Search

Context Neurourological patients often encounter bacteriuria without any symptoms or may experience symptoms suspicious of urinary tract infections (UTIs). However, there is a lack of guidelines that unequivocally state the definition of UTIs in this specific patient group. Objective To present all used definitions of UTIs in neurourological patients. Evidence acquisition This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were identified by electronic search of Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov without a time limitation (last search September 2020) and by screening of reference lists and reviews. The occurrences of the various UTI definitions were counted and the frequencies calculated. Evidence synthesis After screening 7164 abstracts, we included 32 studies enrolling a total of 8488 patients with a neurourological disorder who took part in an interventional clinical study. UTI definitions were heterogeneous. The concordance to predefined definitions was low. Conclusions Interventional clinical studies rarely report specific definitions for UTIs, and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed. Patient summary Patients suffering from neurological disorders often experience symptoms in their lower urinary tract that resemble urinary tract infections. Furthermore, they can have positive urine cultures without symptoms (the so-called asymptomatic bacteriuria). However, clinical studies rarely report specific definitions for urinary tract infections, and when it is done, they are heterogeneous. A generally accepted urinary tract infection definition for neurourological patients is urgently needed. Take Home Message Interventional clinical studies on neurourological patients rarely report specific definitions for urinary tract infections (UTIs), and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.

Context Controversy still exists regarding the balance of benefits and harms for the different surgical options for neurogenic stress urinary incontinence (N-SUI). Objective To identify which surgical option for N-SUI offers the highest cure rate and best safety without compromising urinary tract function and bladder management. Evidence acquisition A systematic review was performed under the auspices of the European Association of Urology Guidelines Office and the European Association of Urology Neuro-Urology Guidelines Panel according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Evidence synthesis A total of 32 studies were included. Overall, 852 neurourological patients were surgically treated for N-SUI. The treatment offered most often (13/32 studies) was an artificial urinary sphincter (AUS; 49%, 416/852) and was associated with a need for reintervention in one-third of patients. More than 200 surgical revisions were described. Overall, 146/852 patients (17%) received concomitant bladder augmentation, mainly during placement of an AUS (42%, 62/146) or autologous sling (34% of women and 14% of men). Following pubovaginal sling placement, dryness was achieved in 83% of cases. A significant improvement in N-SUI was observed in 87% (82/94) of women following placement of a synthetic midurethral sling. Efficacy after insertion of an adjustable continence therapy device (ACT 40%, proACT 60%) was reported for 38/128 cases (30%). The cure rate for bulking agents was 35% (9/25) according to 2/32 studies, mainly among men (90%). The risk of bias was highly relevant. Baseline and postoperative cystometry were missing in 13 and 28 studies, respectively. Conclusions The evidence is mainly reported in retrospective studies. More than one intervention is often required to achieve continence because of coexisting neurogenic detrusor overactivity, low compliance, or the onset of complications in the medium and long term. Urodynamic data are needed to better clarify the success of N-SUI treatment with the different techniques. Patient summary Our review shows that insertion of an artificial urinary sphincter for urinary incontinence is effective but is highly associated with a need for repeat surgery. Other surgical options may have lower continence rates or a risk of requiring intermittent catheterization, which patients should be informed about before deciding on surgery for their incontinence.

Line transect aerial surveys are widely used for estimating abundance of biological populations, including threatened species. However, estimates obtained with data collected from aircraft are often underestimated because of visibility bias and bias in estimating group sizes from a fast-moving platform. An assessment of multiple sources of bias in aerial surveys were carried out in Brazilian coastal waters by experiments on multiple survey platforms (i.e., boat, airplane and helicopter). These studies focused on evaluating visibility bias (perception and availability bias) and potential differences in the estimation of group sizes from different types of platforms used in franciscana (Pontoporia blainvillei) abundance surveys. The ultimate goal was to develop correction factors to improve accuracy of estimates of density and population size for this threatened dolphin. Estimates of density and group sizes computed from boats were assumed to be unbiased and were compared to estimates of these quantities obtained from an airplane in the same area and period. In addition, helicopter surveys were conducted in two areas where water turbidity differed (clear vs. murky waters) to determine surfacing-diving intervals of franciscana groups and to estimate availability for aerial platforms. Abundance computed from the aerial survey data underestimated the true abundance by about 4-5 times, with ~70% of the total bias resulting from visibility bias (~80% from availability bias and ~20% from perception bias) and ~30% from bias in estimates of group size. The use of multiple survey platforms in contrasting habitats provided the opportunity to compute correction factors that can be used to refine range wide abundance estimates of the threatened franciscana given certain assumptions are met. Visibility bias and group size bias were substantial and clearly indicate the importance for accounting for such correction factors to produce unequivocal population assessment based on aerial survey data.

Context: The role of urodynamic studies (UDSs) in the diagnosis of lower urinary tract symptoms (LUTS) is crucial. Although expert statements and guidelines underline their value for clinical decision-making in various clinical settings, the academic debate as to their impact on patient outcomes continues. Objective: To summarise the evidence from all randomised controlled trials assess-ing the clinical usefulness of UDS in the management of LUTS. Evidence acquisition: For this systematic review, searches were performed without language restrictions in three electronic databases until November 18, 2020. The inclusion criteria were randomised controlled study design and allocation to receive UDS or not prior to any clinical management. Quality assessment was per-formed by two reviewers independently, using the Cochrane Collaboration & rsquo;s tool for assessing the risk of bias. A random-effect meta-analysis was performed on the uniformly reported outcome parameters. Evidence synthesis: Eight trials were included, and all but two focused on women with pure or predominant stress urinary incontinence (SUI). A meta-analysis of six studies including 942 female patients was possible for treatment success, as defined by the authors (relative risk 1.00, 95% confidence interval: 0.93 & ndash;1.07), indi-cating no difference in efficacy when managing women with UDS. Conclusions: Although UDSs are not replaceable in diagnostics, since there is no other equivalent method to find out exactly what the lower urinary tract problem is, there are little data supporting its impact on outcomes. Randomised controlled trials have focussed on a small group of women with uncomplicated SUI and showed no added value, but these findings cannot be extrapolated to the overall patient population with LUTS, warranting further well-designed trials. Patient summary: Despite urodynamics being the gold standard to assess lower uri-nary tract symptoms (LUTS), as it is the only method that can specify lower urinary tract dysfunction, more studies assessing the clinical usefulness of urodynamic studies (UDSs) in the management of LUTS are needed. UDS investigation is not increasing the probability of success in the treatment of stress urinary incontinence. (c) 2022 The Authors. Published by Elsevier B.V. on behalf of European Association of Urology. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/).

Background Urodynamic investigations have a pivotal role in the diagnosis of lower urinary tract symptoms. Despite expert statements and guidelines supporting their usefulness for clinical decision making in various clinical domains, the academic debate remains controversial. Objective To provide a metaepidemiological inventory of studies assessing the diagnostic properties of urodynamic investigations. Design, setting, and participants Systematic searches without language restrictions were performed in (Pre-)Medline, EMBASE, and the Cochrane Library from inception until August 31, 2018. Checking of reference lists of included studies and reviews complemented searches. Records were compiled and screened for possible inclusion by reading title and abstracts by two teams of two research fellows. Inclusion criteria were as follows: prospective data collection and urodynamic investigations performed either as a diagnostic test or using a therapy monitoring instrument. No a priori selection on clinical domain was done. Double reading was performed on records marked “included.” Extraction into a developed and piloted matrix was performed in duplicate and checked by a third research fellow. Outcome measurements and statistical analysis Of each included article, study specifics, objective, study design, type of data collection, clinical domain, type and description of test used, and type of outcome were extracted and attributed to a framework. Results and limitations Electronic searches retrieved 20 841 records. After screening, 299 abstracts were considered relevant. The main reasons for exclusion were as follows: animal studies, no primary data, editorial/opinion based on published data or reviews, primary objective of the study being not the assessment of urodynamic investigations, and post hoc (opportunistic) correlation studies. Conclusions To our knowledge, this is the first comprehensive collection of studies assessing the clinical usefulness of urodynamic investigations. The collection is the starting point for a series of systematic reviews assessing the diagnostic properties of urodynamic investigations. Patient summary The usefulness of urodynamic investigations for clinical decision making is under debate. We established an inventory of diagnostic studies on urodynamics to assess the value of urodynamics in various clinical applications.

The ability of the central nervous system to regenerate over long distances after a lesion is restricted by the presence of physical and biochemical barriers, neuronal growth programs changes, and a non-permissive tissue environment. The myelin-derived membrane protein Nogo-A exerts repulsive and neurite growth-inhibitory functions that can critically affect the axonal regeneration capability. Suppression of Nogo-A signaling via function-blocking antibodies, receptor-bodies or genetic manipulation showed a relevant increase in the functional recovery including locomotion and lower urinary tract function in spinal cord injured rodents as well as hand function in monkeys. The currently on-going phase II clinical trials will elucidate the potential relevance of Nogo-A suppression for a novel therapeutic management of spinal cord injury in human patients.

Low back joint compression forces have been linked to the development of chronic back pain. Back-support exoskeletons controllers based on low back compression force estimates could potentially reduce the incidence of chronic pain. However, progress has been hampered by the lack of robust and accurate methods for compression force estimation. Electromyography (EMG)-driven musculoskeletal models have been proposed to estimate lumbar compression forces. Nonetheless, they commonly underrepresented trunk musculoskeletal geometries or activation–contraction dynamics, preventing validation across large sets of conditions. Here, we develop and validate a subject-specific large-scale (238 muscle–tendon units) EMG-driven musculoskeletal model for the estimation of lumbosacral moments and compression forces, under eight box-lifting conditions. Ten participants performed symmetric and asymmetric box liftings under 5 and 15 kg weight conditions. EMG-driven model-based estimates of L5/S1 flexion–extension moments displayed high correlation, R2 (mean range: 0.88–0.94), and root mean squared errors between 0.21 and 0.38 Nm/kg, with respect to reference inverse dynamics moments. Model-derived muscle forces were utilized to compute lumbosacral compression forces, which reached eight times participants body weight in 15 kg liftings. For conditions involving stooped postures, model-based analyses revealed a predominant decrease in peak lumbar EMG amplitude during the lowering phase of liftings, which did not translate into a decrease in muscle–tendon forces. During eccentric contraction (box-lowering), our model employed the muscle force–velocity relationship to preserve muscle force despite significant EMG reduction. Our modeling methodology can inherently account for EMG-to-force non-linearities across subjects and lifting conditions, a crucial requirement for robust real-time control of back-support exoskeletons.

Current clinical decision-making is based on rapid and subjective functional tests such as 10 m walking. Moreover, greater accuracy can be achieved at the expense of rapidity and costs. In biomechanical laboratories, advanced technologies and musculoskeletal modeling can quantitatively describe the biomechanical reasons underlying gait disorders. Our work aims to blend clinical rapidity and biomechanical accuracy through multi-channel (MC) electromyography (EMG) clustering and real-time neuro-musculoskeletal (NMS) modeling techniques integrated into a sensorized wearable garment that is quick to set up. Here we present a unique pipeline that goes from MC EMG signals to ankle torque estimation following two steps: (1) non-negative matrix factorization (NNMF)-based EMG clustering for the extraction of muscle-specific activations and (2) subject-specific EMG-driven NMS modeling. The results show the potential of NNMF as an electrode clustering tool, as well as the ability to predict joint torque during movements that were not used for the EMG clustering.

The in vivo estimation of α-motoneuron (MN) properties in humans is crucial to characterize the effect that neurorehabilitation technologies may elicit over the composite neuro-musculoskeletal system. Here, we combine biophysical neuronal modelling, high-density electromyography and convolutive blind-source separation along with numerical optimization to estimate geometrical and electrophysiological properties of in vivo decoded human MNs. The proposed methodology implements multi-objective optimization to automatically tune ionic channels conductance and soma size of MN models for minimizing the error between several features of simulated and in vivo decoded MN spike trains. This approach will open new avenues for the closed-loop control of motor restorative technologies such as wearable robots and neuromodulation devices.Clinical Relevance- This work proposes a non-invasive framework for the in vivo estimation of person-specific α-motoneuron properties. This will enable predicting neuronal adaptations in response to neurorehabilitation therapies in the intact human.

Background Ultrasound is generally used to measure postvoid residual (PVR) in daily clinical practice for a basic assessment of voiding dysfunction. In animal research, however, PVR is measured mostly by expelling the urine with gentle squeezing of the bladder. Objective To assess the translational value of measuring PVR by ultrasound in awake rats with the aim of obtaining directly comparable data sets in patients and rodent models. Design, setting, and participants A prospective animal study was conducted in 10 rats with large, incomplete thoracic spinal cord injury resulting in severe bladder impairment. Lower urinary tract function was assessed by urodynamics with implanted bladder catheter and external urethral sphincter electrodes, allowing for repeated measurements over time. Immediately after the last micturition cycle in the urodynamic investigation, PVR was first assessed by ultrasound using a 7.5 MHz linear probe and then by manually expelling the urine via gentle pressure on the abdomen. Outcome measurements and statistical analysis PVR was measured by ultrasound and by manually expelling the urine. Paired t test was used to analyze the difference between the two measurements 1 and 2 wk after spinal cord injury. Results and limitations PVR assessed by ultrasound was equal to and not statistically different from the volumes obtained by manual expulsion in intact rats, both before injury and during the first 2 wk after spinal cord injury (intact: 0.16 ± 0.07 vs 0.14 ± 0.09 ml, p = 0.08; week 1: 1.67 ± 0.53 vs 1.71 ± 0.55 ml, p = 0.67; week 2: 1.16 ± 0.35 vs 0.98 ± 0.43 ml, p = 0.11). The main limitation of ultrasound for measuring PVR is the restricted availability of ultrasound machines in animal research laboratories. Conclusions Ultrasound is a valuable translational tool to measure PVR in awake rats reflecting the situation in humans. Patient summary We measured postvoid residual by ultrasound in awake rats, analogous to clinical examination in humans. Ultrasonography provided similar values to the generally used manual bladder expulsion.

Loss of bladder control is common after spinal cord injury (SCI) and no causal therapies are available. Here we investigated whether function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe SCI could prevent development of neurogenic lower urinary tract dysfunction. Bladder function of rats with SCI was repeatedly assessed by urodynamic examination in fully awake animals. Four weeks after SCI, detrusor sphincter dyssynergia had developed in all untreated or control antibody-infused animals. In contrast, 2 weeks of intrathecal anti-Nogo-A antibody treatment led to significantly reduced aberrant maximum detrusor pressure during voiding and a reduction of the abnormal EMG high-frequency activity in the external urethral sphincter. Anatomically, we found higher densities of fibers originating from the pontine micturition center in the lumbosacral gray matter in the anti-Nogo-A antibody-treated animals, as well as a reduced number of inhibitory interneurons in lamina X. These results suggest that anti-Nogo-A therapy could also have positive effects on bladder function clinically.SIGNIFICANCE STATEMENTAfter spinal cord injury, loss of bladder control is common. Detrusor sphincter dyssynergia is a potentially life-threatening consequence. Currently, only symptomatic treatment options are available. First causal treatment options are urgently needed in humans. In this work, we show that function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe spinal cord injury could prevent development of neurogenic lower urinary tract dysfunction, in particular detrusor sphincter dyssynergia. Anti-Nogo-A therapy has entered phase II clinical trial in humans and might therefore soon be the first causal treatment option for neurogenic lower urinary tract dysfunction.

The objective of the present paper is to use the well known Ross-Macdonald models as a prototype, incorporating spatial movements, identifying different times scales and proving a singular perturbation result using a system of local and non-local diffusion. This results can be applied to the prototype model, where the vector has a fast dynamics, local in space, and the host has a slow dynamics, non-local in space.

Aim To systematically assess all available evidence on efficacy and safety of catheterization for treating neurogenic lower urinary tract dysfunction (NLUTD) in patients with multiple sclerosis (MS). Methods This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies were identified by electronic search of Embase, Medline, Scopus, Cochrane register (last search March 3, 2018) and by screening of reference lists and reviews. Results After screening 7'015 articles, we included four studies (one prospective and two retrospective cohort studies, one retrospective cross-sectional study), in which a total of 445 patients were enrolled. No randomized controlled trial was available. Catheterization substantially increased quality of life, post void residual, and incontinence episodes in all included studies. Pooling of data for meta-analysis was not possible due to the heterogeneity of reported outcomes. Adverse events were reported in two studies only. Risk of bias and confounding was intermediate. Conclusions Preliminary data suggests beneficial effects of catheterization on the urological outcome in patients with MS. However, although intermittent and indwelling catheterization is used frequently in daily clinical practice in the MS population, the evidence base is very limited and well-designed, properly sampled, and powered studies are urgently needed.

Neurogenic lower urinary tract dysfunction typically develops after spinal cord injury. We investigated the time course and the anatomical changes in the spinal cord that may be causing lower urinary tract symptoms following injury. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. Animals underwent a large, incomplete spinal transection at the T8/9 spinal level. At 1, 2–3, and 4 weeks after injury, the animals underwent urodynamic investigations. Urodynamic investigations showed detrusor overactivity and detrusor-sphincter-dyssynergia appearing over time at 3–4 weeks after injury. Lower urinary tract dysfunction was accompanied by an increase in density of C-fiber afferents in the lumbosacral dorsal horn. CRF-positive Barrington's and 5-HT-positive bulbospinal projections drastically decreased after injury, with partial compensation for the CRF fibers at 3–4 weeks. Interestingly, a decrease over time was observed in the number of GABAergic neurons in the lumbosacral dorsal horn and lamina X, and a decrease of glutamatergic cells in the dorsal horn. Detrusor overactivity and detrusor-sphincter-dyssynergia might therefore arise from a discrepancy in inhibitory/excitatory interneuron activity in the lumbosacral cord as well as input changes which develop over time after injury. The processes point to spinal plastic changes leading to malfunction of the important physiological pathway of lower urinary tract control.

Inadequate subscapularis repair has been advocated as one of the contributing factors for dislocation in reverse total shoulder arthroplasty; nonetheless the need to restore the subscapularis tendon integrity is under debate. The aim of this systematic review was to answer the question: does subscapularis reattachment following reverse total shoulder arthroplasty improve joint stability, range of motion and functional scores?The literature was systematically screened in accordance with PRISMA guidelines looking for papers evaluating clinical outcomes of reverse total shoulder arthroplasty in relation to the management of subscapularis tendon. Studies comparing clinical outcomes, complications and dislocation rate with or without subscapularis repair were included. Studies in which reverse total shoulder arthroplasty was performed for trauma or tumors were excluded. The methodology of included articles was scored with MINORS scale and the Risk of Bias was assessed adopting the ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions) developed by the Cochrane Group. A meta-analysis was also performed combining the studies to increase the sample size and hence the power to obtain meaningful data.The database search identified 1062 records, and 6 full-text articles were finally included. A total number of 1085 reverse total shoulder arthroplasty were assessed on. Except for one study, lateralized prosthetic designs have been used. Dislocation occurred in 0.8% (5/599 patients) of the patient with repaired subscapularis and in 1.6% (8/486 patients) of the tenotomized patients, and subscapularis repair was not associated with a higher risk of dislocation (pooled Peto OR: 0.496, 95% CI: 0.163 to 1.510, p = 0.217). Qualitative assessment revealed no differences in the range of motion and clinical scores.Subscapularis repair after reverse total shoulder arthroplasty produces no clinically meaningful benefits, particularly using lateralized prosthetic designs. Subscapularis re-attachment does not improve implant stability, nor increases range of motion or clinical scores. Given these results, keeping in mind the antagonistic effect of the repaired subscapularis on external rotation, no evidence lead to suggest subscapularis reattachment following reverse total shoulder arthroplasty with lateralized prosthetic designs.

Certain subterranean environments of Earth have naturally accumulated long-lived radionuclides, such as 238U, 232Th and 40K, near the presence of liquid water. In these natural radioactive environments (NRE), water radiolysis can produce chemical species of biological importance, such as H2. Although the proposal of radioactive decay as an alternative source of energy for living systems has existed for more than thirty years, this hypothesis gained strength after the recent discovery of a peculiar ecosystem in a gold mine in South Africa, whose existence is dependent on chemical species produced by water radiolysis. In this work, we calculate the chemical disequilibrium generated locally by water radiolysis due gamma radiation and analyse the possible contribution of this disequilibrium for the emergence of life, considering conditions of early Earth and having as reference the alkaline hydrothermal vent (AHV) theory. Results from our kinetic model points out the similarities between the conditions caused by water radiolysis and those found on alkaline hydrothermal systems. Our model produces a steady increase of pH with time, which favours the precipitation of minerals with catalytic activity for protometabolism, as well as a natural electrochemical gradient in this aqueous environment. In conclusion, we described a possible free-energy conversion mechanism that could be a requisite for emergence of life in Hadean Earth., Comment: 51 pages, 9 figures, supplementary material included. Astrobiology

Inhibitory GABAergic interneurons create different brain activity patterns that correlate with behavioural states. In this characterizing study, we used single‐cell RNA‐Seq to analyse anatomically‐ and electrophysiologically identified hippocampal oriens‐lacunosum moleculare (OLM) interneurons. OLMs express somatostatin (Sst), generate feedback inhibition and play important roles in theta oscillations and fear encoding. Although an anatomically‐ and biophysically homogenous population, OLMs presumably comprise of two functionally distinct types with different developmental origins, inferred from the expression pattern of serotonin type‐3a (5‐HT3a, or Htr3a) receptor subunit and 5‐HT excitability in a set of OLMs. To broadly characterize OLM cells, we used the Sst‐Cre and the BAC transgenic Htr3a‐Cre mouse lines and separately analysed SstCre‐OLM and Htr3aCre‐OLM types. We found a surprisingly consistent expression of Npy in OLMs, which was previously not associated with the identity of this type. Our analyses furthermore revealed uniform expression of developmental origin‐related genes, including transcription factors and neurexin isoforms, without providing support for the current view that OLMs may originate from multiple neurogenic zones. Together, we found that OLMs constitute a highly homogenous transcriptomic population. Finally, our results revealed surprisingly infrequent expression of Htr3a in only ~10% of OLMs and an apparently specific expression of the 5‐HT3b subunit‐coding gene Htr3b in Htr3aCre‐OLMs, but not in SstCre‐OLMs. However, additional in situ hybridization experiments suggested that the differential expression of Htr3b may represent an unexpected consequence arising from the design of the Htr3a‐Cre BAC transgenic line., Somatostatin‐expressing oriens‐lacunosum moleculare (OLM) interneurons represent a key inhibitory cell type presumed to be developmentally diverse, generated in both MGE and CGE neurogenic zones. Winterer et al. used single‐cell RNA‐Seq to investigate OLM cells and found an unexpectedly high genetic homogeneity, expression of NPY and only MGE‐associated developmental markers.

Background Atrial fibrillation is highly prevalent among the elderly population, which is also frequently prone to thromboembolic complications. Anticoagulant prophylaxis is underused in the elderly due to fear of bleeding, which tends to be more frequent and severe within this group. Randomized controlled trials and several observational studies have shown the comparative effectiveness of direct oral anticoagulant (DOAC) against vitamin K antagonists (VKA), and their superior safety, at least in terms of intracranial bleeding. However, for patients aged 85 or older, there is still insufficient literature, leaving unanswered the question of which prophylaxis to use. Purpose The aim of the study is to compare the incidence of established outcomes and to investigate the net clinical benefit between DOAC and VKA in patients aged ≥85 years. Methods A cohort of 553 outpatients from the real world began treatment using DOACs at our clinic. The prospective follow-up on average lasted 1.97 years. Main endpoints were stroke and systemic thromboembolism, major hemorrhage, myocardial infarction and mortality for all causes. A sample of the 160 patients aged ≥85 years was compared with the remaining younger ones and with a second cohort of 298 outpatients aged ≥85 years. Retrospectively analyzed, with follow-ups at our center, who started VKAs; the average time was 2.03 years. The “net clinical benefit” of DOACs against VKAs was calculated as the difference between thromboembolic events with VKAs and with DOACs, minus the difference (weighted by 1.5) between spontaneous intracranial bleeding with DOACs and VKAs. Results In terms of thromboembolic events, DOACs and VKAs (2.43% p-y vs. 1.82% p-y, p=0.975) have shown comparable efficacy in a higher risk sample (CHA2DS2-VASc score: 5.2 vs. 4.5; p Conclusions DOACs are as effective in very old patients with atrial fibrillation compared to very old patients receiving VKAs, but they are associated with increased major bleeding. The same is true when compared with younger DOACs users. TTR, representing quality achieved by the anticoagulation with a VKA, can influence the comparison with DOACs. Considering ischemic strokes and spontaneous intracranial hemorrhages, there is however a net benefit for DOACs use in specific categories of elderly patients.

Background Due to the fear of increased risk of bleeding, anticoagulation treatment is underutilized in the prevention of stroke in elderly patients with non-valvular atrial fibrillation (NVAF). Although direct oral anticoagulants (DOAC) are safer than VKA, still little is known about the risk factors associated with bleeding in elderly patients treated with DOAC. Furthermore, it is still uncertain whether the risk scores that are currently used can serve to effectively identify higher bleeding risk in elderly subjects. Purpose The aim of this study was to identify predictors of bleeding in a cohort of elderly people affected by NVAF treated with DOAC, and to evaluate the accuracy of risk scores for bleeding used at present. Methods Data on outpatients aged ≥75 years, naïve for DOAC therapy, who started therapy with Dabigatran, Rivaroxaban, Apixaban or Edoxaban for the prevention of thromboembolism during FANV were analyzed. HASBLED, ATRIA, OBRI and ORBIT scores were calculated for each patient. Patients had follow-up for 12 months during which deaths, therapy discontinuation and adverse events such as thromboembolism and bleeding were reported. Potential predictors of bleeding and the predictive value of each bleeding score were tested using univariate Cox regression; testing accuracy was evaluated using ROC curves. Results A total of 291 patients (52.9% female, mean age 82.85±5.18 years) had a median follow-up time of 11 (10–12) months. The incidence rate of major bleeding was 4.7 per 100 patient-years, the rate of intracranial bleeding was 0.4 per 100 patient-years. Patients who had major bleeding were more often affected by heart failure (63.6% vs 25%; p=0.009) and thrombocytopenia (36.4% vs 7.4%; p=0,009). However in the multivariate analysis only heart failure remained statistically associated with major bleeding (HR 3.83, 95% CI 1.06–13.85; p=0.041). None of tested bleeding risk scores was able to predict major bleeding in our cohort. HASBLED and ORBIT scores were able to predict major and non-major clinically relevant bleeding (HR 1.32; 95% CI 1.01–1.71; p=0.042 and HR 1.20; 95% CI 1.00- 1.43; p=0.046); only the ORBIT score was found to be statistically significant, but with weak discriminatory power at ROC curves (AUC 0.59; 95% CI 0.51–0.68; p=0.041). Conclusions In our cohort of elderly patients aged 75 or older, anticoagulated for NVAF, heart failure history was the only effective predictor of major bleeding risk during DOAC treatment. None of the bleeding risk scores used currently have demonstrated a good discriminatory power in our cohort. As predictive factors of bleedings in DOAC-treated patients may not be the same as those for VKA-treated patients and those in elderly may also be differ in younger people, it calls for more investigation on the topic.

Vector-borne diseases are becoming increasingly widespread in a growing number of countries and it has the potential to invade new areas and habitats, either associated to changes in vectors habitats, human circulation or climate changes. From the dynamical point of view, the spatial-temporal interaction of models that try to adjust to such events are rich and challenging. The first challenges are to address the dynamics of the vectors (very fast and local) and the dynamics of humans (very heterogeneous and non-local). The objective of the present paper is to use the well-known Ross-Macdonald models, incorporating spatial movements, identifying different times scales and estimate in a suitable way the parameters. We will concentrate in a practical example, a simplified space model, and apply to Dengue’s spread in the state of Rio de Janeiro, Brazil.

Stroke is a major cause of serious disability due to the brain's limited capacity to regenerate damaged tissue and neuronal circuits. After ischemic injury, a multiphasic degenerative and inflammatory response is coupled with severely restricted vascular and neuronal repair, resulting in permanent functional deficits. Although clinical evidence indicates that revascularization of the ischemic brain regions is crucial for functional recovery, no therapeutics that promote angiogenesis after cerebral stroke are currently available. Besides vascular growth factors, guidance molecules have been identified to regulate aspects of angiogenesis in the central nervous system (CNS) and may provide targets for therapeutic angiogenesis. In this study, we demonstrate that genetic deletion of the neurite outgrowth inhibitor Nogo-A or one of its corresponding receptors, S1PR2, improves vascular sprouting and repair and reduces neurological deficits after cerebral ischemia in mice. These findings were reproduced in a therapeutic approach using intrathecal anti-Nogo-A antibodies; such a therapy is currently in clinical testing for spinal cord injury. These results provide a basis for a therapeutic blockage of inhibitory guidance molecules to improve vascular and neural repair after ischemic CNS injuries.