Additional Major Risk Factors Research Articles

Timing of Anticoagulation Resumption and Risk of Ischemic and Hemorrhagic Complications in Patients With ICH and Mechanical Heart Valves.

In patients with mechanical heart valves and recent intracranial hemorrhage (ICH), clinicians need to balance the risk of thromboembolism during the period off anticoagulation and the risk of hematoma expansion on anticoagulation. The optimal timing of anticoagulation resumption is unknown. We aimed to investigate the relationship between reversal therapy and ischemic stroke, between duration off anticoagulation and risk of ischemic strokes or systemic embolism and between timing of anticoagulation resumption and risk of rebleeding and ICH expansion. We conducted a retrospective cohort observational study in 3 tertiary hospitals. Consecutive adult patients with mechanical heart valves admitted for ICH between January 1, 2000, and July 13, 2022, were included. The primary end points of our study were thromboembolic events (cerebral, retinal, or systemic) while off anticoagulation and ICH expansion after anticoagulation resumption (defined by the following criteria: increase by one-third in intracerebral hematoma volume, increase by one-third in convexity subdural hemorrhage diameter, or visually unequivocal expansion of other ICH locations to the naked eye). A total of 171 patients with mechanical heart valves who experienced ICH were included in the final analysis. Most of the patients (79.5%) received reversal therapy for anticoagulation. Patients who received anticoagulation reversal therapy did not have increased risk of thromboembolic complications. Time off anticoagulation was not associated with risk of ischemic stroke; only 2 patients had a stroke within 7 days of the ICH, and both had additional major risk factors of thromboembolism. The rate of ischemic stroke/transient ischemic attack while off anticoagulation was lower than the rate of ICH expansion once anticoagulation was resumed (6.4% vs 9.9%). Furthermore, patients who developed ICH expansion had higher mortality compared with patients who had ischemic stroke while being off anticoagulation (41% vs 9%). Use of intravenous heparin bridging upon resumption of warfarin was strongly associated with increased risk of ICH expansion as compared with restarting warfarin without a heparin bridge. Withholding anticoagulation for at least 7 days after ICH may be safe in patients with mechanical heart valves. Heparin bridging during anticoagulation resumption may be associated with increased risk of bleeding.

Reconsidering the effectiveness of low-dose aspirin in prevention of pre-eclampsia among otherwise low risk twin gestations: A historical cohort study.

To investigate the effectiveness of low-dose aspirin (LDA) in the prevention of pre-eclampsia (PE) among otherwise low-risk twin gestations. A historical cohort study consisting of all pregnant individuals with dichorionic diamniotic (DCDA) twin pregnancy who delivered between 2014 and 2020. Patients treated with LDA were matched by a 1:4 ratio to individuals who were not treated with LDA by age, body mass index and parity. During the study period, 2271 individuals carrying DCDA pregnancies delivered at our center. Of these, 404 were excluded for one or more additional major risk factors. The remaining cohort consisted of 1867 individuals of whom 142 (7.6%) were treated with LDA and were compared with a 1:4 matched group of 568 individuals who were not treated. The rate of preterm PE did not differ significantly between the two groups (18 [12.7%] in the LDA group vs. 55 [9.7%] in the no-LDA group; P= 0.294, adjusted odds ratio 1.36, 95% confidence interval 0.77-2.40). There were no other significant between-group differences. Low-dose aspirin treatment in pregnant individuals with DCDA twin gestations without additional major risk factors was not associated with a reduction in the rate of preterm PE.

Aspirin for primary prevention of cardiovascular disease in diabetes.

Aspirin for primary prevention of cardiovascular disease in diabetes.

Determinants and Time Trends for Ischaemic and Haemorrhagic Stroke in a Large Chinese Population.

BackgroundThe clinical epidemiology of stroke has been widely investigated in Caucasian populations, but the changes over time in the proportion of ischaemic to haemorrhagic strokes is less clear, especially in the Chinese population.AimsOur objective was to study the determinants and time trends for ischaemic and haemorrhagic stroke, in relation to age, in a large Chinese population cohort.MethodsUsing a medical insurance database in the southwest of China from 2001 to 2012, time trends in age-adjusted ischaemic and haemorrhagic stroke incidence and the contributing risk factors associated with age were investigated.ResultsAmong 425,901 individuals without prior stroke (52.4% male, median age 54), the rate of ischaemic stroke (per 1000 patient-years) decreased between 2002–2007, then remained broadly similar between 2008–2012. The rate of haemorrhagic stroke showed a similar trend, being approximately 1.3–1.9 from 2008–2012. Compared to patients age<65, ischaemic and haemorrhagic stroke incidences (rate, 95% confidential interval, CI) were higher in the elderly population (age <65 versus age ≥65: ischaemic: 3.64, 3.33–4.00, vs 14.33, 14.01–14.60; haemorrhagic: 1.09, 1.00–1.10 vs 2.52,2.40–2.70, respectively, both p<0.001). There were no significant differences in haemorrhagic stroke rates between the elderly and the very elderly population. Ischaemic and haemorrhagic stroke shared similar risk factors (age, hypertension, coronary artery disease (CAD), vascular disease, and diabetes mellitus) (all p<0.05). In subjects age<75 years, CAD (7.17, 4.14–12.37) and diabetes mellitus (3.27, 2.42–4.42) contributed most to the developing of haemorrhagic stroke (all p<0.001). Amongst the very elderly, vascular disease (2.24, 1.49–3.37) was an additional major risk factor for haemorrhagic stroke, together with CAD and diabetes mellitus (all p<0.001).ConclusionIn this large Chinese cohort, there was an increased risk of ischaemic stroke compared to haemorrhagic stroke with ageing. CAD, vascular disease, diabetes mellitus, and hypertension were major contributors to the development of hemorrhagic stroke in the very elderly Chinese population.

Nonbacterial thrombotic endocarditis associated with chronic hypoxia and secondary polycythemia

A 72-year-old man with a past medical history significant for chronic obstructive pulmonary disease (COPD), witnessed nocturnal apnea and persistent 80-pack-year tobacco use presented with a new-onset of aphasia. MRI brain demonstrated restricted perfusion in the left temporoparietal area and insular cortex, consistent with subacute embolic strokes. Investigation for the etiology was notable for secondary polycythemia and non-specific mitral valve thickening on transthoracic echocardiography (TTE). Subsequent transesophageal echocardiography (TEE) showed a heterogenous,1.1 cm mass on the anterior mitral valve leaflet. Following warfarin bridge therapy, surgical resection revealed a sterile thrombus, consistent with nonbacterial thrombotic endocarditis (NBTE). Chronic hypoxia has been implicated in the pathogenesis of NBTE in both human and animal studies. While animal models have suggested a direct causal relationship, human studies are largely limited to isolated case reports, which have almost uniformly been confounded by the presence of other disorders of hypercoaguability, such as malignancy or disseminated intravascular coagulation (DIC). Unique in comparison to prior studies, this report demonstrates a case of NBTE in the setting of chronic oxygen deprivation and secondary polycythemia in a patient without any additional major risk factors.

Étude comparant le fondaparinux à une héparine de bas poids moléculaire dans la prévention de la maladie thromboembolique veineuse en cas d’immobilisation rigide ou semi-rigide après traumatisme isolé non chirurgical du membre inférieur au-dessous du genou

BackgroundIn several small studies, anticoagulant therapy reduced the incidence of venous thromboembolism (VTE) in patients with isolated lower-limb injuries. Objective: To compare the efficacy and safety of fondaparinux 2.5 mg (1.5 mg in patients with a creatinine clearance between 30 and 50 ml/min) over nadroparin 2,850 antifactor Xa IU.Patients/methodsIn this international, multicenter, randomized, open-label study, patients with an isolated nonsurgical unilateral below-knee injury, having at least one additional major risk factor for VTE and requiring (in the investigator’s opinion) rigid or semi-rigid immobilization for 21–45 days with thromboprophylaxis up to complete mobilization, received subcutaneously once-daily either fondaparinux or nadroparin. The primary efficacy outcome was the composite of VTE (symptomatic or ultrasonographically detected asymptomatic deep-vein thrombosis of the lowerlimb or symptomatic pulmonary embolism) and death up to complete mobilization. The main safety outcome was major bleeding.ResultsOne thousand three hundred and forty-nine patients (mean age: 46 years) were randomized, 88.7% had a bone fracture, and 83.8% had a plaster cast fitted (mean duration of immobilization: 34 days). The primary efficacy outcome occurred in 15/584 patients (2.6%) in the fondaparinux group and 48/586 patients (8.2%) in the nadroparin group (odds ratio: 0.30; 95% CI: [0.15–0.54]; P < 0.001). A single major bleed was experienced by fondaparinux-treated patients and none by nadroparin-treated patients. These results were maintained up to the end of follow-up.ConclusionsFondaparinux 2.5 mg/day may be a valuable therapeutic option over nadroparin 2,850 anti-factor Xa IU/day for preventing VTE after below-knee injury requiring prolonged immobilization in patients with additional risk factors. ClinicalTrials.gov number NCT00843492.

Comparison of fondaparinux with low molecular weight heparin for venous thromboembolism prevention in patients requiring rigid or semi‐rigid immobilization for isolated non‐surgical below‐knee injury

In several small studies, anticoagulant therapy reduced the incidence of venous thromboembolism (VTE) in patients with isolated lower-limb injuries. To compare the efficacy and safety of fondaparinux 2.5mg (1.5mg in patients with a creatinine clearance between 30 and 50mLmin(-1) ) over nadroparin 2850 anti-factor Xa IU. In this international, multicenter, randomized, open-label study, patients with an isolated non-surgical unilateral below-knee injury having at least one additional major risk factor for VTE and requiring, in the Investigator's opinion, rigid or semi-rigid immobilization for 21-45days with thromboprophylaxis up to complete mobilization received subcutaneously once-daily either fondaparinux or nadroparin. The primary efficacy outcome was the composite of VTE (symptomatic or ultrasonographically detected asymptomatic deep vein thrombosis of the lower limb or symptomatic pulmonary embolism) and death up to complete mobilization. The main safety outcome was major bleeding. We randomized 1349 patients (mean age 46years): 88.7% had a bone fracture, and 83.8% had a plaster cast fitted (mean duration of immobilization, 34days). The primary efficacy outcome occurred in 15 of 584 patients (2.6%) in the fondaparinux group and 48 of 586 patients (8.2%) in the nadroparin group (odds ratio, 0.30; 95% confidence interval [CI], 0.15-0.54; P<0.001). A single major bleed was experienced by fondaparinux-treated patients and none by nadroparin-treated patients. These results were maintained up to the end of follow-up. Fondaparinux 2.5mgday(-1) may be a valuable therapeutic option over nadroparin 2850 anti-FXa IUday(-1) for preventing VTE after below-knee injury requiring prolonged immobilization in patients with additional risk factors.

Risk Factors for Death and Severe Sequelae in Malawian Children With Bacterial Meningitis, 1997–2010

Acute bacterial meningitis (ABM) causes significant death and disability in children worldwide, with HIV recognized as an established risk factor for infection and negative outcomes. However, additional major risk factors for death and disability in pediatric ABM remain unclear. We conducted a retrospective analysis of case data from 3 departmental studies of ABM involving 1784 children <15 years old who attended Queen Elizabeth Central Hospital in Blantyre, Malawi during 1997 to 2010. Univariate and multivariate logistic regression models were used to estimate the effects of HIV seropositivity, impaired consciousness and causative organism on death and severe sequelae. Impaired consciousness or coma at the time of admission was strongly associated with death (coma: odds ratio [OR] = 14.4, 95% confidence interval [CI]: 9.42, 22.1) and severe sequelae (Coma: OR = 3.27, 95% CI: 2.02, 5.29) in multivariate logistic regression models. HIV seropositivity was significantly associated with increased odds of death (OR = 1.65, 95% CI: 1.20, 2.26) but not with developing severe sequelae (OR = 0.88, 95% CI: 0.56, 1.38). After adjustment, infection with Salmonella spp. was associated with increased odds of death (OR = 2.11, 95% CI: 1.06, 4.08) and pneumococcal meningitis was associated with increased odds of severe sequelae (OR = 1.84, 95% CI: 1.03, 3.29). Impaired consciousness and HIV infection increased the odds of death from ABM in Malawian children. Use of pneumococcal conjugate vaccine could greatly reduce the burden of ABM in Malawi.

Recent topics related to nephrogenic systemic fibrosis associated with gadolinium‐based contrast agents

Nephrogenic systemic fibrosis is a progressive, potentially fatal, multiorgan-system fibrosing disease related to exposure of patients with renal failure to gadolinium-based contrast agents used in magnetic resonance imaging. Between 1997 and 2007, more than 500 cases of nephrogenic systemic fibrosis in patients with severe renal insufficiency (glomerular filtration rate less than 30 mL/min/1.73 m(2)) were reported, and no known cases of nephrogenic systemic fibrosis have occurred in patients with a glomerular filtration rate of more than 30 mL/min/1.73 m(2) without acute kidney injury. Additional major risk factors are use of high-dose and specific gadolinium-based contrast agents, a pro-inflammatory state. Although the mechanism of nephrogenic systemic fibrosis is unclear and there is no consistently-effective therapy, nephrogenic systemic fibrosis is an entity that can be eliminated by observing recent recommended guidelines for gadolinium-based contrast agents and nephrogenic systemic fibrosis. This article reviews current knowledge about nephrogenic systemic fibrosis and focuses mainly on how to prevent it.

Nephrogenic Systemic Fibrosis and Its Impact on Abdominal Imaging

The objective of this article is to review the current knowledge about nephrogenic systemic fibrosis (NSF) and how to prevent it. More than 300 cases of NSF in patients with severe chronic renal insufficiency or acute renal failure or in patients undergoing dialysis have been reported in the peer-reviewed literature, with an overwhelming majority occurring within weeks to months after injection of a gadolinium-based contrast agent (GBCA). Because administration of a high dose of a GBCA is a primary risk factor and because most high-dose magnetic resonance (MR) imaging applications involve abdominal imaging (eg, liver and abdominal MR angiography), NSF cases have been associated with abdominal MR imaging. Additional major risk factors for developing NSF include proinflammatory conditions, failure to perform dialysis promptly after GBCA administration, use of nonionic linear contrast agents, hyperphosphatemia, and younger age. Recent recommendations to use GBCAs with caution in patients with acute renal failure, patients receiving dialysis, or patients with an estimated glomerular filtration rate of less than 30 mL/min have resulted in virtually no new NSF cases being reported with onset in 2008 or 2009 in spite of a high level of awareness about this entity. In conclusion, NSF has been virtually eliminated by using caution in administering GBCAs to patients known to have severe or acute renal failure. In these patients, avoid high doses; and for patients undergoing dialysis, schedule MR imaging to occur just before a dialysis session to ensure rapid elimination of gadolinium.

Is the Interruption of Antiretroviral Treatment During Pregnancy an Additional Major Risk Factor for Mother‐to‐Child Transmission of HIV Type 1?

There is currently an experts' agreement discouraging interruption of antiretroviral treatment (ART) during the first trimester of pregnancy in women infected with human immunodeficiency virus type 1 (HIV-1). However, this recommendation is poorly supported by data. We evaluated the effects of discontinuing ART during pregnancy on the rate of mother-to-child transmission. Logistic regression models were performed in a prospective cohort of 937 children who were perinatally exposed to HIV-1 to estimate adjusted odds ratios for confounding factors on mother-to-child transmission, including maternal interruption of ART. Among 937 pregnant women infected with HIV-1, ART was interrupted in 81 (8.6%) in the first trimester and in 11 (1.2%) in the third trimester. In the first trimester, the median time at suspension of ART was 6 weeks (interquartile range [IQR], 5-6 weeks) and the time without treatment was 8 weeks (IQR, 7-11 weeks). In the third trimester, the median time at suspension of ART was 32 weeks (IQR, 23-36 weeks) and the time without treatment was 6 weeks (IQR, 2-9 weeks). The plasma viral load was similar in women who had treatment interrupted in the first trimester and in those who did not have treatment interrupted. Overall, the rate of mother-to-child transmission in the whole cohort was 1.3% (95% confidence interval [CI], 0.7%-2.3%), whereas it was 4.9% (95% CI, 1.9%-13.2%) when ART was interrupted in the first trimester and 18.2% (95% CI, 4.5%-72.7%) when ART was interrupted in the third trimester. In the multiple logistic regression models, only interruption of ART during either the first or the third trimester, maternal mono- or double therapy, delivery by a mode other than elective cesarean delivery, and a viral load at delivery >4.78 log(10) copies/mL were independently associated with an increased rate of mother-to-child transmission. Discontinuing ART during pregnancy increases the rate of mother-to-child transmission of HIV-1, either when ART is stopped in the first trimester and subsequently restarted or when it is interrupted in the third trimester. This finding supports recommendations to continue ART in pregnant women who are already receiving treatment for their health.

Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection

Background:600 000 deaths worldwide are estimated to be directly or indirectly attributable to respiratory syncytial virus (RSV).Objectives:To determine: (1) the mortality rate; and (2) risk factors for death in children...

Restraint Urged in Adding Antidepressant to Mood Stabilizer

Restraint Urged in Adding Antidepressant to Mood Stabilizer

Design and baseline characteristics from the KAN-QUIT disease management intervention for rural smokers in primary care

Objective To describe the design, implementation, baseline data, and feasibility of establishing a disease management program for smoking cessation in rural primary care. Method The study is a randomized clinical trial evaluating a disease management program for smoking cessation. The intervention combined pharmacotherapy, telephone counseling, and physician feedback, and repeated intervention over two years. The program began in 2004 and was implemented in 50 primary care clinics across the State of Kansas. Results Of eligible patients, 73% were interested in study participation. 750 enrolled participants were predominantly Caucasian, female, employed, and averaged 47.2 years of age (SD = 13.1). In addition to smoking, 427 (57%) had at least one additional major risk factor for cardiovascular disease (diabetes, hypertension, high cholesterol, heart disease or stroke). Participants smoked on average 23.7 (SD = 10.4) cigarettes per day, were contemplating (61%) or preparing to quit (30%), were highly motivated and confident of their ability to quit smoking, and reported seeing their physicians multiple times in the past twelve months (Median = 3.50; Mean = 5.48; SD = 6.58). Conclusion Initial findings demonstrate the willingness of patients to enroll in a two-year disease management program to address nicotine dependence, even among patients not ready to make a quit attempt. These findings support the feasibility of identifying and enrolling rural smokers within the primary care setting.

Inflow Stenoses in Dysfunctional Hemodialysis Access Fistulae and Grafts

The aim of the study is to prospectively determine the incidence of inflow stenoses in dysfunctional hemodialysis access arteriovenous fistulae (AVFs) and grafts (AVGs). Contrast-enhanced magnetic resonance angiography (CE-MRA) was performed of 66 dysfunctional AVFs and 35 AVGs in 56 men and 45 women (mean age, 62 years; age range, 31 to 86 years). Complete inflow (from the subclavian artery), shunt region, and complete outflow (including subclavian vein) were shown at CE-MRA. In addition to standard digital subtraction angiography (DSA) of the shunt region and outflow, DSA of the complete inflow was obtained through access catheterization of all cases in which CE-MRA showed an inflow stenosis. Vascular stenosis is defined as greater than 50% decrease in luminal diameter compared with an uninvolved vascular segment located adjacent to the stenosis. Endovascular intervention of stenoses was performed in connection with DSA. CE-MRA showed 19 arterial stenoses in 14 patients (14%). DSA confirmed 18 of these lesions in 13 patients and showed no additional inflow lesions. Of the 13 patients, 7 patients had arterial stenoses only and 6 patients had accompanying stenoses in the shunt region and/or outflow. Referral criteria for the 13 patients to undergo access evaluation had been decreased flow rates (9 patients), steal symptoms (2 patients), and insufficient access maturation (2 patients). Access flow of the 9 patients with a low-flow access improved from 477 +/- 74 mL/min to 825 +/- 199 mL/min after angioplasty. One patient with steal symptoms became symptom free after angioplasty. Endovascular intervention in 3 patients proved to be unsuccessful. Inflow stenoses are not uncommon in dysfunctional hemodialysis access shunts. We suggest that radiological evaluation comprise assessment of the complete arterial inflow.

Dietary and serum vitamins and minerals as predictors of myocardial infarction and stroke in elderly subjects

According to a widespread hypothesis, antioxidative vitamins and trace elements may protect the body against atherosclerotic diseases, especially in the elderly. We assessed dietary and serum vitamins and minerals for prediction of acute myocardial infarction (AMI) and stroke in elderly subjects. In a population-based health survey with special emphasis on the diet, subjects aged 65-99 years were followed up for up to 10 years. The study population consisted of 361 men and 394 women. Information on individual food consumption was elicited by means of dietary history interviews. Serum vitamins and mineral elements were analysed utilizing commonly applied biochemical methods. Prediction analyses were based on 130 cases accumulated in the AMI group, 70 subjects in the stroke group, and corresponding control subjects. The cases were determined on the basis of revised information from the National Register of Cases of Death, and from the National Hospital Discharge Register. Low intake of vitamin D (p = 0.011) and low serum levels of 1,25-dihydroxy-vitamin D (p = 0.0053) were significantly predictive of stroke when adjusted for age, gender, smoking and functional capacity. On the other hand, high dietary intakes of two flavonoids, luteolin (p = 0.0096) and kaempferol (p = 0.002) were associated with lowered risk of AMI. Furthermore, low serum levels of iron predicted both AMI (p = 0.013) and stroke (p = 0.019). The results remained essentially unchanged when adjusted for additional major risk factors of atherosclerosis. From the items in the dietary interview, low intakes of vitamin D and certain flavonoids emerged as the sole predictors of AMI and stroke. In biochemical analyses, on the other hand, these disorders were predicted only by low levels of 1,25-dihydroxy-vitamin D and iron in the serum.

Long-term absolute benefit of lowering blood pressure in hypertensive patients according to the JNC VI risk stratification.

Blood pressure (BP) levels alone have been traditionally used to make treatment decisions in patients with hypertension. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) recently recommended that risk strata, in addition to BP levels, be considered in the treatment of hypertension. We estimated the absolute benefit associated with a 12 mm Hg reduction in systolic BP over 10 years according to the risk stratification system of JNC VI using data from the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. The number-needed-to-treat to prevent a cardiovascular event/death or a death from all causes was reduced with increasing levels of baseline BP in each of the risk strata. In addition, the number-needed-to-treat was much smaller in persons with > or =1 additional major risk factor for cardiovascular disease (risk group B) and in those with a history of cardiovascular disease or target organ damage (risk group C) than in those without additional major risk factors for cardiovascular disease (risk group A). Specifically, the number-needed-to-treat to prevent a death from all causes in patients with a high-normal BP, stage 1 hypertension, or stage 2 or 3 hypertension was, respectively, 81, 60, and 23 for those in risk group A; 19, 16, and 9 for those in risk group B; and 14, 12, and 9 for those in risk group C. Our analysis indicated that the absolute benefits of antihypertensive therapy depended on BP as well as the presence or absence of additional cardiovascular disease risk factors and the presence or absence of preexisting clinical cardiovascular disease or target organ damage.

Physician Practices in the Prevention of Venous Thromboembolism

To determine the rate of use of prophylaxis for venous thromboembolism in high-risk hospital patients. A retrospective medical record review. A community-wide study in 16 short-stay hospitals in central Massachusetts. A total of 2017 patients with multiple risk factors for venous thromboembolism. On the basis of age, length of hospitalization, and the presence of at least one additional major risk factor, 17% of 151,349 discharges (25,410 patients) were identified as being at high risk for venous thromboembolism. Eight percent of these discharges were randomly selected for medical record review. Prophylaxis for venous thromboembolism was received by 32% of these high-risk patients. Prophylaxis use among the 16 study hospitals varied widely, ranging from 9% to 56%, and was higher in teaching hospitals than in nonteaching hospitals (44% compared with 19%; P less than 0.001). One or more of the following methods of prophylaxis was used: low-dose heparin (78%), intermittent calf compression (13%), warfarin (12%), and inferior vena caval filter (3%). Use of prophylaxis increased with the number of risk factors identified (P less than 0.001). Prophylaxis for venous thromboemobolism is underused, particularly in nonteaching hospitals.