Do all sedatives promote biological sleep electroencephalogram patterns? A machine learning framework to identify biological sleep promoting sedatives using electroencephalogram.

BACKGROUND: Sedatives are commonly used to promote sleep in intensive care unit patients. However, it is not clear whether sedation-induced states are similar to the biological sleep. We explored if sedative-induced states resemble biological sleep using multichannel electroencephalogram (EEG) recordings. METHODS: Multichannel EEG datasets from two different sources were used in this study: (1) sedation dataset consisting of 102 healthy volunteers receiving propofol (N = 36), sevoflurane (N = 36), or dexmedetomidine (N = 30), and (2) publicly available sleep EEG dataset (N = 994). Forty-four quantitative time, frequency and entropy features were extracted from EEG recordings and were used to train the machine learning algorithms on sleep dataset to predict sleep stages in the sedation dataset. The predicted sleep states were then compared with the Modified Observer's Assessment of Alertness/ Sedation (MOAA/S) scores. RESULTS: The performance of the model was poor (AUC = 0.55-0.58) in differentiating sleep stages during propofol and sevoflurane sedation. In the case of dexmedetomidine, the AUC of the model increased in a sedation-dependent manner with NREM stages 2 and 3 highly correlating with deep sedation state reaching an AUC of 0.80. CONCLUSIONS: We addressed an important clinical question to identify biological sleep promoting sedatives using EEG signals. We demonstrate that propofol and sevoflurane do not promote EEG patterns resembling natural sleep while dexmedetomidine promotes states resembling NREM stages 2 and 3 sleep, based on current sleep staging standards.

The Value of Ischemic Cardiac Biomarkers to Predict Spontaneous Breathing Trial or Extubation Failure: A Systematic Review.

Background: It is unclear whether other cardiac biomarkers than NT-proBNP can be useful in the risk stratification of patients weaning from mechanical ventilation. The aim of this study is to summarize the role of ischemic cardiac biomarkers in predicting spontaneous breathing trial (SBT) or extubation failure. Methods: We systematically searched Embase, MEDLINE, Web of Science, and Cochrane Central for studies published before January 2024 that reported the association between ischemic cardiac biomarkers and SBT or extubation failure. Data were extracted using a standardized form and methodological assessment was performed using the QUIPS tool. Results: Seven observational studies investigating four ischemic cardiac biomarkers (Troponin-T, Troponin-I, CK-MB, Myoglobin) were included. One study reported a higher peak Troponin-I in patients with extubation failure compared to extubation success (50 ng/L [IQR, 20-215] versus 30 ng/L [IQR, 10-86], p = 0.01). A second study found that Troponin-I measured before the SBT was higher in patients with SBT failure in comparison to patients with SBT success (100 ± 80 ng/L versus 70 ± 130 ng/L, p = 0.03). A third study reported a higher CK-MB measured at the end of the SBT in patients with weaning failure (SBT or extubation failure) in comparison to weaning success (8.77 ± 20.5 ng/mL versus 1.52 ± 1.42 ng/mL, p = 0.047). Troponin-T and Myoglobin as well as Troponin-I and CK-MB measured at other time points were not found to be related to SBT or extubation failure. However, most studies were underpowered and with high risk of bias. Conclusions: The association with SBT or extubation failure is limited for Troponin-I and CK-MB and appears absent for Troponin-T and Myoglobin, but available studies are hampered by significant methodological drawbacks. To more definitively determine the role of ischemic cardiac biomarkers, future studies should prioritize larger sample sizes, including patients at risk of cardiac disease, using stringent SBTs and structured timing of laboratory measurements before and after SBT.

Plasma Neurofilament Light Chain as a Biomarker for Poor Outcome After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Neurofilament light chain (NfL), a biomarker reflecting neuro-axonal damage, may be useful in improving clinical outcome prediction after aneurysmal subarachnoid hemorrhage (aSAH). We explore the robust and additional value of NfL to neurologic and radiologic grading scales in predicting poor outcome after aSAH. METHODS: In this prospective cohort study conducted in a single tertiary center, blood samples were collected of aSAH patients within 24 hours after ictus and before endovascular/surgical intervention. The primary endpoint was poor outcome at 6 months' follow-up. Receiver operating curves (ROC), area under the curve (AUC, 95% CI) and model-fit (Nagelkerke R2) were calculated for NfL, neurologic grading scale (WFNS), modified Fisher, age ,and sex. A combined ROC and AUC were calculated for variables with an AUC ≥ 0.70. RESULTS: A total of 66 (42%) had poor outcome. The AUC of NfL for poor outcome was 0.70 (0.62-0.78). Combining NfL and WFNS resulted in a slightly higher model fit and not-significantly higher AUC for predicting poor outcome (R2 0.51; AUC 0.86, 0.80-0.92) compared with WFNS alone. When patients were stratified according to hemorrhage severity, median NfL [IQR] levels were significantly higher in poor grade (14 [7-32] pg/mL) than good grade patients (7 [5-14] pg/mL). Within poor grade patients, median NfL [IQR] levels were significantly higher in non-survivors (19 [11-36] pg/mL) than survivors (7 [6-13] pg/mL). CONCLUSION: In the entire aSAH cohort, plasma NfL has an acceptable predictive performance but does not improve clinical outcome prediction. However, NfL may have potential value in subgroups based on hemorrhage severity.

Ultra-Early and Short-Term Tranexamic Acid Treatment in Patients With Good- and Poor-Grade Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND AND OBJECTIVES: The results of the ULTRA trial showed that ultra-early and short-term treatment with tranexamic acid (TXA) does not improve clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). Possibly, the lack of a beneficial effect in all patients with aSAH is masked by antagonistic effects of TXA in certain subgroups. In this post hoc subgroup analysis, we investigated the effect of TXA on clinical outcome in patients with good-grade and poor-grade aSAH. METHODS: The ULTRA trial was a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment. Participants received ultra-early and short-term TXA in addition to usual care or usual care only. This post hoc subgroup analysis included only ULTRA participants with confirmed aSAH and available World Federation of Neurosurgical Societies (WFNS) grade on admission. Patients were categorized into those with good-grade (WFNS 1-3) and poor-grade (WFNS 4-5) aSAH. The primary outcome was clinical outcome assessed by the modified Rankin scale (mRS). Odds ratios (ORs) and adjusted ORs (aORs) with 95% CIs were calculated using ordinal regression analyses. Analyses were performed using the as-treated principle. In all patients with aSAH, no significant effect modification of TXA on clinical outcome was observed for admission WFNS grade (p = 0.10). RESULTS: Of the 812 ULTRA participants, 473 patients had (58%; N = 232 TXA, N = 241 usual care) good-grade and 339 (42%; N = 162 TXA, N = 176 usual care) patients had poor-grade aSAH. In patients with good-grade aSAH, the TXA group had worse clinical outcomes (OR: 0.67, 95% CI 0.48-0.94, aOR 0.68, 95% CI 0.48-0.94) compared with the usual care group. In patients with poor-grade aSAH, clinical outcomes were comparable between treatment groups (OR: 1.04, 95% CI 0.70-1.55, aOR 1.05, 95% CI 0.70-1.56). DISCUSSION: This post hoc subgroup analysis provides another important argument against the use of TXA treatment in patients with aSAH, by showing worse clinical outcomes in patients with good-grade aSAH treated with TXA and no clinical benefit of TXA in patients with poor-grade aSAH, compared with patients treated with usual care. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid, given for <24 hours within the first 24 hours, does not improve the 6-month outcome in good-grade or poor initial-grade aneurysmal SAH.

Impact of time to start of tranexamic acid treatment on rebleed risk and outcome in aneurysmal subarachnoid hemorrhage.

INTRODUCTION: The ULTRA-trial investigated effectiveness of ultra-early administration of tranexamic acid (TXA) in subarachnoid hemorrhage (SAH) and showed that TXA reduces the risk of rebleeding without concurrent improvement in clinical outcome. Previous trials in bleeding conditions, distinct from SAH, have shown that time to start of antifibrinolytic treatment influences outcome. This post-hoc analysis of the ULTRA-trial investigates whether the interval between hemorrhage and start of TXA impacts the effect of TXA on rebleeding and functional outcome following aneurysmal SAH. PATIENTS AND METHODS: A post-hoc comparative analysis was conducted between aneurysmal SAH patients of the ULTRA-trial, receiving TXA and usual care to those receiving usual care only. We assessed confounders, hazard ratio (HR) of rebleeding and odds ratio (OR) of good outcome (modified Rankin Scale 0-3) at 6 months, and investigated the impact of time between hemorrhage and start of TXA on the treatment effect, stratified into time categories (0-3, 3-6 and >6 h). RESULTS: Sixty-four of 394 patients (16.2%) in the TXA group experienced a rebleeding, compared to 83 of 413 patients (19.9%) with usual care only (HR 0.86, 95% confidence interval (CI): 0.62-1.19). Time to start of TXA modifies the effect of TXA on rebleeding rate (p < 0.001), with a clinically non-relevant reduction observed only when TXA was initiated after 6 h (absolute rate reduction 1.4%). Tranexamic acid treatment showed no effect on good outcome (OR 0.96, 95% CI: 0.72-1.27) with no evidence of effect modification on the time to start of TXA (p = 0.53). DISCUSSION AND CONCLUSIONS: This study suggests that the effect of TXA on rebleeding is modified by time to treatment, providing a protective, albeit clinically non-relevant, effect only when started after 6 h. No difference in functional outcome was seen. Routine TXA treatment in the aneurysmal SAH population, even within a specified time frame, is not recommended to improve functional outcome.

Erratum: Missed Proximal Tracheoesophageal Fistula (TEF) in a Neonate with Type D Esophageal Atresia.

[This corrects the article DOI: 10.1055/a-2227-6389.].

Sodium and Its Impact on Outcome After Aneurysmal Subarachnoid Hemorrhage in Patients With and Without Delayed Cerebral Ischemia.

OBJECTIVES: To perform a detailed examination of sodium levels, hyponatremia and sodium fluctuations, and their association with delayed cerebral ischemia (DCI) and poor outcome after aneurysmal subarachnoid hemorrhage (aSAH). DESIGN: An observational cohort study from a prospective SAH Registry. SETTING: Tertiary referral center focused on SAH treatment in the Amsterdam metropolitan area. PATIENTS: A total of 964 adult patients with confirmed aSAH were included between 2011 and 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 277 (29%) developed DCI. Hyponatremia occurred significantly more often in DCI patients compared with no-DCI patients (77% vs. 48%). Sodium levels, hyponatremia, hypernatremia, and sodium fluctuations did not predict DCI. However, higher sodium levels were significantly associated with poor outcome in DCI patients (DCI onset -7, DCI +0, +1, +2, +4, +5, +8, +9 d), and in no-DCI patients (postbleed day 6-10 and 12-14). Also, hypernatremia and greater sodium fluctuations were significantly associated with poor outcome in both DCI and no-DCI patients. CONCLUSIONS: Sodium levels, hyponatremia, and sodium fluctuations were not associated with the occurrence of DCI. However, higher sodium levels, hypernatremia, and greater sodium fluctuations were associated with poor outcome after aSAH irrespective of the presence of DCI. Therefore, sodium levels, even with mild changes in levels, warrant close attention.

Unintentional Suture Fistula Between the Proximal and Distal Esophagus in a Preterm Neonate with Type C Esophageal Atresia.

We present the case of a patient with gross type C esophageal atresia in a preterm neonate (gestational age of 31 weeks + 1 day) with a birth weight of 1,470 g. The fistula was released via a thoracotomy, but no primary anastomosis could be made, due to an unexpected long gap. The distal esophagus was closed and approximated to the blind pouch using traction sutures until an adjacent position was reached. A gastrostomy was created for enteral feeding. Although a second attempt to make an anastomosis was unsuccessful, the patient unexpectedly developed a suture fistula 6 weeks after the first procedure, enabling feeding via a nasogastric tube. Over time, six dilations were necessary. Full enteral feeding was achieved at the age of 6 months. Our case confirms sparse reports that deliberately creating a suture fistula may be a solution in esophageal atresia patients when an unexpected long gap prohibits a primary anastomosis.

Missed Proximal Tracheoesophageal Fistula (TEF) in a Neonate with Type D Esophageal Atresia.

We present the case of a patient with the rare type D esophageal atresia (EA), diagnosed after correction of an EA initially diagnosed as type C. Routine postoperative contrast esophagogram showed a missed proximal tracheoesophageal fistula. This case report illustrates the potential difficulties to diagnose type D EA.

Genotype by Environment Interactions (G*E) of Chickens Tested in Ethiopia Using Body Weight as a Performance Trait.

Ethiopia is a developing nation that could highly benefit from securing food via improved smallholder poultry farming. To support farmer and breeding decisions regarding which chicken strain to use in which Ethiopian environment, G*E analyses for body weight (BW) of growing male and female chickens were conducted. Research questions were (1) if a G*E is present for BW and (2) which strain performs best in which environment in terms of predicted BW. Analyses were performed using predicted BW at four different ages (90, 120, 150, and 180 days) of five strains (Horro, Koekoek, Kuroiler, Sasso-Rhode Island Red (S-RIR), and Sasso) tested in five Ethiopian regions (Addis Ababa, Amhara, Oromia, South Region, and Tigray) that are part of three Agro-Ecological Zones (AEZ) (cool humid, cool sub-humid, and warm semi-arid). The indigenous Horro strain was used as a control group to compare four other introduced tropically adapted strains. The dataset consisted of 999 female and 989 male farm-average BW measurements. G*E was strongly present (p < 0.001) for all combinations of strain and region analyzed. In line with previous research, Sasso was shown to have the highest predicted BW, especially at an early age, followed by Kuroiler. Horro had the lowest predicted BW at most ages and in most regions, potentially due to its young breeding program. The highest predicted BW were observed in Tigray, Oromia, and Amhara regions, which are in the main part of the cool sub-humid AEZ.

Postoperative Load Bearing in Periprosthetic Femoral Fractures Around Hip Arthroplasty: A Survey Among Orthopedic Surgeons in the Netherlands.

INTRODUCTION: Permissive weight bearing (PWB) has relatively recently been implemented to optimize rapid clinical recovery and restoration of function in patients suffering lower extremity fractures. PWB shows outcome advantages in this patient category. Currently, there are no decisive recommendations on postoperative load-bearing management after surgically treated periprosthetic femoral fractures (PPFF) around hip arthroplasty. The objective is to investigate the current postoperative practice of weight-bearing instructions for patients with surgically treated PPFF, accounting for differences in types of periprosthetic fractures and treatment options among Dutch orthopedic surgeons. MATERIALS AND METHODS: An online survey was distributed among the members of the hip and trauma working groups of the Dutch Orthopedic Association. RESULTS: The response rate was 13% (n=75). The main finding was that postoperative load bearing regimes in Vancouver A, B, and C PPFFs differed greatly among Dutch orthopedic surgeons, and there was no decisive guideline or consensus in postoperative load bearing regimes after surgically treated PPFF was used in the Netherlands. CONCLUSION: In the absence of decisive guidelines or consensus, more research is needed to explore the efficacy of PWB after surgically treated PPFF.

Prevalence and risk factors associated with the occurrence of Campylobacter sp. in children aged 6-24 months in peri-urban Nairobi, Kenya.

Introduction: Campylobacter bacteria is a major cause of foodborne-related bacterial gastroenteritis in humans worldwide. It is known to cause diarrhea in young children which has been shown to directly affect their weight and height as a result of malnutrition. Severe cases of diarrhea can also lead to death. Most of the burden is experienced in resource-limited countries in Africa and Southeast Asia where the disease is linked to poor hygiene and sanitation. The objective of this study was to determine the prevalence of Campylobacter in children aged between 6 and 24 months in Nairobi, Kenya and identify potential risk factors associated with their occurrence. Methods: A cross-sectional study was carried out between May to December 2021. A total of 585 randomly selected households were visited in two wards (Uthiru/Ruthimitu and Riruta) in Dagoretti South sub-county, Nairobi. A questionnaire regarding how children's food is handled, the major foods consumed, sanitation and hygiene, and animal ownership was conducted among caregivers to identify associated risk factors. Stool samples were collected from 540/585 children and screened for the presence of Campylobacter using culture-based methods and confirmed through PCR. Results: Of the 540 children's stool samples processed, Campylobacter isolates were detected in 4.8% (26/540). Campylobacter jejuni (C. jejuni) was the most common species in 80.8% of positive samples compared to Campylobacter coli (C. coli) in 26.9% of samples. In six samples, both C. jejuni and C. coli were isolated, while in four samples, it was not possible to speciate the Campylobacter. Drinking cow's milk (OR 4.2, 95% CI 1.4 - 12.6) and the presence of animal feces in the compound (OR 3.4, 95% CI 1.1 - 10.3) were found to be statistically associated with Campylobacter carriage in children. Discussion: The carriage of Campylobacter in children in this community indicates a need for further investigation on source attribution to understand transmission dynamics and inform where to target interventions. Awareness creation among caregivers on good personal and food hygiene is needed, including boiling milk before consumption. Implementation of biosecurity measures at the household level is highly recommended to reduce contact between animals and humans.

Paradoxical exacerbation of sclerouveitis following Rituximab infusion.

PURPOSE: To report on an unexpected side effect of Rituximab (RTX), a B-cell targeting monoclonal agent, in a patient with severe sclerouveitis, leading to severe visual loss. METHODS: Observational case report. RESULTS: A 61-year-old female was treated with RTX for a severe sclerouveitis occurring with granulomatosis with polyangiitis. Initially it responded partly to high dose of oral corticosteroids, however, her sclerouveitis recurred after two months during tapering below 20mg daily. The days following the RTX infusions, aggravation of the intraocular inflammation was seen, endangering visual acuity. No evidence for an infection or other cause were found. High doses of oral corticosteroids were started within one week, where after the ocular inflammation resolved. For persisting hypotony and chorioretinal detachment a combined pars plana vitrectomy with phacoemulsification and silicone oil tamponade was performed. The retina remained attached under oil tamponade with partial improvement of the BCVA to finger counting. CONCLUSION: Ophthalmologist should be aware of the possibility of this paradoxical local reaction to RTX infusion, particularly in bilateral and/or severe cases, which carry a risk of a poor outcome.

Aneurysm treatment within 6 h versus 6-24 h after rupture in patients with subarachnoid hemorrhage.

BACKGROUND: The risk of rebleeding after aneurysmal subarachnoid hemorrhage (aSAH) is the highest during the initial hours after rupture. Emergency aneurysm treatment may decrease this risk, but is a logistic challenge and economic burden. We aimed to investigate whether aneurysm treatment <6 h after rupture is associated with a decreased risk of poor functional outcome compared to aneurysm treatment 6-24 h after rupture. METHODS: We used data of patients included in the ULTRA trial (NCT02684812). All patients in ULTRA were admitted within 24 h after aneurysm rupture. For the current study, we excluded patients in whom the aneurysm was not treated <24 h after rupture. We calculated crude and adjusted risk ratios (aRR) with 95% confidence intervals using Poisson regression analyses for poor functional outcome (death or dependency, assessed by the modified Rankin Scale) after aneurysm treatment <6 h versus 6-24 h after rupture. Adjustments were made for age, sex, clinical condition on admission (WFNS scale), amount of extravasated blood (Fisher score), aneurysm location, tranexamic acid treatment, and aneurysm treatment modality. RESULTS: We included 497 patients. Poor outcome occurred in 63/110 (57%) patients treated within 6 h compared to 145/387 (37%) patients treated 6-24 h after rupture (crude RR: 1.53, 95% CI: 1.24-1.88; adjusted RR: 1.36, 95% CI: 1.11-1.66). CONCLUSION: Aneurysm treatment <6 h is not associated with better functional outcome than aneurysm treatment 6-24 h after rupture. Our results do not support a strategy aiming to treat every patient with a ruptured aneurysm <6 h after rupture.

Cutaneous Lesions of Mastocytosis: Mast Cell Count, Morphology, and Immunomolecular Phenotype.

ABSTRACT: Mastocytosis is a condition characterized by accumulation of clonal mast cells (MCs) that often involves the skin. Pathologists are often challenged with skin biopsies with a question of cutaneous lesions of mastocytosis (CLM) including cutaneous mastocytosis, mastocytosis in the skin, or systemic mastocytosis. The histopathological criteria for CLM remain poorly defined due to heterogeneity of the published literature and the lack of comparative prospective studies. MC count is greatly influenced by detection and counting techniques, criteria for viable MCs used, anatomical location biopsied, and the dermal level that is analyzed. Although MC numbers in CLM can be significantly higher compared with healthy controls and a patient with other inflammatory skin diseases, in some instances, considerable overlap exists. Based on the largest studies published, it is suggested that a number of MCs between 75 and 250 MCs/mm 2 are a range in which CLM should be considered and, above 250 MC/mm 2 , a diagnosis of CLM can be made. A recent study showed a high specificity of >95% of a MC count >139 MC/mm 2 compared with patients with other inflammatory skin diseases. Noteworthy, the total number and percentage of MCs is significantly higher in children compared with adults, particularly in polymorphic maculopapular cutaneous mastocytosis. In difficult cases, ancillary techniques such as D816V mutation analysis on formalin-fixed paraffin-embedded tissue have a high sensitivity and specificity. There is no enough evidence that immunohistochemistry of CD25, CD2, or CD30 has any additional value in the diagnosis, subtyping, or clinical course of mastocytosis.

Sex Differences in the Anti-Hypertensive Effect of Calcium-Channel Blockers: A Systematic Review and Meta-Analysis.

Cardiovascular disease (CVD) is the number one cause of death worldwide, with hypertension as the leading risk factor for both sexes. As sex may affect responsiveness to antihypertensive compounds, guidelines for CVD prevention might necessitate divergence between females and males. To this end, we studied the effectiveness of calcium channel blockers (CCB) on blood pressure (BP), heart rate (HR) and cardiac function between sexes. We performed a systematic review and meta-analysis on studies on CCB from inception to May 2020. Studies had to present both baseline and follow-up measurements of the outcome variables of interest and present data in a sex-stratified manner. Mean differences were calculated using a random-effects model. In total, 38 studies with 8202 participants were used for this review. In females as compared to males, systolic BP decreased by -27.6 mmHg (95%CI -36.4; -18.8) (-17.1% (95%CI -22.5;-11.6)) versus -14.4 mmHg (95%CI -19.0; -9.9) (-9.8% (95%CI -12.9;-6.7)) (between-sex difference p < 0.01), diastolic BP decreased by -14.1 (95%CI -18.8; -9.3) (-15.2%(95%CI -20.3;-10.1)) versus -10.6 mmHg (95%CI -14.0; -7.3) (-11.2% (95%CI -14.8;-7.7)) (between-sex difference p = 0.24). HR decreased by -1.8 bpm (95%CI -2.5; -1.2) (-2.5% (95%CI -3.4; -1.6)) in females compared to no change in males (0.3 bpm (95% CI -1.2; 1.8)) (between-sex difference p = 0.01). In conclusion, CCB lowers BP in both sexes, but the observed effect is larger in females as compared to males.

Clinical response following hypertension induction for clinical delayed cerebral ischemia following subarachnoid hemorrhage: A retrospective, multicenter, cohort study.

BACKGROUND: Hypertension induction (HTI) is often used for treating delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH); however, high-quality studies on its efficacy are lacking. We studied immediate and 3-/6-month clinical efficacy of HTI in aSAH patients with clinical DCI. METHODS: A retrospective, multicenter, comparative, observational cohort study in aSAH patients with clinical deterioration due to DCI, admitted to three tertiary referral hospitals in the Netherlands from 2015 to 2019. Two hospitals used a strategy of HTI (HTI group) and one hospital had no such strategy (control group). We calculated adjusted relative risks (aRR) using Poisson regression analyses for the two primary (clinical improvement of DCI symptoms at days 1 and 5 after DCI onset) and secondary outcomes (DCI-related cerebral infarction, in-hospital mortality, and poor clinical outcome [modified Rankin Scale 4-6] assessed at 3 or 6 months), using the intention-to-treat principle. We also performed as-treated and per-protocol analyses. RESULTS: The aRR for clinical improvement on day 1 after DCI in the HTI group was 1.63 (95% CI 1.17-2.27) and at day 5 after DCI 1.04 (95% CI 0.84-1.29). Secondary outcomes were comparable between the groups. The as-treated and per-protocol analyses yielded similar results. CONCLUSIONS: No clinical benefit of HTI is observed 5 days after DCI due to spontaneous reversal of DCI symptoms in patients treated without HTI. The 3-/6-month clinical outcome was similar for both groups. Therefore, these data suggest that one may consider to not apply HTI in aSAH patients with clinical DCI.

The Representation of Females in Studies on Antihypertensive Medication over the Years: A Scoping Review.

BACKGROUND: The leading global risk factor for cardiovascular-disease-related morbidity and mortality is hypertension. In the past decade, attention has been paid to increase females' representation. The aim of this study is to investigate whether the representation of females and presentation of sex-stratified data in studies investigating the effect of antihypertensive drugs has increased over the past decades. METHODS: After systematically searching PubMed and Embase for studies evaluating the effect of the five major antihypertensive medication groups until May 2020, a scoping review was performed. The primary outcome was the proportion of included females. The secondary outcome was whether sex stratification was performed. RESULTS: The search resulted in 73,867 articles. After the selection progress, 2046 studies were included for further analysis. These studies included 1,348,172 adults with a mean percentage of females participating of 38.1%. Female participation in antihypertensive studies showed an increase each year by 0.2% (95% CI 0.36-0.52), p < 0.01). Only 75 (3.7%) studies performed sex stratification, and this was the highest between 2011 and 2020 (7.2%). CONCLUSION: Female participation showed a slight increase in the past decade but is still underrepresented compared to males. As data are infrequently sex-stratified, more attention is needed to possible sex-related differences in treatment effects to different antihypertensive compounds.

Exploring Sex Differences of Beta-Blockers in the Treatment of Hypertension: A Systematic Review and Meta-Analysis.

AIMS: In the prevention of cardiovascular morbidity and mortality, early recognition and adequate treatment of hypertension are of leading importance. However, the efficacy of antihypertensives may be depending on sex disparities. Our objective was to evaluate and quantify the sex-diverse effects of beta-blockers (BB) on hypertension and cardiac function. We focussed on comparing hypertensive female versus male individuals. METHODS AND RESULTS: A systematic search was performed for studies on BBs from inception to May 2020. A total of 66 studies were included that contained baseline and follow up measurements on blood pressure (BP), heart rate (HR), and cardiac function. Data also had to be stratified for sex. Mean differences were calculated using a random-effects model. In females as compared to males, BB treatment decreased systolic BP 11.1 mmHg (95% CI, -14.5; -7.8) vs. 11.1 mmHg (95% CI, -14.0; -8.2), diastolic BP 8.0 mmHg (95% CI, -10.6; -5.3) vs. 8.0 mmHg (95% CI, -10.1; -6.0), and HR 10.8 beats per minute (bpm) (95% CI, -17.4; -4.2) vs. 9.8 bpm (95% CI, -11.1; -8.4)), respectively, in both sexes' absolute and relative changes comparably. Left ventricular ejection fraction increased only in males (3.7% (95% CI, 0.6; 6.9)). Changes in left ventricular mass and cardiac output (CO) were only reported in males and changed -20.6 g (95% CI, -56.3; 15.1) and -0.1 L (95% CI, -0.5; 0.2), respectively. CONCLUSIONS: BBs comparably lowered BP and HR in both sexes. The lack of change in CO in males suggests that the reduction in BP is primarily due to a decrease in vascular resistance. Furthermore, females were underrepresented compared to males. We recommend that future research should include more females and sex-stratified data when researching the treatment effects of antihypertensives.