ESM 6.8 A flowsheet approach to the patient with (recent onset) spontaneous episodic vestibular syndrome from Neuro-Ophthalmology and Neuro-Otology Textbook

: A vascular etiology should always be on the differential diagnosis of the recent onset of the spontaneous (unprovoked) episodic vestibular syndrome (EVS), especially in the older population and when vascular risk factors are present. However, young patients can suffer from vascular events too - be especially concerned in patients with recent onset head/neck pain and vertigo. Unfortunately, the evaluation and management of this population is not one size fits all, but this flowchart offers a framework to the approach of the spontaneous EVS when the diagnosis is unknown and a vascular etiology is possible. First, are you seeing the patient in the midst of one of their typical attacks? If so and if spontaneous nystagmus is present during an episode (e.g., transient ischemic attack [TIA], Meniere's, vestibular migraine), the ‘HINTS Plus' exam can be applied (HIT=head impulse test; Bi/Vertical=bidirectional in lateral gaze or spontaneous vertical nystagmus; Uni=unidirectional nystagmus). However, seeing the pattern of a "peripheral" HINTS exam in the EVS is an uncommon situation and a comprehensive vestibular history and examination is necessary in this scenario (in addition to evaluating gait, stance, and coordination, cranial nerves, strength and sensation, and looking for peripheral (increased contralesional nystagmus) or central (reversal of horizontal nystagmus or "cross-coupling" where horizontal head-shaking causes vertical [usually downbeat] nystagmus) patterns of head-shaking-induced nystagmus. More often than not, the attack has subsided and the clinician is seeing the patient in the asymptomatic inter-ictal phase. Or, perhaps the patient is in the midst of an attack but there's no spontaneous nystagmus (e.g., ictally, there may or may not be nystagmus during a vestibular migraine attack). These two situations are common, and for each, the neurologic examination (especially evaluating gait, stance and coordination) and a thorough history are most important. Symptomatically, the presence of head motion intolerance, nausea and imbalance is suggestive of a vestibular etiology (although this by itself doesn't tell you whether you're dealing with a central disorder like a TIA, vestibular migraine, or a peripheral disorder like Meniere's) as compared to a non-vestibular etiology (e.g., cardiac arrhythmia, hypoglycemia). Be concerned by the Dangerous D's(1) or new sudden, sustained or severe head or neck pain (i.e., vertebral artery dissection until proven otherwise). If there are no clues in the neuro-vestibular history and examination, calculate the ABCD2 score next.(2, 3) While there is no specific benign/dangerous cut-off for this score, a score of 3-4 or more should be enough to initiate the TIA/stroke work-up expeditiously. However, a patient with a vestibular TIA can still have a score of 2 or less! Finally, don't forget about non-neurologic/non-vestibular etiologies, and be especially concerned by cardiorespiratory symptoms or transient loss of consciousness. A head CT scan is insufficient to evaluate for stroke unless there are focal findings on exam, a severe headache or change in mental status (e.g., posterior fossa hemorrhage), or if the patient is in a thrombolytic window. Brain MRI and MR angiogram head and neck (or MRI and CT angiogram) is preferable as the initial neuroimaging modality. - - : A flowsheet approach to the patient with (recent onset) spontaneous episodic vestibular syndrome1. Newman-Toker DE, Edlow JA. TiTrATE: A Novel, Evidence-Based Approach to Diagnosing Acute Dizziness and Vertigo. Neurol Clin. 2015;33(3):577-99, viii. 2. Newman-Toker DE, Kerber KA, Hsieh YH, Pula JH, Omron R, Saber Tehrani AS, et al. HINTS outperforms ABCD2 to screen for stroke in acute continuous vertigo and dizziness. Acad Emerg Med. 2013;20(10):986-96. 3. Saber Tehrani AS, Kattah JC, Kerber KA, Gold DR, Zee DS, Urrutia VC, et al. Diagnosing Stroke in Acute Dizziness and Vertigo: Pitfalls and Pearls. Stroke. 2018;49(3):788-95

ESM 6.7 A flowsheet approach to the patient with acute onset prolonged vertigo from Neuro-Ophthalmology and Neuro-Otology Textbook

: A vascular etiology should always be on the differential diagnosis of the acute onset prolonged vertigo, especially in the older population and when vascular risk factors are present. However, young patients can suffer from vascular events too - be especially concerned in patients with recent onset head/neck pain and vertigo. Unfortunately, the evaluation and management of this population is not one size fits all, but this flowchart offers a framework to the approach of acute onset prolonged vertigo when the diagnosis is unknown and a vascular etiology is possible. First, is spontaneous nystagmus present? If so, this is the acute vestibular syndrome (AVS), and the ‘HINTS Plus' examination should be applied (HIT=head impulse test; Bi/Vertical=bidirectional in lateral gaze or spontaneous vertical nystagmus; Uni=unidirectional nystagmus). If the pattern is that of a "peripheral" HINTS exam, vestibular neuritis is almost always the cause, but at least a cursory neurologic examination should always be performed as well, especially evaluation of gait, stance and coordination (e.g., if the patient can't sit and stand independently, this is very worrisome…most vestibular neuritis patients will be able to take a few steps independently at least, although imbalance may be severe in others). Also, look closely at the function of the cranial nerves, in addition to sensation and strength in the arms and legs. Finally, 15 cycles of 2-3 Hz horizontal head-shaking is a valuable bedside maneuver to evaluate for peripheral (increased contralesional nystagmus) or central (reversal of horizontal nystagmus or "cross-coupling" where horizontal head-shaking causes vertical [usually downbeat] nystagmus) patterns of head-shaking-induced nystagmus. If the symptomatic patient does not have spontaneous nystagmus, this is a more difficult situation. In addition to the ocular motor/vestibular exam, a comprehensive neurologic evaluation becomes even more important in this scenario. Symptomatically, the presence of head motion intolerance, nausea and imbalance is suggestive of a vestibular etiology (although this by itself doesn't tell you whether you're dealing with a central disorder like stroke, vestibular migraine, or a peripheral disorder like Meniere's) as compared to a non-vestibular etiology (e.g., severe anemia). Look closely for truncal, limb or gait ataxia, evaluate sensory and motor function in the limbs as well as on the face with emphasis on the cranial nerve exam. Perform the HINTS Plus exam, but realize that the rules of HINTS cannot be applied to triage the patient who does not have spontaneous nystagmus (e.g., symmetric acute onset bilateral vestibular loss may not cause nystagmus, although a bilaterally abnormal head impulse test will be seen). Assess saccades looking specifically for dysmetria (e.g., with a lateral medullary [Wallenberg] syndrome, ipsilesional hypermetria [and ocular lateropulsion] and contralesional hypometria) and impaired smooth pursuit, which can be significantly impaired with certain stroke syndromes (e.g., flocculus/paraflocculus, middle cerebellar peduncle). If there are any neurologic abnormalities, assume that the etiology is central until proven otherwise. If the neuro-vestibular examination and history is normal, is there a medical explanation (e.g., toxicity from lithium, benzodiazepines, anti-seizure medication; severe anemia) or a vestibular explanation (e.g., long and strong migraine history, and the patient is experiencing a prolonged attack with associated photophobia and phonophobia) - while a stroke is unlikely in these examples, urgent neuroimaging may still be warranted. If the neuro-vestibular history (including no Dangerous D's(1) and no new head/neck pain) and exam are unremarkable, risk stratify using the ABCD2 score.(2, 3) While there is no specific benign/dangerous cut-off for this score, a score of 3-4 or more should be enough to initiate the stroke work-up expeditiously. However, a patient with a vestibular stroke or TIA can still have a score of 2 or less! Finally, don't forget about non-neurologic/non-vestibular etiologies, and be especially concerned by cardiorespiratory symptoms or transient loss of consciousness. A head CT scan is insufficient to evaluate for stroke unless there are focal findings on exam, a severe headache or change in mental status (e.g., posterior fossa hemorrhage), or if the patient is in a thrombolytic window. Brain MRI and MR angiogram head and neck (or MRI and CT angiogram) is preferable as the initial neuroimaging modality. - - : A flowsheet approach to the patient with acute onset prolonged vertigo1. Newman-Toker DE, Edlow JA. TiTrATE: A Novel, Evidence-Based Approach to Diagnosing Acute Dizziness and Vertigo. Neurol Clin. 2015;33(3):577-99, viii. 2. Newman-Toker DE, Kerber KA, Hsieh YH, Pula JH, Omron R, Saber Tehrani AS, et al. HINTS outperforms ABCD2 to screen for stroke in acute continuous vertigo and dizziness. Acad Emerg Med. 2013;20(10):986-96. 3. Saber Tehrani AS, Kattah JC, Kerber KA, Gold DR, Zee DS, Urrutia VC, et al. Diagnosing Stroke in Acute Dizziness and Vertigo: Pitfalls and Pearls. Stroke. 2018;49(3):788-95

Risk of adverse pregnancy outcomes in women with periodontal disease and the effectiveness of interventions in decreasing this risk: protocol for systematic overview of systematic reviews

Abstract Background Periodontal disease is an inflammatory disease of the tissues supporting the teeth. Women who have periodontal disease while pregnant may be at risk of adverse pregnancy outcomes. Although the association between periodontal disease and adverse pregnancy outcomes has been addressed in a considerable number of systematic reviews and meta-analyses, there are important differences in the conclusions of these reviews. Systematic reviews assessing the effectivity of various therapeutic interventions to treat periodontal disease during pregnancy to try and reduce adverse pregnancy outcomes have also arrived at different conclusions. We aim to provide a systematic overview of systematic reviews comparing the frequency of adverse pregnancy outcomes between women with and without periodontal disease and/or evaluating the effect of preventive and therapeutic interventions for periodontal disease before or during pregnancy on adverse pregnancy outcomes. Methods We will include systematic reviews reporting on studies comparing adverse pregnancy outcomes: (i) between women with or without periodontal disease before

Modulation of small intestinal small chain fatty acid profile induced by 2 weeks consumption with 2 fermented milk products; a randomized, exploratory, cross-over, double blind, controlled study in ileostomy patients

Short chain fatty acid profiling of ileostomy samples. 16 volunteers received yogurt, L. rhamnosus or placebo in different orders. Ileostomy samples were collected in the morning after breakfast at the beginning and at the end of the 2 weeks intervention period. The samples were collected for the INSIDE explorative dietary study. The study was aimed to characterize the impact of fermented food may have on the small intestinal environment and systematically

TruCulture: Systemic immune adaptation and responsiveness induced by 2-wks consumption with 2 fermented milk products; a randomized, exploratory, cross-over, double blind, controlled study in ileostomy patients

Immunophenotyping of whole blood after ex-vivo stimulus. The samples were collected for the INSIDE explorative dietary study. The study was aimed to characterize the impact of fermented food may have on the small intestinal microbiota and systematically

Metabolites Serum: Serum metabolites changes induced by 2-wks consumption with 2 fermented milk products; a randomized, exploratory, cross-over, double blind, controlled study in ileostomy patients

Metabolites profiling of blood samples. The samples were collected for the INSIDE explorative dietary study. The study was aimed to characterize the impact of fermented food may have on the small intestinal microbiota and systematically

16S: Modulation of small intestinal microbial composition induced by 2 weeks consumption with 2 fermented milk products; a randomized, exploratory, cross-over, double blind, controlled study in ileostomy patients

Metataxonomic profiling (16S) of ileostomy samples. The samples were collected for the INSIDE double-blinded, placebo controlled explorative dietary study. The study was aimed to characterize the impact of fermented food may have on the small intestinal microbiota and systematically. Subjects participated in an approximately 100 days long trial with 3 intervention periods. 27 ileal effluent samples were collected per subject allowing a longitudinal analysis of the impact that consumpion of milk fermented products may have on the small intestinal microbial composition

Biomarkers: Blood biomarkers and proteome response by 2-wks consumption with 2 fermented milk products; a randomized, exploratory, cross-over, double blind, controlled study in ileostomy patients

Biomarkers profiling of human blood serum. The samples were collected for the INSIDE explorative dietary study. The study was aimed to characterize the impact of fermented food may have on the small intestinal microbiota and systematically

Metatranscriptome: Modulation of small intestinal microbial activity induced by 2 weeks consumption with 2 fermented milk products; a randomized, exploratory, cross-over, double blind, controlled study in ileostomy patients

Ileostomy effluent samples were collected for metatranscriptomic profiling. The samples were collected for the INSIDE explorative diatry study. The study was aimed to characterize the impact of fermented food may have on the small intestinal microbiota and systematically. Please note: the data files belonging to this dataset comprise a total size of 173 GB. Due to its size, the data is archived on DANS secure storage outside of EASY. A file list with an overview of all available files is available on the Data files tab. Please contact DANS in order to obtain acccess to the files

Urine metabolites changes induced by 2-wks consumption with 2 fermented milk products; a randomized, exploratory, cross-over, double blind, controlled study in ileostomy patients

Metabolites profiling of urine samples. The samples were collected for the INSIDE explorative dietary study. The study was aimed to characterize the impact of fermented food may have on the small intestinal microbiota and systematically