Brooklyn, Maryland

Higher vs Lower Lumber Epidural Catheter Insertion During Labour: A Randomised Trial to Compare Efficacy.

Epidural analgesia is widely used in different types of surgeries and procedures. Pregnant women in labour compromise the single largest group benefiting from epidural analgesia. During first stage of labour (dilatation of the cervix), an epidural should cover the sensory dermatomes from T10 to L1 to achieve a good pain relief. In the second stage of labour (descent of the baby through the cervical canal), pain is mediated via S2-S4 nerve roots. Accordingly, labour epidurals are commonly placed at the lower lumbar (L3-L4) interspace.1 A study was conducted by Moore et al., comparing high vs low lumbar epidural, showed that lower epidurals provide superior perineal analgesia, when used with a patient-controlled epidural analgesia (PCEA) infusion with continuous epidural infusion (CEI), but provided less pain relief early in labour. Another study, a metanalysis showed that another mode of delivery of the local anaesthetics is more effective; which is the Programmed Intermittent Epidural Boluses (PIEB) with PCEA. The incidence of breakthrough pain, the rates of local anaesthetic usage were significantly reduced, the labour duration was statistically shorter, and the maternal satisfaction score was significantly improved in the PIEB + PCEA group compared with that in the CEI + PCEA group. This is a prospective randomised study where women will be randomised to a high or low epidural catheter to determine which is superior for maternal analgesia efficacy and satisfaction. Randomised to intervention 'high epidural' or 'low epidural' groups. Within these groups there are two subgroups based on the specific lumbar vertebral level; high epidural (L 1,2 or L 2,3 levels) and low epidural (L 3,4 or L 4,5 levels).

Measurement and Impact of Physical Impairment in Amyotrophic Lateral Sclerosis: Use of Digital Technologies - a Precision ALS Project

The primary aim of this study is to investigate the validity and usability of novel digital technologies in the measurement of physical impairments (speech, swallow, strength, dexterity, mobility, and respiration) in ALS and the adherence to their use over time. The technologies that will be used in the study are as follows: 1. Speech Intelligibility Test (SIT) - software that measures speech intelligibility 2. ModalityAi- an online system that collects and analyses speech samples 3. Iowa Oral Performance Instrument (IOPI) - a device that measures tongue strength and endurance 4. Grip dynamometer - a device that measures grip strength 5. Index-eTap - a novel device and an app that measure dexterity 6. GaitKeeper - an app that measures walking 7. ActiGraph - a device that measures physical activity 8. MIR Spirometer - a device and app that measure breathing 9. Telehealth in Motor Neurone Disease (TiM) - an app that measures symptoms reported by the participant (patient reported outcome measures) Usability will be measured by means of a questionnaire called the System Usability Scale (SUS) and a semi-structured interview with a researcher. The objectives of the study are to: 1. Quantify the adherence to, usability and validity of novel digital technologies in measurement of physical parameters in ALS. 2. To compare the adherence to, usability and validity of actigraphy with devices worn on the wrist and hip concurrently for remote activity measurement. 3. To compare the adherence to, usability and validity of remote spirometry conducted independently or with clinician support via video consultation. 4. To examine the ability of Index-eTap to detect meaningful change over time in people with ALS/MND. 5. To examine the impact of impairments in cognition and behaviour on the use of digital technologies. 6. To examine the utility of audio-visual recordings for multimodal analysis of speaker samples using Modality software to analyse speech, cognitive-linguistic and facial muscle movement metrics. 7. To investigate the validity of combining data from validated technologies to form a unified scale sensitive to changes in physical impairments in ALS. 8. To develop optimal methods of summarising and visualising data relating to ALS physical impairments, for researchers working in the field of ALS Participants will complete regular assessments of physical function remotely ('at-home') using novel digital technologies and will in parallel complete three researcher-led ('in-person') assessments of comparable constructs. The in-person assessments will take place either in the clinical research centre, Beaumont Hospital or during an outreach home visit by a member of the research team, based on participant preference. On recruitment to the study, baseline demographic and clinical information will be collected from the participant and their Beaumont Hospital medical record. Participants will be followed up for one year. Participants will be recruited over 18 months. The anticipated total study duration is approximately 3 years, including data analysis. In-person assessments: The researcher will administer traditional assessments (as gold standard comparison for remote measurements) and will complete assessments using novel technologies where appropriate. In-person assessments will take place at baseline, 3 months and 12 months (or at withdrawal from the study). This assessment battery will include: - Speech intelligibility/rate: assessed using Speech Intelligibility Test (SIT) software and Zoom H1 dictaphone (traditional assessment) - Tongue strength and endurance: assessed using Iowa Oral Performance Instrument (IOPI) Pro device (traditional assessment) - Hand grip strength: Analogue Jamar Hydraulic Handgrip Dynamometer (traditional assessment) - Finger dexterity: Index-eTap device (this is a prototype device which is currently only suitable for use with a researcher and will be completed in person) - Mobility: GaitKeeper (this is a research-use novel gait analysis system, which requires testing in ALS for both in-person and for remote use) - Slow Vital Capacity (SVC): assessed using Micro Medical or equivalent desktop Spirometer device (traditional assessment) - Sniff Nasal Inspiratory Pressure (SNIP): assessed using MicroRPM device (traditional assessment) - Peak Cough Flow (PCF): Analogue peak flow meter device and facemask (traditional assessment) Additionally traditional validated questionnaires and rating scales will be completed: - Bulbar function: Centre for Neurological Studies Bulbar Function Scale (CNS-BFS) - Food texture description: Functional Oral Intake Scale (FOIS) - Upper limb function: Disability of Arm, Shoulder and Hand (DASH) - Overall function: ALS Functional Rating Scale - revised (ALSFRS-r) Following the baseline assessments, participants will be provided with the technologies appropriate for their use at home and will be trained in their use. Thereafter, participants will complete 'at-home' assessments, using technologies either independently or with support via video or phone call following a defined schedule. Participants will be asked to use a minimum of 2 suitable technologies, which will be selected by the researchers based on their clinical presentation. Participants will be provided with the option to opt-out of using a technology that they feel it would be overly burdensome for them. Researchers will maintain regular contact with participants, via phone call or video call and will 'check-in' regularly regarding how they are managing with the at-home assessments. These will include: - Multimodal assessment of speech and facial movement: using the Modality online system - Tongue strength: using Iowa Oral Performance Instrument (IOPI) Trainer device - Hand grip strength: Prototype strength ergometer device (5 participants will use this novel prototype device designed in Trinity College Dublin) - Mobility: using GaitKeeper app - Activity: using ActiGraph GT9X Link device to monitor activity - Slow Vital Capacity (SVC): using Medical International Research (MIR) Spirobank Smart spirometer device. This is used with an app and will be completed every second month via video call and every second month independently by the participant guided by the app. - Peak Cough Flow (PCF): using an analogue peak flow meter device (completed independently with score entered on TiM). - Telehealth in MND (TiM) on MyPathway: a remote monitoring system where patient-reported outcome measures are completed online. This is currently in clinical use in the Beaumont Hospital clinical service. It will collect usual questionnaires and study specific questionnaires - Communication Effectiveness Index - modified (CETI-m) - Eating Assessment Tool (EAT-10) - ALSFRS-r (self-reported) Validity of the remote measures and the novel technologies will be assessed by comparing traditional assessment methods to novel methods. After using a technology at least twice, a subset of participants will be invited to complete the System Usability Scale (SUS) questionnaire and a semi-structured interview regarding their experience using the technology. Percentage adherence to the remote monitoring schedule will also be quantified. The study will operate in accordance with data protection legislation (GDPR), the declaration of Helsinki, and with Irish and EU legal and ethical requirement for cyber-protection of sensitive patient data. A data protection impact assessment (DPIA) has been completed and approved by the Beaumont Hospital and Trinity College Dublin ethics boards. Data sharing agreements are also in place for any of the relevant technologies included in the study. This study is part of a larger research program entitled Precision ALS [www.precisionals.ie]. Precision ALS is a European project which aims to collect large amounts of data about people with MND all over Europe, to make research in ALS/MND more powerful.

Implementation of a Standardized Algorithm for Coronary Calcification With Plaque Modification

Investigational strategy: Calcium modification algorithm to guide coronary intervention with an High Definition Intra Vascular Ultrasound (HD IVUS) imaging guided pathway that provides a systematic approach to coronary modification. Objectives: The aim of this study is to validate a comprehensive and intravascular imaging-based calcium modification algorithm for the treatment of moderate to severely calcified coronary lesions. Study Population: Patients with coronary artery disease with evidence of moderate to severely calcified coronary arterial lesions that are planned for percutaneous intervention requiring calcium modification. Design: CYCLOPES is a prospective, multicenter, open-label, single arm trial assessing the feasibility and efficacy of an intracoronary ultrasound guided algorithm for calcium modification in patients undergoing percutaneous coronary intervention (PCI) for chronic calcific coronary artery disease. The study will enrol 500 patients who will undergo PCI with calcium modification. Participants will be enrolled prospectively in 25 sites in Ireland, Switzerland, the United Kingdom, Spain, France, Italy and Germany (7 countries). All patients will have coronary angiography (QCA) and intravascular ultrasound (IVUS) imaging with 60MHz HD IVUS of the calcified lesion at baseline. The lesion will be characterized based on calcium distribution and morphology as assessed by HD IVUS. Depending on the specific lesion characteristics, the appropriate method for calcium modification will be chosen and performed in line with the CYCLOPES calcium modification algorithm included in the study protocol. The calcific lesion will be imaged for a second time by 60MHz HD IVUS following calcium modification. The operator will then proceed, if no further lesion preparation is required, to deploy a bioabsorbable polymer Everolimus eluting stent using standard stenting techniques, post dilatation will be performed at the operator's discretion. The treated lesion will be assessed again using intravascular ultrasound following stent deployment and optimization. The primary end points will be the post stenting minimal stent area (MSA) at the site of maximum calcification relative to reference lumen area assessed with 60MHz HD IVUS and target lesion failure (TLF) at 1-year post-procedure. All HD IVUS determined endpoints will be assessed at an independent imaging core laboratory. Participants will be assessed with clinic or phone visits at hospital discharge, 1 month and 12-month time points post procedure.

Precision Diagnosis and Care for Families With Pulmonary Fibrosis in Ireland

Exoskeleton Training for Spinal Cord Injury Neuropathic Pain (ExSCIP)

Background and Rationale: Following SCI, approximately 53% of people develop neuropathic pain (NP). Irish SCI data identifies high pain intensity and pain interference levels with NP and significantly poorer quality of life (QoL) than other pain phenotypes. Individuals can describe NP as more debilitating than the other consequences of SCI, as their most persistent health issue and adequate pain relief as an unmet need. International data identify the proportional burden of NP following SCI as significant. Ninety-four percent of individuals are prescribed >1 medication, the mean number of physician office visits in a 6-month period due to SCI NP is reported as 2 and the total annualised cost of NP per subject in the United States (US) is reported as $26,270 (direct $8,636, indirect $17,634). The presence of pain is further associated with lower return to work rates following injury, and more than a third of individuals with SCI in employment report frequent pain interference with their work . Pain interference with function, health status and work are noted to be significantly worse in individuals with more severe NP, where overall work impairment is reported at 38%. NP after SCI is multi-faceted and heterogenous, making isolation of specific mechanisms more challenging. Mechanisms hypothesised for NP after SCI include neuronal hyperexcitability (central and peripheral sensitisation) and corticothalamic maladaptive neuroplasticity. Additionally, NP symptom severity post SCI has been reported to be associated with a combination of residual spinothalamic tract (STT) function below the level of injury and with catastrophising pain coping mechanisms. The mechanistic effects of sensorimotor stimulation on NP stem from Phantom Limb Pain research (PLP) with significant reversal of cortical dysfunction in the primary somatosensory cortex of individuals with PLP evident. Similar maladaptive cortical reorganisation is hypothesised to be associated with NP in SCI. This is further supported by data garnered from electroencephalography (EEG) studies showing that changes in oscillatory brain activity known as thalamo-cortical dysrhythmia, are associated with the presence of NP. NP in SCI is associated with an EEG power signal increase in the theta band and possibly high beta band but a decrease in the high-alpha-low-beta band. In addition, NP in SCI is associated with decreased reactivity of alpha band power signals in response to eye opening. Thus it has applications as a biomarker for current NP and as a predictor of development of future NP. The mainstay of NP treatment after SCI is pharmacotherapy with anticonvulsants and antidepressants to reduce pain intensity. Pregabalin/gabapentin, duloxetine, amitriptyline and/or opioids are the first- and second-line treatments recommended, although severe pain remains refractory to these treatments in 2⁄3 of sufferers. Survey data report high use of non-steroidal anti-inflammatories and paracetamol. Significant side-effects of medications are reported. SCI patients are particularly prone to central nervous system related side effects which are often intolerable. These, together with fear of medication dependency, result in poor adherence to pharmacological regimens leading to a call for non-pharmacological treatment options for people with NP after SCI. Virtual reality (immersive virtual walking virtual illusion/imagined walking) has shown promise for reducing NP intensity and interference after SCI. Virtual illusion interventions show evidence of direct and corrective stimulation to the reorganised sensorimotor areas in SCI patients with NP, supporting the theory that NP mechanisms are reversible. However, actual sensorimotor intervention studies are inconclusive in SCI at this point with limited focus on walking despite compelling preclinical studies showing prevention and/or reversal of SCI neuropathic pain. Notably in animal studies, other exercise paradigms including swimming and stance training had only transient or no effects on SCI-induced NP suggesting that the rhythmic stimulation of proprioceptive and mechanosensory afferents together with weight bearing experienced in walking might be necessary to reduce NP. The exoskeleton intervention itself is not new within the neurorehabilitation space for SCI. However, no RCTs to date have specifically recruited participants with moderate-to-severe NP in order to assess its mechanistic effects on NP. The ExSCIP randomised feasibility trial addresses this current knowledge gap, examining exoskeleton-based walking 3 times per week, as a mechanistic-based intervention for NP after SCI. It will test the feasibility and acceptability of an exoskeleton, and whether it demonstrates positive signals in reduction of NP intensity and interference levels to warrant onward progression to a definitive trial. Aims and Objectives: The overall aim of this study is to examine the feasibility and acceptability of an exoskeleton, mechanistic-targeted, walking intervention for NP in people with SCI. The primary objectives for the study are: 1. Implement an exoskeleton training programme for people with below level NP > 6 months after a traumatic SCI. 2. Pilot and assess the impact of an exoskeleton-based walking intervention in NP > 6 months after SCI, examining feasibility outcomes and short and long-term (6 months) changes in pain intensity and pain interference. The ExSCIP study is a phase 2 randomised, single blinded, feasibility trial with the aim of examining progression criteria for a definitive trial. Progression criteria are based on consideration of the primary objectives around feasibility and the potential for effectiveness and implementation in clinical practice. Quantitative and qualitative process evaluation data will be analysed to consider the following continuation criteria. - Successful uptake, recruitment, and retention. - Successful implementation of the ExSCIP intervention. - Process evaluation indicates that ExSCIP is acceptable to people with NP after SCI and to staff delivering the intervention. - A positive effect on pain and pain interference outcomes are identified and are meaningful. - Cost analysis indicates that the ExSCIP intervention might be cost effective. The intervention will be delivered in the Motion Analysis Laboratory at University College Dublin (UCD). Participant Screening: Stage 1: Phone Screening: NP will be screened for as a minimum criterion initially by phone. This phone screening will do the following: - Confirm their SCI diagnosis (e.g. traumatic aetiology and >6 months post injury). - Confirm they are on a stable medication regimen. - Confirm they are exoskeleton naïve. - Screen for the presence of NP using the Spinal Cord Injury Pain Instrument (SCIPI). - Inquire into anthropometric details, e.g. the candidate's height and weight to give further indication relating to their potential suitability/compatibility with the exoskeleton. - Once the phone screening has been completed, candidates deemed to be potentially suitable to participate in the trial will be booked in for an in-person assessment. Potential participants will be provided with a study information leaflet at this point and informed consent will be sought from participants to complete an in-person assessment. A 1 week grace period will be given to participants between provision of the study information leaflet and obtaining informed consent. Stage 2: In-Person Assessment: An in-person assessment to confirm participant suitability will be performed by an independent assessor. The assessment will entail the following steps: Confirmation of presence of moderate to severe below level NP: - NP will be confirmed based on a neurological examination, a score of ≥4 on the Douleur Neuropathique 4 (DN4) and a comprehensive pain history. - This will be supported by the use of the ISCIP Pain Classification. - Moderate and severe NP as confirmed above will be described as pain ≥ 3 and ≥ 6 on the 0-10 Numerical Rating Scale (NRS) for NP (averaged over a week). Anthropometric and clinical assessment for compatibility for use of exoskeleton: - Participants will undergo an anthropometric assessment to ensure no height, weight, joint range of movement or muscle spasticity restrictions to exoskeleton use apply. Stage 3: Informed consent and data collection: - Candidates who meet inclusion criteria will be provided with a study information leaflet (see Figure 2) and asked to provide written informed consent that they agree to participate in the study via a consent form. - The independent assessor will then collect data at baseline for the outcome measures outlined: (Please refer to outcomes section for full details): Data/statistical analysis: Descriptive statistics and estimation using 95% CIs will be the main focus of the analysis. The number of participants recruited and retained, and information on missing or incomplete data from all outcome measures will be explored. Baseline demographics and outcome variables will be compared at all assessment times within groups. For categorical measures, frequencies and percentages will be presented and for continuous measures, the mean and standard deviation (SD) will be reported. For continuous measures which show evidence of some skew a median and interquartile range may also be presented or substituted for the mean and SD. Within group change scores and their 95% CI will be examined in relation to the MCID. Repeated measures ANOVAs will be used to compare between group differences of continuous variables across the three time points. Statistical significance will be determined α-priori at an alpha level of 0.05. For analysis of EEG data, this will be an exploratory analysis using a multilevel linear mixed model (LMM) approach to examine differences between the intervention groups over time in the EEG alpha, beta and theta band power. Repeated measures within participants will be modelled as a random effect. Fixed effects in the model, will include group assignment and time. The moderating effects of pain intensity and interference will also be evaluated. The LMM will study both main effects and interaction effects using the R package lme4 to fit the models. Models will be compared using Likelihood Ratio Tests (LRT) to assess the significance of effects. Statistical significance will be determined α-priori at an alpha level of 0.05. When all data is collected, data analysis will be conducted by a data processor blinded to group allocation. A full statistical analysis plan will be prepared prior to final analysis. Statistical analysis will be conducted using SPSS version 29 software and analysis will be conducted as intention to treat (ITT) and per protocol.

AI-enabled Endoscopic Prediction of Post-operative Recurrence in Crohn's Disease

Background: Up to 70% of Crohn's disease (CD) patients will undergo a surgical resection in their lifetime. However, surgery is non-curative since 50% of patients have a recurrence, and about one-third need repeat surgery. The tools currently used to assess CD recurrences, such as faecal calprotectin (FCP), cross-sectional imaging (small bowel ultrasound, MRI scan) and conventional endoscopy, have a limited role in predicting early Post-Operative CD recurrence (POCr). Distinguishing inflammatory disease recurrence from post-surgical ischemic or suture-related alterations poses a significant challenge. Endoscopic Enhanced imaging (EEI) techniques like virtual electronic chromoendoscopy (VCE) and biopsy-like probe-based confocal laser endomicroscopy (pCLE) combined with artificial intelligence, can improve the detection of mucosal/vascular changes before major alterations become evident. VCE is available simply by switching a button. The pCLE probe will be passed through the endoscope channel like a biopsy forceps, enabling real-time, histology-like images of the intestine's lining and the gut barrier. Study summary: This is a multicentre prospective international observational study. This study aims to introduce a novel multidimensional approach to precision imaging, enabling the identification and stratification of high-risk patients who can potentially benefit from early treatments to halt the progression of CD. The investigators will develop a novel endoscopic assessment system using EEI to evaluate early post-surgical changes and predict POCr. By integrating with immune marker profiling, clinical data, and AI assessment of EEI and histology, the investigators further plan to improve risk stratification and reduce interobserver variability. A detailed exploratory analysis will only be done in a cohort of patients in Ireland. The correlation between the new scoring system and established endoscopic and histologic scores, cross-sectional imaging, and non-invasive markers of inflammation will be evaluated. A multimodal machine learning model will be developed on EEI videos, histology, clinical data and immune molecular analysis to stratify patients' risk of early recurrence and long-term outcomes. The study will be divided into three phases: - In the first phase, descriptor criteria for the assessment of post-operative Crohn's Disease will be defined. Gastroenterologists experienced in IBD endoscopy will review images and videos from an existing library showing the different grade of inflammation of the modified Rutgeerts score. These will be used for a stepwise discussion. A round table discussion using modified Delphi method will be conducted to ensure equal participation and identify the best component descriptors of endoscopic recurrence of CD. The components that achieved 100% consensus will be selected and the most important endoscopy predictive variables will be confirmed by using a machine learning technique. Finally, a new endoscopic score will be generated. Further, the investigators will first validate the new endoscopic score using the first 30 consecutive VCE and pCLE videos of POCr patients recruited in the multicenter PROSPER study. A structured consensus will be conducted with experts in Inflammatory Bowel Disease, endoscopy and histology to define the endoscopic findings of mucosal, vascular and intestinal barrier function. Subsequently, the investigators will prospectively validate the score in a large cohort of POCr patients enrolled in the PROSPER study and assess the diagnostic accuracy of the new scoring system in predicting post-surgical recurrence. Clinical information, blood, saliva, stool, and bowel specimens will be taken. Cross-sectional imaging (magnetic resonance imaging -MRI-, intestinal ultrasound -IUS-), endoscopy VCE and pCLE (in equipped centres) will be performed according to stool calprotectin 3 months after surgery. Patients will be followed up for 24 months and the results of the follow-up colonoscopy performed, as standard of care, within 18 months from the index colonoscopy, will be collected. - In the second phase, the investigators will externally validate and reproduce the new scoring system by gastroenterologists using a computerized training module. - In the third phase, an advanced computer-aided quantitative analysis of videos, images from VCE and pCLE, and digital histology will be developed and validated to enhance the prediction of POCr. Additionally, further machine learning models will be developed, utilizing comprehensive data from blood, stool, cross-sectional imaging, endoscopy, histology, immune markers, and OMICs to predict POCr and long-term outcomes.

A Randomised Control Clinical Trial Investigating the Effect of H-PRF on Implant Stability and Marginal Bone Levels

This is a parallel arm, randomised control clinical Trial (RCT) on a cohort of Dublin Dental University Hospital patients who are having dental implants placed in the maxilla or mandible. Study sample: 1. Subjects will be recruited from a population of patients who have been referred to Dublin University Dental Hospital from general practice or specialist practice for provision of implants 2. Subjects will be recruited from a population of patients who have been referred from another department within the Dublin Dental Hospital for provision of implants. Enrolment and Consent: Participants will be selected via two methods: 1. Subjects will be recruited from a population of patients who have been referred to Dublin University Dental Hospital from general practice or specialist practice for provision of implants. 2. Subjects will be recruited from a population of patients who have been referred from another department within the Dublin Dental University Hospital for provision of implants. Patients being referred for implants to the Dublin Dental University hospital initially attend a dental implant assessment appointment. If at that appointment they are deemed suitable to be enrolled in the study, a gatekeeper, Ms Niamh Leonard, will invite the patient to take part in the research study. (Please note that Ms Niamh Leonard is an experienced gatekeeper and an administrator in the Division of Restorative Dentistry and Periodontology in the Dublin Dental Hospital, but is not involved in study patient's care. She will only be involved in inviting patients to take part in the study). Patients will have an opportunity to discuss the study in detail and will be provided with a written copy of the Patient Information Leaflet (PIL) to take home. For any question that may arise regarding the research or the surgical procedure patients will be able to contact the co-investigator (Dr Rawan Kahatab) as the contact details appear on the information leaflet. Patients will be given time (at least 7 days) to consider their participation and can contact the gatekeeper if they opt to participate. Patients will sign a freely given informed consent form prior to their enrolment in the study. If a single patient will be receiving more than one dental implants and there are numerous implant sites that qualify for entry into the research, only one of the implant sites will be randomly selected for the study. If a patient opts not to participate, it will not affect their care. Randomisation: At the time of surgery, each patient will select a numbered, sealed envelope with the treatment group allocation. Each envelope will correspond to a number on a computer-generated randomisation list created prior to enrolment of study participants. The operator will then use either the H-PRF or not use H-PRF when placing the implant depending on what was revealed when the envelope was opened. Neither the operator or the patient can be blinded to the arm chosen as blood sample will only be taken for the H-PRF group. The blood sample collection and surgeries will be performed by Dr Rawan Kahatab. H-PRF is used regularly in the DDUH and the clinical protocol will not deviate from standard procedures used at the hospital. H-PRF preparation protocol involves taking a sample of venous blood from patients using a butterfly needle to collect up to 8-9ml tubes of blood. After the first tube is collected, it would immediately be placed in a horizontal centrifuge machine, balanced out with 3 tubes of water, to ensure the centrifuge is properly balanced. A set rpm and time will be chosen, and the centrifuge will run until the time is complete. The H-PRF clots would then be ready and taken out of the tubes to separate them from the red blood cells. Peri-apical radiographs of the surgical site are taken pre-operatively, at implant placement and at implant restoration for all implants placed at the Dublin Dental University Hospital. Similar studies that have previously been carried out to assess the effect of PRF on implant stability have focused on PRF produced from fixed-angle systems as opposed to horizontal ones. However, they have followed a very similar design to our proposed design. For example, in a study by Tabrizi et al., (2017), a split-mouth randomised clinical trial was performed. Twenty patients with missing teeth in the molar region of the maxilla, requiring bilateral implants, were included. PRF was used on one side (group 1); no PRF was used on the other (group 2). Implant stability was assessed by resonance frequency analysis (RFA) at 2, 4, and 6 weeks after placement. At 2 weeks, the mean ISQ was 60.60 ± 3.42 in group 1 and 58.25 ± 3.64 in group 2; at 4 weeks it was 70.30 ± 3.36 in group 1 and 67.15 ± 4.33 in group 2; at 6 weeks it was 78.45 ± 3.36 in group 1 and 76.15 ± 2.94 in group 2. Significant differences in RFA were found between the groups at 2 weeks (P = 0.04), 4 weeks (P = 0.014), and 6 weeks (P = 0.027) after placement. The study results suggest that the use of PRF may enhance the post-insertion stability of dental implants placed in the posterior maxilla during the healing period. In another study by Oncu et al., (2015), twenty healthy patients with adequate alveolar bone and two or more adjacent missing teeth extracted at least 6 months previously were included. A minimum of two tapered implants were placed in each patient. After surgical preparation of the implant sockets, PRF that had been prepared preoperatively was placed randomly into one of the sockets. Resonance frequency measurements were made after implant placement and at 1 week and 1 month postoperatively. Mean implant stability quotients (ISQs) of the PRF implants was 69.3 ± 10.5, and mean ISQs for the PRF- implants was 64.5 ± 12.2 at the end of the first week. The mean ISQs at 4 weeks postoperatively were 77.1 ± 7.1 for the PRF+ group and 70.5 ± 7.7 for the group without PRF. In this study, PRF application increased implant stability during the early healing period, as evidenced by higher ISQ values. Based on the results of these studies and the fact that H-PRF is an even more superior biomaterial than PRF, our study should achieve outcomes that are just as successful.

PICSI Impact on Euploidy in Assisted Reproduction

A Study of a Potential Disease Modifying Treatment in Individuals at Risk for or With a Type of Early Onset AD Caused by a Genetic Mutation

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive decline in cognitive function and the ability to perform activities of daily living. The amyloid hypothesis of AD postulates that the accumulation of amyloid beta (Aβ) is an early and necessary event in the pathogenesis of AD. This hypothesis suggests that interventions that slow the accumulation of Aβ plaque in the brain or increase clearance of Aβ may be able to slow the progression of the AD clinical syndrome. AD occurs on a continuum from asymptomatic (preclinical) to mild cognitive impairment (MCI), and then to dementia in mild, moderate, and severe stages. Evidence from both genetic at-risk and age at-risk cohorts, such as in dominantly inherited AD (DIAD) suggests that the pathophysiological process of AD begins well more than a decade before the clinical stage now recognized as AD dementia, and that neurodegeneration is already apparent on MRI by the stage of mild cognitive impairment. Recent clinical trial data suggest that treating AD during the earlier stages could have the greatest potential benefit on the disease by slowing progression The ability to identify individuals destined to develop Alzheimer's disease (AD) with a high degree of confidence provides a unique opportunity to assess the efficacy of therapies at asymptomatic and very early stages of dementia. Families with known disease-causing mutations are extremely rare and are geographically dispersed throughout the world. Participants in this study will not yet have developed any clinical symptoms of AD; they will be "asymptomatic" carriers of mutations that cause DIAD and would be expected to perform normally on standard cognitive and functional testing. Further, most mutation carriers will have levels of AD-associated amyloid beta (Aβ) and non-Aβ biomarkers that are the same as non-carriers. Amyloid beta is a protein that accumulates in the brain of people with AD. Although we do not understand exactly what causes AD, the abnormal accumulation of amyloid beta protein in the brain is thought to play an important role in the symptoms of AD. Recent research studies indicate that amyloid beta may start building up in the brain 15 years or more before the onset of memory loss. Imaging and fluid biomarkers will be used to demonstrate that the treatment compounds have engaged their therapeutic targets. A set of cognitive measures designed to assess the very earliest and most subtle cognitive changes will be collected. The overall objectives of this study are to evaluate the biomarker effect, safety, and tolerability of investigational study drugs in participants who are known to have an AD-causing mutation. The primary objective of Stage 1 is to determine if treatment with the study drug prevents or slows the rate of Aβ pathological disease accumulation demonstrated by Aβ PiB positron emission tomography (PET) imaging. The primary objective of Stage 2 is to evaluate the effect of early anti-amyloid treatment on disease progression by assessing downstream non-Aβ biomarkers of AD (e.g., CSF total tau, NfL, MRI volume) compared to a control group from the DIAN Obs natural history study and the DIAN-TU-001 placebo-treated participants. Remternetug is a monoclonal antibody. The mechanism of action of remternetug is to target and remove aggregated amyloid plaque, a key pathological hallmark of AD, via microglial-mediated clearance. Remternetug has demonstrated the ability to reduce brain amyloid plaque. The remternetug arm is part of Master Protocol DIAN-TU-002 (NCT05552157)

ENVELOP: Wound Care Following Pilonidal Sinus Surgery

Pilonidal sinus disease (PSD) is a chronic inflammatory condition of the skin and subcutaneous tissues arising from hair follicles in the natal cleft. The definitive aetiology of the condition is unknown, however, it is theorised that it is the result of either the obstruction and subsequent inflammation of hair follicles or secondary to hair penetrating through the skin into the subcutaneous tissue. This results in infection, abscess formation, chronic discharge and pain. PSD is a common condition affecting 26 per 10,000 population, with the prevalence reaching 1.1% in young adult males. PSD causes a significant burden on healthcare services due to high rates of recurrence and readmission following surgery, together with negative impacts on patients' quality of life and self-image. An effective management strategy for the disease is necessary to ensure that post-operative outcomes are optimised and patient-reported outcomes are satisfactory in those whose PSD requires surgery. The objective of this multicentre, national RCT is to prospectively investigate the effect of negative pressure wound therapy compared to leaving open with standard wound care on time to wound healing following surgical excision of chronic PSD.