scholarly journals Independent risk factors for simvastatin-related myopathy and relevance to different types of muscle symptom

2020 ◽  
Vol 41 (35) ◽  
pp. 3336-3342 ◽  
Author(s):  
Jemma C Hopewell ◽  
Alison Offer ◽  
Richard Haynes ◽  
Louise Bowman ◽  
Jing Li ◽  
...  

Abstract Aims Statins are widely used to prevent cardiovascular events, but little is known about the impact of different risk factors for statin-related myopathy or their relevance to reports of other types of muscle symptom. Methods and results An observational analysis was undertaken of 171 clinically adjudicated cases of myopathy (defined as unexplained muscle pain or weakness with creatine kinase >10× upper limit of normal) and, separately, of 15 208 cases of other muscle symptoms among 58 390 individuals with vascular disease treated with simvastatin for a mean of 3.4 years. Cox proportional hazards models were used to identify independent predictors of myopathy. The rate of myopathy was low: 9 per 10 000 person-years of simvastatin therapy. Independent risk factors for myopathy included: simvastatin dose, ethnicity, sex, age, body mass index, medically treated diabetes, concomitant use of niacin-laropiprant, verapamil, beta-blockers, diltiazem and diuretics. In combination, these risk factors predicted more than a 30-fold risk difference between the top and bottom thirds of a myopathy risk score (hazard ratio : 34.35, 95% CI: 12.73–92.69, P across thirds = 9·1 × 10−48). However, despite the strong association with myopathy, this score was not associated with the other reported muscle symptoms (P across thirds = 0.93). Likewise, although SLCO1B1 genotype was associated with myopathy, it was not associated with other muscle symptoms. Conclusions The absolute risk of simvastatin-related myopathy is low, but individuals at higher risk can be identified to help guide patient management. The lack of association of the myopathy risk score with other muscle symptoms reinforces randomized placebo-controlled evidence that statins do not cause the vast majority of reported muscle symptoms.

2021 ◽  
Vol 8 (2) ◽  
pp. 27-33
Author(s):  
Jiping Zeng ◽  
Ken Batai ◽  
Benjamin Lee

In this study, we aimed to evaluate the impact of surgical wait time (SWT) on outcomes of patients with renal cell carcinoma (RCC), and to investigate risk factors associated with prolonged SWT. Using the National Cancer Database, we retrospectively reviewed the records of patients with pT3 RCC treated with radical or partial nephrectomy between 2004 and 2014. The cohort was divided based on SWT. The primary out-come was 5-year overall survival (OS). Logistic regression analysis was used to investigate the risk factors associated with delayed surgery. Cox proportional hazards models were fitted to assess relations between SWT and 5-year OS after adjusting for confounding factors. A total of 22,653 patients were included in the analysis. Patients with SWT > 10 weeks had higher occurrence of upstaging. Using logistic regression, we found that female patients, African-American or Spanish origin patients, treatment in academic or integrated network cancer center, lack of insurance, median household income of <$38,000, and the Charlson–Deyo score of ≥1 were more likely to have prolonged SWT. SWT > 10 weeks was associated with decreased 5-year OS (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.15–1.33). This risk was not markedly attenuated after adjusting for confounding variables, including age, gender, race, insurance status, Charlson–Deyo score, tumor size, and surgical margin status (adjusted HR, 1.13; 95% CI, 1.04–1.24). In conclusion, the vast majority of patients underwent surgery within 10 weeks. There is a statistically significant trend of increasing SWT over the study period. SWT > 10 weeks is associated with decreased 5-year OS.


2015 ◽  
Vol 25 (4) ◽  
pp. 751-757 ◽  
Author(s):  
Hitoshi Hareyama ◽  
Kenichi Hada ◽  
Kumiko Goto ◽  
Sawako Watanabe ◽  
Minako Hakoyama ◽  
...  

ObjectiveLower extremity lymphedema (LEL) is a major long-term complication of radical surgery. We aimed to estimate the incidence and grading of LEL in women who underwent lymphadenectomy and to evaluate risk factors associated with LEL.Materials and MethodsWe retrospectively reviewed 358 patients with cervical, endometrial, and ovarian cancer who underwent transabdominal complete systematic pelvic and para-aortic lymphadenectomy between 1997 and 2011. Lower extremity lymphedema was graded according to criteria of the International Society of Lymphology. Incidence of LEL and its correlation with various clinical characteristics were investigated using Kaplan-Meier survival and Cox proportional hazards methods.ResultsOverall incidence of LEL was 21.8% (stage 1, 60%; stage 2, 32%; and stage 3, 8%). Cumulative incidence increased with observation period: 12.9% at 1 year, 20.3% at 5 years, and 25.4% at 10 years. Age, cancer type, stage (International Federation of Gynecology and Obstetrics), body mass index, hysterectomy type, lymphocyst formation, lymph node metastasis, and chemotherapy were not associated with LEL. Multivariate analysis confirmed that removal of circumflex iliac lymph nodes (hazard ratio [HR], 4.28; 95% confidence interval [CI], 2.09–8.77; P < 0.0001), cellulitis (HR, 3.48; 95% CI, 2.03–5.98; P < 0.0001), and number of removed lymph nodes (HR, 0.99; 95% CI, 0.98–0.99; P = 0.038) were independent risk factors for LEL.ConclusionsPostoperative LEL incidence increased over time. The results of the present study showed a significant correlation with removal of circumflex iliac lymph nodes and cellulitis with the incidence of LEL. Multicenter or prospective studies are required to clarify treatment efficacies.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Jie Yang ◽  
Yongfang Zhou ◽  
Yan Kang ◽  
Binbin Xu ◽  
Peng Wang ◽  
...  

Background. Delirium is a primary adverse event in ventilated patients who receive long-term monosedative treatment. Sequential sedation may reduce these adverse effects. This study evaluated risk factors for delirium in sequential sedation patients. Methods. A total of 141 patients who underwent sequential sedation were enrolled. Delirium was diagnosed using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scale. Univariate and multivariate Cox proportional hazards regressions were used to predict risk factors. Results. Older age (≥51) (RR = 2.432, 95% CL 1.316–4.494, p=0.005), higher SOFA score (≥14) (RR = 2.022, 95% CL 1.076–3.798, p=0.029), regular smoking (RR = 2.366, 95% CL 1.277–4.382, p=0.006), and higher maintenance dose of midazolam (RR = 1.052, 95% CL 1.000–1.107, p=0.049) and fentanyl (RR = 1.045, 95% CL 1.019–1.072, p=0.001) when patients met sequential criteria, were independent risk factors of delirium. Sequential sedation with dexmedetomidine (RR = 0.448, 95% CL 0.209–0.963, p=0.040) was associated with a lower risk of delirium. Conclusions. Older age, higher SOFA score, regular smoking, and higher maintenance dose of midazolam and fentanyl when patients met sequential criteria were independent risk factors of delirium in sequential sedation patients. Sequential sedation with dexmedetomidine reduced risk of delirium.


2018 ◽  
Vol 14 (1) ◽  
pp. 61-68 ◽  
Author(s):  
Maria Carlsson ◽  
Tom Wilsgaard ◽  
Stein Harald Johnsen ◽  
Liv-Hege Johnsen ◽  
Maja-Lisa Løchen ◽  
...  

Background Studies on the relationship between temporal trends in risk factors and incidence rates of intracerebral hemorrhage are scarce. Aims To analyze temporal trends in risk factors and incidence rates of intracerebral hemorrhage using individual data from a population-based study. Methods We included 28,167 participants of the Tromsø Study enrolled between 1994 and 2008. First-ever intracerebral hemorrhages were registered through 31 December 2013. Hazard ratios (HRs) for intracerebral hemorrhage were analyzed by Cox proportional hazards models, risk factor levels over time by generalized estimating equations, and incidence rate ratios (IRR) by Poisson regression. Results We registered 219 intracerebral hemorrhages. Age, male sex, systolic blood pressure (BP), diastolic BP, and hypertension were associated with intracerebral hemorrhage. Hypertension was more strongly associated with non-lobar intracerebral hemorrhage (HR 5.08, 95% CI 2.86–9.01) than lobar intracerebral hemorrhage (HR 1.91, 95% CI 1.12–3.25). In women, incidence decreased significantly (IRR 0.46, 95% CI 0.23–0.90), driven by a decrease in non-lobar intracerebral hemorrhage. Incidence rates in men remained stable (IRR 1.27, 95% CI 0.69–2.31). BP levels were lower and decreased more steeply in women than in men. The majority with hypertension were untreated, and a high proportion of those treated did not reach treatment goals. Conclusions We observed a significant decrease in intracerebral hemorrhage incidence in women, but not in men. A steeper BP decrease in women may have contributed to the diverging trends. The high proportion of untreated and sub-optimally treated hypertension calls for improved strategies for prevention of intracerebral hemorrhage.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1029-1029
Author(s):  
Xiudong Lei ◽  
Siobhan P. Lynch ◽  
Limin Hsu ◽  
Funda Meric-Bernstam ◽  
Thomas A. Buchholz ◽  
...  

1029 Background: The impact of multifocality (MF) and multicentricity (MC) on locoregional (LR) control for invasive breast cancer, and the optimal local treatment strategy for these tumors, is unknown. In particular, there is disagreement in the literature regarding the use of Breast Conservation Therapy (BCT). We evaluated a large single institution cohort of MF and MC breast cancers to determine if they had inferior LR control rate when compared to their unifocal counterparts. Methods: MF and MC were defined pathologically as more than one lesion in the same quadrant and more than one lesion in separate quadrants, respectively. Patients were categorized by presence or absence of MF or MC disease and by the LR treatment modality received – BCT (n=256), mastectomy alone (n=466), or mastectomy plus post-mastectomy radiation therapy (n=184). 10 patients who underwent BCT for MC disease against physician advice were excluded. MF and MC tumors were analyzed both as a group and as separate entities. Kaplan-Meier product limit method was used to calculate 5-year LR control rate. Cox proportional hazards models were fit to determine independent associations of MF/MC disease with LR control. Results: Median follow up was 52 months. Out of 3722 patients with stage I-III disease who did not receive neoadjuvant chemotherapy, 906 (24%) had MF (n=673) or MC (n=233) disease. 5-year rate of LR control rate was 99% in the MF group, 96% in the MC group, and 98% in the unifocal group, (P = 0.44). Subset analysis revealed no statistical difference in LR control regardless of the type of LR treatment, (P = 0.67 in the BCT group, P = 0.37 in the mastectomy alone group, and P = 0.29 in the mastectomy plus post-mastectomy radiation therapy group). There were 21 in-breast recurrences after BCT (8.2%). After controlling for other risk factors, MF and MC did not have an independent impact on LR control rate. Conclusions: MF and MC disease are not independent risk factors for LR recurrence. Patients with MF and MC breast cancer had similar rates of LR control to their unifocal counterparts, regardless of LR treatment modality. Our data suggest that BCT is a safe option for patients with MF tumors and that MF or MC disease alone is not an indication for post-mastectomy radiation therapy.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
George Howard ◽  
Brett Kissela ◽  
Dawn O Kleindorfer ◽  
Monika M Safford ◽  
Mary Cushman ◽  
...  

Introduction: Risk factors for incident stroke have been shown to also be associated with risk for recurrent stroke; however, to our knowledge there has not been a cohort with risk factors measured in a sufficient number of stroke-free and prevalent stroke cases to contrast the impact of the risk factors between incident and recurrent stroke. Methods: REGARDS recruited 30,239 participants between 2003 and 2007. Participants were stratified into those reporting and not reporting a physician-diagnosed stroke at baseline. Proportional hazards analysis was used to assess the role of risk factors for stroke. Results: Over 6.2 years of follow-up, there were 825 strokes among 25,849 (3.2%) participants without stroke/TIA at baseline, and 310 strokes among 3,101 (10.0%) with stroke/TIA at baseline. In those stroke-free at baseline, there was an age-by-race interaction (p = 0.0003) with a substantially higher risk among blacks than whites at age 45 (HR = 2.69; 95% CI: 1.85 - 3.91), but with increasing age to age 85 this disparity disappeared (HR = 0.95; 95% CI: 0.74 - 1.23). However, there was a constant (p = 0.98) 21% non-significantly higher risk among blacks over the entire age range. For both blacks and whites, the impact of increasing age had a substantially smaller impact on recurrent than incident stroke. The traditional risk factors had a generally smaller impact for recurrent than incident stroke (significantly for atrial fibrillation and heart disease), however, they remained significantly associated with increased risk for recurrent stroke (see table). Discussion: The role of race and age differed for incident versus recurrent stroke, while the traditional risk factors persisted as indicators of higher risk for recurrent stroke. The smaller impact of stroke risk factors on recurrent stroke should be interpreted with caution, as the higher event rate in this group could imply that the risk factors still have a powerful effect on absolute risk.


2021 ◽  
pp. 089686082110189
Author(s):  
Mu-Chi Chung ◽  
Tung-Min Yu ◽  
Ming-Ju Wu ◽  
Ya-Wen Chuang ◽  
Chih-Hsin Muo ◽  
...  

Background: The impact of peritoneal dialysis-associated peritonitis (PD peritonitis) on long-term outcomes is uncertain. This nationwide retrospective study was conducted in Taiwan to understand the incidence, risk factors and long-term outcomes of PD peritonitis. Methods: A total of 11,202 incident adult peritoneal dialysis (PD) patients from 2000 to 2010 were collected from a Longitudinal Health Insurance Database and followed up until the end of 2011. Definition of peritonitis, the primary outcome, simultaneously met the diagnosis of peritonitis (International Classification of Diseases, Ninth Revision, Clinical Modification 567) and antibiotic use. Secondary outcomes included the impact of peritonitis on PD discontinuation and survival. Cox proportional hazards models with and without time-dependent variables were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: There were 7634 peritonitis episodes in 4245 patients during the follow-up period. The overall incidence of peritonitis was 0.18 episodes per patient-year. Peritonitis-associated risk factors included older age, female gender, chronic heart failure, cerebrovascular disease, liver cirrhosis and lower monthly income. In an adjusted Cox hazard proportional regression with the time-dependent model, peritonitis patients had a higher risk of PD discontinuation (HR 2.71, 95% CI 2.52–2.92) and mortality (HR 1.68, 95% CI 1.57–1.81) compared to patients without peritonitis. The adjusted HRs for mortality increased with each prior episode: one episode, two episodes and more than two episodes (all p < 0.05). The adjusted HRs for PD discontinuation also increased with the frequency of peritonitis. These negative effects were greatest during the first year and persisted significantly after 5 years. In a sensitivity analysis in which peritonitis within 30 days of death or PD discontinuation was excluded, peritonitis patients still had significantly increased risk of PD discontinuation and mortality compared to patients without peritonitis. Conclusions: Although peritonitis incidence was low, our findings reveal that peritonitis carried acute and long-term sequelae of higher PD discontinuation and lower patient survival.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Motlalepula Sebilo ◽  
Neo R.T. Ledibane ◽  
Simbarashe Takuva

Background: Antiretroviral treatment (ART) has been associated with the development of certain cardiometabolic diseases (CMDs). The burden of CMDs amongst ART-experienced patients in sub-Saharan Africa was unknown.Objective: We quantified the burden of CMDs and identified the associated risk factors in a large treatment cohort on ART at a high-volume facility in Lesotho.Methods: In this retrospective cohort study, we extracted data from the daily dispensing electronic system and routine clinical records of 785 adults on ART between 2011 and 2015 in Maseru, Lesotho. CMD was defined as a diagnosis of hypertension, diabetes mellitus or dyslipidaemia (singly or collectively). Descriptive statistics were used to describe the disease burden; Kaplan–Meier curves and cause-specific Cox proportional hazards models were fitted to examine the impact of the ART regimen and identify the risk factors associated with the occurrence of CMD.Results: Of the 785 participants, 473 (60%) were women. The median age of the group was 42 years, interquartile range (IQR), 36–51 years. The overall incidence of CMD was 5.6 (95% confidence interval [CI] = 4.4–7.1) per 100 person-months of follow-up. The median time to onset of CMD was 16.6 months (IQR = 7.4–23.4). ART was not associated with the occurrence of CMD (cause-specific hazard ratio [CHR] = 1.55; 95% CI = 0.14–16.85; P = 0.72). Higher body mass index (BMI) was associated with the occurrence of diabetes mellitus (CHR = 1.19; 95% CI = 1.14–1.38; P = 0.026).Conclusion: The incidence of CMD in this relatively young patient population is low yet noteworthy. We recommend that patients living with HIV and AIDS should be routinely screened for CMD. Higher BMI is generally associated with the occurrence of CMD.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9783
Author(s):  
Khalid Hussain Al-Ahmadi ◽  
Mohammed Hussain Alahmadi ◽  
Ali Saeed Al-Zahrani ◽  
Maged Gomaa Hemida

About 83% of laboratory-confirmed Middle East respiratory syndrome coronavirus (MERS-CoV) cases have emerged from Saudi Arabia, which has the highest overall mortality rate worldwide. This retrospective study assesses the impact of spatial/patient characteristics for 14-and 45-day MERS-CoV mortality using 2012–2019 data reported across Saudi regions and provinces. The Kaplan–Meier estimator was employed to estimate MERS-CoV survival rates, Cox proportional-hazards (CPH) models were applied to estimate hazard ratios (HRs) for 14-and 45-day mortality predictors, and univariate local spatial autocorrelation and multivariate spatial clustering analyses were used to assess the spatial correlation. The 14-day, 45-day and overall mortality rates (with estimated survival rates) were 25.52% (70.20%), 32.35% (57.70%) and 37.30% (56.50%), respectively, with no significant rate variations between Saudi regions and provinces. Nationally, the CPH multivariate model identified that being elderly (age ≥ 61), being a non-healthcare worker (non-HCW), and having an underlying comorbidity were significantly related to 14-day mortality (HR = 2.10, 10.12 and 4.11, respectively; p < 0.0001). The 45-day mortality model identified similar risk factors but with an additional factor: patients aged 41–60 (HR = 1.44; p < 0.0001). Risk factors similar to those in the national model were observed in the Central, East and West regions and Riyadh, Makkah, Eastern, Madinah and Qassim provinces but with varying HRs. Spatial clusters of MERS-CoV mortality in the provinces were identified based on the risk factors (r2 = 0.85–0.97): Riyadh (Cluster 1), Eastern, Makkah and Qassim (Cluster 2), and other provinces in the north and south of the country (Cluster 3). The estimated HRs for the 14-and 45-day mortality varied spatially by province. For 45-day mortality, the highest HRs were found in Makkah (age ≥ 61 and non-HCWs), Riyadh (comorbidity) and Madinah (age 41–60). Coming from Makkah (HR = 1.30 and 1.27) or Qassim province (HR = 1.77 and 1.70) was independently related to higher 14-and 45-day mortality, respectively. MERS-CoV patient survival could be improved by implementing appropriate interventions for the elderly, those with comorbidities and non-HCW patients.


2006 ◽  
Vol 52 (5) ◽  
pp. 845-852 ◽  
Author(s):  
Ronit Calderon-Margalit ◽  
Bella Adler ◽  
Joseph H Abramson ◽  
Jaime Gofin ◽  
Jeremy D Kark

Abstract Background: The association of butyrylcholinesterase (BuChE) with Alzheimer disease and the association of this disease with cardiovascular risk factors raise interest in the association of BuChE activity with cardiovascular risk factors and mortality. Methods: A baseline cross-sectional study was conducted between 1985 and 1987, encompassing residents ≥50 years of age living in a Jewish neighborhood in western Jerusalem. Interviews were followed by examinations and nonfasting blood sampling (available for 1807 participants). Follow-up data to April 1996 on mortality and causes of death were obtained through record linkage with the Israeli Population Registry. Results: BuChE activity was inversely related to age and was positively associated with serum concentrations of albumin (r = 0.35; P &lt;0.001), cholesterol (r = 0.31; P &lt;0.001), and triglycerides (r = 0.30; P &lt;0.001). Enzyme activity was associated with measures of overweight, obesity, and body fat distribution (e.g., body mass index, r = 0.20; P &lt;0.001). In multivariate analysis, the associations of enzyme activity with serum cholesterol, triglycerides, and albumin persisted strongly. After adjustment by Cox proportional hazards regression for other predictors of mortality in this population, individuals in the lowest quintile of BuChE activity had significantly higher mortality than those in the highest quintile [hazard ratios (95% confidence intervals): all-cause mortality, 1.62 (1.15–2.30); cardiovascular deaths, 1.79 (1.05–3.05)]. The association was attenuated by introduction of serum albumin into the models. Conclusions: This is the first study to report on the association between BuChE and mortality. The relatively strong association of BuChE with serum lipid and albumin concentrations requires elucidation. Our results suggest that low BuChE activity may be a nonspecific risk factor for mortality in the elderly.


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