Disease-modifying Medications Research Articles

Improving Access to Dementia Care in the Era of Monoclonal Antibody Treatments for Alzheimer's Disease: a Pilot Clinical Protocol Using Abbreviated Neuropsychological Assessment.

To meet the growing demand for timely diagnosis in the new era of disease-modifying medications for Alzheimer's disease (AD), the present study aimed to reduce clinic wait times by developing and refining an abbreviated neuropsychological battery to assess individuals with a suspected amnestic process (i.e., Early-Stage AD Pathway). Early-Stage AD Pathway patients were referred by an internal neurology provider who determined that the patient had: (1) an amnestic clinical presentation, (2) a normal neurological examination, and (3) a Montreal Cognitive Assessment total score between 18 and 25. These patients were scheduled for a 2-h neuropsychological evaluation, including a brief clinical interview and an abbreviated testing battery. We evaluated n = 19 patients in the Early-Stage AD Pathway and compared them to 114 older adults referred via traditional clinic procedures (i.e., General Clinic). Most individuals evaluated via the Early-Stage AD Pathway were diagnosed with mild cognitive impairment (MCI; 68.4%) or mild dementia (21.1%) through the neuropsychological evaluation. Rate of diagnosis of MCI/dementia was comparable between groups. The average number of days between initial referral and completion of the neuropsychological evaluation was significantly lower (Mdiff = 145.8days, U = 1867.500, p < 0.001) for the Early-Stage AD Pathway group than for the General Clinic group, as the former could be scheduled more flexibly. Implementing an abbreviated neuropsychological assessment process significantly reduced the time between referral and evaluation to identify individuals who may be eligible for emerging pharmacological treatments for AD and/or non-pharmacological interventions in a timely manner.

Nanotheranostic Approach for Targeting Tauopathies in Alzheimer's Disease: Mechanistic Insight and Recent Advances

aims: This article first provides an introduction to tauopathy in AD before summarizing current research on the creation of tau-oriented multi-target directed ligands and small compounds as therapies that target tau alteration, aggregation, and degradation. background: The most prevalent type of dementia, Alzheimer's disease (AD), is typified by the presence of intracellular tau protein neurofibrillary tangles and extracellular amyloid plaques. There are currently about 50 million people who have dementia, and by 2030, that number is predicted to rise to 75 million, placing a significant financial strain on the nation's healthcare system. objective: The overall goal of this work is to present a thorough and critical review of small compounds that are being investigated as potential treatment candidates for AD tauopathy. method: Novel disease-modifying treatments are desperately needed to combat this illness, given the consequences on patients' quality of life and the mounting financial strain. There are currently no disease-modifying medications available; instead, the majority of available therapies are symptomatic ones such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers. result: The primary focus of therapeutic research against AD has shifted to tau-targeting strategies following multiple unsuccessful attempts to create medications against amyloidopathy. conclusion: The majority of current pharmacologic research focuses on developing drugs with multiple pharmacological payloads or combining them into a single delivery platform, which may be a promising strategy for completing multiple functions at once. Recent studies have shown that NPs can effectively cross the blood-brain barrier and exhibit inhibitory effects that enhance targeting and effectiveness at specific pH and temperature ranges other: As of right now, there isn't an anti-amyloid drug on the market to treat AD. AD may be such a complex disease that a multimodal approach will be needed to stop its progression.

Practical guide for disease-modifying medication management of children and adolescents with sickle cell disease.

Hydroxyurea has historically been the sole disease-modifying medication (DMM) for sickle cell disease (SCD). However, 3 newer DMMs, L-glutamine, voxelotor, and crizanlizumab, were approved for children and adolescents with SCD since 2017. Despite their emergence, treatment barriers, including access, affordability, and nonadherence, limit the optimization of DMMs in the clinical setting. Furthermore, there is limited work outlining real-world use and safety of the newer DMMs, and no published guidelines advise how best to select between DMMs or to use multiple in combination. Meanwhile, each DMM is associated with unique characteristics, such as tolerability, cost, and route of administration, which must be considered when weighing these options with patients and families. This article discusses DMMs for SCD and offers practical guidance on using the available DMMs in real-world settings based on published peer-reviewed studies and considering patient preferences. The recent withdrawal of one of these DMMs (voxelotor) from the market highlights the need for additional DMMs and evidence-based practices for adding DMMs and when to progress towards curative therapies.

Knowledge and Attitudes toward New Disease-Modifying Treatments for Alzheimer's Disease among Nursing Home Directors

ObjectivesNursing home (NH) administrator perceptions regarding the utility of Alzheimer's disease (AD) disease-modifying medications in NHs are important because many short and long-stay residents have mild AD. This study examined the interest of directors of nursing (DoNs) in using new AD disease-modifying treatments, changes in attitudes based on differences in costs to the NH, and characteristics (DoN and NH) associated with such changes. DesignThis is a cross-sectional study. Setting and ParticipantsThis study is based on a 2022 nationally representative survey of 340 NH DoNs, which was drawn from a stratified random sample of US NHs with ≥30 beds and with a 26.6% response rate. MethodsWe conducted a descriptive analysis to assess the awareness of new AD disease-modifying treatments and the support for their use. We applied logistic regression models to explore the associations between the interest of the DoN in using these new AD treatments and various characteristics. ResultsMost (86%) DoNs stated that they would at least sometimes support the usage of a new disease-modifying medication if there were no NH costs. This percentage was lower if the NH costs per resident were $2000 per year (51.3%) and $20,000 per year (14%). NHs with moderate shares of dual-eligible residents were more sensitive to cost. Conclusions and ImplicationsOur findings indicated that the interest of DoNs in using disease-modifying treatments for dementia varies widely according to the cost to the NHs. The uptake of new AD medications in the NH setting should be monitored, and targeted efforts may be needed to mitigate inequities in access for less-resourced NHs.

Evaluating the effectiveness of the Smart About Meds (SAM) mobile application among patients discharged from hospital: protocol of a randomised controlled trial

IntroductionAlmost half of patients discharged from hospital are readmitted or return to the emergency department (ED) within 90 days. Non-adherence to medication changes made during hospitalisation and the use of...

Atypical Presentation of Congenital Insensitivity to Pain With Anhidrosis Leading to Diagnostic Odyssey.

Congenital insensitivity to pain with anhidrosis (CIPA) (OMIM 256800) is a rare autosomal-recessive condition, also known as hereditary sensory and autonomic neuropathy type IV (HSAN-IV). The most commonly reported features include anhidrosis, intellectual disability, self-mutilation, febrile episodes, impaired temperature perception, recurrent infections and/or autonomic nervous system impairment. Major joint destruction and joint deformity known as Charcot (neuropathic) joints are also seen in CIPA patients attributed to insensitivity to joint pain. We present a case of a 46-year-old female affected with CIPA with a known NTRK1 variant and previously unidentified variant. Minigene reporter constructs were generated encompassing the exon 8 to exon 13 of the NTRK1 gene using the reference sequence and one harboring c.1483 + 5G > A variant identified in our proband. Minigene constructs were transfected into HEK293T cells, and the transcript was analysed for splicing to evaluate the effect of this variant in splicing. The patient (46-year-old female) exhibited right ankle joint deformity around 5 years of age. Patient also experienced lumbar compression and knee damage in adulthood. She had undergone a significant number of evaluations without clear diagnosis. Her presentation lacked many of the common clinical presentations of CIPA, and therefore, the focus of her evaluation was directed towards her unexplained joint deformities. Exome sequencing revealed a known pathogenic variant in NTRK1 (c.851-33T > A:p.? [Intron 7]) and a novel NTRK1 variant (c.1483 + 5G > A:p.? [Intron 11]), which was later re-classified as likely pathogenic. The patient was started on a biologic disease-modifying anti-rheumatic medication (bDMARD) due to a possible inflammatory etiology of her joint deformity. Molecular diagnosis allowed for modification of her treatment and surveillance strategies. Our minigene splicing assay demonstrated that the presence of the c.1483 + 5G > A variant has a negative effect on splicing, supporting the pathogenicity of this novel variant.

“The Past is a Foreign Country”: Time Shelter and exploring dementia and memory impairment representation in literature and the arts

Abstract Background Due to ageing populations, the WHO estimates that by 2050 the number of people living with dementia worldwide will more than triple to 152 million. For those working in geriatric medicine and memory services, we regularly interact with and advocate for patients coming to terms with memory impairments. One common theme often encountered during the patient dementia and cognitive impairment diagnosis journey is fear of loss of the sense of “self”, which can be informed by the negative and often inaccurate cultural narrative around dementia. Methods Recent promising breakthroughs in the development of disease modifying medications for Alzheimer’s disease, as well as greater emphasis on lifelong brain health and earlier diagnosis, represents a potential source of hope. This presentation will aim to explore the cultural narrative around the “lived experience” of dementia, which is often extremely negative and emphasises hopelessness. We look to some of the most commonly referenced narrative works, which can often form the foundation of many patient's prior knowledge of cognitive impairment and dementia before coming to the memory clinic. Results This presentation aims to examine the narrative works familiar to many patients (such as “The Father” and “Still Alice”) as well as some more recent efforts, including this year’s International Booker Prize-winning novel “Time Shelter” by Georgi Gospodinov. This darkly humorous book describes the arrival of a strange new ‘clinic for the past’ offering promising treatment for people with dementia. Conclusion Many works of narrative fiction explore dementia and memory impairment. While some are well-informed and researched, many lack empathy or even clinical accuracy. Narrative works can have an enormous impact on the widespread perception and understanding of diseases such as dementia. By exploring the potential for sensitive and accurate representation of dementia in popular culture, we aim to promote equity in this vulnerable and growing population.

A Meta-Analysis Examining the Effect of Perioperative Biologic Disease-Modifying Anti-Rheumatic Medications on Postoperative Wound Complications in Various Orthopedic Surgeries.

This meta-analysis was designed to compare the risk of postoperative wound complications in various orthopedic surgeries (OSs) affected by the perioperative use of biologic disease-modifying anti-rheumatic drugs (bDMARDs). The odds ratio (OR) and mean difference (MD), with 95% confidence intervals (CIs), were calculated using dichotomous or continuous random or fixed-effect models, based on the meta-analysis data. This study incorporated 14 investigations conducted between 2005 and 2023, encompassing a total population of 19,021 individuals undergoing diverse OSs. Participants who continued their bDMARDs exhibited a substantially higher incidence of postoperative surgical site infections (OR, 1.39; 95% CI, 1.12-1.72, p = 0.002) compared to those who withheld bDMARDs. However, the study did not find any statistically significant difference between the continuation or withholding of bDMARDs regarding delayed wound healing (OR, 2.02; 95% CI, 1.00-4.06, p = 0.05) or disease flares (OR, 0.59; 95% CI, 0.28-1.25, p = 0.17). The results show that patients who continued their bDMARDs had a notably higher incidence of postoperative surgical site infections. However, no significant differences were observed in delayed wound healing or disease flares when compared to those who withheld bDMARDs. It is important to acknowledge the limitations of this analysis, such as the relatively small number of participants and the limited number of studies available for certain comparisons, which may impact the validity of the findings.

The Potential Clinical Utility of an Artificial Intelligence Model for Identification of Vertebral Compression Fractures in Chest Radiographs

PurposeTo assess the ability of the Annalise Enterprise CXR Triage Trauma (Annalise AI Pty Ltd, Sydney, NSW, Australia) artificial intelligence model to identify vertebral compression fractures on chest radiographs and its potential to address undiagnosed osteoporosis and its treatment. Materials and methodsThis retrospective study used a consecutive cohort of 596 chest radiographs from four US hospitals between 2015 and 2021. Each radiograph included both frontal (anteroposterior or posteroanterior) and lateral projections. These radiographs were assessed for the presence of vertebral compression fracture in a consensus manner by up to three thoracic radiologists. The model then performed inference on the cases. A chart review was also performed for the presence of osteoporosis-related International Classification of Diseases, 10th revision diagnostic codes and medication use for the study period and an additional year of follow-up. ResultsThe model successfully completed inference on 595 cases (99.8%); these cases included 272 positive cases and 323 negative cases. The model performed with area under the receiver operating characteristic curve of 0.955 (95% confidence interval [CI]: 0.939-0.968), sensitivity 89.3% (95% CI: 85.7%-92.7%) and specificity 89.2% (95% CI: 85.4%-92.3%). Out of the 236 true-positive cases (ie, correctly identified vertebral compression fractures by the model) with available chart information, only 86 (36.4%) had a diagnosis of vertebral compression fracture and 140 (59.3%) had a diagnosis of either osteoporosis or osteopenia; only 78 (33.1%) were receiving a disease-modifying medication for osteoporosis. ConclusionThe model identified vertebral compression fracture accurately with a sensitivity 89.3% (95% CI: 85.7%-92.7%) and specificity of 89.2% (95% CI: 85.4%-92.3%). Its automated use could help identify patients who have undiagnosed osteoporosis and who may benefit from taking disease-modifying medications.

Deciphering the Role of Peroxisome Proliferator-activated Receptor α and Phosphodiesterase Type 5 Targets in Alzheimer's Disease.

The most prevalent cause of dementia is Alzheimer's disease (AD). Although the global AD rate is on a constant rise, medical research is yet to find a cure for this neurological condition. Current available therapeutic drugs for AD treatment only provide symptomatic alleviation. Therefore, it is essential to establish effective AD treatment strategies in addressing clinical needs. The development of disease-modifying treatments for use in the disease's early stages and the advancement of symptomatic drugs principally used in the disease's later stages are priorities in AD research. Given that the etiology of AD is difficult to comprehend, using a multimodal therapy intervention that targets molecular targets of AD-related degenerative processes is a practical strategy to change the course of AD progression. The current review article discussed PPAR-α (Peroxisome proliferator-activated receptor-α) and PDE5 (Phosphodiesterase type 5) targets with evidence for their preclinical and clinical importance. Furthermore, we support the targets with AD-related processes, functions, and remedial measures. A unique synergistic method for treating AD may involve the beneficial combinatorial targeting of these two receptors. Furthermore, we reviewed different PDE chemical families in this research and identified PDE5 inhibitors as one of the promising AD-related experimental and clinical disease-modifying medications. Lastly, we suggest jointly targeting these two pathways would be more beneficial than monotherapy in AD treatments.

Risk Assessment and Personalized Treatment Options in Inherited Dilated Cardiomyopathies: A Narrative Review.

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both genetic and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variants that can be transmitted from one generation to another can be a significant contributor to causing family or sporadic hereditary DCM. Genetic variants also play a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a large range of phenotypic expressions. It is crucial to select patients who are most probable to gain advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the relationships between genotype and phenotype, risk assessment, and personalized therapy for both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.

The therapeutic benefits of NSAIDs and physical therapy in knee osteoarthritis.

Osteoarthritis (OA) has been established as a progressive wear and tear disease of the synovial joints, which also involves a certain degree of inflammation. Considering there is no disease modifying medication available at the moment, the current guidelines focus on the symptomatic treatment of the affection. Our study aimed to evaluate the therapeutic advantages of the synergistic use of non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy in the treatment of knee osteoarthritis (KOA). The study comprised 46 individuals who were diagnosed with KOA and were admitted to the Department of Physical Medicine and Rehabilitation at the Emergency Clinical County Hospital of Craiova, Romania, between January 2021 and April 2022. All the participants received the same combination of pharmacological (Diclofenac 150 mg∕day, no more than 10 days∕month as needed) and non-pharmacological treatment (a 24-week plan of physical therapy). The patient group exhibited a statistically significant reduction in both the average Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index (p=0.0142) and the average Visual Analog Scale (VAS) (p=0.0023). Additionally, there was a statistically significant increase in both the average Knee Outcome Survey-Activities of Daily Living (KOS-ADL) (p=0.0128) and the average Oxford Knee Score (OKS) (p=0.0023). The study found a significant positive correlation between higher VAS ratings and cholesterol levels (p=0.0092), but no significant correlation between VAS scores and triglyceride levels (p=0.0986). Patients were evaluated for a further 24 weeks beyond the conclusion of the research to see if surgical intervention was necessary during this time. Our investigation tracked the WOMAC, VAS, KOS-ADL, and OKS measurements in a cohort of patients with KOA. The results demonstrate that the utilization of NSAIDs in conjunction with physical therapy effectively alleviates pain and enhances joint functionality.

A nationwide, population-based study on specialized care for acute heart failure throughout the COVID-19 pandemic.

The COVID-19 pandemic disrupted the delivery of care for patients with heart failure (HF), leading to fewer HF hospitalizations and increased mortality. However, nationwide data on quality of care and long-term outcomes across the pandemic are scarce. We used data from the National Heart Failure Audit (NHFA) linked to national records for hospitalization and deaths. We compared pre-COVID (2018-2019), COVID (2020), and late/post-COVID (2021-2022) periods. Data for 227 250 patients admitted to hospital with HF were analysed and grouped according to the admission year and the presence of HF with (HFrEF) or without reduced ejection fraction (non-HFrEF). The median age at admission was 81 years (interquartile range 72-88), 55% were men (n = 125 975), 87% were of white ethnicity (n = 102 805), and 51% had HFrEF (n = 116 990). In-hospital management and specialized cardiology care were maintained throughout the pandemic with an increasing percentage of patients discharged on disease-modifying medications over time (p < 0.001). Long-term outcomes improved over time (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.90-0.95, p < 0.001), mainly driven by a reduction in cardiovascular death. Receiving specialized cardiology care was associated with better long-term outcomes both for those who had HFrEF (HR 0.79, 95% CI 0.77-0.82, p < 0.001) and for those who had non-HFrEF (HR 0.87, 95% CI 0.85-0.90, p < 0.001). Despite the disruption of healthcare systems, the clinical characteristics of patients admitted with HF were similar and the overall standard of care was maintained throughout the pandemic. Long-term survival of patients hospitalized with HF continued to improve after COVID-19, especially for HFrEF.

Role of the Glymphatic System in Alzheimer's Disease and Treatment Approaches: A Narrative Review.

Currently, there is unavailability of disease-modifying medication for Alzheimer's disease (AD), a debilitating neurological disorder. The pathogenesis of AD appears to be complex and could be influenced by the glymphatic system present in the central nervous system (CNS). Amyloid-beta (Aβ) and other metabolic wastes are eliminated from the brain interstitium by the glymphatic system, which encompasses perivascular channels and astroglial cells. Dysfunction of the glymphatic system, which could occur due to decreased aquaporin 4 (AQP4) expression, aging-related alterations in the human brain, and sleep disruptions, may contribute to the pathogenesis of AD and also accelerate the development of AD by causing a buildup of harmful proteins like Aβ. Promising approaches have been examined for reducing AD pathology, including non-pharmacological therapies that target glymphatic function, like exercise and sleep regulation. In addition, preclinical research has also demonstrated the therapeutic potential of pharmaceutical approaches targeted at augmenting AQP4-mediated glymphatic flow. To identify the precise processes driving glymphatic dysfunction in AD and to find new treatment targets, more research is required. Innovative diagnostic and treatment approaches for AD could be made possible by techniques such as dynamic contrast-enhanced MRI, which promises to evaluate glymphatic function in neurodegenerative diseases. Treatment options for AD and other neurodegenerative diseases may be improved by comprehending and utilizing the glymphatic system's function in preserving brain homeostasis and targeting the mechanisms involved in glymphatic functioning. This review intends to enhance the understanding of the complex link between AD and the glymphatic system and focuses on the function of AQP4 channels in promoting waste clearance and fluid exchange.

#837 Information needs and emotional impact when receiving a diagnosis of chronic kidney disease: insights from DISCOVER CKD

Abstract Background and Aims Chronic kidney disease (CKD) is often a silent condition, with symptoms typically not appearing until a large proportion of kidney function has been lost. Therapeutic interventions, e.g., disease-modifying medications, blood pressure and diabetes control, and lifestyle changes, can delay CKD progression, particularly if instigated early. However, psychological distress can reduce adherence to interventions. It is important patients are adequately informed about their diagnosis to improve adherence and reduce the impact of distress. Multinational, real-world data on patient experiences with CKD, particularly about clinical management, treatment patterns and quality of life, are limited. This DISCOVER CKD sub-study aimed to capture the emotions elicited by patients at CKD diagnosis and their perceptions of the information received. Method DISCOVER CKD (NCT04034992) is a multinational cohort study that aims tocharacterise the epidemiology of CKD and describe patient characteristics, CKD progression, clinical outcomes, the patient journey, practice patterns, and clinical management. The current analysis includes a subset of patients from the USA, UK, Japan, and Spain, who participated in 1-2-1 telephone interviews about their CKD experience, including their disease journey and interactions with the healthcare system. Interview topics in DISCOVER CKD were informed by a pilot study that utilised data from PatientsLikeMe, an online network for patients to share personal stories and health data. Qualitative interviews, conducted in the local language by trained interviewers, January–June 2023, lasted ∼60–90 minutes. Transcribed interviews were translated into English for coding (MAXQDA Plus 2022 v22.3.0) and analysis. The study received research ethics board approval and all participants provided written informed consent. Results 103 patients (mean age 63.1 years; 42.7% female; 51.5% with type 2 diabetes) were interviewed. Most had CKD stage 3A (22.3%) or 3B (28.2%); 26.2% had stage 4 or 5 no dialysis and 9.7% were stage 4 (n = 1) or 5 on dialysis. Average time since diagnosis was 9.5 years. Over one-third (38.8%; n = 40/103) of participants did not recall any specific symptoms or signs of CKD prior to diagnosis. Of the pre-diagnosis symptoms reported, the most common was fatigue (21.4%; n = 22/103), then high blood pressure (15.5%; n = 16/103) and swelling (11.7%; n = 12/103). With respect to patient experiences, 55.2% (n = 32/58) said they did not feel sufficient information about CKD was provided at diagnosis and 59.2% (n = 45/76) said no information about their CKD stage was shared. Participants felt overwhelmed and confused about the diagnostic process and struggled to understand the information provided to them, including information about kidney function and symptoms. To supplement their understanding, participants reported using additional sources of information, including the internet (52.9%; n = 36/68), other healthcare professionals (HCPs) (19.1%; n = 13/68), books/printed information (11.8%; n = 8/68) and patient support groups (8.8%; n = 6/68). The most common emotions experienced at the time of diagnosis were worry and fear (28.2%; n = 29/103), then shock/surprise (25.2%; n = 26/103) (Figure). For those reporting no reaction (27.2%; n = 28/103), many stated the condition had no discernible effect on their daily lives. Reasons for fear or worry were related to the potential for disease progression. Conclusion Many patients expressed dissatisfaction with the information they received at their CKD diagnosis. This suggests that HCPs could dedicate more time to explaining the diagnosis, the characteristics and severity of CKD, likelihood of progression, and the benefits of self-management and adherence to intervention. This could be particularly important for those without symptoms at the time of diagnosis, and patients who rely on HCPs as their primary source of information. Patients should be asked what information they want to receive and be directed to trusted sources. The diagnostic process was a highly emotional experience for many patients and counselling or psychological therapy should be considered.

Enrolment of the first paediatric cohort into the Australian lupus registry and biobank: A single-centre experience.

We aim to report on the feasibility of establishment of the first paediatric cohort as part of the longitudinal database of the Australian Lupus Registry and Biobank (ALRB) and to describe the enrolment data with a focus on clinical characteristics, serological data, treatment strategies and patient/parent-reported outcome measures. All patients under the age of 18years with a diagnosis of systemic lupus erythematosus (SLE) attending the paediatric rheumatology service of a single, tertiary hospital were identified. Patients were enrolled in the ALRB if they met ≥4/11 of the American College of Rheumatology (ACR) 1997 SLE classification criteria or the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria. Enrolment data including demographics, clinical characteristics, serological profiles, disease activity and damage assessments were recorded. Peds-QL Rheumatology and General Modules were used to assess patient and parent-reported outcomes. Twenty-seven patients were eligible for inclusion, with 26 patients (96%) consenting for enrolment. Twenty-five patients (92%) consented for biobanking. Twenty patients (77%) were female. The median age at enrolment was 16years (interquartile range (IQR) 13.7, 17.4). The median disease duration from diagnosis was 3.2years (IQR 1.4, 5.3). Sixteen patients (62%) had synovitis, 16 (62%) had cutaneous involvement, 4 (15%) had serositis, 17 (65%) had haematological involvement and 7 (27%) had renal involvement at enrolment. Nineteen patients (73%) were prescribed at least two disease-modifying anti-rheumatic medications (DMARDs). Hydroxychloroquine (n = 22, 85%) and mycophenolate mofetil (n = 9, 35%) were the most commonly prescribed DMARDs. The median SLEDAI-2K score was 2 (IQR 2, 4). Six patients (23%) had active disease (SLEDAI-2K ≥6) at enrolment. Three patients (11.5%) had reported damage using the SLICC/ACR Damage Index. Twenty-three children (88%) and eighteen parents (69%) completed the Paediatric Quality of Life Inventory. Quality of life scores reported across domains of physical, emotional, social and school functioning at enrolment were comparable to previously studied paediatric cohorts with SLE and other chronic diseases. We have established our centre as the first paediatric participating site of the ALRB, providing contemporary data on the clinical characteristics, serological profile and health-related quality of life outcomes of Australian children with SLE. Paediatric involvement with this national registry will provide a unique perspective for future clinical and scientific research. Collection of Australian-specific paediatric longitudinal data will also enable a broader understanding of SLE within a multicultural Australian population.

Therapeutic management of fibrosis in systemic sclerosis patients - an analysis from the Swiss EUSTAR cohort.

Systemic sclerosis is a chronic autoimmune connective tissue disease leading to microvascular and fibrotic manifestations in multiple organs. Several treatment options and recommendations from different European countries are available. In this study, for which the ambit is Switzerland specifically, we aim to describe the treatment patterns of systemic sclerosis patients with fibrotic manifestations. Systemic sclerosis patients were selected from six Swiss tertiary centres recorded in the multicentre, prospective European Scleroderma Trials and Research (EUSTAR) registry. Patients fulfilling the 2013 ACR/EULAR systemic sclerosis classification criteria at baseline were included. To determine the differences in treatment of varying degrees of fibrosis, four groups were identified: (1) patients with a modified Rodnan skin score (mRSS) >0; (2) those with mRSS ≥7; (3) those with interstitial lung disease (SSc-ILD), diagnosed by either chest X-Ray or high-resolution computed tomography; and (4) patients fulfilling one of the additional criteria for extensive interstitial lung disease, defined as interstitial lung disease involvement of >20% in high-resolution computed tomography, dyspnea NYHA-stage 3/4, or a predicted forced vital capacity (FVC) of <70%. A total of 590 patients with systemic sclerosis fulfilled the inclusion criteria. In this cohort, 421 (71.4%) had mRSS >0, of whom 195 (33.1%) had mRSS ≥7; interstitial lung disease was diagnosed in 198 of 456 (43.4%), of whom 106 (18.0 %) showed extensive interstitial lung disease. Regarding non-biologic disease-modifying medications (DMARDs), the most frequently prescribed was methotrexate, followed by hydroxychloroquine and mycophenolate mofetil. Rituximab and tocilizumab were most frequently used among the biologic DMARDs. Specifically, 148/372 (39.8%) of treated patients with skin fibrosis received methotrexate, mycophenolate mofetil or rituximab, and 80/177 (45.2%) with interstitial lung disease received cyclophosphamide, mycophenolate mofetil, tocilizumab or rituximab. Most patients received a proton-pump inhibitor, and few patients underwent hematopoietic stem cell transplantation. Overall, in Switzerland, a wide range of medications is prescribed for systemic sclerosis patients. This includes modern, targeted treatments for which randomised controlled clinical trial have been recently reported.

The risk of CKD progression remains high in patients treated with ACE inhibitors and ARBs, MRAs and SGLT2 inhibitors. Have we already achieved the therapeutic ceiling in CKD? (The CON part)

ABSTRACT Renin-Angiotensin-System (RAS) inhibitors remained the only effective nephro-protective treatments until recent landmark trials showed that sodium-glucose co-transporter 2 (SGLT2) inhibitors and non-steroid mineral receptor antagonists added-on RAS inhibitor therapy dramatically slowed renal disease progression in patients with chronic kidney disease (CKD). However, despite this impressive advancement, a substantial proportion of patients remains at high risk of renal and cardiovascular events. Thus, we are still far from achieving the therapeutic ceiling in CKD. However, we are entering a new era in the management of patients with CKD with innovative methodological approaches to test disease-modifying medications in the context of personalized medicine.

P143: New therapies for Alzheimer’s dementia and its implications on healthcare system: are we ready?

Objective:The amyloid hypothesis suggests that errors in production, accumulation, or disposal of beta-amyloid are the primary causes of Alzheimer's disease (AD). Since this was hypothesized, there has been significant effort in developing treatments that prevent the build-up of amyloid beta (Aβ) plaques in the brain. A disease modifying therapy (DMT) changes the clinical progression of AD by interfering in its pathophysiological mechanisms.The aim of this article is to review the current literature regarding the role of new DMTs for Alzheimer’s dementia and assess the preparedness of health care systems to implement these treatment options.Methods:Review of the most recent literature regarding the role of new DMTs for Alzheimer’s dementia and the challenges faced by the health care system to implement these treatment options. The research was carried out through the PubMed and UptoDate databases, using the terms “amyloid hypothesis”, “Alzheimer”, “disease modifying treatments” and “dementia”.Results:Research has been focusing on developing monoclonal antibodies as potential DMTs that target Aβ. Aducanumab, a human antibody, or immunotherapy, is the only disease-modifying medication currently approved to treat AD. It targets the Aβ protein and helps to reduce amyloid plaques and is currently the only FDA approved medication to slow the progression of AD. Lecanemab, a humanized IgG1 monoclonal antibody, binds to Aβ soluble protofibrils with high affinity. Even though there is considerable optimism about its potential, lecanemab will probably be more useful to patients on early stages of the disease.Conclusion:DMTs administration obeys to certain needs such as a vacancy in Day Hospital for infusion and regular monitorization and for lumbar punction. It demands a complex network involving general practitioner, neurologist, psychiatrist, psychologist, and social services. It also involves a genetic study and complementary diagnosis exams such as PET (Positron emission tomography) scans and MRIs (Magnetic resonance imaging), which are expensive. There is an emerging need to develop enhanced and safer treatments.

Developing an AI-based decision engine for disease-modifying therapy in heart failure – A pilot study

Abstract Aim Heart failure is an escalating burden on global health care systems. Modernizing heart failure care is inevitable, with eHealth products poised to play an important role. However, eHealth devices that can initiate and adjust heart failure medication are currently lacking. Consequently, this study aimed to develop an artificial intelligence-based decision engine to provide guideline-based recommendations for disease-modifying medication in heart failure patients. Methods and Results We developed the decision engine by converting the ESC heart failure guidelines into Business Process Model and Notation, a visual modeling language suitable for developing complex decision engines. A safety evaluation, based on clinical parameters, was conducted to ascertain the system’s applicability to specific cases. The decision engine renders specific decisions concerning disease- modifying therapy for heart failure patients. We defined 72 virtual heart failure patient scenarios, encompassing a broad spectrum of baseline characteristics and background medication. All recommendations offered by the engine were evaluated by an independent heart failure specialist. All but three recommendations (94%) were identical to the treatment decisions by the heart failure specialist and all (100%) were in line with the 2021 ESC heart failure guidelines. Conclusion The decision engine offers guideline-based recommendations for disease-modifying therapy, positioning it as a tool to enhance self-care among heart failure patients. To validate our results, the decision engine is being prospectively tested in real-world patients in a multicenter clinical trial (NCT04699253).