Incidence, predictive factors and severity of methotrexate-related liver injury in rheumatoid arthritis: a longitudinal cohort study

Abstract Objectives The aims were to determine the incidence rate, predictive factors and severity of liver injury that develops during MTX treatment for RA and to evaluate the role of pretreatment hepatic fat deposition. Methods We used an ongoing real-life registry containing RA patients who had started MTX between August 2007 and April 2018 at participating institutions. The liver-to-spleen attenuation ratio on CT scans at enrolment was used to evaluate pretreatment fat deposition quantitatively. Patients were followed until persistent transaminitis developed or until the end of the study. Liver biopsy was performed for patients who presented with persistent transaminitis. Results We followed 289 new MTX users without pretreatment elevations of transaminases (mean follow-up time, 58.3 months). Hepatic fat deposition was detected in half of the patients at enrolment. During follow-up, persistent transaminitis occurred at a crude incidence rate of 3.13 per 100 person-years, and the cumulative incidence at 5 years was estimated to be 13%. A multivariate Fine–Gray regression analysis showed that the most important predictive factors were pre-existing moderate to severe fat deposition (adjusted hazard ratio, 7.69; 95% CI: 3.10, 19.10) and obesity (adjusted hazard ratio, 2.68; 95% CI: 1.37, 5.25). Non-alcoholic steatohepatitis (NASH) was the most predominant pattern in liver biopsy samples. Hepatic fibrosis was found in 90% of samples, but most cases were not advanced. Conclusion Aggravation of underlying fatty liver to NASH with fibrosis seems to be an important mechanism of liver injury that occurs in MTX-treated RA patients.

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Association Between Kawasaki Disease and Childhood Epilepsy: A Nationwide Cohort Study in Taiwan

Frontiers in Neurology ◽

10.3389/fneur.2021.627712 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chien-Heng Lin ◽

Jung-Nien Lai ◽

Inn-Chi Lee ◽

I-Ching Chou ◽

Wei-De Lin ◽

...

Keyword(s):

Kawasaki Disease ◽

Confidence Interval ◽

Incidence Rate ◽

Significant Risk ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Cardiac Complications ◽

Research Database ◽

Seizure Disorders

Background: Kawasaki disease is a common vasculitis of childhood in East Asia. The complications following Kawasaki disease mostly included cardiovascular sequelae; non-cardiac complications have been reported but less studied. This study investigated potential epilepsy following Kawasaki disease in Taiwanese children.Objectives: Through National Health Insurance Research Database, we retrospectively analyzed the data of children aged <18 years with clinically diagnosed Kawasaki disease from January 1, 2000 to December 31, 2012 in Taiwan. These patients were followed up to estimate the incidence of epilepsy in the Kawasaki cohort in comparison with that in the non-Kawasaki cohort in Taiwan.Results: A total of 8,463 and 33,872 patients in the Kawasaki and non-Kawasaki cohorts were included in the study, respectively. Of the total eligible study subjects, 61.1% were boys and 38.9% were girls; most patients with newly diagnosed Kawasaki disease were aged <5 years [88.1%]. Patients with Kawasaki disease showed a higher incidence rate [47.98 vs. 27.45 every 100,000 person years] and significantly higher risk [adjusted hazard ratio = 1.66, 95% confidence interval = 1.13–2.44] of epilepsy than those without the disease. Additionally, female sex [adjusted hazard ratio = 2.30, 95% confidence interval = 1.31–4.04] and age <5 years [adjusted hazard ratio = 1.82, 95% confidence interval = 1.22–2.72] showed a significantly higher risk of epilepsy in the Kawasaki cohort.Conclusion: Results revealed a higher incidence rate and significant risk of epilepsy in Taiwanese children with Kawasaki disease than in those without the disease. Therefore, children diagnosed with Kawasaki disease are recommended follow-up as they have a high risk of epilepsy and seizure disorders.

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Prevalence and Predictive Factors of Transient and Permanent Congenital Hypothyroidism in Fars Province, Iran

10.21203/rs.3.rs-311411/v1 ◽

2021 ◽

Author(s):

Ashkan Habib ◽

Alireza Shojazadeh ◽

Mohadeseh Molayemat ◽

Asadollah Habib ◽

Marjan Jeddi ◽

...

Keyword(s):

Incidence Rate ◽

Congenital Hypothyroidism ◽

Predictive Factors ◽

Cross Sectional Study ◽

Thyroid Stimulating Hormone ◽

Fars Province ◽

Venous Sampling ◽

Cross Sectional ◽

Outpatient Visits

Abstract Introduction: There is no data on the number as well as the prevalence of congenital hypothyroidism (CH) in the Fars province. Hence, we designed this study to analyze the latest data and the possible predictive factors on transient and permanent CH in this province.Method: This cross sectional study is based on the Fars province screening data from 2013 till 2016. A total of 294,214 newborns were screened with 938 confirmed cases of CH, which were included in this study. After recall and completion of the missing data, follow-up data for 642 CH cases with thyroid stimulating hormone (TSH) concentrations and levothyroxine doses for ten outpatient visits and final transient vs. permanent CH diagnosis were included.Results: The incidence rate was 1:313.66, and out of the 642 CH cases, 66.04% had permanent CH, while 33.96% had transient CH. TSH level trend during the outpatient visits were not statistically different between the two groups (P=0.312). A cutoff point of >2.25 levothyroxine µg/kg (sensitivity: 76.11%, specificity: 58.52%) at the third year and a TSH concentration of >43.35 mIU/L at the venous sampling (initial TSH) (sensitivity: 31.66%, specificity: 90.32%) were the predictive factors for permanent CH.Conclusion: Fars province has one of the highest incidence rate of CH in Iran. Levothyroxine dose at the 3rd year and the 1st venous TSH sample are the predictive factors for permanent CH in the Iranian population; however, TSH concentrations during follow ups are unreliable predictors.

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Association between physical activity, occupational sitting time and mortality in a general population: An 18-year prospective survey in Tanushimaru, Japan

European Journal of Preventive Cardiology ◽

10.1177/2047487318810020 ◽

2018 ◽

Vol 27 (7) ◽

pp. 758-766 ◽

Cited By ~ 6

Author(s):

Akiko Sakaue ◽

Hisashi Adachi ◽

Mika Enomoto ◽

Ako Fukami ◽

Eita Kumagai ◽

...

Keyword(s):

Physical Activity ◽

General Population ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Sitting Time ◽

Inverse Association ◽

Physical Activity Questionnaire ◽

Occupational Sitting ◽

Activity Questionnaire

Aims It is well known that a decline in physical activity is associated with an increase of all-cause death including cardiovascular events and cancer. Few studies have examined the association between occupational sitting time and mortality. Therefore, we investigated this issue in a general population. Methods Physical activity and occupational sitting time were measured using the Baecke physical activity questionnaire in 1999. The questionnaire generated indices in three physical activity categories: work, sport and leisure-time. A total physical activity index was calculated by adding these three indices. The Baecke physical activity questionnaire was able to evaluate occupational sitting time. Hazard ratios and 95% confidence intervals (CIs) were calculated using Cox's proportional hazard regression models. Results We enrolled a total of 1680 participants, who were followed up for 15.9 ± 3.8 years. The final follow-up rate was 93%. During the follow-up period, 397 subjects died. A significant inverse association ( p < 0.0001) was found between physical activity and mortality after adjustment for age and sex. Compared with lower levels of physical activity, the adjusted hazard ratio for mortality at higher levels of physical activity was 0.85 (95% CI: 0.78–0.92). Longer occupational sitting time was also significantly associated with higher mortality ( p < 0.01). The adjusted hazard ratio for mortality at longer occupational sitting time was 1.16 (95% CI: 1.05–1.27). These findings were observed in males, but not in females. Conclusions Our data demonstrated that higher levels of physical activity are associated with a reduced risk of cancer and cardiovascular death. Further, longer occupational sitting time is associated with increased mortality.

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Infection-Related Acute Care Events among Patients with Glomerular Disease

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.05900420 ◽

2020 ◽

Vol 15 (12) ◽

pp. 1749-1761

Author(s):

Dorey A. Glenn ◽

Candace D. Henderson ◽

Michelle O’Shaughnessy ◽

Yichun Hu ◽

Andrew Bomback ◽

...

Keyword(s):

Risk Factors ◽

Serum Albumin ◽

Acute Care ◽

Incidence Rates ◽

Hazard Ratio ◽

Glomerular Disease ◽

Urinary Protein ◽

Adjusted Hazard Ratio ◽

Creatinine Ratio

Background and objectivesInfections contribute to patient morbidity and mortality in glomerular disease. We sought to describe the incidence of, and identify risk factors for, infection-related acute care events among Cure Glomerulonephropathy Network (CureGN) study participants.Design, setting, participants, & measurementsCureGN is a prospective, multicenter, cohort study of children and adults with biopsy sample–proven minimal change disease, FSGS, membranous nephropathy, or IgA nephropathy/vasculitis. Risk factors for time to first infection-related acute care events (hospitalization or emergency department visit) were identified using multivariable Cox proportional hazards regression.ResultsOf 1741 participants (43% female, 41% <18 years, 68% White), 163 (9%) experienced infection-related acute care events over a median follow-up of 17 months (interquartile range, 9–26 months). Unadjusted incidence rates of infection-related acute care events were 13.2 and 6.2 events per 100 person-years among pediatric and adult participants, respectively. Among participants with versus without corticosteroid exposure at enrollment, unadjusted incidence rates were 50.6 and 28.6 per 100 person-years, respectively, during the first year of follow-up (adjusted hazard ratio for time to first infection, 1.31; 95% CI, 0.89 to 1.93), and 4.1 and 1.1 per 100 person-years, respectively, after 1 year of follow-up (hazard ratio, 2.99; 95% CI, 1.54 to 5.79). Hypoalbuminemia combined with nephrotic-range proteinuria (serum albumin ≤2.5 g/dl and urinary protein-creatinine ratio >3.5 mg/mg), compared with serum albumin >2.5 g/dl and urinary protein-creatinine ratio ≤3.5 mg/mg, was associated with higher risk of time to first infection (adjusted hazard ratio, 2.49; 95% CI, 1.51 to 4.12).ConclusionsAmong CureGN participants, infection-related acute care events were common and associated with younger age, corticosteroid exposure, and hypoalbuminemia with proteinuria.

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Betahistine in the Treatment of Peripheral Vestibular Vertigo: Results of a Real-Life Study in Primary Care

Ear Nose & Throat Journal ◽

10.1177/0145561319849946 ◽

2019 ◽

Vol 99 (6) ◽

pp. 356-360

Author(s):

Guillermo Sanchez-Vanegas ◽

Carlos Castro-Moreno ◽

Diana Buitrago

Keyword(s):

Primary Care ◽

Incidence Rate ◽

Cumulative Incidence ◽

Primary Care Physicians ◽

Real Life ◽

Global Improvement ◽

Life Study ◽

Observational Prospective Cohort Study ◽

Vestibular Vertigo

The present research was carried out with the objective to establish the clinical effect and safety of betahistine (48 mg daily), for the management of peripheral vestibular vertigo, in patients treated by primary care physicians in Colombia. An observational prospective cohort study was conducted including patients older than 15 years with clinical diagnosis of peripheral vestibular vertigo who were candidates to be treated with betahistine (48 mg daily). A sample size of 150 individuals was calculated, and weekly follow-ups were planned for 12 weeks. Rotatory movement sensation, loss of balance, and global improvement scale from 0 to 100 points were evaluated. Complete improvement was defined when the patient reached a level of 100 points. We calculated average weekly improvement, cumulative incidence of complete improvement, incidence rate of complete improvement, and the probability of complete improvement as a function of time. After the first week, the average improvement was 56.6 points (95% confidence interval [CI]: 50.4-62.7). At the end of week 12, it was 89.3 points (95% CI: 86.5-92.2). Sixty-one percent of the patients had achieved complete improvement at the end of the second week. After the sixth week, the percentage of cumulative improvement was 72%, and after 12 weeks of follow-up, the cumulative incidence of complete improvement was 73% (95% CI: 65%-80%). Based on the follow-up times, a complete improvement incidence rate of 16 cases per 100 people/week was calculated (95% CI: 13-19). We concluded that Betahistine (48 mg daily) has a positive effect, controlling the symptoms associated with benign paroxysmal vertigo, with an adequate safety profile.

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Incidence and Risk of Venous Thromboembolism Among Taiwan Osteoporotic Fracture Population under Osteoporosis Pharmacological Treatments

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-3114 ◽

2014 ◽

Vol 99 (5) ◽

pp. 1599-1607 ◽

Cited By ~ 4

Author(s):

Tzu-Chieh Lin ◽

Cheng-Han Lee ◽

Chyun-Yu Yang ◽

Yea-Huei Kao Yang ◽

Swu-Jane Lin

Keyword(s):

Venous Thromboembolism ◽

Confidence Interval ◽

Osteoporotic Fracture ◽

Osteoporotic Fractures ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Osteoporosis Therapy ◽

Treatment Scenario ◽

Fracture Population

Context: There was no clear evidence for the association between oral bisphosphonates or raloxifene and venous thromboembolism (VTE). There might also be ethnic differences in VTE risk. Objective: The purpose of this study was to compare the incidence and risk of VTEs for different classes of osteoporosis drugs in the Taiwanese osteoporotic fracture population. Design: This was a retrospective cohort study from 2003 to 2007, with up to 6 years follow-up. Setting: Enrollees were participants in Taiwan National Health Insurance. Patients: Patients older than 50 years who had vertebral or hip fractures and were new to osteoporosis therapy were recruited. Intervention: Patients were classified into the alendronate, calcitonin, or raloxifene group according to exposure after follow-up. Main Outcome Measure: The primary outcome of our study was all incident VTEs, including deep vein thrombosis and pulmonary embolism. Cox proportional hazard models were used to compare the relative VTE risk among alendronate, raloxifene, and calcitonin groups under an on-treatment scenario. Results: There were 25 443, 9642, and 31 900 patients in the alendronate, raloxifene, and calcitonin groups, and the mean age was 74.5 years (SD, 9.6). The incidence of VTE in the alendronate, raloxifene, and calcitonin groups was 11.2, 8.5, and 18.8 per 10 000 person-years. Results from Cox analyses showed that alendronate or raloxifene recipients did not have a higher risk for VTE than calcitonin recipients (adjusted hazard ratio for alendronate, 0.84; 95% confidence interval, 0.47–1.51; adjusted hazard ratio for raloxifene, 0.64; 95% confidence interval, 0.33–1.28). Conclusion: This retrospective analysis found that the incidence of VTE in Taiwanese patients with osteoporosis was low, and the risk of VTE was similar across alendronate, raloxifene, and calcitonin recipients in patients with osteoporotic fractures who were new to osteoporosis therapy.

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Stroke Risks in Adult Survivors of Preterm Birth: National Cohort and Cosibling Study

Stroke ◽

10.1161/strokeaha.120.033797 ◽

2021 ◽

Author(s):

Casey Crump ◽

Jan Sundquist ◽

Kristina Sundquist

Keyword(s):

Ischemic Stroke ◽

Preterm Birth ◽

Large Population ◽

Adult Survivors ◽

Small Sample ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

National Cohort

Background and Purpose: Clinicians will increasingly encounter adult patients who were born preterm and will need to understand their long-term sequelae. Adult survivors of preterm birth have been reported to have increased risks of hypertension and other stroke risk factors. However, their stroke risks have seldom been examined and the findings are discrepant, possibly due to small sample sizes, insufficient follow-up, or survivor bias. We examined whether preterm birth is associated with stroke in a large population-based cohort. Methods: A national cohort study was conducted of all 2 140 866 singletons born in Sweden from 1973 to 1994 who survived to age 18 years, who were followed up for first-time stroke through 2015 (maximum age 43 years). Cox regression was used to examine stroke risks associated with gestational age at birth, adjusting for other perinatal and parental factors. Cosibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. Results: In 28.0 million person-years of follow-up, 4861 (0.2%) people were diagnosed with stroke. At ages 18 to 43 years, the adjusted hazard ratio for stroke associated with preterm birth (<37 weeks) was 1.26 (95% CI, 1.12–1.43; P <0.001), and further stratified was 1.42 (1.11–1.81; P =0.005) for early preterm (22–33 weeks) and 1.22 (1.06–1.40; P =0.004) for late preterm (34–36 weeks), compared with full-term (39–41 weeks). Positive associations were found with both hemorrhagic stroke (early preterm: adjusted hazard ratio, 1.42 [95% CI, 1.04–1.94]; any preterm: 1.15 [0.97–1.35]) and ischemic stroke (early preterm: adjusted hazard ratio, 1.33 [95% CI, 0.87–2.03]; any preterm: 1.31 [1.07–1.60]). These findings were similar in men and women and only partially explained by shared determinants of preterm birth and stroke within families. Conclusions: In this large national cohort, preterm birth was associated with increased risks of both hemorrhagic and ischemic stroke in adulthood. Preterm birth survivors need early preventive evaluation and long-term clinical follow-up to reduce their lifetime risk of stroke.

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Cyproterone Acetate and risk of Meningioma

10.1101/2020.12.29.20248395 ◽

2021 ◽

Author(s):

Anders P. Mikkelsen ◽

Iben K. Greiber ◽

Nikolai M. Scheller ◽

Malene Hilden ◽

Øjvind Lidegaard

Keyword(s):

Cumulative Dose ◽

Cyproterone Acetate ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Response Relationship ◽

Dose Response Relationship ◽

National Healthcare ◽

Background Population ◽

Increased Risk

AbstractCyproterone acetate (CPA) is a synthetic steroid hormone. We assessed the association between the use of CPA and the risk of developing meningioma.In a historical prospective cohort study, using Danish national healthcare registers we included a cohort of 5,730,654 individuals, among whom 1,982 were exposed to CPA. During follow-up, we identified 8,957 cases of meningioma, of which 16 were exposed to CPA. From 2013 to 2019 the number of new users increased from 18.1 to 62.3 new users per million, while the proportion of new users who were transgender increased from 18.4 to 68.3%. Analyses showed a significantly increased risk of meningioma according to cumulative dose of CPA; 0.1-10 grams of CPA, incidence rate 78.8 (95% CI 15.7-141.9) per 100.000 person years and adjusted hazard ratio 7.0 (3.1-15.6); >10 grams of CPA, incidence 187.5 (71.3-303.7) and adjusted hazard ratio 19.2 (10.3-35.8), as compared to the background population.In conclusion, the cumulative dose of CPA was associated with an increased incidence and hazard ratio of meningioma, showing a dose-response relationship. The number of new CPA users increased more than 3-fold from 2013 to 2019, primarily driven by new transgender users.

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Elevated Lp(a) (Lipoprotein[a]) Levels Increase Risk of 30-Day Major Adverse Cardiovascular Events in Patients Following Carotid Endarterectomy

Stroke ◽

10.1161/strokeaha.120.030616 ◽

2020 ◽

Vol 51 (10) ◽

pp. 2972-2982 ◽

Cited By ~ 1

Author(s):

Farahnaz Waissi ◽

Mirthe Dekker ◽

Nathalie Timmerman ◽

Renate M. Hoogeveen ◽

Joelle van Bennekom ◽

...

Keyword(s):

Risk Factor ◽

Carotid Endarterectomy ◽

Cardiovascular Events ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Major Adverse Cardiovascular Events ◽

Lipoprotein A ◽

Kaplan Meier ◽

Increased Risk

Background and Purpose: General population studies have shown that elevated Lp(a) (lipoprotein[a]) levels are an emerging risk factor for cardiovascular disease and subsequent cardiovascular events. The role of Lp(a) for the risk of secondary MACE in patients undergoing carotid endarterectomy (CEA) is unknown. Our objective is to assess the association of elevated Lp(a) levels with the risk of secondary MACE in patients undergoing CEA. Methods: Lp(a) concentrations were determined in preoperative blood samples of 944 consecutive patients with CEA included in the Athero-Express Biobank Study. During 3-year follow-up, major adverse cardiovascular events (MACE), consisting of myocardial infarction, stroke, and cardiovascular death, were documented. Results: After 3 years follow-up, Kaplan-Meier cumulative event rates for MACE were 15.4% in patients with high Lp(a) levels (>137 nmol/L; >80th cohort percentile) and 10.2% in patients with low Lp(a) levels (≤137 nmol/L; ≤80th cohort percentile; log-rank test: P =0.047). Cox regression analyses adjusted for conventional cardiovascular risk factors revealed a significant association between high Lp(a) levels and 3-year MACE with an adjusted hazard ratio of 1.69 (95% CI, 1.07–2.66). One-third of MACE occurred within 30 days after CEA, with an adjusted hazard ratio for the 30-day risk of MACE of 2.05 (95% CI, 1.01–4.17). Kaplan-Meier curves from time point 30 days to 3 years onward revealed no significant association between high Lp(a) levels and MACE. Lp(a) levels were not associated with histological carotid plaque characteristics. Conclusions: High Lp(a) levels (>137 nmol/L; >80th cohort percentile) are associated with an increased risk of 30-day MACE after CEA. This identifies elevated Lp(a) levels as a new potential risk factor for secondary cardiovascular events in patients after carotid surgery. Future studies are required to investigate whether Lp(a) levels might be useful in guiding treatment algorithms for carotid intervention.

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Preterm delivery and long term mortality in women: national cohort and co-sibling study

BMJ ◽

10.1136/bmj.m2533 ◽

2020 ◽

pp. m2533 ◽

Cited By ~ 1

Author(s):

Casey Crump ◽

Jan Sundquist ◽

Kristina Sundquist

Keyword(s):

Environmental Factors ◽

Confidence Interval ◽

Preterm Delivery ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Term Delivery ◽

National Cohort ◽

Long Term Mortality

Abstract Objectives To examine the long term mortality associated with preterm delivery in a large population based cohort of women, and to assess for potential confounding by shared familial factors. Design National cohort study. Setting Sweden. Participants All 2 189 477 women with a singleton delivery in 1973-2015. Main outcome measures All cause and cause specific mortality up to 2016, identified from nationwide death records. Cox regression was used to calculate hazard ratios while adjusting for confounders, and co-sibling analyses assessed the potential influence of unmeasured shared familial (genetic and environmental) factors. Results In 50.7 million person years of follow-up, 76 535 (3.5%) women died (median age at death was 57.6). In the 10 years after delivery, the adjusted hazard ratio for all cause mortality associated with preterm delivery (<37 weeks) was 1.73 (95% confidence interval 1.61 to 1.87), and when further stratified was 2.20 (1.63 to 2.96) for extremely preterm delivery (22-27 weeks), 2.28 (2.01 to 2.58) for very preterm delivery (28-33 weeks), 1.52 (1.39 to 1.67) for late preterm delivery (34-36 weeks), and 1.19 (1.12 to 1.27) for early term delivery (37-38 weeks) compared with full term delivery (39-41 weeks). These risks declined but remained significantly raised after longer follow-up times: for preterm versus full term births, 10-19 years after delivery, the adjusted hazard ratio was 1.45 (95% confidence interval 1.37 to 1.53); 20-44 years after delivery, the adjusted hazard ratio was 1.37 (1.33 to 1.41). These findings did not seem to be attributable to shared genetic or environmental factors within families. Several causes were identified, including cardiovascular and respiratory disorders, diabetes, and cancer. Conclusions In this large national cohort of women, the findings suggested that preterm and early term delivery were independent risk factors for premature mortality from several major causes. These associations declined over time but remained raised up to 40 years later.

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