Identification and Characterization of CC-AMP1-like and CC-AMP2-like Peptides in Capsicum spp.

Antimicrobial peptides (AMPs) are compounds with a variety of bioactive properties. Especially promising are their antibacterial activities, often toward drug-resistant pathogens. Across different AMP sources, AMPs expressed within plants are relatively underexplored with a limited number of plant AMP families identified. Recently, we identified the novel AMPs CC-AMP1 and CC-AMP2 in ghost pepper plants (Capsicum chinense x frutescens), exerting promising antibacterial activity and not classifying into any known plant AMP family. Herein, AMPs related to CC-AMP1 and CC-AMP2 were identified within both Capsicum annuum and Capsicum baccatum. In silico predictions throughout plants were utilized to illustrate that CC-AMP1-like and CC-AMP2-like peptides belong to two broader AMP families, with three-dimensional structural predictions indicating that CC-AMP1-like peptides comprise a novel subfamily of α-hairpinins. The antibacterial activities of several closely related CC-AMP1-like peptides were compared with a truncated version of CC-AMP1 possessing significantly more activity than the full peptide. This truncated peptide was further characterized to possess broad-spectrum antibacterial activity against clinically relevant ESKAPE pathogens. These findings illustrate the value in continued study of plant AMPs toward characterization of novel AMP families, with CC-AMP1-like peptides possessing promising bioactivity.

Outcomes of mechanical thrombectomy in acute stroke patients with atrial fibrillation detected after stroke versus known atrial fibrillation.

We aim to compare the outcomes in patients with atrial fibrillation detected after stroke (AFDAS) and their counterparts with known AF (KAF) presenting with large vessel occlusion (LVO) treated with mechanical thrombectomy (MT). This observational, prospective study included consecutive patients with acute LVO ischemic stroke of the anterior circulation with AFDAS, KAF and without AF. The primary study outcome was functional independence at 90 days after stroke. The secondary study outcomes were variation of the NIHSS score at 24 h, rate of successful reperfusion, death at 90 days and rate of immediate complications post-procedure. Overall, our cohort included 518 patients with acute ischemic stroke and LVO treated with MT, with 289 (56.8%) without a diagnosis of AF; 107 (21%) with AFDAS; 122 (22.2%) with KAF. There was no significant difference in terms of functional independence at 90 days after stroke between the three groups. Regarding the secondary study outcome, the rate of symptomatic intracranial haemorrhage (sICH) and/or parenchymal hematoma (PH) were significantly higher in the group of patients without AF (respectively, P = 0.030 and < 0.010). Logistic regression analysis showed that the subtypes of AF were not statistically significantly associated with functional independence at 90 days after stroke and with the likelihood of any ICH. Our results suggest that the subtypes of AF are not associated with clinical and safety outcomes of MT in patients with acute stroke and LVO. Further studies are needed to confirm our findings.

Effect of AMPK activation and glucose availability on myotube LAT1 expression and BCAA utilization.

Those with insulin resistance often display increased circulating branched-chain amino acids (BCAA), which has been largely attributable to reduced BCAA catabolic capacity. Metabolic stimuli such as exercise activates AMP-activated kinase (AMPK), which promotes the metabolism of BCAA and induction/activation of BCAA catabolic enzymes. Though much attention has been paid to BCAA catabolic machinery, few studies have assessed the effect of AMPK activation on the predominant BCAA transporter, L-type amino acid transporter 1 (LAT1). This study assessed the effect of AMPK activation on LAT1 expression via common chemical AMPK activators in a cell model of skeletal muscle. C2C12 myotubes were treated with either 1 mM AICAR, 1 mM Metformin, or filter-sterilized water (control) for 24 h with either low- (5 mM) or high-glucose (25 mM) media. LAT1 and pAMPK protein content were measured via western blot. BCAA media content was measured using liquid chromatography-mass spectrometry. AICAR treatment significantly increased pAMPK and reduced LAT1 expression. Collectively, pAMPK and LAT1 displayed a significant inverse relationship independent of glucose levels. During low-glucose experiments, AICAR-treated cells had higher BCAA media content compared to other groups, and an inverse relationship between LAT1 and BCAA media content was observed, however, these effects were not consistently observed during high-glucose conditions. Further investigation with AICAR with and without concurrent LAT1 inhibition (via JPH203) also revealed reduced BCAA utilization in AICAR-treated cells regardless of LAT1 inhibition (which also independently reduced BCAA utilization). pAMPK activation via AICAR (but not Metformin) may reduce LAT1 expression and BCAA uptake in a glucose-dependent manner.

Multidisciplinary team discussion: the emerging gold standard for management of cardiopulmonary complications of connective tissue disease.

Cardiopulmonary complications of connective tissue diseases (CTDs), particularly pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD), are major determinants of morbidity and mortality. Multidisciplinary meetings may improve diagnostic accuracy and optimise treatment. We review the literature regarding multidisciplinary meetings in CTD-ILD and PAH and describe our tertiary centre experience of the role of the multidisciplinary meeting in managing CTD-PAH.

Congruent Prosody Reduces Cognitive Effort in Memory for Spoken Sentences: A Pupillometric Study with Young and Older Adults.

BACKGROUND: In spite of declines in working memory and other processes, older adults generally maintain good ability to understand and remember spoken sentences. In part this is due to preserved knowledge of linguistic rules and their implementation. Largely overlooked, however, is the support older adults may gain from the presence of sentence prosody (pitch contour, lexical stress, intra-and inter-word timing) as an aid to detecting the structure of a heard sentence. METHODS: Twenty-four young and 24 older adults recalled recorded sentences in which the sentence prosody corresponded to the clausal structure of the sentence, when the prosody was in conflict with this structure, or when there was reduced prosody uninformative with regard to the clausal structure. Pupil size was concurrently recorded as a measure of processing effort. RESULTS: Both young and older adults' recall accuracy was superior for sentences heard with supportive prosody than for sentences with uninformative prosody or for sentences in which the prosodic marking and causal structure were in conflict. The measurement of pupil dilation suggested that the task was generally more effortful for the older adults, but with both groups showing a similar pattern of effort-reducing effects of supportive prosody. CONCLUSIONS: Results demonstrate the influence of prosody on young and older adults' ability to recall accurately multi-clause sentences, and the significant role effective prosody may play in preserving processing effort.

Myocardial fibrosis and arrhythmic burden in systemic sclerosis.

OBJECTIVES: Cardiac complications of SSc are a leading cause of SSc-associated death. Cardiac imaging for identifying substrate abnormality may be useful in predicting risk of cardiac arrhythmias or future cardiac failure. The aim of this study was to quantify the burden of asymptomatic fibro-inflammatory myocardial disease using cardiac magnetic resonance imaging (CMR) and assess the relationship between asymptomatic myocardial fibrosis and cardiac arrhythmias in SSc. METHODS: Thirty-two patients with SSc with no documented history of pulmonary vascular or heart disease underwent CMR with gadolinium and 24-h ambulatory ECG. Focal myocardial fibrosis was assessed using post-gadolinium imaging and diffuse fibro-inflammatory myocardial disease quantified using T1- and T2-mapping. CMR results were compared with an age- and sex-matched control group. RESULTS: Post-gadolinium focal fibrosis was prevalent in SSc but not controls (30% vs 0%, p < 0.01).. T1-mapping values (as a marker of diffuse fibrosis) were greater in SSc than controls [saturated recovery single-shot acquisition (SASHA): 1584 ms vs 1515 ms, P < 0.001; shortened Modified look locker sequence (ShMOLLI): 1218 ms vs 1138 ms, p < 0.001]. More than one-fifth (22.6%) of the participants had ventricular arrhythmias on ambulatory ECG, but no associations between focal or diffuse myocardial fibrosis and arrhythmias were evident. CONCLUSION: In SSc patients without evidence of overt cardiac disease, a high burden of myocardial fibrosis and arrhythmias was identified. However, there was no clear association between focal or diffuse myocardial fibrosis and arrhythmias, suggesting CMR may have limited use as a screening tool to identify SSc patients at risk of future significant arrhythmias.

Mechanical thrombectomy in acute basilar artery stroke: a systematic review and Meta-analysis of randomized controlled trials.

BACKGROUND: The evidence for mechanical thrombectomy in acute basilar artery occlusion has until now remained inconclusive with basilar artery strokes associated with high rates of death and disability. This systematic review and meta-analysis will summarize the available evidence for the effectiveness of mechanical thrombectomy in acute basilar artery occlusion compared to best medical therapy. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials using Embase, Medline and the Cochrane Central Register of Controlled Trials (CENTRAL). We calculated risk ratios (RRs) and 95% confidence intervals (CIs) to summarize the effect estimates for each outcome. RESULTS: We performed a random effects (Mantel-Haenszel) meta-analysis of the four included randomized controlled trials comprising a total of 988 participants. We found a statistically significant improvement in the rates of those with a good functional outcome (mRS 0-3, RR 1.54, 1.16-2.06, p = 0.003) and functional independence (mRS 0-2, RR 1.69, 1.05-2.71, p = 0.03) in those who were treated with thrombectomy when compared to best medical therapy alone. Thrombectomy was associated with a higher level of sICH (RR 7.12, 2.16-23.54, p = 0.001) but this was not reflected in a higher mortality rate, conversely the mortality rate was significantly lower in the intervention group (RR 0.76, 0.65-0.89, p = 0.0004). CONCLUSIONS: Our meta-analysis of the recently presented randomized controlled studies is the first to confirm the disability and mortality benefit of mechanical thrombectomy in basilar artery stroke.

Delivering telemedicine consultations for patients with transient ischaemic attack during the COVID-19 pandemic in a comprehensive tertiary stroke centre in the United Kingdom.

BACKGROUND AND PURPOSE: The global COVID-19 pandemic led many stroke centres worldwide to shift from in-person to telemedicine consultations to assess patients with transient ischaemic attacks (TIAs). We aimed to investigate the impact of telemedicine during the COVID-19 pandemic on the management and outcome of the patients with TIA. METHODS: We retrospectively analysed data from a registry of consecutive TIA patients assessed at the Stroke Department, Imperial College Health Care Trust, London, during the national lockdown period (between March 23 2020 and 30 June 2020). As controls, we evaluated the clinical reports and stroke quality metrics of patients presenting to the TIA clinic in the same period of 2019. RESULTS: Between 23 March 2020 and 30 June 2020, 136 patients were assessed using the telemedicine TIA clinic, compared to 180 patients evaluated with face-to-face consultation in the same period in 2019. Patients' characteristics were similar in both groups. At 3 months after the TIA, there were no significant differences in the proportion of patients admitted to the hospital for recurrent TIA/stroke or any other cardiovascular cause from the 2020 period compared to the same period in 2019. CONCLUSIONS: Our analysis showed that during the pandemic, our telemedicine consultations of TIA patients were not associated with an increased 3-month rate of recurrent TIA/stroke or cardiovascular hospital admissions. More robust studies looking at this model of care will be needed to assess its long-term effects on patients and health care systems.

Impact of COVID-19 Pandemic on a Regional Stroke Thrombectomy Service in the United Kingdom.

INTRODUCTION: We examined the impact of the coronavirus disease 2019 (COVID-19) pandemic on our regional stroke thrombectomy service in the UK. METHODS: This was a single-center health service evaluation. We began testing for COVID-19 on 3 March and introduced a modified "COVID Stroke Thrombectomy Pathway" on 18 March. We analyzed the clinical, procedural and outcome data for 61 consecutive stroke thrombectomy patients between 1 January and 30 April. We compared the data for January and February ("pre-COVID," n = 33) versus March and April ("during COVID," n = 28). RESULTS: Patient demographics were similar between the 2 groups (mean age 71 ± 12.8 years, 39% female). During the COVID-19 pandemic, (a) total stroke admissions fell by 17% but the thrombectomy rate was maintained at 20% of ischemic strokes; (b) successful recanalization rate was maintained at 81%; (c) early neurological outcomes (neurological improvement following thrombectomy and inpatient mortality) were not significantly different; (d) use of general anesthesia fell significantly from 85 to 32% as intended; and (e) time intervals from onset to arrival, groin puncture, and recanalization were not significantly different, whereas internal delays for external referrals significantly improved for door-to-groin puncture (48 [interquartile range (IQR) 39-57] vs. 33 [IQR 27-44] minutes, p = 0.013) and door-to-recanalization (82.5 [IQR 61-110] vs. 60 [IQR 55-70] minutes, p = 0.018). CONCLUSION: The COVID-19 pandemic has had a negative impact on the stroke admission numbers but not stroke thrombectomy rate, successful recanalization rate, or early neurological outcome. Internal delays actually improved during the COVID-19 pandemic. Further studies should examine the effects of the COVID-19 pandemic on longer term outcome.

Brief Report: Relationship Between Cotinine Levels and Peripheral Endogenous Concentrations of Oxytocin, ß-Endorphin, and Orexin in Individuals With Both Alcohol and Nicotine Use Disorders.

BACKGROUND AND OBJECTIVES: In this secondary analysis of a pilot clinical trial with individuals with alcohol and nicotine use disorders, we investigate the relationship between serum concentrations of oxytocin, ß-endorphin, melatonin, α-melanocyte-stimulating hormone, substance P, and orexin, with objective biomarkers (salivary cotinine and serum γ-glutamyl transferase [GGT]) as well as with self-reported smoking and alcohol drinking. METHODS: Biomarkers for a total of N = 19 participants were analyzed using multiplexed, competitive format immune-assay (peptides) and enzyme competitive immunoassay (saliva). A regression analysis using Pearson's correlation coefficient was utilized to determine correlations. We controlled for multiple comparisons, checked for collinearities, and ran two-sided statistical tests. RESULTS: We found significant positive correlations for cotinine and oxytocin (P = .002), ß-endorphin (P = .008), and orexin (P < .001), but not for either GGT or self-reported smoking or alcohol drinking. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These preliminary results suggest a relationship between cotinine and oxytocin, ß-endorphin, and orexin, which opens up new potential hypotheses on the potential role of these endocrine pathways in tobacco smokers. (Am J Addict 2021;30:88-91).

Decreasing Radiation Exposure in Pediatric Clavicle and Metatarsal Fractures: A QI Initiative.

BACKGROUND: Protecting the pediatric population from unnecessary medical radiation is an important public health initiative. Efforts have been made to reduce radiation exposure in the treatment of pediatric fractures without compromising quality of care. Using a standardized protocol for imaging of pediatric clavicle and metatarsal fractures is a reliable method for reducing pediatric radiation exposure in the management of these fractures. METHODS: In the year 2015, the senior author altered follow-up imaging practices for 2 common pediatric fractures: metatarsal and clavicular. Initial radiographic evaluation included the standard 3 views for metatarsal fractures and 2 views for clavicle fractures. This standard diagnostic procedure remained constant throughout the study. Follow-up x-rays from 2009 to 2014 routinely included 3 views of the foot and 2 views of the clavicle. The protocol was changed and from 2016 to 2019, follow-up x-rays for fractures routinely included 2 views of the foot and 1 view of the clavicle, thereby decreasing the number of x-rays utilized to manage these fractures. RESULTS: There was a significant reduction in the number of clavicle x-rays (P<0.001) and metatarsal x-rays (P=0.004) taken in follow-up between the time-periods. Median values for metatarsal views decreased by 1, matching the adjustment in protocol. In addition, the vast majority of clavicle fractures (90.80%) were managed with 1 follow-up view in 2016 to 2019 compared with 2 views (72.48%) from 2009 to 2014. CONCLUSIONS: This study achieved a reduction in radiation exposure in pediatric patients with nonoperatively managed clavicle and metatarsal fractures. Improving the quality of care of patients through decreasing the number of x-rays taken protects individuals from adverse side effects, as well as offers various public health benefits in terms of reduction in expenditures. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Melanoma Skin Self-Examination Education During Mammography: Health Burden of Women Impairs Implementation.

Identification of barriers to seeking health care for a concerning mole found during skin self-examination (SSE) by women educated during screening mammography. In this sequential mixed methods research, interviews with women who found a concerning mole and did not have health-care follow-up were analyzed and a survey was created. One year after SSE education, barriers to having health care for a self-identified concerning mole were assessed. The electronic medical records for all participants, who received education, were reviewed to ascertain who received health care related to a concerning mole or a screening mammogram. Among the 280 women who performed SSE, 85 found a concerning mole. Nine months later 51 women did not receive health care for the mole. Barriers were the burden of other medical concerns, fear of what the doctor will find, feeling like nothing is wrong, and being too busy. A positive screening mammogram (Fisher's two-sided exact test, p < 0.001) and a history of indoor tanning (Fisher's two-sided exact test, p = 0.011) were significantly associated with lack of follow-up for a concerning mole. Targeted melanoma self-identification with SSE relies upon participants initiating performance and seeking medical care for a concerning mole. The burden of a positive screening mammogram reported to women at about the same time as they identified the concerning mole was associated with failing to seek care for their concerning mole. Reminders to check moles for change 4 months after identifying a concerning mole may benefit women. Clinicaltrials.gov NCT03512457.

Placental Growth Factor as an Indicator of Maternal Cardiovascular Risk After Pregnancy.

BACKGROUND: Angiogenic placental growth factor (PlGF) concentrations rise during pregnancy, peaking at the end of midpregnancy. Low PlGF concentrations during pregnancy are associated with pregnancy complications with recognized later-life cardiovascular risk. We hypothesized that low PlGF concentrations, especially in midpregnancy, identify not only a subset of women at risk for pregnancy complications but also women with greater cardiovascular risk factor burden after pregnancy regardless of pregnancy outcome. METHODS: In a population-based prospective cohort study of 5475 women, we computed gestational age-adjusted multiples of the medians of early pregnancy and midpregnancy PlGF concentrations. Information on pregnancy complications (preeclampsia, small for gestational age, and spontaneous preterm birth) was obtained from hospital registries. Six years after pregnancy, we measured maternal systolic and diastolic blood pressures, cardiac structure (aortic root diameter, left atrial diameter, left ventricular mass, and fractional shortening), carotid-femoral pulse wave velocity, and central retinal arteriolar and venular calibers. Blood pressure was also measured 9 years after pregnancy. RESULTS: Women were on average 29.8 (SD, 5.2) years of age in pregnancy, were mostly European (55.2%), and 14.8% developed a pregnancy complication. Quartile analysis showed that especially women with midpregnancy PlGF in the lowest quartile (the low-PlGF subset) had a larger aortic root diameter (0.40 mm [95% CI, 0.08-0.73]), left atrial diameter (0.34 mm [95% CI, -0.09 to 0.78]), left ventricular mass (4.6 g [95% CI, 1.1-8.1]), and systolic blood pressure (2.3 mm Hg [95% CI, 0.93-3.6]) 6 years after pregnancy than women with the highest PlGF. Linear regression analysis showed that higher midpregnancy PlGF concentrations were associated with a smaller aortic root diameter (-0.24 mm [95% CI, -0.39 to -0.10]), smaller left atrial diameter (-0.75 mm [95% CI, -0.95 to -0.56]), lower left ventricular mass (-3.9 g [95% CI, -5.5 to -2.3]), and lower systolic blood pressure (-1.1 mm Hg [95% CI, -1.7 to -0.46]). These differences persisted after the exclusion of women with complicated pregnancies. CONCLUSIONS: Women with low PlGF in midpregnancy have a greater aortic root diameter, left atrial diameter, and left ventricular mass and higher systolic blood pressure 6 and 9 years after pregnancy compared to women with higher PlGF, including women with uncomplicated pregnancies. The pathophysiological implications of lower PlGF concentrations in midpregnancy might provide insight into the identification of pathways contributing to greater cardiovascular risk factor burden.

Maternal cardiovascular adaptation to twin pregnancy: a population-based prospective cohort study.

BACKGROUND: In women with singleton pregnancies, maternal adaptation is considered a stress test for later life cardiovascular disease. The aim of this study was to assess maternal adaptation in women with twin pregnancies compared to women carrying singletons during and after pregnancy. METHODS: This was a population based prospective cohort study of 91 women with twin pregnancies and 8107 women carrying singletons. The association of twin pregnancy and maternal adaptation was examined using regression analyses. In pregnancy, we measured soluble fms-like tyrosine kinase-1 (sFLT-1), placental growth (PGF) factor, systolic (SBP) and diastolic blood pressure (DBP), and the occurrence of pre-eclampsia (PE). After pregnancy, measurements were obtained on SBP and DBP, cardiac function, retinal calibres, intima media thickness and distensibility of the common carotid artery. RESULTS: sFLT-1 and PGF concentrations were higher in early (13.4 weeks) and mid-pregnancy (20.4 weeks) in women with twin pregnancies compared to women with singleton pregnancies. Women with twin pregnancies had a different DBP pattern in pregnancy. Women with twin pregnancies were more likely to have PE (odds ratio 3.63; 95% CI [1.76 to 7.48]). Six and ten years after pregnancy, no differences in maternal adaptation were observed. CONCLUSIONS: Women with twin pregnancies show an altered adaptation during pregnancy compared to women with singleton pregnancies. This is associated with a substantially increased incidence of PE, but does not lead to persistent altered maternal adaptation years after pregnancy.

Reducing preoperative anxiety with Child Life preparation prior to intravenous induction of anesthesia: A randomized controlled trial.

BACKGROUND: Induction of anesthesia can be stressful: Up to 60% of children suffer significant anxiety immediately before surgery. Anxiety is associated with higher postoperative analgesia requirements, higher incidence of emergence delirium, and detrimental effects on sleep and behavior. Child Life preparation includes role-play, expectation-setting, and teaching coping strategies. AIM : The aim of this trial was to determine whether preoperative Child Life preparation reduces anxiety prior to intravenous induction of anesthesia. METHODS: Children aged 3-10 years, with no known preexisting anxiety and no preoperative anxiolytics, undergoing elective day surgery lasting ≤ 2 hours, were enrolled in a randomized controlled trial. Each child's baseline anxiety was assessed in the anesthetic care unit, using the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF, observational scores from 22.9, minimal anxiety, to 100, maximal anxiety) as the primary outcome. The child was randomly assigned to intervention (minimum 15 minutes Child Life preparation) or control (standard practice without Child Life preparation). Participants entered the operating room with one parent. A researcher (blinded to group allocation) scored the child's operating room anxiety using mYPAS-SF, up to the first attempt at intravenous cannulation. RESULTS: Fifty-nine children completed the study, aged median [interquartile range] 5 [3-7] years. Baseline mYPAS-SF anxiety was 29.2 [22.9-37.5] for all children, and operating room anxiety was 29.2 [22.9-49.0]. Operating room anxiety was higher than baseline in 16/31 (52%) children in the control group and 6/28 (21%) in the Child Life preparation group. ANCOVA revealed a significant effect of baseline mYPAS-SF anxiety and group on operating room anxiety (F = 10.31, P < .001, adjusted R2  = .24); individual parameter estimates indicated that Child Life preparation reduced operating room anxiety by 13.8 (95% CI 4.4-23.1) points compared to control, P = .005. CONCLUSION: A brief, targeted Child Life preparation session had a statistically significant effect on reducing preoperative anxiety prior to intravenous induction of anesthesia in young children, with no known preexisting anxiety. This effect may be clinically important and suggests that Child Life can be a valuable component of pediatric surgical care. Further research is required in specific populations.

Automated Continuous Electrocardiogram Monitoring Accelerates the Detection of Atrial Fibrillation after Ischemic Stroke or Transient Ischemic Attack on a Hyper Acute Stroke Unit.

BACKGROUND AND AIM: Rapid and sensitive detection of atrial fibrillation (AF) is of paramount importance for initiation of adequate preventive therapy after stroke. Stroke Unit care includes continuous electrocardiogram monitoring (CEM) but the optimal exploitation of the recorded ECG traces is controversial. In this retrospective single-center study, we investigated whether an automated analysis of continuous electrocardiogram monitoring (ACEM), based on a software algorithm, accelerates the detection of AF in patients admitted to our Stroke Unit compared to the routine CEM. METHODS: Patients with acute ischemic stroke or transient ischemic attack were consecutively enrolled. After a 12-channel ECG on admission, all patients received CEM. Additionally, in the second phase of the study the CEM traces of the patients underwent ACEM analysis using a software algorithm for AF detection. Patients with history of AF or with AF on the admission ECG were excluded. RESULTS: The CEM (n = 208) and ACEM cohorts (n= 114) did not differ significantly regarding risk factors, duration of monitoring and length of admission. We found a higher rate of newly-detected AF in the ACEM cohort compared to the CEM cohort (15.8% versus 10.1%, P < .001). Median time to first detection of AF was shorter in the ACEM compared to the CEM cohort [10 hours (IQR 0-23) versus 46.50 hours (IQR 0-108.25), P < .001]. CONCLUSIONS: ACEM accelerates the detection of AF in patients with stroke compared with the routine CEM. Further evidences are required to confirm the increased rate of AF detected using ACEM.

Phosphodiesterase 5 inhibitors for pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) comprises a group of complex and heterogenous conditions, characterised by elevated pulmonary artery pressure, and which left untreated leads to right-heart failure and death. PH includes World Health Organisation (WHO) Group 1 pulmonary arterial hypertension (PAH); Group 2 consists of PH due to left-heart disease (PH-LHD); Group 3 comprises PH as a result of lung diseases or hypoxia, or both; Group 4 includes PH due to chronic thromboembolic occlusion of pulmonary vasculature (CTEPH), and Group 5 consists of cases of PH due to unclear and/or multifactorial mechanisms including haematological, systemic, or metabolic disorders. Phosphodiesterase type 5 (PDE5) inhibitors increase vasodilation and inhibit proliferation. OBJECTIVES: To determine the efficacy of PDE5 inhibitors for pulmonary hypertension in adults and children. SEARCH METHODS: We performed searches of CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to 26 September 2018. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials that compared any PDE5 inhibitor versus placebo, or any other PAH disease-specific therapies, for at least 12 weeks. We include separate analyses for each PH group. DATA COLLECTION AND ANALYSIS: We imported studies identified by the search into a reference manager database. We retrieved the full-text versions of relevant studies, and two review authors independently extracted data. Primary outcomes were: change in WHO functional class, six-minute walk distance (6MWD), and mortality. Secondary outcomes were haemodynamic parameters, quality of life/health status, dyspnoea, clinical worsening (hospitalisation/intervention), and adverse events. When appropriate, we performed meta-analyses and subgroup analyses by severity of lung function, connective tissue disease diagnosis, and radiological pattern of fibrosis. We assessed the evidence using the GRADE approach and created 'Summary of findings' tables. MAIN RESULTS: We included 36 studies with 2999 participants (with pulmonary hypertension from all causes) in the final review. Trials were conducted for 14 weeks on average, with some as long as 12 months. Two trials specifically included children.Nineteen trials included group 1 PAH participants. PAH participants treated with PDE5 inhibitors were more likely to improve their WHO functional class (odds ratio (OR) 8.59, 95% confidence interval (CI) 3.95 to 18.72; 4 trials, 282 participants), to walk 48 metres further in 6MWD (95% CI 40 to 56; 8 trials, 880 participants), and were 22% less likely to die over a mean duration of 14 weeks (95% CI 0.07 to 0.68; 8 trials, 1119 participants) compared to placebo (high-certainty evidence). The number needed to treat to prevent one additional death was 32 participants. There was an increased risk of adverse events with PDE5 inhibitors, especially headache (OR 1.97, 95% CI 1.33 to 2.92; 5 trials, 848 participants), gastrointestinal upset (OR 1.63, 95% CI 1.07 to 2.48; 5 trials, 848 participants), flushing (OR 4.12, 95% CI 1.83 to 9.26; 3 trials, 748 participants), and muscle aches and joint pains (OR 2.52, 95% CI 1.59 to 3.99; 4 trials, 792 participants).Data comparing PDE5 inhibitors to placebo whilst on other PAH-specific therapy were limited by the small number of included trials. Those PAH participants on PDE5 inhibitors plus combination therapy walked 19.66 metres further in six minutes (95% CI 9 to 30; 4 trials, 509 participants) compared to placebo (moderate-certainty evidence). There were limited trials comparing PDE5 inhibitors directly with other PAH-specific therapy (endothelin receptor antagonists (ERAs)). Those on PDE5 inhibitors walked 49 metres further than on ERAs (95% CI 4 to 95; 2 trials, 36 participants) (low-certainty evidence). There was no evidence of a difference in WHO functional class or mortality across both treatments.Five trials compared PDE5 inhibitors to placebo in PH secondary to left-heart disease (PH-LHD). The quality of data were low due to imprecision and inconsistency across trials. In those with PH-LHD there were reduced odds of an improvement in WHO functional class using PDE5 inhibitors compared to placebo (OR 0.53, 95% CI 0.32 to 0.87; 3 trials, 285 participants), and those using PDE5 inhibitors walked 34 metres further compared to placebo (95% CI 23 to 46; 3 trials, 284 participants). There was no evidence of a difference in mortality. Five trials compared PDE5 inhibitors to placebo in PH secondary to lung disease/hypoxia, mostly in COPD. Data were of low quality due to imprecision of effect and inconsistency across trials. There was a small improvement of 27 metres in 6MWD using PDE5 inhibitors compared to placebo in those with PH due to lung disease. There was no evidence of worsening hypoxia using PDE5 inhibitors, although data were limited. Three studies compared PDE5 inhibitors to placebo or other PAH-specific therapy in chronic thromboembolic disease. There was no significant difference in any outcomes. Data quality was low due to imprecision of effect and heterogeneity across trials. AUTHORS' CONCLUSIONS: PDE5 inhibitors appear to have clear beneficial effects in group 1 PAH. Sildenafil, tadalafil and vardenafil are all efficacious in this clinical setting, and clinicians should consider the side-effect profile for each individual when choosing which PDE5 inhibitor to prescribe.While there appears to be some benefit for the use of PDE5 inhibitors in PH-left-heart disease, it is not clear based on the mostly small, short-term studies, which type of left-heart disease stands to benefit. These data suggest possible harm in valvular heart disease. There is no clear benefit for PDE5 inhibitors in pulmonary hypertension secondary to lung disease or chronic thromboembolic disease. Further research is required into the mechanisms of pulmonary hypertension secondary to left-heart disease, and cautious consideration of which subset of these patients may benefit from PDE5 inhibitors. Future trials in PH-LHD should be sufficiently powered, with long-term follow-up, and should include invasive haemodynamic data, WHO functional class, six-minute walk distance, and clinical worsening.

Deceleration of fetal growth rate as alternative predictor for childhood outcomes: a birth cohort study.

BACKGROUND: Small for gestational age (SGA) is frequently used to define fetal growth restriction (FGR). However, FGR describes a slowdown in fetal growth and is not synonymous with SGA, which may introduce misclassification. We investigated the effect of both on delivery and childhood outcomes. METHODS: From a prospective population-based cohort study we included 7959 live singleton births with data available on second trimester estimated fetal weight (EFW) and birth weight. We used a decrease in growth of > 40 percentiles between second trimester EFW and birthweight to define a deceleration in growth. SGA was defined as birthweight

Fetal Growth and Placental Growth Factor Umbilical Cord Blood Levels.

OBJECTIVE: We assessed whether umbilical cord blood placental growth factor (PlGF) levels at delivery are associated with fetal growth. METHODS: From a prospective population-based cohort study we included 3,461 live singleton births. Fetal growth was assessed by birth weight, fetal growth pattern, and fetal growth restriction (FGR; decrease in growth between the second trimester and birth of ≥40 percentiles). In all analyses the highest PlGF multiple of the median (MoM) quintile was used as the reference category. RESULTS: Umbilical cord PlGF was neither correlated with maternal second-trimester PlGF (p = 0.08) nor placental weight (p = 0.18), suggesting that PlGF from umbilical cord blood was of fetal origin. Lower PlGF MoM quintiles were associated with a lower birth weight (lowest quintile -0.60 standard deviation [95% confidence interval -0.71 to -0.48, p for trend <0.001]) and a different fetal growth pattern (p < 0.001). Finally, lower PlGF MoM quintiles were associated with FGR (lowest quintile odds ratio 2.00 [95% confidence interval 1.25 to 3.21, p for trend <0.001]). CONCLUSION: Lower umbilical cord PlGF levels are associated with lower birth weight, deviating fetal growth patterns, and a higher odds of FGR. Hence, cord blood PlGF might be a promising biomarker to determine deviations in fetal growth and FGR retrospectively, enabling follow-up of these neonates.