Meta-analysis of multi-modality therapies in sinonasal undifferentiated carcinoma-A timely update.

OBJECTIVES: Sinonasal undifferentiated carcinoma (SNUC) is a rare but aggressive tumour with very poor prognosis. There are currently no well-established clinical trials to guide therapy and the impact of various treatment modalities on survival is not well defined. We aim to provide an updated systematic review on current treatment modalities on survival outcomes. DESIGN AND SETTING: Individual patient data were extracted, and survival data pooled in a one-stage meta-analysis. Descriptive statistics were analysed using the Kaplan-Meier method. Patient-level comparisons stratified by treatment modalities, adjusted for demographics, were conducted using shared-frailty Cox regression. PARTICIPANTS AND MAIN OUTCOME MEASURES: Participants include all patients diagnosed with SNUC based on histological evidence. We looked at the overall cumulative survival outcome for different treatment modalities and overall survival by treatment modality in low versus high stage SNUC patients. RESULTS AND CONCLUSION: Seventeen studies were identified, comprising 208 patients from 1993 to 2020. There was no significant difference in cumulative overall survival in low versus high stage patients, and no significant difference in outcomes by treatment modality. The overall cumulative survival of SNUC is 30% at 95 months. Among patients treated with various combinations of treatment modalities, patients with chemoradiotherapy had the highest cumulative survival of 42% at 40 months. Definitive chemoradiotherapy was associated with improved disease survival rate. Regardless of tumour stage, patients should be treated early and aggressively, with no superiority of one treatment regimen over another. Trimodality treatment does not confer survival advantage over bimodality treatment.

Potential Embolic Sources in Embolic Stroke of Undetermined Source Patients with Patent Foramen Ovale.

INTRODUCTION: A patent foramen ovale (PFO) may coexist with other potential embolic sources (PESs) in patients with embolic stroke of undetermined source (ESUS), leading to difficulty in attributing the stroke to either the PFO or other PESs. We aimed to investigate the prevalence and predictors of concomitant PESs in ESUS patients with PFOs. METHODS: A retrospective cohort study was conducted in a tertiary stroke centre. Consecutive patients with ESUS and a concomitant PFO admitted between 2012 and 2021 were included in the study. Baseline characteristics and investigations as a part of stroke workup including echocardiographic and neuroimaging data were collected. PESs were adjudicated by 2 independent neurologists after reviewing the relevant workup. RESULTS: Out of 1,487 ESUS patients, a total of 309 patients who had a concomitant PFO with mean age of 48.8 ± 13.2 years were identified during the study period. The median Risk of Paradoxical Embolism (RoPE) score for the study cohort was 6 (IQR 5-7.5). Of the 309 patients, 154 (49.8%) only had PFO, 105 (34.0%) patients had 1 other PES, 34 (11.0%) had 2 PES, and 16 (5.2%) had 3 or more PES. The most common PESs were atrial cardiopathy (23.9%), left ventricular dysfunction (22.0%), and cardiac valve disease (12.9%). The presence of additional PESs was associated with age ≥60 years (p < 0.001), RoPE score ≤6 (p ≤0.001), and the presence of comorbidities including diabetes mellitus (p = 0.004), hypertension (p≤ 0.001), and ischaemic heart disease (p = 0.011). CONCLUSION: A large proportion of ESUS patients with PFOs had concomitant PESs. The presence of concomitant PESs was associated with older age and a lower RoPE score. Further, large cohort studies are warranted to investigate the significance of the PES and their overlap with PFOs in ESUS.

Propensity-score matched analysis of patent foramen ovale closure in real-world study cohort with cryptogenic ischemic stroke.

INTRODUCTION: Patent foramen ovale (PFO) occurs in 25% of the general population and in 40% of cryptogenic ischemic stroke patients. Recent trials support PFO closure in selected patients with cryptogenic stroke. We examined the outcomes of transcatheter PFO closure in a real-world study cohort with cryptogenic stroke. METHODS: Consecutive ischemic stroke patients who were classified as cryptogenic on the TOAST aetiology and diagnosed with a PFO were included. All patients underwent either transcatheter PFO closure or medical therapy. A 2:1 propensity score matching by sex and Risk-of-Paradoxical-Embolism (RoPE) score was performed. Multivariable regression models adjusted for sex and RoPE score. RESULTS: Our cohort comprised 232 patients with mean age 44.3 years (SD 10.8) and median follow-up 1486.5 days. 33.2% were female. PFO closure (n=84) and medical therapy (n=148) groups were well-matched with <10% mean-difference in sex and RoPE score. Two patients in the treated group (2.4%) and seven in the control group (4.7%) had a recurrent ischemic stroke event. Multivariable Cox regression demonstrated a hazard-ratio of 0.26 (95%CI 0.03-2.13, P=0.21) for PFO closure compared to control. The incidence of atrial fibrillation (AF) detected post-PFO closure was similar between the treated and control (1.19% vs 1.35%, multivariable logistic regression odds-ratio 0.90, 95%CI 0.04-9.81, P=0.94). There were no major periprocedural complications documented. The difference in restricted mean survival-time free from stroke at two years between treated and control was 26.2 days (95%CI 5.52-46.85, P=0.013). CONCLUSIONS: In this Asian cohort, we report a low incidence of ischemic stroke recurrence and new-onset AF in patients who underwent PFO closure. When compared to the medical therapy group, there was no significant difference in the incidence of stroke recurrence and new-onset AF. Further studies involving larger real-world cohorts are warranted to identify patients who are more likely to benefit from PFO closure.

A cross-sectional study of knowledge and practices in the management of patients with Parkinson's disease amongst public practice-based general practitioners and geriatricians.

BACKGROUND: As most patients are likely to first interface with their community general practitioner (GP) or geriatrician for chronic healthcare conditions, these non-neurologists practitioners are well-placed to diagnose, initiate treatment in symptomatic Parkinson's disease (PD) patients, and provide regular and timely management of their PD. However, current studies suggest that the role of the GP and geriatrician in providing holistic care for PD patients may be limited by factors such as patient perceptions, and a lack of knowledge base in the quality measures of care. This paper aims to better understand the different management styles between GPs and geriatricians practicing in public institutions in Singapore, qualify the difficulties they face in providing patient-centric care for PD patients, and identify any gaps in quality measures of care. METHODS: A questionnaire was completed anonymously by GPs (n = 43) and geriatricians (n = 33) based at public institutions, on a voluntary basis before a compulsory didactic teaching on PD. Questions were modelled after quality measures set out by the American Academy of Neurology, specifically eliciting information on falls, non-motor symptoms, exercise regime and medication-related symptoms. "PD management practices and styles" questions were answered by the respondents on a 4-point Likert scale. RESULTS: Geriatricians spent more time in consult with PD patients compared with GPs (median [Q1-Q3] = 20 [15-30] vs 10 [10-15] minutes, p <  0.001). Geriatricians were more comfortable initiating PD medications than GPs (OR = 11.8 [95% CI: 3.54-39.3], p <  0.001), independent of gender, years of practice and duration of consult. Comfort in initiating dopamine replacement therapy (OR 1.06 [1.00-1.36], p = 0.07; aOR = 1.14 [1.02-1.26], p = 0.02) also increased with physician's years of practice. Unfamiliarity with the types and/or doses of the medications was the most cited barrier faced by GPs (76.7%). Geriatricians were more likely than GPs to ask about falls (100% vs 86.0%, p = 0.025), non-motor symptoms (75.8% vs 53.5%, p = 0.049) and the patient's regular physical activities (72.7% vs 41.9%, p = 0.01). CONCLUSIONS: This study identified key patterns in the management practices and styles of non-neurologists physicians, and identified gaps in current practice. Our data suggests that interventions directed at education on PD medication prescriptions and provision of patient PD education, creation of best clinical practice guidelines, and accreditation by national bodies may instil greater confidence in practitioners to initiate and continue patient-centric PD care. A longer consultation duration with PD patients should be considered to allow physicians to get a greater scope of the patient's needs and better manage them.

The role of intracranial pressure variability as a predictor of intracranial hypertension and mortality in critically ill patients.

OBJECTIVE: Intracranial pressure (ICP) monitoring is a widely utilized and essential tool for tracking neurosurgical patients, but there are limitations to the use of a solely ICP-based paradigm for guiding management. It has been suggested that ICP variability (ICPV), in addition to mean ICP, may be a useful predictor of neurological outcomes, as it represents an indirect measure of intact cerebral pressure autoregulation. However, the current literature regarding the applicability of ICPV shows conflicting associations between ICPV and mortality. Thus, the authors aimed to investigate the effect of ICPV on intracranial hypertensive episodes and mortality using the eICU Collaborative Research Database version 2.0. METHODS: The authors extracted from the eICU database 1,815,676 ICP readings from 868 patients with neurosurgical conditions. ICPV was computed using two methods: the rolling standard deviation (RSD) and the absolute deviation from the rolling mean (DRM). An episode of intracranial hypertension was defined as at least 25 minutes of ICP > 22 mm Hg in any 30-minute window. The effects of mean ICPV on intracranial hypertension and mortality were computed using multivariate logistic regression. A recurrent neural network with long short-term memory was used for time-series predictions of ICP and ICPV to prognosticate future episodes of intracranial hypertension. RESULTS: A higher mean ICPV was significantly associated with intracranial hypertension using both ICPV definitions (RSD: aOR 2.82, 95% CI 2.07-3.90, p < 0.001; DRM: aOR 3.93, 95% CI 2.77-5.69, p < 0.001). ICPV was significantly associated with mortality in patients with intracranial hypertension (RSD: aOR 1.28, 95% CI 1.04-1.61, p = 0.026, DRM: aOR 1.39, 95% CI 1.10-1.79, p = 0.007). In the machine learning models, both definitions of ICPV achieved similarly good results, with the best F1 score of 0.685 ± 0.026 and an area under the curve of 0.980 ± 0.003 achieved with the DRM definition over 20 minutes. CONCLUSIONS: ICPV may be useful as an adjunct for the prognostication of intracranial hypertensive episodes and mortality in neurosurgical critical care as part of neuromonitoring. Further research on predicting future intracranial hypertensive episodes with ICPV may help clinicians react expediently to ICP changes in patients.

Association of Shunt Size and Long-Term Clinical Outcomes in Patients with Cryptogenic Ischemic Stroke and Patent Foramen Ovale on Medical Management.

INTRODUCTION: Patent foramen ovale (PFO) is a potential source of cardiac embolism in cryptogenic ischemic stroke, but it may also be incidental. Right-to-left shunt (RLS) size may predict PFO-related stroke, but results have been controversial. In this cohort study of medically-managed PFO patients with cryptogenic stroke, we aimed to investigate the association of shunt size with recurrent stroke, mortality, newly detected atrial fibrillation (AF), and to identify predictors of recurrent stroke. METHODS: Patients with cryptogenic stroke who screened positive for a RLS using a transcranial Doppler bubble study were included. Patients who underwent PFO closure were excluded. Subjects were divided into two groups: small (Spencer Grade 1, 2, or 3; n = 135) and large (Spencer Grade 4 or 5; n = 99) shunts. The primary outcome was risk of recurrent stroke, and the secondary outcomes were all-cause mortality and newly detected AF. RESULTS: The study cohort included 234 cryptogenic stroke patients with medically-managed PFO. The mean age was 50.5 years, and 31.2% were female. The median period of follow-up was 348 (IQR 147-1096) days. The rate of recurrent ischemic stroke was higher in patients with large shunts than in those with small shunts (8.1% vs. 2.2%, p = 0.036). Multivariate analyses revealed that a large shunt was significantly associated with an increased risk of recurrent ischemic stroke [aOR 4.09 (95% CI 1.04-16.0), p = 0.043]. CONCLUSIONS: In our cohort of cryptogenic stroke patients with medically managed PFOs, those with large shunts were at a higher risk of recurrent stroke events, independently of RoPE score and left atrium diameter.

Prevalence of depression, anxiety and post-traumatic stress in war- and conflict-afflicted areas: A meta-analysis.

Background: With the rise of fragility, conflict and violence (FCV), understanding the prevalence and risk factors associated with mental disorders is beneficial to direct aid to vulnerable groups. To better understand mental disorders depending on the population and the timeframe, we performed a systematic review to investigate the aggregate prevalence of depression, anxiety and post-traumatic stress symptoms among both civilian and military population exposed to war. Methods: We used MEDLINE (PubMed), Web of Science, PsycINFO, and Embase to identify studies published from inception or 1-Jan, 1945 (whichever earlier), to 31-May, 2022, to reporting on the prevalence of depression, anxiety and post-traumatic stress symptoms using structured clinical interviews and validated questionnaires as well as variables known to be associated with prevalence to perform meta-regression. We then used random-effects bivariate meta-analysis models to estimate the aggregate prevalence rate. Results: The aggregate prevalence of depression, anxiety and post-traumatic stress during times of conflict or war were 28.9, 30.7, and 23.5%, respectively. Our results indicate a significant difference in the levels of depression and anxiety, but not post-traumatic stress, between the civilian group and the military group respectively (depression 34.7 vs 21.1%, p < 0.001; anxiety 38.6 vs 16.2%, p < 0.001; post-traumatic stress: 25.7 vs 21.3%, p = 0.256). The aggregate prevalence of depression during the wars was 38.7% (95% CI: 30.0-48.3, I 2 = 98.1%), while the aggregate prevalence of depression post-wars was 29.1% (95% CI: 24.7-33.9, I 2 = 99.2%). The aggregate prevalence of anxiety during the wars was 43.4% (95% CI: 27.5-60.7, I 2 = 98.6%), while the aggregate prevalence of anxiety post-wars was 30.3% (95% CI: 24.5-36.9, I 2 = 99.2%). The subgroup analysis showed significant difference in prevalence of depression, and anxiety between the civilians and military group (p < 0.001). Conclusion: The aggregate prevalence of depression, anxiety and post-traumatic stress in populations experiencing FCV are 28.9, 30.7, and 23.5%, respectively. There is a significant difference in prevalence of depression and anxiety between civilians and the military personnels. Our results show that there is a significant difference in the prevalence of depression and anxiety among individuals in areas affected by FCV during the wars compared to after the wars. Overall, these results highlight that mental health in times of conflict is a public health issue that cannot be ignored, and that appropriate aid made available to at risk populations can reduce the prevalence of psychiatric symptoms during time of FCV. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=337486, Identifier 337486.

Predicting Clinical Outcomes in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy with Machine Learning : A Systematic Review and Meta-analysis.

PURPOSE: Conventional predictive models are based on a combination of clinical and neuroimaging parameters using traditional statistical approaches. Emerging studies have shown that the machine learning (ML) prediction models with multiple pretreatment clinical variables have the potential to accurately prognosticate the outcomes in acute ischemic stroke (AIS) patients undergoing thrombectomy, and hence identify patients suitable for thrombectomy. This article summarizes the published studies on ML models in large vessel occlusion AIS patients undergoing thrombectomy. METHODS: We searched electronic databases including PubMed from 1 January 2000 up to 14 October 2019 for studies that evaluated ML algorithms for the prediction of outcomes in stroke patients undergoing thrombectomy. We then used random-effects bivariate meta-analysis models to summarize the studies. RESULTS: We retained a total of five studies that evaluated ML (4 support vector machine, 1 decision tree model) with a combined cohort of 802 patients. The prevalence of good functional outcome defined by 90-day mRS of 0-2 when available. Random effects model demonstrated that the AUC was 0.846 (95% confidence interval, CI 0.686-0.902). A pooled diagnostic odds ratio of 12.6 was computed. The pooled sensitivity and specificity were 0.795 (95% CI 0.651-0.889) and 0.780 (95% CI 0.634-0.879), respectively. CONCLUSION: ML may be useful as an adjunct to clinical assessment to predict functional outcomes in AIS patients undergoing thrombectomy, and hence identify suitable patients for treatment. Further studies validating ML models in large multicenter cohorts are necessary to explore this further.