.88 years (interquartile range (IQR), 1.59–3.93). The incidence of HF was 3.2%, corresponding to an incidence rate of 11.1 per 1000 person-years. The increased risk of HF was seen in patients receiving a combination of anthracycline and trastuzumab therapy, patients treated with radiotherapy or palliative-intent chemotherapy, and baseline left ventricular ejection fraction <65%, respectively. There were no statistically significant differences in other risk factors for HF, such as age, cardiovascular comorbidities, and cumulative doxorubicin dose. In conclusion, the incidence of HF was consistently high in patients receiving combination anthracyclines trastuzumab regimens. A reduced baseline left ventricular ejection fraction, radiotherapy, and palliative-intent chemotherapy were associated with an increased risk of HF. Intensive cardiac monitoring in breast cancer patients with an increased risk of HF should be advised to prevent undesired cardiac outcomes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.


2021 ◽  
Author(s):  
Di Zhang ◽  
Yizhou Sun ◽  
Lei Lian ◽  
Bang Hu ◽  
Heng Zhang ◽  
...  

2022 ◽  
Vol 104-B (1) ◽  
pp. 45-52
Author(s):  
Liam Zen Yapp ◽  
Nick D. Clement ◽  
Matthew Moran ◽  
Jon V. Clarke ◽  
A. Hamish R. W. Simpson ◽  
...  

Aims The aim of this study was to determine the long-term mortality rate, and to identify factors associated with this, following primary and revision knee arthroplasty (KA). Methods Data from the Scottish Arthroplasty Project (1998 to 2019) were retrospectively analyzed. Patient mortality data were linked from the National Records of Scotland. Analyses were performed separately for the primary and revised KA cohorts. The standardized mortality ratio (SMR) with 95% confidence intervals (CIs) was calculated for the population at risk. Multivariable Cox proportional hazards were used to identify predictors and estimate relative mortality risks. Results At a median 7.4 years (interquartile range (IQR) 4.0 to 11.6) follow-up, 27.8% of primary (n = 27,474/98,778) and 31.3% of revision (n = 2,611/8,343) KA patients had died. Both primary and revision cohorts had lower mortality rates than the general population (SMR 0.74 (95% CI 0.73 to 0.74); p < 0.001; SMR 0.83 (95% CI 0.80 to 0.86); p < 0.001, respectively), which persisted for 12 and eighteight years after surgery, respectively. Factors associated with increased risk of mortality after primary KA included male sex (hazard ratio (HR) 1.40 (95% CI 1.36 to 1.45)), increasing socioeconomic deprivation (HR 1.43 (95% CI 1.36 to 1.50)), inflammatory polyarthropathy (HR 1.79 (95% CI 1.68 to 1.90)), greater number of comorbidities (HR 1.59 (95% CI 1.51 to 1.68)), and periprosthetic joint infection (PJI) requiring revision (HR 1.92 (95% CI 1.57 to 2.36)) when adjusting for age. Similarly, male sex (HR 1.36 (95% CI 1.24 to 1.49)), increasing socioeconomic deprivation (HR 1.31 (95% CI 1.12 to 1.52)), inflammatory polyarthropathy (HR 1.24 (95% CI 1.12 to 1.37)), greater number of comorbidities (HR 1.64 (95% CI 1.33 to 2.01)), and revision for PJI (HR 1.35 (95% 1.18 to 1.55)) were independently associated with an increased risk of mortality following revision KA when adjusting for age. Conclusion The SMR of patients undergoing primary and revision KA was lower than that of the general population and remained so for several years post-surgery. However, approximately one in four patients undergoing primary and one in three patients undergoing revision KA died within tenten years of surgery. Several patient and surgical factors, including PJI, were associated with the risk of mortality within ten years of primary and revision surgery. Cite this article: Bone Joint J 2022;104-B(1):45–52.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Andrew J Kruger ◽  
Matthew Flaherty ◽  
Padmini Sekar ◽  
Mary Haverbusch ◽  
Charles J Moomaw ◽  
...  

Background: Intracerebral hemorrhage (ICH) has the highest short and long-term morbidity and mortality rates of stroke subtypes. While increased intracranial pressure due to the presence of intraventricular hemorrhage (IVH) may relate to early poor outcomes, the mechanism of reduced 3-month outcome with IVH is unclear. We hypothesized that IVH may cause symptoms similar to normal pressure hydrocephalus (NPH), specifically urinary incontinence and gait disturbance. Methods: We used interviewed cases from the Genetic and Environmental Risk Factors for Hemorrhagic Stroke Study (7/1/08-12/31/12) that had 3-month follow-ups available. CT images were analyzed for ICH volume and location, and IVH presence and volume. Incontinence and dysmobility were defined by Barthel Index at 3 months. We chose a Barthel Index score of bladder less than 10 and mobility less than 15 to define incontinence and dysmobility, respectively. Multivariate analysis was used to assess independent risk factors for incontinence and dysmobility. ICH and IVH volumes were log transformed because of non-normal distributions. Results: Barthel Index was recorded for 308 ICH subjects, of whom 106 (34.4%) had IVH. Presence of IVH was independently associated with both incontinence (OR 2.7; 95% CI 1.4-5.2; p=.003) and dysmobility (OR 2.5; 95% CI 1.4-4.8; p=.003). The Table shows that increasing IVH volume was also independently associated with both incontinence and dysmobility after controlling for ICH location, ICH volume, age, baseline mRS, and admission GCS. Conclusion: Our data show that patients with IVH after ICH are at an increased risk for developing the NPH-like symptoms of incontinence and dysmobility. This may explain the worse long-term outcomes of patients who survive ICH with IVH than those who had ICH alone. Future studies are needed to confirm this finding, and to determine the effect of IVH interventions such as shunt or intraventricular thrombolysis.


Hematology ◽  
2016 ◽  
Vol 2016 (1) ◽  
pp. 323-330 ◽  
Author(s):  
Flora E. van Leeuwen ◽  
Andrea K. Ng

Abstract Long-term survivors of Hodgkin lymphoma (HL) experience several late adverse effects of treatment, with second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) being the leading causes of death in these patients. Other late effects have also been identified, such as pulmonary dysfunction, endocrinopathies (thyroid dysfunction, infertility), neck muscle atrophy, and persistent fatigue. HL survivors have two- to fourfold increased risks to develop SMNs and CVD compared with the general population. With respect to SMNs, radiotherapy is associated with 1.5- to 15-fold increased risk of solid malignancies. The relative risk (RR) of solid tumors increases steadily with increasing follow-up time from 5 to 15 years since radiotherapy, and remains elevated for at least 40 years. The RR of solid SMNs increases strongly with younger age at first treatment. Risks of lung, breast, and gastrointestinal (GI) cancers increase with higher radiation dose. Alkylating agent chemotherapy, especially procarbazine, does not only increase risk of leukemia but also of solid malignancies, in particular, cancers of the lung and GI tract. In contrast, gonadotoxic chemotherapy decreases the risk of radiation-associated breast cancer, through induction of premature menopause. Smoking appears to multiply the radiation- and chemotherapy-associated risks of lung cancer. Both radiotherapy and chemotherapy for HL may cause cardiovascular toxicity. Radiotherapy increases the risk of coronary heart disease, valvular heart disease, congestive heart failure (HF), and pericarditis, whereas anthracycline-containing chemotherapy increases the risks of HF and valvular heart disease. Cardiovascular toxicity following radiotherapy is usually observed from 5 to at least 35 years after therapy, whereas anthracycline-related toxicity is already observed during treatment, up to at least 25 years. The joint effects of anthracyclines, radiotherapy, and conventional cardiovascular risk factors (eg, hypertension, smoking, and physical inactivity) appear to be additive rather than multiplicative. HL survivors need lifelong risk-based screening for selected SMNs and CVDs. Furthermore, preventive strategies should include lifestyle and drug-based interventions to minimize exposure to conventional risk factors for cancer and CVD.


Sign in / Sign up

Export Citation Format

Share Document