Loneliness and cardiovascular disease and the role of late‐life depression

Objective

Loneliness and depression have a strong reciprocal influence, and both predict adverse health outcomes at old age. Therefore, this study examines whether loneliness is associated with the presence of cardiovascular diseases taking into account the role of late‐life depression.

Methods

Cross‐sectional data of 477 older adults in the Netherlands Study of Depressed Older Persons were used. Logistic regression analysis was performed to examine the relation between loneliness and cardiovascular disease. Depression was added to the regression model to examine whether depression is an explanatory factor in the association between loneliness and cardiovascular disease. Interaction terms between loneliness and depression and between loneliness and sex were introduced in the regression model to investigate whether depressed and non‐depressed participants, and men and women differed in their association between loneliness and cardiovascular disease.

Results

Of the overall group, 61% were lonely, 28% had a history of cardiovascular disease and 74% were depressed. Loneliness and cardiovascular disease were not associated in the overall group after adjustment for confounders (continuous: odds ratio [OR] = 1.04, 95% confidence interval [CI] = 0.98–1.10), p = 0.25; dichotomous: OR = 1.27, 95% CI = 0.80–2.03, p = 0.32). For women, there was an association between loneliness and cardiovascular diseases (continuous: OR = 1.13, 95% CI = 1.06–1.21, p < 0.001; dichotomous: OR = 2.64, 95% CI = 1.50–4.65, p = 0.001), but this association was not present in men (OR = 0.96, 95% CI = 0.88–1.05, p = 0.38). This association remained significant after adjustment for confounders, but it lost significance after adding depression to the model.

Conclusion

For women only, there was an association between loneliness and cardiovascular disease. However, this association was explained by depression, indicating that loneliness in its own right seems not related with cardiovascular disease. Copyright © 2017 John Wiley & Sons, Ltd.     

First-line levetiracetam versus enzyme-inducing antiseizure medication in glioma patients with epilepsy

Objective

This study aimed to directly compare the effectiveness of first-line monotherapy levetiracetam (LEV) versus enzyme-inducing antiseizure medications (EIASMs) in glioma patients.

Methods

In this nationwide retrospective observational cohort study, Grade 2–4 glioma patients were included, with a maximum duration of follow-up of 36 months. Primary outcome was antiseizure medication (ASM) treatment failure for any reason, and secondary outcomes were treatment failure due to uncontrolled seizures and due to adverse effects. For estimation of the association between ASM treatment and ASM treatment failure, multivariate cause-specific cox proportional hazard models were estimated, adjusting for potential confounders.

Results

In the original cohort, a total of 808 brain tumor patients with epilepsy were included, of whom 109 glioma patients were prescribed first-line LEV and 183 glioma patients first-line EIASMs. The EIASM group had a significantly higher risk of treatment failure for any reason compared to LEV (adjusted hazard ratio [aHR] = 1.82, 95% confidence interval [CI] = 1.20–2.75, p = .005). Treatment failure due to uncontrolled seizures did not differ significantly between EIASMs and LEV (aHR = 1.32, 95% CI = .78–2.25, p = .300), but treatment failure due to adverse effects differed significantly (aHR = 4.87, 95% CI = 1.89–12.55, p = .001).

Significance

In this study, it was demonstrated that LEV had a significantly better effectiveness (i.e., less ASM treatment failure for any reason or due to adverse effects) compared to EIASMs, supporting the current neuro-oncology guideline recommendations to avoid EIASMs in glioma patients.     

Measuring change in perceived well‐being of family caregivers: validation of the Spanish version of the Perceived Change Index (PCI‐S) in Chilean dementia caregivers

Objective

Few instruments evaluate family caregiver perceptions of challenges caring for persons with dementia and improvement or worsening in these areas. To address this measurement gap, we examine psychometric properties of a Spanish version of the 13‐item Perceived Change Index (PCI‐S), originally validated with English‐speaking caregivers.

Methods

Cross‐sectional study with 94 caregivers of persons with mild to moderate dementia in Chile. Interviews included caregiver demographics, burden, health perception, distress with behaviours, dementia severity, behavioural symptoms and functionality.

Results

Caregiver mean age was 55.9 (SD ± 14.14) years and mean years caregiving was 3 (SD ± 2.60). The scale had strong internal consistency (Cronbach α = 0.94), and inter‐observer consistency (CCI = 0.99; 95% CI = 0.95–0.99). Two factors were identified: Management skills (α = 0.89), and somatic well‐being and affects (α = 0.92), explaining 63% of scale variance. Significant associations supporting convergent validity were observed for PCI‐S and subscales with caregiver burden (p < 0.01), health perceptions (p < 0.01), depressive symptoms (p < 0.01) and distress with behaviours (p < 0.01); and in persons with dementia, functionality (p < 0.05), dementia severity (p < 0.05) and behavioural symptoms (p < 0.01) in expected directions. In logistic regression models, perceived worsening (PCI‐S and subscale scores) was associated with more behavioural symptoms (OR = 1.07; 95% CI = 1.03–1.15) and caregiver burden (OR = 1.48; 95% CI = 1.18–1.86); whereas perceived improvement was associated with higher physical functioning (OR = 0.95; 95% CI = 0.91–0.99) in persons with dementia. PCI‐S scores were not associated with socio‐demographic characteristics reflecting divergent validity.

Conclusions

Spanish version of the 13‐item Perceived Change Index and its two‐factor solution is a valid and reliable measure with clinical utility to detect improvement or worsening in caregivers concerning daily care challenges. Copyright © 2017 John Wiley & Sons, Ltd.     

Implication of heart rate variability on cerebral small vessel disease: A potential therapeutic target

Objective

This study aimed to investigate the relationships of heart rate variability (HRV) with the presence, severity, and individual neuroimaging markers of cerebral small vessel disease (CSVD).

Method

A total of 4676 participants from the Third China National Stroke Registry (CNSR-III) study were included in this cross-sectional analysis. CSVD and its markers, including white matter hyperintensity (WMH), lacunes, enlarged perivascular spaces (EPVS), cerebral microbleeds (CMBs), and brain atrophy (BA), were evaluated. Two common HRV parameters, including the square root of the mean of the sum of the squares of differences between adjacent N–N intervals (RMSSD) and the standard deviation of all N–N intervals (SDNN), were used to evaluate the function of the autonomic nervous system (ANS). Binary or ordinal logistic regression analyses were performed to investigate the association between HRV and CSVD. In addition, two-sample mendelian randomization (MR) analyses were performed to investigate the causality of HRV with CSVD.

Results

RMSSD was significantly associated with total burden of CSVD (Wardlaw's scale, common odds ratio [cOR] 0.80, 95% confidence interval [CI] 0.67–0.96, p = 0.02; Rothwell's scale, cOR 0.75, 95% CI 0.60–0.93, p = 0.008) and the presence of CSVD (Rothwell, OR 0.75, 95% CI 0.60–0.93, p = 0.008). However, no significant associations between SDNN and the presence or total burden of CSVD were observed. Moreover, RMSSD was related to WMH burden (OR 0.80, 95% CI 0.66–0.96, p = 0.02), modified WMH burden (cOR 0.82, 95% CI 0.69–0.97, p = 0.02), and Deep-WMH (OR 0.75, 95% CI 0.62–0.91, p = 0.003), while SDNN was related to Deep-WMH (OR 0.80, 95% CI 0.66–0.96, p = 0.02) and BA (cOR 0.80, 95% CI 0.68–0.95, p = 0.009). Furthermore, adding HRV to the conventional model based on vascualr risk factors enhanced the predictive performance for CSVD, as validated by the integrated discrimination index (p < 0.05). In addition, no causality between HRV and CSVD was observed in two-sample MR analyses.

Conclusion

Decreased HRV may be a potential risk factor of CSVD, implying the possible role of the ANS in the pathogenesis of CSVD.     

Preexisting mental health disorders and risk of opioid use disorder in young people: A case-control study

Aim

Opioid use disorder (OUD) is a leading cause of preventable mortality amongst young people worldwide. Early identification and intervention of modifiable risk factors may reduce future OUD risk. The aim of this study was to explore whether the onset of OUD is associated with preexisting mental health conditions such as anxiety and depressive disorders in young people.

Methods

A retrospective, population-based case-control study was conducted from 31 March 2018 until 01 January 2002. Provincial administrative health data were collected from Alberta, Canada. Cases: Individuals 18–25 years on 01 April 2018, with a previous record of OUD. Controls: Individuals without OUD were matched to cases, on age/sex/index date. Conditional logistic regression analysis was used to control for additional covariates (e.g., alcohol-related disorders, psychotropic medications, opioid analgesics, and social/material deprivation).

Results

We identified N = 1848 cases and N = 7392 matched controls. After adjustment, OUD was associated with the following preexisting mental health conditions: Anxiety disorders, aOR = 2.53 (95% CI = 2.16–2.96); depressive disorders, aOR = 2.20 (95% CI = 1.80–2.70); alcohol-related disorders, aOR = 6.08 (95% CI, 4.86–7.61); anxiety and depressive disorders, aOR = 1.94 (95% CI = 1.56–2.40); anxiety and alcohol-related disorders, aOR = 5.22 (95% CI = 4.03–6.77); depressive and alcohol-related disorders, aOR = 6.47 (95% CI = 4.73–8.84); anxiety, depressive and alcohol-related disorders, aOR = 6.09 (95% CI = 4.41–8.42).

Discussion

Preexisting mental health conditions such as anxiety and depressive disorders are risk factors for future OUD in young people. Preexisting alcohol-related disorders showed the strongest association with future OUD and demonstrated an additive risk when concurrent with anxiety/depression. As not all plausible risk factors could be examined, more research is still needed.     

Definition of a Geriatric Depression Scale cutoff based upon quality of life: a population‐based study

Objectives

The cutoff scores for the Geriatric Depression Scale (GDS) commonly adopted in clinical and research settings are based upon other neuropsychological tests. However, any intervention for depression should aim at improving subjective quality of life (QoL). We searched for a GDS cutoff level that might identify a decrease in perceived QoL using a scale that also allows formal cost‐effectiveness calculations.

Methods

Quality of life was assessed by the Health Utilities Index, Mark 3 in all 344 residents of Tuscania (Italy) aged 75 years and above. Mood was assessed by both the 30‐item GDS and the derived 15‐item GDS. The association of GDS with low QoL was analyzed by multivariable logistic regression. Receiver operating characteristic curve analysis was adopted to estimate the overall predictive value and the best GDS cutoff for poor QoL.

Results

The 30‐item GDS score was associated with increased probability of a worse QoL (odds ratio (OR) = 1.07, 95% confidence (CI) = 1.02–1.12, p = 0.003); also, it was a fair predictor of worse QoL (area under the curve (AUC) = 0.72; 95% CI = 0.67–0.76). The best GDS score cutoff for identifying a poor QoL was above 9/30. Results were similar (OR = 1.07, 95% CI = 1.02–1.12, p = 0.003, and AUC = 0.72, 95% CI = 0.67–0.76) for the short GDS form for a cutoff above 5/15.

Conclusions

Among older subjects, depressive symptoms are associated with reduced QoL; GDS scores above 9/30 or 5/15 best predict poor perceived health‐related QoL. These cutoff scores could therefore identify subjects in whom treatment is more likely to improve QoL and to yield a favorable cost‐effectiveness ratio. Copyright © 2017 John Wiley & Sons, Ltd.     

Retinal layer thickness predicts disability accumulation in early relapsing multiple sclerosis

Background and purpose

This study was undertaken to investigate baseline peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) thickness for prediction of disability accumulation in early relapsing multiple sclerosis (RMS).

Methods

From a prospective observational study, we included patients with newly diagnosed RMS and obtained spectral-domain optical coherence tomography scan within 90 days after RMS diagnosis. Impact of pRNFL and GCIPL thickness for prediction of disability accumulation (confirmed Expanded Disability Status Scale [EDSS] score ≥ 3.0) was tested by multivariate (adjusted hazard ratio [HR] with 95% confidence interval [CI]) Cox regression models.

Results

We analyzed 231 MS patients (mean age = 30.3 years, SD = 8.1, 74% female) during a median observation period of 61 months (range = 12–93). Mean pRNFL thickness was 92.6 μm (SD = 12.1), and mean GCIPL thickness was 81.4 μm (SD = 11.8). EDSS ≥ 3 was reached by 28 patients (12.1%) after a median 49 months (range = 9–92). EDSS ≥ 3 was predicted with GCIPL < 77 μm (HR = 2.7, 95% CI = 1.6–4.2, p < 0.001) and pRNFL thickness ≤ 88 μm (HR = 2.0, 95% CI = 1.4–3.3, p < 0.001). Higher age (HR = 1.4 per 10 years, p < 0.001), incomplete remission of first clinical attack (HR = 2.2, p < 0.001), ≥10 magnetic resonance imaging (MRI) lesions (HR = 2.0, p < 0.001), and infratentorial MRI lesions (HR = 1.9, p < 0.001) were associated with increased risk of disability accumulation, whereas highly effective disease-modifying treatment was protective (HR = 0.6, p < 0.001). Type of first clinical attack and presence of oligoclonal bands were not significantly associated.

Conclusions

Retinal layer thickness (GCIPL more than pRNFL) is a useful predictor of future disability accumulation in RMS, independently adding to established markers.     

High-risk carotid plaques and incident ischemic stroke in patients with atrial fibrillation in the Cardiovascular Health Study

Background and purpose

Whether carotid artery disease could improve stroke risk stratification tools in patients with atrial fibrillation (AF) remains uncertain. This study was undertaken to investigate the risk of ischemic stroke associated with occlusive and nonocclusive carotid atherosclerotic disease in patients with AF in the prospective population-based Cardiovascular Health Study.

Methods

We included participants aged ≥65 years with AF. We used multivariable Cox regression analysis to explore the risk of ischemic stroke associated with the percentage of carotid stenosis, plaque irregularity, echogenicity, and vulnerability (markedly irregular, ulcerated, or hypoechoic plaques).

Results

A total of 1398 participants were included (55.2% female, 61.7% aged 65–74 years). The maximum carotid stenosis was <50%, 50%–99%, and 100% in 94.5%, 5%, and 0.5% of participants, respectively. High-risk plaques based on echogenicity and plaque irregularity were found in 25.6% and 8.9% of participants, respectively. After a median follow-up of 10.9 years (interquartile range = 7.5–15.6), 298 ischemic strokes were recorded. There was no difference in the incidence of ischemic stroke according to the degree of carotid artery stenosis (p = 0.44), plaque echogenicity (low vs. high risk, p = 0.68), plaque irregularity (low vs. high risk, p = 0.55), and plaque vulnerability (p = 0.86). The CHA₂DS₂-VASc score was associated with an increased risk of ischemic stroke (adjusted hazard ratio = 1.28, 95% confidence interval = 1.18–1.40, p < 0.001). Both maximum grade of stenosis and plaque vulnerability were not associated with incident ischemic stroke (all p > 0.05).

Conclusions

Neither the degree of carotid stenosis nor the presence of vulnerable plaques was associated with incident ischemic stroke in this cohort of individuals with AF. This suggests that carotid disease was probably not a significant contributor to ischemic stroke in this population.     

Retinal ganglion cell loss is associated with future disability worsening in early relapsing–remitting multiple sclerosis

Background and purpose

Thinning of the retinal combined ganglion cell and inner plexiform layer (GCIP) as measured by optical coherence tomography (OCT) is a common finding in patients with multiple sclerosis. This study aimed to investigate whether a single retinal OCT analysis allows prediction of future disease activity after a first demyelinating event.

Methods

This observational cohort study included 201 patients with recently diagnosed clinically isolated syndrome or relapsing–remitting multiple sclerosis from two German tertiary referral centers. Individuals underwent neurological examination, magnetic resonance imaging, and OCT at baseline and at yearly follow-up visits.

Results

Patients were included at a median disease duration of 2.0 months. During a median follow-up of 59 (interquartile range = 43–71) months, 82% of patients had ongoing disease activity as demonstrated by failing the no evidence of disease activity 3 (NEDA-3) criteria, and 19% presented with confirmed disability worsening. A GCIP threshold of ≤77 μm at baseline identified patients with a high risk for NEDA-3 failure (hazard ratio [HR] = 1.7, 95% confidence interval [CI] = 1.1–2.8, p = 0.04), and GCIP measures of ≤69 μm predicted disability worsening (HR = 2.2, 95% CI = 1.2–4.3, p = 0.01). Higher rates of annualized GCIP loss increased the risk for disability worsening (HR = 2.5 per 1 μm/year increase of GCIP loss, p = 0.03).

Conclusions

Ganglion cell thickness as measured by OCT after the initial manifestation of multiple sclerosis may allow early risk stratification as to future disease activity and progression.     

Brain-specific biomarkers in urine as a non-invasive approach to monitor neuronal and glial damage

Background and purpose

This study evaluates the quantitative measurability of glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and total tau (t-tau) in urine of patients with acute cerebral damage.

Methods

Serum and urine samples were prospectively collected from patients with an acute ischemic stroke or intracerebral hemorrhage (target group) and compared to healthy subjects (control group); samples were measured using ultrasensitive single-molecule arrays (Simoa®). Glomerular barrier function was assessed based on albumin–creatinine ratio (ACR); biomarker–creatinine ratios were calculated for correction of urine dilution.

Results

Ninety-three urine–serum pairs in the target group and 10 urine–serum pairs in the control group were measured. The mean absolute concentration ± standard deviation in urine of the target and control groups were 184.7 ± 362.4 pg/ml and 27.3 ± 24.1 pg/ml for GFAP (r = 0.3 [Wilcoxon effect size], p = 0.007), 17.5 ± 38.6 pg/ml and 0.9 ± 0.3 pg/ml for NfL (r = 0.4, p < 0.005), 320.2 ± 443.3 pg/ml and 109.6 ± 116.8 pg/ml for UCH-L1 (r = 0.26, p = 0.014), and 219.5 ± 255.8 pg/ml and 21.1 ± 27.1 pg/ml for t-tau (r = 0.37, p < 0.005), respectively, whereas biomarker–creatinine ratio was significantly different only for NfL (r = 0.29, p = 0.015) and t-tau (r = 0.32, p < 0.01). In patients with intact glomerular barrier (ACR < 30 mg/g), only NfL in urine was significantly different between the target and control group and showed a significant correlation with the respective serum concentrations (r = 0.58 [Pearson's correlation-coefficient], p < 0.005).

Conclusion

All four investigated biomarkers could be measured in urine, with NfL and t-tau showing the strongest effect size after correction for urine dilution. NfL revealed the most accurate relation between serum and urine concentrations in patients with intact kidney function.     

Association of blood-based biomarkers with radiologic markers and cognitive decline in atrial fibrillation patients

BackgroundAtrial fibrillation (AF) has been associated with an increased risk of silent brain infarcts (SBI) and cognitive impairment, even in patients with low embolic risk. We aimed to test the association between 11 blood-biomarkers representing different AF-related pathways, and SBI, white matter hyperintensities (WMH), and cognitive decline in patients with AF and low embolic risk.MethodsThe present study followed a cross-sectional design. 70 patients with a history of AF and CHADS₂ score ≤1, and 10 controls with neither AF nor SBI were included. All patients underwent a 3T brain MRI. Cortical and large subcortical ischemic lesions were considered presumed embolic origin lesions. White matter hyperintensities (WMH) were measured according to the Fazekas scale. A subset of patients underwent cognitive evaluation with the MoCA test. Circulating proteins were measured under blind conditions in a laboratory at Roche Diagnostics, Germany.Results45 patients presented SBI in the MRI, and 25 did not. Ang-2, FGF-23, and BMP-10 were increased in patients with SBI. Ang-2 was elevated only in patients with embolic infarcts, whereas FGF-23 and BMP-10 tended to be elevated in patients with both types of infarcts. Ang-2 (OR = 1.56 [0.94-2.59], p = 0.087), and BMP-10 (OR = 4.83 [0.99–23.60], p = 0.052) were the biomarkers that showed the highest association with SBI when entered in a multivariable logistic regression model corrected by age. No biomarker was found associated with WMH or mild cognitive impairment.ConclusionsBMP-10, and Ang-2 were increased in patients with SBI. Its usefulness to detect SBI in AF patients should be further explored.     

Clozapine as a first‐ or second‐line treatment in schizophrenia: a systematic review and meta‐analysis

Objective

No consensus exists on whether clozapine should be prescribed in early stages of psychosis. This systematic review and meta‐analysis therefore focus on the use of clozapine as first‐line or second‐line treatment in non‐treatment‐resistant patients.

Methods

Articles were eligible if they investigated clozapine compared to another antipsychotic as a first‐ or second‐line treatment in non‐treatment‐resistant schizophrenia spectrum disorders (SCZ) patients and provided data on treatment response. We performed random‐effects meta‐analyses.

Results

Fifteen articles were eligible for the systematic review (N = 314 subjects on clozapine and N = 800 on other antipsychotics). Our meta‐analysis comparing clozapine to a miscellaneous group of antipsychotics revealed a significant benefit of clozapine (Hedges’ g = 0.220, P = 0.026, 95% CI = 0.026–0.414), with no evidence of heterogeneity. In addition, a sensitivity analysis revealed a significant benefit of clozapine over risperidone (Hedges’ g = 0.274, P = 0.030, 95% CI = 0.027–0.521).

Conclusion

The few eligible trials on this topic suggest that clozapine may be more effective than other antipsychotics when used as first‐ or second‐line treatment. Only large clinical trials may comprehensively probe disease stage‐dependent superiority of clozapine and investigate overall tolerability.     

Gapless Electrocardiogram-Monitoring in stroke at high risk of atrial fibrillation

Background and purpose

Previous studies investigating prolonged electrocardiogram (ECG)-monitoring after ischemic stroke had significant gaps between the index event and the beginning of long-term monitoring. Atrial fibrillation (AF) detection might be higher if prolonged cardiac rhythm documentation is performed with a gapless approach without any interruption of monitoring time.

Methods

This investigator-initiated, prospective study included patients with acute ischemic stroke or transient ischemic attack at three study centers. Participants received gapless ECG-monitoring via telemetry during stroke-unit admission until implantation of an insertable cardiac monitor (ICM) within the first days after the index event. Patients acted as their own controls and also received standard 24–72-h Holter ECG.

Results

A total of 110 patients were included, of whom 86 (78.2%) had an embolic stroke of unknown source, 14 (12.7%) had small-vessel disease, and 10 (9.1%) had large-artery disease. AF was newly diagnosed in 17 (15.5%) patients via ICM monitoring, compared to one (0.9%) patient via Holter ECG during 6 months of follow-up (p < 0.001). The detection rate of AF within the first 30 days was 10.0%, which accounted for 64% of all new AF diagnoses. The median duration of the detected episodes was 1.7 (interquartile range = 0.2–4.7) h. All patients with new onset AF were treated with oral anticoagulation.

Conclusions

Gapless ECG-monitoring is an effective strategy to significantly increase the detection rate of AF after ischemic stroke. This finding supports the use of long-term ECG-monitoring with a gapless approach without any interruption in monitoring time as the gold standard for clinical practice.     

Outcomes in minor stroke patients treated with intravenous thrombolysis

Aims

Our study aimed to describe the short-, medium-, and long-term outcomes of intravenous thrombolysis in minor stroke, and to explore the relationship between thrombolysis and clinical outcomes.

Methods

Our study included ischemic minor stroke patients (National Institutes of Health Stroke Scale score ≤ 5) within 4.5 h from symptom onset from the Third China National Stroke Registry (CNSR-III) between August 2015 and March 2018. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0–1 at 3 months. The secondary outcomes included mRS score of 0–1 at discharge, 6 months, and 1 year. The safety outcomes were symptomatic intracerebral hemorrhage (sICH) at 24–36 h and all-cause mortality. The association between intravenous thrombolysis and clinical outcomes was studied using multivariable models.

Results

A total of 1905 minor ischemic stroke patients were included. Overall 527 patients (28%) received intravenous t-PA (IV t-PA) and 1378 patients (72%) in the non-IV t-PA group. Of them, 18.85% (359/1905) participants had a disabled outcome (defined as mRS score ≥ 2) at discharge, 12.8% (242/1885) at 3 months, 13.9% (262/1886) at 6 months, and 13.9% (260/1871) at 1 year. In multivariable analysis, IV t-PA was associated with favorable functional outcomes at discharge (adjusted odds ratio [aOR] 1.49; 95% confidence interval [CI] 1.13–1.96; p = 0.004), 3 months (aOR 1.51; 95% CI 1.09–2.10; p = 0.01), 6 months (aOR 1.64; 95% CI 1.19–2.27; p = 0.003), and 1 year (aOR 1.52; 95% CI 1.10–2.10; p = 0.01). Symptomatic ICH occurred in 3 (0.6%) patients in IV t-PA versus 2 (0.1%) in the non-IV t-PA group. No significant differences were found in all-cause mortality between the two groups.

Conclusions

Intravenous t-PA may be safe and effective in minor stroke (NIHSS ≤ 5) within a 4.5-h window and further randomized controlled trials are warranted.     

Fenfluramine provides clinically meaningful reduction in frequency of drop seizures in patients with Lennox–Gastaut syndrome: Interim analysis of an open-label extension study

Objective

This study was undertaken to evaluate the long-term safety and effectiveness of fenfluramine in patients with Lennox–Gastaut syndrome (LGS).

Methods

Eligible patients with LGS who completed a 14-week phase 3 randomized clinical trial enrolled in an open-label extension (OLE; NCT03355209). All patients were initially started on .2 mg/kg/day fenfluramine and after 1 month were titrated by effectiveness and tolerability, which were assessed at 3-month intervals. The protocol-specified treatment duration was 12 months, but COVID-19-related delays resulted in 142 patients completing their final visit after 12 months.

Results

As of October 19, 2020, 247 patients were enrolled in the OLE. Mean age was 14.3 ± 7.6 years (79 [32%] adults) and median fenfluramine treatment duration was 364 days; 88.3% of patients received 2–4 concomitant antiseizure medications. Median percentage change in monthly drop seizure frequency was −28.6% over the entire OLE (n = 241) and −50.5% at Month 15 (n = 142, p < .0001); 75 of 241 patients (31.1%) experienced ≥50% reduction in drop seizure frequency. Median percentage change in nondrop seizure frequency was −45.9% (n = 192, p = .0038). Generalized tonic–clonic seizures (GTCS) and tonic seizures were most responsive to treatment, with median reductions over the entire OLE of 48.8% (p < .0001, n = 106) and 35.8% (p < .0001, n = 186), respectively. A total of 37.6% (95% confidence interval [CI] = 31.4%–44.1%, n = 237) of investigators and 35.2% of caregivers (95% CI = 29.1%–41.8%, n = 230) rated patients as Much Improved/Very Much Improved on the Clinical Global Impression of Improvement scale. The most frequent treatment-emergent adverse events were decreased appetite (16.2%) and fatigue (13.4%). No cases of valvular heart disease (VHD) or pulmonary arterial hypertension (PAH) were observed.

Significance

Patients with LGS experienced sustained reductions in drop seizure frequency on fenfluramine treatment, with a particularly robust reduction in frequency of GTCS, the key risk factor for sudden unexpected death in epilepsy. Fenfluramine was generally well tolerated; VHD or PAH was not observed long-term. Fenfluramine may provide an important long-term treatment option for LGS.     

Physical activity and sleep problems in 38 low- and middle-income countries

ObjectiveAlthough physical activity (PA) is associated with a reduction of a wide range of sleep problems, it remains uncertain whether complying with the international guidelines of 150 min of moderate to vigorous PA per week can reduce sleep problems in adults. This research investigated the relationship between compliance with the PA recommendations of the World Health Organization and sleep problems in 38 low- and middle-income countries (LMICs).MethodsCross-sectional, community-based data from the World Health Survey were analyzed. Adjusted logistic regression analyses were undertaken to explore the relationship between PA levels using the International Physical Activity Questionnaire and self-reported sleep problems (such as difficulties falling asleep, waking up frequently during the night or waking up too early in the morning) in the last 30 days.ResultsAcross 204,315 individuals (38.6 ± 16.1 years; 49.3% males), the overall prevalence (95% CI) of low PA and sleep problems were 29.9% (29.1–30.8%) and 7.5% (7.2–7.9%), respectively. After adjusting for socio-demographics, obesity, chronic physical conditions, depression, and anxiety; not complying with PA recommendations was associated with higher odds for sleep problems overall [odds ratio (OR) = 1.23, 95% CI = 1.10–1.38] as well as across the entire age range: 18–34 years (OR = 1.26; 95% CI = 1.02–1.57); 35–64 years (OR = 1.17; 95% CI = 1.01–1.35); and age ≥65 years (OR = 1.40; 95% CI = 1.11–1.76).ConclusionsNot complying with international PA recommendations is associated with higher odds of sleep problems, independently of depression and anxiety in LMICs. Future longitudinal and interventional studies are warranted to assess whether increasing PA levels may improve sleep problems in this setting.     

Association of Atrial Fibrillation Detected after Stroke with Cardiac Dysfunction and Features of Neurogenic Cardiac Injury

ObjectivesUnderstanding the link between markers of cardiac injury and atrial fibrillation (AF) detected after stroke (AFDAS) may help refine stroke risk stratification and therapeutic approaches in AFDAS.Materials and methodsWe retrospectively analyzed 988 adult patients admitted for acute ischemic stroke and transient ischemic attack, who presented within 4.5 h from last known well. Pertinent clinical variables including features of neurogenic cardiac injury (so-called stroke heart syndrome [SHS]) as well as electrocardiographic and echocardiographic markers of cardiac dysfunction, and AF status (no AF n = 574; known AF n = 311; AFDAS; n = 103) were collected. Multivariable logistic regression was used to determine the independent associations of variables with AFDAS.ResultsA total of 264 (26.7%) subjects fulfilled criteria for SHS. Of these, 174 of had SHS features other than AFDAS (non-AF SHS). Among 677 subjects without known AF, presence of non-AF SHS was associated with a 5-fold odds of AFDAS (OR 5.0, 95%-CI 3.1–8.0, p < 0.001). After adjustment, non-AF SHS (OR 3.2, 95%-CI 1.6–6.4, p = 0.001) and the left atrial volume index (OR 1.04, 95%-CI 1.01–1.08, p = 0.004) remained independently associated with AFDAS.ConclusionsThe presence of non-AF SHS features and the left atrial volume index were independently associated with AFDAS indicating diverse mechanisms relating to new onset AF. A better understanding of the links between these markers and AFDAS may help uncover potentially modifiable risk factors for AFDAS as well as aid treatment decisions in patients at risk for new onset AF and ischemic stroke.     

War exposure,posttraumatic stress disorder,and complex posttraumatic stress disorder among parents living in Ukraine during the Russian war

Background

High rates of posttraumatic stress disorder (PTSD) have been documented in war-affected populations. The prevalence of Complex PTSD (CPTSD) has never been assessed in an active war zone. Here, we provide initial data on war-related experiences, and prevalence rates of ICD-11 PTSD and CPTSD in a large sample of adults in Ukraine during the Russian war. We also examined how war-related stressors, PTSD, and CPTSD were associated with age, sex, and living location in Ukraine.

Method

Self-report data were gathered from a nationwide sample of 2004 adult parents of children under 18 from the general population of Ukraine approximately 6 months after Russia's invasion.

Results

All participants were exposed to at least one war-related stressor, and the mean number of exposures was 9.07 (range = 1–26). Additionally, 25.9% (95% CI = 23.9%, 27.8%) met diagnostic requirements for PTSD and 14.6% (95% CI = 12.9%, 16.0%) met requirements for CPTSD. There was evidence of a strong dose–response relationship between war-related stressors and meeting criteria for PTSD and CPTSD. Participants who had the highest exposure to war-related stressors were significantly more likely to meet the requirements for PTSD (OR = 4.20; 95% CI = 2.96–5.95) and CPTSD (OR = 8.12; 95% CI = 5.11–12.91) compared to the least exposed.

Conclusions

Humanitarian responses to the mental health needs of the Ukrainian population will need to take account of posttraumatic stress reactions. Education in diagnosing and treating PTSD/CPTSD, especially in the situation of a significant lack of human resources and continuing displacement of the population, is necessary.     

Factors affecting the outcomes of tirofiban after endovascular treatment in acute ischemic stroke: Experience from a single center

Aims

To investigate the predicted factors influencing the outcomes in acute ischemic stroke (AIS) patients who received tirofiban after endovascular treatment (EVT) and the optimal administration of tirofiban.

Methods

In this retrospective study, AIS patients who received EVT followed by tirofiban between January 2017 and October 2021 were enrolled. The dose and duration of tirofiban were adjusted by trained clinicians according to the patient's clinical status. A reduction of at least four points on the National Institutes of Health Stroke Scale (NIHSS) after tirofiban compared with that before tirofiban was defined as an effective response. A modified ranking scale (mRS) of 0–2 was defined as a favorable outcome at a 90-day follow-up.

Results

A total of 260 consecutive patients were enrolled, and 36.5% of patients achieved a favorable outcome. The modified thrombolysis in cerebral infarction (mTICI) 2b-3 occurred in 93.5% of patients. Symptomatic intracerebral hemorrhage (sICH) occurred in 6.2% of patients, and the mortality at 90-day follow-up was 16.9%. Duration of tirofiban >24 h (adjusted OR: 2.545; 95% CI: 1.008–6.423; p = 0.048) and effective response to tirofiban (adjusted OR: 25.562; 95% CI: 9.794–66.715; p < 0.001) were related to the favorable outcome (mRS 0–2). Higher NIHSS (adjusted OR: 0.855; 95% CI: 0.809–0.904; p < 0.001) and glucose level on admission (adjusted OR: 0.843; 95% CI: 0.731–0.971; p = 0.018) were predictive for the unfavorable outcome (mRS 3–6).

Conclusions

An effective response to tirofiban is an independent factor in predicting the long-term efficacy outcome, and extending the duration of tirofiban is beneficial for neurological improvement.     

Associations between testing and treatment pathways in lesional temporal or extratemporal epilepsy: A census survey of NAEC center directors

Objective

The evaluation to determine candidacy and treatment for epilepsy surgery in persons with drug-resistant epilepsy (DRE) is not uniform. Many non-invasive and invasive tests are available to ascertain an appropriate treatment strategy. This study examines expert response to clinical vignettes of magnetic resonance imaging (MRI)–positive lesional focal cortical dysplasia in both temporal and extratemporal epilepsy to identify associations in evaluations and treatment choice.

Methods

We analyzed annual report data and a supplemental epilepsy practice survey reported in 2020 from 206 adult and 136 pediatric epilepsy center directors in the United States. Non-invasive and invasive testing and surgical treatment strategies were compiled for the two scenarios. We used chi-square tests to compare testing utilization between the two scenarios. Multivariable logistic regression modeling was performed to assess associations between variables.

Results

The supplemental survey response rate was 100% with 342 responses included in the analyses. Differing testing and treatment approaches were noted between the temporal and extratemporal scenarios such as chronic invasive monitoring selected in 60% of the temporal scenario versus 93% of the extratemporal scenario. Open resection was the most common treatment choice; however, overall treatment choices varied significantly (p < .001). Associations between non-invasive testing, invasive testing, and treatment choices were present in both scenarios. For example, in the temporal scenario stereo-electroencephalography (SEEG) was more commonly associated with fluorodeoxyglucose–positron emission tomography (FDG-PET) (odds ratio [OR] 1.85; 95% confidence interval [CI] 1.06–3.29; p = .033), magnetoencephalography (MEG) (OR 2.90; 95% CI 1.60–5.28; p = <.001), high density (HD) EEG (OR 2.80; 95% CI 1.27–6.24; p = .011), functional MRI (fMRI) (OR 2.17; 95% CI 1.19–4.10; p = .014), and Wada (OR 2.16; 95% CI 1.28–3.66; p = .004). In the extratemporal scenario, choosing SEEG was associated with increased odds of neuromodulation over open resection (OR 3.13; 95% CI 1.24–7.89; p = .016).

Significance

In clinical vignettes of temporal and extratemporal lesional DRE, epilepsy center directors displayed varying patterns of non-invasive testing, invasive testing, and treatment choices. Differences in practice underscore the need for comparative trials for the surgical management of DRE.