Drug efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of postmenopausal osteoporosis: a network meta-analysis of randomized controlled trials.

OBJECTIVE: This study aims to compare the efficacy and safety of denosumab, teriparatide, zoledronic acid, and ibandronic acid for the treatment of women with postmenopausal osteoporosis. MATERIALS AND METHODS: Randomized controlled trials (RCTs) were searched in Medline, Embase, and Cochrane up to April 2022. Statistical analysis was performed using R 4.1.3 software, and quality evaluation was conducted using Review Manager 5.3. RESULTS: 51 RCTs containing 39,095 patients met our selection criteria. The efficacy results indicated that teriparatide was more effective than ibandronic acid in reducing vertebral fractures [relative risk (RR) = 0.536; 95% confidence interval (CI) (0.266, 0.998)]. Denosumab [mean difference (MD) = -4.19; 95% CI (-8.03, -0.355)] and teriparatide [MD = 4.64; 95% CI (1.60, 7.72)] showed better efficacy than ibandronic acid in improving spine bone mineral density (BMD). Denosumab showed better efficacy than teriparatide in improving radius BMD [MD = -4.14; 95% CI (-6.72, -1.54)], hip bone mineral density (BMD) [MD = -2.01; 95% CI (-3.80, -0.162)], and one-third radius BMD [MD = -3.63; 95% CI (-7.04, -0.151)]. Denosumab was associated with the greatest benefit in increasing radius BMD [the surface under the cumulative ranking curve area (SUCRA) = 0.999], hip BMD [surface under the cumulative ranking curve area (SUCRA) = 0.979], femoral neck BMD (SUCRA = 0.971), one-third radius BMD (SUCRA = 0.994) and preventing vertebral fractures (SUCRA = 0.806). Teriparatide was associated with the greatest benefit in preventing non-vertebral fractures (SUCRA = 0.927) and improving spine BMD (SUCRA = 0.899). The safety results indicated that teriparatide was safer than zoledronic acid regarding the risk of adverse events [RR = 0.958; 95% CI (0.919, 0.988)]. Teriparatide was associated with the greatest benefit in preventing adverse events (SUCRA = 0.908) and serious adverse events (SUCRA = 0.813). CONCLUSIONS: Our current results suggested that when considering both safety and efficacy, denosumab or teriparatide might be a better choice for women with postmenopausal osteoporosis.

Differentiation of primary central nervous system lymphomas from high-grade gliomas by rCBV and percentage of signal intensity recovery derived from dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging.

PURPOSE: Primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG) may have similar enhancement patterns on magnetic resonance imaging (MRI), making the differential diagnosis difficult or even impractical. Relative cerebral blood volume (rCBV) and percentage of signal intensity recovery derived from dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MR imaging may help distinguish PCNSL from HGG. The purpose of this study was to evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of these two imaging parameters used alone or in combination for differentiating PCNSL from HGG. METHODS: A total of 12 patients with PCNSL and 26 patients with HGG were examined using a 3T scanner. rCBV and percentage of signal intensity recovery were obtained and receiver operating characteristic (ROC) analysis was performed to determine optimum thresholds for tumor differentiation. Sensitivity, specificity, PPV, NPV, and accuracy for identifying the tumor types were also calculated. RESULTS: The optimum threshold of 2.56 for rCBV provided sensitivity, specificity, PPV, NPV, and accuracy of 96.2, 90, 92.6, 94.7, and 93.5%, respectively, for determining PCNSL. A threshold value of 0.89 for percentage of signal intensity recovery optimized differentiation of PCNSL and HGG with a sensitivity, specificity, PPV, NPV, and accuracy of 100, 88.5, 87, 100, and 93.5%, respectively. Combining rCBV with the percentage of signal intensity recovery further improved the differentiation of PCNSL and HGG with a specificity of 98.5% and an accuracy of 95.7%. CONCLUSIONS: The combination of rCBV measurement with percentage of signal intensity recovery can help in more accurate differentiation of PCNSL from HGG.

Carotid endarterectomy for asymptomatic carotid stenosis.

BACKGROUND: Whilst carotid endarterectomy (CEA) is of proven benefit in recently symptomatic patients with severe carotid stenosis, the role of carotid endarterectomy in preventing stroke in patients with asymptomatic carotid stenosis remains uncertain. OBJECTIVES: The objective of this review therefore was to determine the effects of CEA for patients with asymptomatic carotid stenosis. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (June 1998), Medline (1966-Mar 1998), Current Contents (1995-Jan 1997), and reference lists of relevant articles. We contacted researchers in the field to identify additional published and unpublished studies. SELECTION CRITERIA: All completed randomised trials comparing CEA to medical treatment in patients with asymptomatic carotid stenosis. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data and assessed trial quality. Attempts were made to contact investigators to obtain missing information. MAIN RESULTS: Six trials were identified, but two were excluded on methodological grounds. Four trials with 2203 patients were included. In two trials aspirin was only given to patients in the medical group, and in two all patients received aspirin. The net excess "perioperative stroke or death" rate in the surgical group was 2.7% with relative risk 6.52 (95% confidence interval 2.66-15.96). The rates of "perioperative stroke or death or subsequent ipsilateral stroke" were 6.8% in the medical group vs 4.9% in the surgical group with RR 0.73 (0.52-1.02) favouring surgery. The rates of "any stroke or perioperative death" were 10.4% (medical) vs 8.1% (surgical) with RR 0.79 (0.60-1.02). The rates of "any stroke or death" were 23.2% (medical) vs 20.2% (surgical) with RR 0.89 (0.76-1.04). There were too few patients in CEA vs aspirin trials to determine whether aspirin had any confounding effect on outcome. An additional analysis including data from a fifth small unpublished trial altered slightly the risk ratios in favour of surgery and narrowed confidence intervals sufficiently to achieve statistical significance for each outcome. However, inclusion of these data had no appreciable effect on relative or absolute risk reduction. REVIEWER'S CONCLUSIONS: There is some evidence favouring CEA for asymptomatic carotid stenosis, but the effect is at best barely significant, and extremely small in terms of absolute risk reduction.

Ischemic stroke risk and passive exposure to spouses' cigarette smoking. Melbourne Stroke Risk Factor Study (MERFS) Group.

OBJECTIVES: This study investigated the association between ischemic stroke risk and passive exposure to cigarette smoking. METHODS: Risk factors among 452 hospitalized cases of first-episode ischemic stroke were compared with 452 age- and sex-matched "neighbor-hood" controls. RESULTS: The risk of stroke was twice as high for subjects whose spouses smoked as for those whose spouses did not smoke (95% confidence interval = 1.3, 3.1), after adjustment for the subject's own smoking, heart disease, hypertension, diabetes, and education level. These results were confirmed when analysis was limited to those who never smoked. CONCLUSIONS: These findings provide evidence that spousal smoking may be a significant risk factor for ischemic stroke.

Risk factors for stroke due to cerebral infarction in young adults.

BACKGROUND AND PURPOSE: Stroke in the young is particularly tragic because of the potential for a lifetime of disablement. More than 10% of patients with stroke due to cerebral infarction are aged 55 years or younger. While a number of studies have addressed the issue of stroke mechanism in the young, quantitation of risk factors has rarely been undertaken. Given the importance of risk factor assessment in primary prevention, we aimed to assess this using case-control methodology in a hospital-based series and community-based control subjects. METHODS: A total of 201 consecutive patients with first-onset stroke due to cerebral infarction aged 15 to 55 years (mean, 45.5 years) were accrued from four teaching hospitals during 1985 to 1992 and compared with their age- and sex-matched neighborhood controls. Information concerning potential risk factor exposure status was collected by structured questionnaire at interview. Stroke risks were estimated by calculating the odds ratios with multivariate logistic regression. RESULTS: Significantly increased risk of stroke was found among those with diabetes (odds ratio, 11.6 [95% confidence intervals, 1.2 to 115.2]), hypertension (6.8 [3.3 to 13.9]), heart disease (2.7 [1.1 to 6.4]), current cigarette smoking (2.5 [1.3, 5.0]), and long-term heavy alcohol consumption (> or = 60 g/d) (15.3 [1.0 to 232.0]). However, heavy alcohol ingestion (> or = 60 g) within 24 hours preceding stroke onset was not a risk factor (0.9 [0.3 to 3.4]). CONCLUSIONS: Diabetes, hypertension, heart disease, current smoking, and long-term heavy alcohol consumption are major risk factors for stroke in young adults. Given that the majority of these factors are either correctable or modifiable, prevention strategies may have the potential to reduce the impact of stroke in this age group.

Smoking as a risk factor for cortical ischaemia presumably due to carotid occlusive disease.

Smoking is now a well established risk factor for ischaemic stroke. However, the risk associated with smoking may differ between subgroups of ischaemic stroke. To test the hypothesis that cortical ischaemia due to carotid artery occlusive disease, the latter of which has previously been linked to smoking, may have a higher smoking risk compared to other forms of cerebral ischaemia, we identified 178 cases of cortical ischaemia presumably due to carotid occlusive disease in our previous case-control population and compared the odds ratios (OR) for smoking risk in this group with that in group of 244 cases of other forms of cerebral ischaemia combined. All cases were individually matched for age (+/- 5 years) and sex with neighbourhood controls. Multiple conditional logistic regression was used to adjust for potentially confounding factors. The OR for current smokers in the cortical group was higher than that in the non-cortical group [OR 4.4, 95% confidence interval 2.2, 8.9 vs. 2.1 (1.1, 4.1)], particularly for those who smoked more than 60 pack-years [5.5 (2.2, 14.0) vs. 1.5 (0.6, 3.8)] and those who currently smoked more than one pack per day [20.2 (3.3, 122.3) vs. 2.6 (0.8, 8.2)], but not significantly. Overall, there is some evidence to suggest that smoking may be a more potent risk factor for cortical than for other forms of cerebral ischaemia, particularly at high smoking rates. Further studies are needed to substantiate this finding.

The influence of age on atrial fibrillation as a risk factor for stroke.

To determine the influence of age on atrial fibrillation as a risk factor for cerebral infarction, the Austin Hospital Stroke Unit Register from 1977 to 1990 was reviewed. There were 2279 patients with cerebral infarction (excluding lacunar infarction syndromes) with a mean age of 68.3 years who were identified as subjects, and 800 patients with pseudostroke and lacunar infarction syndromes with a mean age of 64.7 years who were identified as controls. Data concerning potential risk factors for stroke (including sex, age, atrial fibrillation, cardiac disease, hypertension, diabetes, peripheral vascular disease and smoking) were analyzed using multivariate regression techniques. It was found that atrial fibrillation was a significant risk factor for cerebral infarction (excluding lacunar infarction) for all age groups, after adjusting for the effects of other risk factors (P less than .001). However, when age was stratified into four groups, the age-specific odds ratios for atrial fibrillation were not significantly different and no significant interactions between atrial fibrillation and age or other risk factors were found (P greater than 0.1). It was concluded that, although with increasing age atrial fibrillation becomes a more frequent cause of stroke, its potency as a risk factor does not increase correspondingly. There was no significant influence of age on the relationship between atrial fibrillation and cerebral infarction.