Factors Associated with Subsequent Cancers in Patients with Moderate or Severe Chronic Graft-Versus-Host Disease after Transplant for Hematologic Malignancy

Among patients who survive over two years post-allo-HSCT, cGVHD and subsequent cancers represent a significant source of morbidity and mortality. Long-term treatment with immunosuppressive agents and cGVHD-related immune dysregulation may promote the development of subsequent cancers. The burden of subsequent cancers has not yet been described in patients with the most severe manifestations of cGVHD, who likely represent a high-risk population. 439 patients were enrolled on the prospective NIH Chronic GVHD Natural History Study from 2004 to 2019, underwent one-week evaluation by subspecialists, and were scored in accordance with 2005 NIH criteria. Follow-up data were collected by annual survey in which patients self-reported cancer diagnoses and provided consent for confirmatory medical records. Cumulative incidence was estimated for non-melanoma skin cancer (NMSC) competing with death, relapse, or cancer other than NMSC and for cancer other than NMSC competing with death or relapse using the method of Gooley. Potential predictors of subsequent cancers including demographics, transplant characteristics, and cGVHD-related factors were assessed using Gray's test in univariable analysis and Cox proportional hazards models in multivariable analysis. Patients must have been free of post-transplant relapse, NMSC (for NMSC analyses only), and cancer other than NMSC at evaluation to be included in analysis. 22 NMSC and 19 cancers other than NMSC were observed among 205 eligible patients, with cumulative incidences at 60 months of 11.2% (95% CI: 6.9-16.7) and 7.3% (95% CI 4.1-11.8), respectively. The most common cancers other than NMSC were oral squamous cell carcinoma and melanoma (n=6 each). Factors associated with NMSC in univariable analysis were older age at transplant, older age at evaluation, having received sirolimus for cGVHD, having received extracorporeal photopheresis or psoralen-ultraviolet therapy for cGVHD as well as higher CRP, higher NK cell count, and greater BMI at evaluation. Only older age at transplant (HR=2.12; 95% CI: 1.35-3.31) and higher CRP (HR=9.61; 95% CI: 1.29-71.73) remained associated in the multivariable model. Factors associated with subsequent cancers other than NMSC in univariable analysis were T-cell depletion, lymphoid malignant indication for transplant, and increasing severity of oral cGVHD by NIH score. Only lymphoid malignant indication for transplant (HR=2.58; 95% CI: 1.31-5.07) remained significant in multivariable analysis. The association of CRP with NMSC may represent an effect of cGVHD-related inflammation, with CRP previously associated with cGVHD severity. Interestingly, sirolimus was associated with increased risk of NMSC despite its purported antineoplastic effects. One study has previously reported increased risk of NMSC in allo-HSCT recipients treated with sirolimus, however, numerous studies have reported that sirolimus reduces risk of NMSC in solid organ recipients. In this study population, sirolimus was often prescribed later in patients already with refractory cGVHD and adjustment for measures of disease severity attenuated this association in multivariable modeling. The association of lymphoid indication with cancers other than NMSC may be attributable to age as patients with lymphoid malignancies were older at transplant than those with other indications. Additionally, differences in pre-transplant therapies for lymphoid vs. other indications may also contribute to this observation. Post-transplant patients with cGVHD are at high risk of developing subsequent cancers, with higher incidence of NMSC than other cancers. This study identifies potential risk groups for subsequent cancers, highlights patients who may benefit from increased surveillance, and reiterates the need for effective cGVHD therapy to mitigate risks associated with long-term immunosuppression and immune dysfunction. Disclosures Cowen: UpToDate: Other: Royalties; Elsevier: Other: Royalties.

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Thyroid cancer and renal transplantation: a meta-analysis

Endocrine Related Cancer ◽

10.1677/erc-09-0191 ◽

2010 ◽

Vol 17 (1) ◽

pp. 159-167 ◽

Cited By ~ 19

Author(s):

Dheeraj Karamchandani ◽

Ramiro Arias-Amaya ◽

Nora Donaldson ◽

Jackie Gilbert ◽

Klaus-Martin Schulte

Keyword(s):

Thyroid Cancer ◽

Renal Transplantation ◽

Meta Analysis ◽

Solid Organ Transplantation ◽

Solid Organ ◽

Post Transplantation ◽

Post Transplant ◽

Increased Risk

Kidney transplantation and the associated immune suppression are associated with a significantly increased risk of developing cancer during long-term follow-up. Thyroid cancer has been recognised as a potential post-transplant risk but has not yet been subject of a focused review. We therefore performed a meta-analysis on data of 50 861 patients with a total follow-up of 198 595 patient-years and identified a 6.9-fold higher standardised incidence ratio (95% confidence interval 5.6–8.7, P<0.001) of thyroid cancer post renal transplantation as compared with a non-transplant group. All such cancers were of papillary type as far as histopathology was known. The mean time to discovery was 6.0 years post transplantation. This puts thyroid cancer into the group of high cancer risk following solid organ transplantation which already includes cervical cancer, non-melanoma skin cancer, oral and lip cancer and haematological malignancies. It is unclear what causes the increased cancer incidence. Inclusion of thyroid ultrasound in long-term post-transplant evaluation may help to ensure timely recognition of this condition.

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Treatment of Postmenopausal Osteoporosis: Focus on Strontium Ranelate

Clinical Medicine Insights Women s Health ◽

10.4137/cmwh.s5149 ◽

2011 ◽

Vol 4 ◽

pp. CMWH.S5149

Author(s):

Bernard Cortet

Keyword(s):

Risk Factors ◽

Hip Fracture ◽

Vertebral Fracture ◽

High Risk ◽

Hip Fractures ◽

Strontium Ranelate ◽

Phase Iii ◽

Increased Risk ◽

Long Term Treatment

Given its increasing incidence and serious complications, osteoporosis requires safe and effective long-term treatment. Strontium ranelate (SR), a new anti-osteoporotic treatment with a unique mode of action, has been investigated in the Spinal Osteoporosis Therapeutic Intervention (SOTI) and the Treatment Of Peripheral OSteoporosis (TROPOS) trials, two major 3-year multinational placebo-controlled Phase III randomized clinical trials. In SOTI, SR treatment reduced the risk of vertebral fracture by 41% (20.9% vs. 32.8%, P < 0.001); in TROPOS, it reduced the risk of non-vertebral fracture by 16% (11.2% vs. 12.9%, P = 0.04), and the risk of hip fracture in patients at high risk by 36% (4.3% vs. 6.4%, P = 0.046). Also SR has been shown to decrease the risk of vertebral fracture after 4 years of treatment and the risk of nonvertebral fracture after 5 years. Also it demonstrated for high risk patients a significant decrease of the risk of hip fractures (–43%) after 5 years of treatment. Unlike antiresorptive agents, SR produced steady and significant BMD increases that correlated directly with decreases in vertebral and hip fracture risk. Preplanned analysis of the pooled dataset from SOTI and TROPOS showed that SR was effective whether or not patients had key risk factors for fractures at baseline. SR was also effective in patients with osteopenia and younger postmenopausal patients aged 50–65 years. It was also effective for preventing both vertebral and nonvertebral fractures in the elderly (>80 years). Also, SR significantly attenuated height loss and decreased back pain. Finally long-term follow-up showed that BMD gains were maintained through a 8 year-period with maintaining the incidence of fracture between the first 3 years and the last 3 years of treatment. The safety profile of SR was almost similar to placebo in both trials. A slight but significant increased risk of thromboembolism events was noted from the pooled phase III studies data. However this increased was not found in a large retrospective observational study. Thus, SR demonstrates broad spectrum safety and efficacy in reducing the risks of both vertebral and non-vertebral (including hip) fractures in a wide variety of patients, and should be considered as a first-line option to treat women at risk of osteoporotic fractures, whatever their age, the severity of the disease, and their risk factors.

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Dose and Time-Dependent Association of Red Blood Cell Transfusion with Increased Risk of GvHD and Worse Survival after Allogeneic HSCT

Blood ◽

10.1182/blood.v124.21.1555.1555 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1555-1555

Author(s):

Sakura Hosoba ◽

Edmund K. Waller ◽

Sheilagh Barclay ◽

Kirk A Easley ◽

Neeta Shenvi ◽

...

Keyword(s):

T Cell ◽

Multivariable Analysis ◽

Time Dependent ◽

Univariable Analysis ◽

Term Survival ◽

Long Term Survival ◽

Post Transplant ◽

Rbc Transfusion ◽

Grade Iii

Abstract Background: Acute graft-versus-host disease (aGvHD) remains a critical barrier to the success of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nearly all patients who undergo allo-HSCT receive red blood cell (RBC) transfusions during the first 30 days post-transplant, but the long-term effects of transfusions on post-transplant outcomes remain unclear. Preclinical and clinical studies indicate that RBC transfusions can activate dendritic cells (DCs) sensitizing transplant recipients to minor histocompatibility antigens (miHA). Initial interactions between donor T cell and DC regulate donor T cell activation and proliferation. We hypothesized that RBC transfusion may contribute to aGvHD in allo-HSCT patients by activating DC and stimulating allo-reactive T cells or other inflammatory pathways. Methods: We conducted a retrospective study of 336 adult allo-HSCT patients at Emory University Hospital from 2007 to 2013. In cases involving multiple transplants, only data relevant to the first allo-HSCT was included. Graft sources were restricted to bone marrow and G-CSF mobilized peripheral blood (excluded cord blood and T cell depleted grafts). 181 patients (54%) were male and 155 (46%) were female. Patients received transplants from matched related donors (n=123, 37%) or matched unrelated donors (n=213, 63%) for treatment of AML (n=132), ALL (n=40), acute leukemia (n=5), MDS (n=41), CML (n=22), CLL (n=15), HD (n=6), NHL (n=33), AA (n=10), MM (n=7) or other diseases (n=25). aGvHD with onset of up to 150 days after allo-HSCT was the primary end-point. Leuko-reduced and irradiated RBC transfusions administered during the week prior to transplant and 30 days post-transplant (while patients were closely monitored at the transplant center) were provided by a single Blood Bank. The median follow up time was 14.6 months post transplantation (range, 0.3 to 65.1 months). The relationship of RBC transfusions to aGvHD was determined as a time-dependent variable or as a function of the total number of RBC units transfused. Results: 306 patients (91%) received RBC transfusions during the observation timeframe, while 30 (9%) did not require transfusion (median 6). 221 patients (66%) developed grade I-IV aGvHD with a distribution of 85 (25%), 72 (21%), 47 (14%), and 11 (3%) of patients with maximum grade of I, II, III and IV, respectively, while 115 (34%) patients did not show any signs of aGvHD. We compared transfusion history, prior to the diagnosis of GvHD, in patients who developed grade 0-II aGvHD (n=272, 81%) vs. grade III-IV aGvHD (n=64, 19%). Patients with grade III-IV aGvHD received more RBC units (median 8) than patients with grade 0-II aGvHD (median 4). In univariable Cox regression analysis, factors significantly associated with grade III-IV acute GvHD were HLA match (HR 2.22, p=0.004), number of RBC units per week (HR=1.26, p<0.001), cumulative number of RBC units (HR=1.09, p<0.0003), and maximum storage age of units transfused (HR per 5 days older =1.12, p=0.02). In multivariable analysis, HLA match (HR=2.148, p=0.008) and number of RBC units transfused weekly (HR=1.293, p=0.0001) were associated with development of grade III-IV aGvHD. Kaplan-Meier analysis showed significantly worse long-term survival for patients with grade III-IV aGvHD (p value from Log-rank test <0.0001). Increased numbers of transfused RBC units (HR per 2 units =1.17, p<0.0001) was also associated with worse long-term survival in univariable analysis, and patients who received 7 or more RBC units had poorer long-term survival (HR=3.56, p<0.0001). In multivariable analysis, grade III-IV aGvHD was associated with worse long-term survival. Conclusion: We have demonstrated a significant association of RBC transfusions with the subsequent development of grade III-IV aGvHD for allo-HSCT patients and shown that patients with grade III-IV aGvHD have poorer long-term survival. While RBC transfusions are associated with worse survival in univariable analysis, based on our multivariable analysis, increased RBC transfusions are only associated with poorer survival in the context of severe aGvHD. These data are consistent with preclinical observation that allogeneic RBC can initiate inflammatory reactions to miHA. The data suggest that new strategies to improve RBC transfusion methods for allo-HSCT patients are needed to help reduce the risk of severe aGvHD and improve survival rates. Disclosures No relevant conflicts of interest to declare.

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1079. The Risk of Cytomegalovirus (CMV) Infection and Recurrence Among Solid Organ Transplant Recipients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1265 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S567-S568

Author(s):

Joanne Reekie ◽

Mark P Khurana ◽

Isabelle P Lodding ◽

Christina Ekenberg ◽

Finn Gustafsson ◽

...

Keyword(s):

High Risk ◽

Organ Transplant ◽

Solid Organ Transplant ◽

Older Age ◽

First Year ◽

Solid Organ ◽

Cmv Infection ◽

Factors Associated ◽

Stopping Treatment ◽

Cmv Prophylaxis

Abstract Background Solid organ transplant (SOT) recipients are at a high risk of developing cytomegalovirus (CMV) post-transplant (tx) with many experiencing a recurrence shortly after clearing the first episode. We aimed to identify risk factors associated with CMV infection and recurrence. Methods SOT recipients (≥ 18 years) transplanted between 2011-2016 were investigated for factors associated with CMV infection within 1 year from baseline and recurrent CMV within 6 months of stopping CMV treatment for the first infection using cumulative incidence curves and Cox proportional hazards models. Baseline was defined as either tx date or date of stopping CMV prophylaxis for those initiating CMV prophylaxis within 7 days of tx. Individuals with breakthrough CMV while on prophylaxis were excluded (n=29). Figure 1 Risk of CMV infection in 755 SOT recipients in the first year from baseline, stratified by CMV serostatus. Baseline was defined either the date of transplant (n=285) or stopping CMV prophylaxis (n=470). Figure 2 Factors associated with CMV infection in the first year from baseline. Baseline was defined either the date of transplant (n=285) or stopping CMV prophylaxis (n=470). Results We included 755 SOT recipients, 173(23%) developed CMV infection within one year of baseline with CMV disease present at diagnosis in 17% of the cases. The risk of CMV infection was lower in patients with low (aHR 0.19, 95%CI 0.12-0.29) and intermediate (aHR 0.26, 95%CI 0.18-0.36) risk CMV IgG serostatus compared to high risk (Figure1). Liver and lung tx, female sex, older age and year of tx were also associated with an increased risk of CMV infection (Figure 2). Among the 470 (62%) patients who received CMV prophylaxis those who received < 85 days had a higher risk of CMV infection than those receiving ≥ 85 days (aHR 1.80, 95%CI 1.19-2.72). 99 recipients were investigated for recurrent CMV; 40 (40%) experienced relapse within 6 months of stopping treatment for their first infection. The risk of recurrent CMV was significantly lower in those with low (aHR 0.20, 95%CI 0.06-0.74) and intermediate risk serostatus (aHR 0.40, 95%CI 0.19-0.84) (Figure 3). Older age (aHR 1.23 per 5 years older, 95%CI 1.06-1.44) was also significantly associated with recurrent CMV infection (Figure 4). Figure 3 Risk of recurrent CMV infection in the 6 months following clearance and stopping of treatment for the first CMV infection (N=99), stratified by CMV serostatus at the time of transplant Figure 4 Factors associated with recurrent CMV infection within 6 months of stopping treatment for the first CMV infection Conclusion Recurrent CMV infection remains a significant complication among SOT recipients, especially in those with high risk CMV IgG serostatus. These findings highlight the necessity to successfully treat and monitor this subgroup following their first infection. Novel medical interventions and strategies to prevent CMV infection are of particular importance to this high risk group. Disclosures All Authors: No reported disclosures

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Angiogenesis Inhibitors as Anti-Cancer Therapy Following Renal Transplantation: A Case Report and Review of the Literature

Current Oncology ◽

10.3390/curroncol28010064 ◽

2021 ◽

Vol 28 (1) ◽

pp. 661-670

Author(s):

Lawrence Kasherman ◽

Jeffrey Doi ◽

Katherine Karakasis ◽

Jeffrey Schiff ◽

Abhijat Kitchlu ◽

...

Keyword(s):

Renal Transplantation ◽

Organ Transplant ◽

Angiogenesis Inhibitors ◽

Solid Organ ◽

Transplant Recipients ◽

Immunosuppressive Medication ◽

Increased Risk ◽

Anti Cancer ◽

Solid Organ Transplant Recipients

Solid organ transplant recipients on long-term immunosuppressive medication are at increased risk of developing malignancy, and treatment of advanced cancers with angiogenesis inhibitors in this context has not been widely studied. We present a case of recurrent high-grade serous ovarian carcinoma treated with paclitaxel and bevacizumab in the context of prior renal transplantation where the patient responded well to treatment with controlled toxicities, discussing the potential for increased rates of adverse events and drug interactions in this select population.

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

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.328 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 77-78

Author(s):

S. Do ◽

J. H. Du ◽

J. X. An ◽

J. Wang ◽

A. Lin

Keyword(s):

Risk Factors ◽

Cumulative Dose ◽

Daily Intake ◽

Retinal Toxicity ◽

Factors Associated ◽

Duration Of Therapy ◽

Increased Risk ◽

Hydroxychloroquine Retinopathy ◽

Risk Of Retinopathy

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

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Long-term mortality rates and associated risk factors following primary and revision knee arthroplasty

The Bone & Joint Journal ◽

10.1302/0301-620x.104b1.bjj-2021-0753.r1 ◽

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 ◽

...

Keyword(s):

General Population ◽

Knee Arthroplasty ◽

Mortality Rates ◽

Factors Associated ◽

Revision Knee Arthroplasty ◽

Risk Of Mortality ◽

Increased Risk ◽

Male Sex ◽

Long Term Mortality

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.

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Infertility Treatments and Long-Term Neurologic Morbidity of the Offspring

American Journal of Perinatology ◽

10.1055/s-0038-1675159 ◽

2018 ◽

Vol 36 (09) ◽

pp. 949-954 ◽

Cited By ~ 5

Author(s):

Shai Levin ◽

Eyal Sheiner ◽

Tamar Wainstock ◽

Asnat Walfisch ◽

Idit Segal ◽

...

Keyword(s):

Medical Center ◽

Cohort Analysis ◽

Multivariable Analysis ◽

Maternal Diabetes ◽

Population Based ◽

Vitro Fertilization ◽

Increased Risk ◽

Attention Deficit Hyperactivity Disorders

Objective To determine the risk of long-term neurologic morbidity among children (up to 18 years) born following in vitro fertilization (IVF) or ovulation induction (OI) treatments as compared with spontaneously conceived. Study Design A population-based cohort analysis was performed, including data from the perinatal computerized database on all singleton infants born at the Soroka University Medical Center (SUMC) between the years 1991 and 2014. This perinatal database was linked and cross-matched with the SUMC computerized dataset of all pediatric hospitalizations. Results Neurologic morbidity was significantly more common in IVF (3.7%) and OI (4.1%) offspring as compared with those following spontaneous pregnancies (3.1%; p = 0.017). In particular, attention deficit/hyperactivity disorders and headaches were more common in the OI group and sleep disorders in the IVF group, whereas autism and cerebral palsy were comparable between the groups. In the Weibull multivariable analysis, while controlling for maternal age, preterm delivery, birthweight centile, maternal diabetes, and hypertensive disorders, IVF (adjusted hazard ratio [HR]: 1.40; 95% confidence interval [CI]: 1.14–1.71; p = 0.001), but not OI (adjusted HR: 1.17' 95% CI: 0.92–1.48; p = 0.196), was noted as an independent risk factor for long-term pediatric neurologic morbidity. Conclusion IVF offspring appear to be at an increased risk of long-term neurologic morbidity up to 18 years of age.

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Pharmacogenetic association between NAT2 gene polymorphisms and isoniazid induced hepatotoxicity: trial sequence meta-analysis as evidence

Bioscience Reports ◽

10.1042/bsr20180845 ◽

2019 ◽

Vol 39 (1) ◽

Cited By ~ 7

Author(s):

Saif Khan ◽

Raju K. Mandal ◽

Abdulbaset Mohamed Elasbali ◽

Sajad A. Dar ◽

Arshad Jawed ◽

...

Keyword(s):

Gene Polymorphisms ◽

Meta Analysis ◽

Term Treatment ◽

Wild Type ◽

Severe Problem ◽

Trial Sequence ◽

Increased Risk ◽

Long Term Treatment ◽

Nat2 Gene

Abstract Hepatotoxicity is a severe problem generally faced by tuberculosis (TB) patients. It is a well-known adverse reaction due to anti-TB drugs in TB patients undergoing long-term treatment. The studies published previously have explored the connection of N-acetyltransferase 2 (NAT2) gene polymorphisms with isoniazid-induced hepatotoxicity, but the results obtained were inconsistent and inconclusive. A comprehensive trial sequence meta-analysis was conducted employing 12 studies comprising 3613 controls and 933 confirmed TB cases using the databases namely, EMBASE, PubMed (Medline) and Google Scholar till December 2017. A significant association was observed with individuals carrying variant allele at position 481C>T (T vs. C: P = 0.001; OR = 1.278, 95% CI = 1.1100–1.484), at position 590G>A (A vs. G: P = 0.002; OR = 1.421, 95% CI = 1.137–1.776) and at position 857G>A (A vs. G: P = 0.0022; OR = 1.411, 95% CI = 1.052–1.894) to higher risk of hepatotoxicity vis-à-vis wild-type allele. Likewise, the other genetic models of NAT2 gene polymorphisms have also shown increased risk of hepatotoxicity. No evidence of publication bias was observed. These results suggest that genetic variants of NAT2 gene have significant role in isoniazid induced hepatotoxicity. Thus, NAT2 genotyping has the potential to improve the understanding of the drug–enzyme metabolic capacity and help in early predisposition of isoniazid-induced hepatotoxicity.

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Case–control study to estimate odds of death within 28 days of positive test for SARS-CoV-2 prior to vaccination for residents of long-term care facilities in England, 2020–2021

Journal of Epidemiology & Community Health ◽

10.1136/jech-2021-218135 ◽

2021 ◽

pp. jech-2021-218135

Author(s):

Karthik Paranthaman ◽

Hester Allen ◽

Dimple Chudasama ◽

Neville Q Verlander ◽

James Sedgwick

Keyword(s):

Long Term Care ◽

Multivariable Analysis ◽

Adverse Outcomes ◽

Positive Test ◽

Mortality Data ◽

Multivariable Logistic Regression Analysis ◽

Term Care ◽

Increased Risk ◽

Care Facilities

BackgroundPersons living in long-term care facilities (LTCFs) are presumed to be at higher risk of adverse outcomes from SARS-CoV-2 infection due to increasing age and frailty, but the magnitude of increased risk is not well quantified.MethodsAfter linking demographic and mortality data for cases with confirmed SARS-CoV-2 infection between March 2020 and January 2021 in England, a random sample of 6000 persons who died and 36 000 who did not die within 28 days of a positive test was obtained from the dataset of 3 020 800 patients. Based on an address-matching process, the residence type of each case was categorised into one of private home and residential or nursing LTCF. Univariable and multivariable logistic regression analysis was conducted.ResultsMultivariable analysis showed that an interaction effect between age and residence type determined the outcome. Compared with a 60-year-old person not living in LTCF, the adjusted OR (aOR) for same-aged persons living in residential and nursing LTCFs was 1.77 (95% CI 1.21 to 2.6, p=0.0017) and 3.95 (95% CI 2.77 to 5.64, p<0.0001), respectively. At 90 years of age, aORs were 0.87 (95% CI 0.72 to 1.06, p=0.21) and 0.74 (95% CI 0.61 to 0.9, p=0.001), respectively. The model had an overall accuracy of 94.2% (94.2%) when applied to the full dataset of 2 978 800 patients.ConclusionThis study found that residents of LTCFs in England had higher odds of death up to 80 years of age. Beyond 80 years, there was no difference in the odds of death for LTCF residents compared with those in the wider community.

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