6-month Period Research Articles

Incidence of Bacteremia and Serious Bacterial Infections in Hyperpyrexic Infants Offered Universal Pneumococcal Conjugate Vaccine 13 and Haemophilus influenzae B Immunization.

High fevers, especially in young children, often alarm clinicians and prompt extensive evaluation based on perceptions of increased risk of serious bacterial infection (SBI), and even brain damage or seizure disorders. The aim of this study was to determine the prevalence of SBI in infants aged 3-36 months with fever ≥40.5°C in a population of infants offered universal pneumococcal conjugate vaccine 13 and Haemophilus influenzae B immunization. This study is a retrospective review of all infants aged 3-36 months with temperature ≥40.5°C presenting to a tertiary care pediatric emergency department over a 30-month period in an era of universal pneumococcal conjugate 13 and H. influenzae B immunization. SBI was recorded in 54 (21.8%) of 247 study infants, most commonly pneumonia 30 patients (12.1%) and urinary tract infection 16 patients (6.5%). Two patients had positive blood cultures, yielding a bacteremia rate of 0.8%. Patients with SBI had a significantly higher WBC count (P < 0.0001) and C-reactive protein levels (P < 0.0001), and were significantly more likely to be hospitalized (P < 0.0001). Although SBI was common (21.8%) in our cohort of hyperpyrexic infants universally offered vaccination with pneumococcal conjugate 13 and H. influenzae B vaccines, bacteremia was a rare finding (0.8%).

#108 Mineral and bone disorders during chronic kidney disease

Abstract Background and Aims The objectives of our work were to describe mineral and bone disorders in patients with chronic kidney disease (CKD) not yet at the dialysis stage and to assess the compliance of phosphocalcic balance indicators with international KDIGO recommendations Method It was a retrospective study conducted over a 10-month period (01 November 2018 to 31 August 2019) in the nephrology and haemodialysis department of the Renaissance University Hospital in Ndjamena. We have included all patients followed up in the unit for non-dialysis CKD, aged over 18 years and consenting to participate to this study. Results A total of 387 patients files were collected, 82 of which have been taken on. The average age of the patients was 52.7 (± 15.8) years, with a male predominance (67.1%). The comorbidities were arterial hypertension (71.9%) and diabetes (24.4%). CKD has predominated in stage V (55%), followed by stage III (23%). Clinical signs were mainly diffuse bone pain (37.8%), pruritus (8.5%), muscle pain (7.3%) and insomnia (8.5%). Disorders in phosphocalcic metabolism have been noticed in stage IV (11.9% and 10.7%) and stage V (40.5% and 34.5%) for hypocalcaemia and hyperphosphataemia. Secondary hyperparathyroidism and 25 OH vitamin D deficiency were respectively 28.8% and 40.5% in stage V CKD. Compliance with international KDIGO recommendations was 59.7%, 53.7% and 37% respectively for serum calcium, serum phosphorus and parathyroid hormone. Radiological fractures were observed in 4.9% of patients. The management of these disorders has focused on calcium carbonate (52.4%), native vitamin D (64.6%) and Cinacalcet (6.1%) administration. Hypocalcaemia (p = 0.005) and hyperphosphataemia (p = 0.0001) were higher in stage V patients, with a significant difference. Conclusion The treatment of mineral and bone disorders has way to go for the majority of patients, due to lack of resources and the exorbitant cost of treatment. Prevention of mineral and bone disorders is a fundamental pillar of CKD treatment for our patients.

Rapid and non-destructive quantification of meat content in the legs of live red king crab (Camtschaticus paralithodes) by near-infrared spectroscopy

Red king crab (RKC) is one of the most widely distributed and well-known of all king crabs. The edible meat of the RKC is in the legs and claws and is considered a delicacy. Occasionally, the content of meat is low, and this is regarded as the single most negative quality attribute. In this study, we elucidated how rapid and non-destructive near-infrared spectroscopy (NIRS) on live RKCs can be used to predict the meat content in the cooked legs. A NIRS prototype (wavelength range 760–1080 nm) was used to obtain spectra from the interior tissue of the crab legs. 99 live crabs (380 legs) were measured over a 10-month period. Calibration models were developed with a prediction error for meat content of 6.4 %-points, which is accurate enough to classify the crabs into low (<80 %) and high meat content. The amount of cooked meat is proportional to the amount protein in the muscle. A limitation with the method is that it may overestimate the meat content if the legs have lost free water due to e.g. injuries in the exoskeleton. The technology described can facilitate a more sustainable RKC fishery and improve the subsequent trade and processing.

#2657 Evaluation of the impact of a nephrologist led acute kidney Injury clinic in a large district general hospital

Abstract Background and Aims Acute kidney injury (AKI) has a significant impact on inpatient hospital admissions costing the NHS in the UK an estimated £1bn. Hospitalisation complicated by AKI results in increased length of stay and mortality and up to a fifth of discharged patients are readmitted to hospital within 30 days. Traditionally district general hospitals in the UK have limited nephrology cover. In our large district general hospital, a new nephrologist led AKI clinic was established to review patients whose inpatient admissions were complicated by a stage 2 or 3 AKI. Over a 7-month period the aim was to evaluate this new clinic and its impact for local patients and the hospital trust. Method Inpatients with stage 2 and 3 AKI were identified by a specialist AKI nurse and nephrologist as suitable for the clinic. A discharge summary was generated with the stage and cause of AKI. Patients were seen within 6 weeks of discharge by either a nephrologist or a specialist AKI nurse. Data was retrospectively collected, and this included diagnosis, causes of AKI, highest stage of AKI, progression of chronic kidney disease (CKD) and referral to tertiary chronic kidney disease services. Using the hospital's own AKI dashboard, we looked at 30-day readmission rates of all AKIs and overall hospital length of stay over this period. Results Retrospective data was collected for 245 patients who attended the clinic over 7 months. 43.9% had a stage 3 AKI, 41.4% had a stage 2 AKI, the remainder of patients were CKD patients with progression or had an underlying glomerular pathology. The most common cause for AKI was hypovolaemia (41.8%) followed by infection/sepsis (37.7%). Most AKIs fully resolved (58.1%), 7% of patients had not resolved and 27% partially resolved. 12.3% of patients were referred onto nephrology tertiary services. Over the course of the 7 months, the trend of 30-day readmission rates dropped from 18.2% to 10.1% (Fig. 1). There was no significant change in hospital length of stay. Conclusion The nephrology led AKI clinic has had a meaningful impact in our post discharge patient care. We have been able to review patients in a timely manner providing them with a holistic approach. A significant number of patients were identified and referred early for specialist tertiary CKD management. Over the 7-month period there was a reduction in 30-day readmission rates however it has not yet affected overall length of stay. This study supports a nephrologist led AKI clinic in a district general hospital.

COVID-19 Impact on Female Patients at Tertiary Care Hospital – A Retrospective Study

Objectives: Corona virus disease-19 (COVID-19) has impacted worldwide leading to a high mortality rate. It has been observed that male mortality rate is higher than females due to which it is crucial to systematically study gender differences in disease manifestations. Our study evaluated the association between mortality in COVID-19-positive cases and gender. Materials and Methods: This retrospective study was conducted in the cardiology department at a tertiary care hospital which included 699 patients with a confirmed positive diagnosis of COVID-19 by reverse transcription polymerase chain reaction and &gt;18 years of age. Data from the medical records of the department were collected during an 8-month period (July 2020–February 2021). Results: Of the 699 patients enrolled in the study within 8 months, 232 (33.1%) were female and 467 (66.7%) were male. Female mortality accounted for 18.99% and male mortality 14.56%. Comparing the severity of the disease, 36% of females showed more severe disease presentation. In the course of the disease with treatment, 51.29% of females required oxygen support. Conclusion: This study showed differences in the mortality rate, ventilation support requirement, and severity of disease in COVID-19 affected males and females.

#1891 Evaluating the safety and effectiveness of Tolvaptan for management of adult Korean ADPKD patients (ESSENTIAL study): final report

Abstract Background and Aims Tolvaptan, a selective vasopressin V2 receptor antagonist, was first approved by Korean FDA in 2015 as a treatment option in autosomal dominant polycystic kidney disease (ADPKD). In order to prescribe Tolvaptan safely and effectively, we designed the phase 4 clinical trial among Korean ADPKD patients with chronic kidney disease (CKD) stage 1-3. Method Korean patients aged 19 to 50 with rapidly progressing ADPKD were enrolled in the study. The dose titration was performed every one week for a total of 4 weeks. The patient was prescribed Tolvaptan with the maximum tolerable dose up to 120 mg per day. A total duration of Tolvaptan prescription was 24 months. The primary outcome was the incidence of treatment emergent adverse events (TEAE) including drug-induced liver injury (DILI). The secondary outcomes were the annual mean percent change of total kidney volume (TKV) and the annual mean change of estimated glomerular filtration rate (eGFR). Results A total of 117 patients were included in the analysis. Mean age was 38.7 ± 8.4 years old and male were predominant (58.1%). The average TKV was 2066 ± 1094 mL and mean eGFR was 79.7 ± 27.7 mL/min/1.73 m2. Mean duration of Tolvaptan exposure was 1.7 ± 0.6 years and the average daily dose of Tolvaptan was 94.4 ± 24.1 mg/day. A total of 489 treatment-emergent adverse events (TEAE) occurred in 106 (90.6%) patients during study duration. The drug-induced liver injury and aquaresis-related adverse events were two most common adverse events. A total of 17 DILI cases (14.5%) occurred during the study period and mostly within 18-month period. However, liver enzymes were normalized after drug discontinuation The patients with previous history of liver disease as well as those who were prescribed higher dose of Tolvaptan demonstrated higher frequency of DILI. Mean growth rate of TKV after Tolvaptan treatment was 4.5 ± 0.5% and mean eGFR decline rate was -3.0 ± 0.39 mL/min/1.73 m2/year. Comparing with the predicted value from calculation, Tolvaptan attenuated both TKV growth and eGFR decline rate. Conclusion This study is the first post-marketing survey assessing the safety and efficacy of Tolvaptan in Korean ADPKD patients. The incidence of DILI was higher than the previous studies and especially in those with liver disease and higher Tolvaptan prescription dose. While Tolvaptan can effectively reduce TKV and attenuate eGFR decline, the clinicians should be aware of higher frequency of DILI among Korean population.

Working together with people with intellectual disability to make a difference: a protocol for a mixed-method co-production study to address inequities in cervical screening participation

IntroductionCervical cancer is one of the most preventable cancers yet remains a disease of inequity for people with intellectual disability, in part due to low screening rates. The ScreenEQUAL project will use an integrated knowledge translation (iKT) model to co-produce and evaluate accessible cervical screening resources with and for this group.MethodsStage 1 will qualitatively explore facilitators and barriers to screening participation for people with intellectual disability, families and support people, healthcare providers and disability sector stakeholders (n ≈ 20 in each group). An accessible multimodal screening resource, accompanying supporting materials for families and support people, and trauma-informed healthcare provider training materials will then be co-produced through a series of workshops. Stage 2 will recruit people with intellectual disability aged 25 to 74 who are due or overdue for screening into a single-arm trial (n = 48). Trained support people will provide them with the co-produced resource in accessible workshops (intervention) and support them in completing pre-post questions to assess informed decision-making. A subset will participate in qualitative post-intervention interviews including optional body-mapping (n ≈ 20). Screening uptake in the 9-months following the intervention will be measured through data linkage. Family members and support people (n = 48) and healthcare providers (n = 433) will be recruited into single-arm sub-studies. Over a 4-month period they will, respectively, receive the accompanying supporting materials, and the trauma-informed training materials. Both groups will complete pre-post online surveys. A subset of each group (n ≈ 20) will be invited to participate in post-intervention semi-structured interviews.Outcomes and analysisOur primary outcome is a change in informed decision-making by people with intellectual disability across the domains of knowledge, attitudes, and screening intention. Secondary outcomes include: (i) uptake of screening in the 9-months following the intervention workshops, (ii) changes in health literacy, attitudes and self-efficacy of family members and support people, and (iii) changes in knowledge, attitudes, self-efficacy and preparedness of screening providers. Each participant group will evaluate acceptability, feasibility and usability of the resources.DiscussionIf found to be effective and acceptable, the co-produced cervical screening resources and training materials will be made freely available through the ScreenEQUAL website to support national, and potentially international, scale-up.

The temporal order of emotional, cognitive, and behavioral gains in daily life during treatment of depression.

Despite the importance for understanding mechanisms of change, little is known about the order of change in daily life emotions, cognitions, and behaviors during treatment of depression. This study examined the within-person temporal order of emotional, cognitive, and behavioral improvements using ecological momentary assessment data. Thirty-two individuals with diagnosed depression completed ecological momentary assessment questions on emotions (sad mood, happy mood), behaviors (social interaction, number of activities), and cognitive variables (worrying, negative self-thoughts) 5 times a day during a 4-month period in which they underwent psychotherapy for depression. Nonparametric change-point analyses were used to determine the timing of gains (i.e., improvements in the mean of each variable) for each individual. We then established whether the first (i.e., earliest) gains in emotions preceded, followed, or occurred in the same week as cognitive and behavioral gains for each individual. Contrary to our hypotheses, first gains in behaviors did not precede first emotional gains (3 times, 8%) more often than they followed them (26 times, 70%). Cognitive gains often occurred in the same week as first emotional gains (43 times, 58%) and less often preceded (13 times, 18%) or followed emotional gains (18 times, 24%). The first improvements in behaviors did not tend to precede the first improvements in emotions likely because fewer behavioral gains were found. The finding that cognitive variables tend to improve around the same time as sad mood may explain why many studies failed to find that cognitive change predicts later change in depressive symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

#2910 Renal toxicities in oncology at a secondary level hospital within the first 6 months of outpatient consultation establishment

Abstract Background and Aims In recent years the discovery of targeted therapies in oncology have been a revolution with spectacular results for patients with advanced neoplasia and metastasis. Representing a more precise approach to interfering with tumorigenesis, these therapies exhibit superior tolerability profile in terms of toxicity and have significantly improved overall survival (1). Numerous studies have demonstrated the increased risk of cancer patients developing acute renal failure and progressing to chronic kidney disease, both contributing to higher mortality. The use of these novel drugs, alongside traditional chemotherapy, coupled with the extended survival of patients with neoplasms has led to a rise in kidney pathologies (2.3). Addressing the need to provide a comprehensive and optimized treatment to this group of patients, the field of Onconephrology has emerged. Its primary objective is to assist in the diagnosis and management of kidney diseases associated with the underlying oncological condition and/or oncotherapeutics. While well-established Onconephrology Clinics predominantly operate in tertiary hospitals worldwide, acknowledging the growing significance of this field, we established an Onconephrology outpatient consultation at our secondary level hospital. In this study, we aim to delineate the incidence of renal toxicities secondary to oncotherapeutics within the first six months of initiating our Onconephrology outpatient consultation. Method Forty-six patients were retrospectively included, and an analysis of oncological and renal variables was conducted to determine the incidence of renal toxicities. Results Out of the forty-six patients evaluated, 12 exhibited renal toxicity secondary to oncotherapeutics, with a mean age of 73.3 years. The most frequent malignancy was lung cancer (n = 6), followed by gastrointestinal tract cancer (n = 2). Most patients presented with metastatic disease (n = 9), and their malignant disease was either in remission (n = 4) or stable (n = 5). Reasons for referral included acute kidney injury (n = 7), acute kidney injury over chronic kidney disease (n = 3), proteinuria (n = 1), and electrolyte abnormalities (n = 1). The diagnoses included acute immune-mediated tubulointerstitial nephritis secondary to checkpoint inhibitors (n = 5), cisplatin renal toxicity (n = 3), acute tubular necrosis secondary to tyrosine kinase inhibitors (n = 2), hypomagnesemia induced by EGFR inhibitor (n = 1), and nephrotic syndrome related to anti-VEGF. Following multidisciplinary intervention, most patients experienced recovery of kidney function (n = 9), while some progressed to chronic kidney disease (n = 2), and other maintained electrolyte imbalances (n = 1). Conclusion This study describes 12 patients with renal toxicities secondary to oncotherapeutics over a 6-month period at a secondary hospital. Most patients exhibited recovery of kidney function, emphasizing the positive outcomes achievable through multidisciplinary care, particularly in the context of the Onconephrology outpatient consultation, even in institutions with limited resources.

#817 Genetic analysis in a group of patients with persistent isolated microscopic hematuria

Abstract Background and Aims Autosomal dominant Alport syndrome (ADAS) is a genetic disease caused by pathogenic variants in COL4A3 and COL4A4 genes. ADAS is the main cause of isolated persistent microscopic hematuria (PMH). However, other diseases like IgA nephropathy (IgAN) can present with PMH. Establishing a precise genetic diagnosis in this type of patients would avoid invasive studies like kidney biopsies. In this study we performed a comprehensive genetic test in a cohort of patients with isolated PMH to evaluate the frequency of ADAS or other genetic abnormalities and compare the clinical characteristics of patients with or without ADAS Method Fifty-two patients with PMH were included in the study. PMH was defined by the presence of 3 or more dysmorphic red blood cells per field in at least 5 consecutive urine sediments and a time-averaged proteinuria &amp;lt;1 gr/day. Average proteinuria was determined for every 6 months of follow-up and time-averaged (TA) proteinuria represented an average of the mean proteinuria measurements in each 6-month period. A comprehensive genetic study using whole exome next-generation sequencing was performed. One hundred and one genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney diseases were analyzed. Patients with known secondary causes of hematuria were excluded. The baseline clinical characteristics of patients with and without ADAS were compared. Patients with pathogenic variants in COL4A5 gene were excluded of this analysis. Results Thirty-one (60%) patients were diagnosed with ADAS (16 patients with pathogenic variants in COL4A3, 15 in COL4A4), 3 (6%) patients (2 women, 1 man) presented pathogenic variant in COL4A5 gene, and the genetic study was negative in the remaining 18 patients (variants of unknown significance in COL4A3 or COL4A4 were found in 3 of the latter). No other genetic abnormalities were detected in the panel of 101 genes. Table 1 shows the baseline clinical characteristics of patients with and without ADAS. Patients with ADAS presented a higher TA proteinuria [0.23 (0.11-0.6) vs 0.08 (0.05-0.16), p = 0.01], and a more frequent familial history of isolated microscopic hematuria (76% vs 40%, p = 0.01) chronic kidney disease (CKD) (44% vs 0%, p = 0.01) or end stage kidney disease (32% vs 0%, p = 0.02). In the multivariate analysis, only a family history of microscopic hematuria was associated with ADAS: OR 5.62 (1.25-25.49, p = 0.02). Conclusion ADAS is the most common cause of PMH. A genetic study should be the first diagnostic step in order to obtain a precise cause of the disease and avoid invasive procedures. A family history of microscopic hematuria and of CKD increases the likelihood of ADAS prior to the performance of genetic test.

#2473 Renal failure in the emergency department: indications for emergency hemodialysis

Abstract Background and Aims kidney failure is a frequent reason for emergency department (ED) visits. Patients may require emergency hemodialysis and this situation may increases mortality risk. We set out to study the clinical relevance and biological characteristics of patients with renal failure presenting to the emergency department with an indication for emergency hemodialysis. Method A prospective observational study conducted in ED conducted over a 6-month period. Patients were included if they were 18 years or older and suffering from acute or chronic renal insufficiency defined by creatinine clearance (CrCL) calculated by MDRD&amp;lt;60 ml/min. Information is recorded on demographics, clinical profile, clinical presentation, laboratory, causes of for emergency hemodialysis and in-hospital complications. Results Eighty one patients were enrolled, among them 61.7% patients had an indication for emergency hemodialysis. Mean age was 61± 12, sex-ratio=1,7. Sixty seven patients (82.7%) were known to have a chronic kidney failure and 17.3 % were discovered at the emergency department at the same hospitalisation period. Clinical profile (%): Anuric patients (11.1), preserved diuresis (40.7). Clinical presentation (%): deterioration of general condition (35.8), dyspnea and chest pain (21) and fever (17.3). Clinical examination showed a peripheral oxygen saturation between 70 and 100% with a mean of 94.81, a respiratory rhythm mean of 20 cycles/min, a systolic blood pressure mean of 134.61 mmHg and a diastolic blood pressure mean of 70 mmHg. biological exams showed that kalemia was between 2.4 and 8.6 and 45 of those patients had kalemia more or equal to 5.5. Twelve per cent of these patients had hyperkalemia signs on the electrocardiogram. The average were 28 mmol/l with a maximum of 83.3 mmol/l. Creatinine values were between 185 et 2620 μmol/l with a median of 81. The value of Ph was between 7.04 and 7.53 with a median of 7.29 mm Hg. The value of HCO3- value was between 4.6 and 28.4 with a median of 14.2. Causes of emergency hemodialysis were acidosis in 12 cases, severe anemia with blood transfusion in 4 cases, hyperkalemia in 10 cases, acute pulmonary oedema in 5 cases and acute renal failure in 6 cases .the evolution of the patients was marked by improvement of 61.7% of the patients, only 3 of the 81 patients died during the hospitalization. Conclusion This study showed that the causes of emergency dialysis can be avoided by improving care and educating patients to improve the prognosis.

Reduced Subsidence With PEEK-Titanium Composite Versus 3D Titanium Cages in a Retrospective, Self-Controlled Study in Transforaminal Lumbar Interbody Fusion.

Retrospective Study. To compare subsidence and radiographic fusion rates of titanium-surface polyetheretherketone (PEEK-Ti) and 3D-Titanium (3D-Ti) cages, implanted within the same patient concurrently, during multi-level transforaminal lumbar interbody fusions (TLIF). Forty-eight patients were treated with both PEEK-Ti and 3D-Ti cages during 2- or 3-level TLIF and instrumented posterolateral fusion (108 spinal levels in all). Equivalent bone graft material was implanted within each patient. Radiographic analysis of CT and/or X-ray imaging was performed retrospectively for each spinal level throughout 12-month follow-up period. Fusion was defined as bridging trabecular bone and subsidence was incursion into one/both vertebral bodies >20% cage height. Outcomes were analyzed with Fisher's exact test. At 6-months post-operative follow-up, incidence of subsidence was significantly lower for PEEK-Ti cages, with 4.8% subsidence, compared to a 27.9% subsidence rate for 3D-Ti cages (P = .007). Fusion rates were comparable at 100% for PEEK-Ti and 95.5% for 3D-Ti. Results at 12-months showed similar but not statistically significant trends of less subsidence with PEEK-Ti than 3D-Ti cages (14.3% PEEK-Ti, 37.5% 3D-Ti), and similar fusion rates of 100% for PEEK-Ti and 91.7% for 3D-Ti. Thirty-nine out of 48 total patients were available for follow-up at 6 months and 20 patients at 12 months. CT availability at 6 and 12-months was 100% and 90%, respectively. A significantly lower subsidence rate was associated with a PEEK-Ti cage, compared to 3D-Ti, 6 months after TLIF. Results may not be generalized across technologies due to differences in cage designs; additional research studies are warranted.

#2638 SGLT2i in CKD with high albuminuria: an observational real-world study

Abstract Background and Aims Dapagliflozin, a sodium–glucose co-transporter-2 inhibitor (SGLT2i), is indicated to treat chronic kidney disease (CKD). Clinical trials have shown that dapagliflozin significantly reduces albuminuria in patients with urine albumin-creatinine ratio (UACR) 200–5000 mg/g and has beneficial effects on estimated glomerular filtration rate (eGFR) decline and combined kidney outcomes. In the DAPA-CKD trial, dapagliflozin led to substantial reductions in the composite of sustained eGFR decline of ≥50%, end-stage kidney disease, and renal or cardiovascular death (hazard ratio [HR], 0.61; 95% confidence interval [CI]: 0.51, 0.72; p &amp;lt; 0.001), with similar reductions observed across UACR subgroups. Furthermore, compared with placebo, dapagliflozin reduced geometric mean UACR by 29.3% (95% CI: –33.1, –25.2; p &amp;lt; 0.0001), with no difference in relative UACR reduction by baseline UACR above or below 1000 mg/g. In the ZENITH-CKD study, over 12 weeks the combination of zibotentan (a novel endothelin A receptor antagonist) and dapagliflozin showed a robust reduction in UACR of 47.7% vs 28.3% for dapagliflozin alone, with this effect maintained in patients with UACR &amp;gt;700 mg/g. It is well known that renal disease progresses more quickly in patients with higher degree of albuminuria than in those with lower levels. We aimed to further characterize renal risk in patients with different levels of residual albuminuria despite standard of care treatment with renin–angiotensin system inhibitors (RASi) and SGLT2i. Methods We used a large USA claims database (Optum's de-identified Clinformatics® Data Mart Database [CDM]) to identify patients aged ≥18 years with CKD, defined as either two eGFR measurements ≤60 mL/min/1.73 m2 taken ≥90 days apart or a first eGFR ≤60 mL/min/1.73 m2 and a CKD diagnosis. Patients were indexed at the date of dapagliflozin 10 mg initiation between 30 April 2021 (date of approval for dapagliflozin in CKD) and March 2023. Patients with prior use of SGLT2i, immunosuppressive drugs, hydroxychloroquine, CKD stage 5 (based on eGFR &amp;lt;15 mL/min/1.73 m2 or dialysis), polycystic kidney disease, or type 1 or gestational diabetes were excluded. Patients were indexed on 1st January 2022 and grouped into two UACR groups: ≥700UACR group (≥700 mg/g) and &amp;lt;700UACR group (200–699 mg/g). Outcomes were UACR changes, eGFR slopes and CKD-associated hospitalizations within 1 year after dapagliflozin initiation. Hazard ratios were estimated using adjusted Cox survival regression. UACR follow-up analyses were restricted to patients with at least one follow-up measurement. Results In the 5908 patients with CKD, median UACRs at index in the ≥700UACR and &amp;lt;700UACR groups were 1414 mg/g and 102 mg/g, respectively. Patients in the ≥700UACR group vs &amp;lt;700UACR group had lower eGFR (40 vs 48 mL/min/1.73 m2), were younger (71 vs 74 years), and both groups had a high burden of comorbidities (heart failure: 38% vs 42%; type 2 diabetes: 74% vs 75%). RASi use was 81% and 74%, respectively. During follow-up, 22% of patients in the ≥700UACR group experienced a CKD-related hospitalization (25.1 events per 100 patient years) as compared to 19.5 events per 100 patient years in the &amp;lt;700UACR group (HR 1.38 [95% CI: 1.16, 1.64, p &amp;lt; 0.001]; Fig. panel A). The eGFR slope (95% Cl) of patients in the ≥700UACR group was –2.44 mL/min/1.73 m2 per year (–3.49, –1.65), compared with a flat eGFR trajectory in patients in the &amp;lt;700UACR group (0.39 [–0.11, 0.96]). In the ≥700UACR group with at least one follow-up measurement (n = 431), UACR lowered from 2077 mg/g to 1674 mg/g (–36.3%) within 1 month of dapagliflozin initiation but remained above 1200 mg/g throughout the 12-month follow-up period (Fig. panel B). Conclusions While treatment with RASi and SGLT2i are associated with reduced risk of renal outcomes in patients with CKD, awareness and management of residual albuminuria remains an area of unmet clinical need. The novel combination of zibotentan/dapagliflozin currently under investigation in the ZENITH High Proteinuria phase III trial (NCT06087835) seeks to address this need.

#2134 Very low protein integrated diet (sVLPD), without keto analogues, in patients with advanced chronic renal failure: clinical and economic benefits

Abstract Background and Aims The integrated very low protein diet (sVLPD) has proven effective in slowing the progression of stage 5 chronic renal failure and in postponing the start of dialysis treatment (1)SVLPD with keto analogues is difficult to implement due to the high number of tablets to be taken (2), therefore, to increase compliance we decided to prescribe, in compliance with the guidelines of normal clinical practice, SVLPD (0.3 g/prot/day) integrated with only essential amino acid drugs without the use of keto analogues, in stage 5 patients and we have verified its effectiveness, safety and clinical and economic effects(3). Method 129 patients were started on dietary therapy (middle age 75.2 ± 13.7, 60.5%male, all with hypertension, 40.3% with diabetes and 24.8% with heart disease) who were tested at the beginning of the observation, every 3 months and for 24 months, characterizing blood chemistry tests and body composition (with impedance analysis). Results During the 24-month observation period 91 patients (70.5%) were compliant with dietary therapy. Chronic kidney disease progression is slowed with average eGFR 11.6 ± 3.3 (compliant) vs. 9.3 ± 2.7 (no compliant) mL/min/1.73 m2, p &amp;lt; 0.001) Urea (mg/dL) 116.1 ± 31.7 (compliant) 174.2 ± 42.2 (no compliant) p &amp;lt; 0.002; and initiation of dialysis treatment (adjusted HR = 0.361, CI 0.200–0.650, p = 0.001) was delayed without evidence of malnutrition, in compliant versus noncompliant patients. Metabolic acidosis was well compensated in both groups with an improving trend in bicarbonate levels in compliant patients. Hemoglobin, uricemia, serum albumin, glycemia (downward trend NS), potassium, sodium, chlorium, calcium, magnesium, pH, lipids remained within normal values. Better blood pressure control was observed in compliant patients compared to non-compliant patients (SBP (mmHg) 136.9 ± 11.8 vs 150.1 ± 7 &amp;lt;0.01), DBP (mmHg) 75 ± 3.1 vs 79.4 ± 1 &amp;lt;0.001) During the observation, there were 24 deaths (13 patients older than 85 years), 20 peritoneal dialysis hospitalizations, 36 hemodialysis hospitalizations, 4 preventive living transplants and 15 renal functional recoveries with eGFR consistently &amp;gt;15 mL/min/ 1.73 m2. The months of dialysis avoided generated gross savings in terms of healthcare expenditure equal to EUR 3,076,470; the expenditure sustained by the Marche region for protein-free products (EUR 90 per patient per month) was EUR 158,358. As a result, the total net savings were EUR 2,918,112. Conclusion This non-interventional longitudinal observational study is part of standard clinical practice and suggests that VLPD supplemented with only essential amino acids is safe and effective and could be widely used to reduce the incidence of dialysis treatments, with a favorable economic impact on the National Health Service.

#2094 Very low protein integrated diet (sVLPD), without keto analogues, in patients with advanced chronic renal failure: clinical and economic benefits

Abstract Background and Aims The integrated very low protein diet (sVLPD) has proven effective in slowing the progression of stage 5 chronic renal failure and in postponing the start of dialysis treatment (1)SVLPD with keto analogues is difficult to implement due to the high number of tablets to be taken(2), therefore, to increase compliance we decided to prescribe, in compliance with the guidelines of normal clinical practice, SVLPD (0.3 g/prot/day) integrated with only essential amino acid drugs without the use of keto analogues, in stage 5 patients and we have verified its effectiveness, safety and clinical and economic effects(3). Method 129 patients were started on dietary therapy (middle age 75.2 ± 13.7, 60.5%male, all with hypertension, 40.3% with diabetes and 24.8% with heart disease) who were tested at the beginning of the observation, every 3 months and for 24 months, characterizing blood chemistry tests and body composition (with impedance analysis). Results During the 24-month observation period 91 patients (70.5%) were compliant with dietary therapy. Chronic kidney disease progression is slowed with average eGFR 11.6 ± 3.3 (compliant) vs. 9.3 ± 2.7 (no compliant) mL/min/1.73 m2, p &amp;lt; 0.001) Urea (mg/dL) 116.1 ± 31.7 (compliant) 174.2 ± 42.2 (no compliant) p &amp;lt; 0.002; and initiation of dialysis treatment (adjusted HR = 0.361, CI 0.200–0.650, p = 0.001) was delayed without evidence of malnutrition, in compliant versus noncompliant patients. Metabolic acidosis was well compensated in both groups with an improving trend in bicarbonate levels in compliant patients. Hemoglobin, uricemia, serum albumin, glycemia (downward trend NS), potassium, sodium, chlorium, calcium, magnesium, pH, lipids remained within normal values. Better blood pressure control was observed in compliant patients compared to non-compliant patients (SBP (mmHg) 136.9 ± 11.8 vs 150.1 ± 7 &amp;lt;0.01), DBP (mmHg) 75 ± 3.1 vs 79.4 ± 1 &amp;lt;0.001) During the observation, there were 24 deaths (13 patients older than 85 years), 20 peritoneal dialysis hospitalizations, 36 hemodialysis hospitalizations, 4 preventive living transplants and 15 renal functional recoveries with eGFR consistently &amp;gt;15 mL/min/ 1.73 m2. The months of dialysis avoided generated gross savings in terms of healthcare expenditure equal to EUR 3,076,470; the expenditure sustained by the Marche region for protein-free products (EUR 90 per patient per month) was EUR 158,358. As a result, the total net savings were EUR 2,918,112. Conclusion This non-interventional longitudinal observational study is part of standard clinical practice and suggests that VLPD supplemented with only essential amino acids is safe and effective and could be widely used to reduce the incidence of dialysis treatments, with a favorable economic impact on the National Health Service.

#1170 Efficacy and safety of telitacicept in IgA nephropathy: a real-world study

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and the specific therapeutic methods are limited in IgAN. Telitacicept is a humanized fusion protein composed of a transmembrane activator and calcium-modulating cyclophilin ligand interactor receptor and human IgG. This study was designed to evaluate the efficacy and safety of telitacicept in adult patients with IgAN in a real-world study. Method Biopsy-proven IgAN patients with 24-hour proteinuria greater than 0.5 g/day who received telitacicept 240 mg once a week were recruited in this study and 1:1 matched with patients who received supportive treatment only or immunosuppressive treatment by propensity score matching. The primary outcome was the change from baseline in 24-hour proteinuria over the 3-month follow-up. Results Twenty-one patients in each group were enrolled. The mean eGFR was 80.1 ml/min/1.73 m2, and the median 24-hour urine protein level was 1.48 g/day. At the end of the 3-month follow-up period, telitacicept reduced median proteinuria by 0.72 g/d (54.6%) from baseline, compared with a reduction of 0.18 g/d (20%) in the supportive treatment group (P &amp;lt; 0.001), and 1.12 g/d (72.1%) in the immunosuppressive treatment group (P = 0.814). Preserved eGFR levels were observed in the telitacicept group (1.9 ml/min/1.73 m2 [4.3%]), while the eGFR level declined in the supportive treatment group (- 2.9 ml/min/1.73 m2 [- 5.8%]) and immunosuppression group (- 6.1 ml/min/1.73 m2 [- 8.4%]). No serious adverse events were observed in the telitacicept treatment group. Injection site reactions were more prevalent in the telitacicept group (8/21 [38.1%]), meanwhile immunosuppression group had more respiratory tract infections (7/21, [33.3%]). Conclusion Telitacicept can reduce proteinuria in patients with IgAN and showed a favourable safety profile in patients with IgAN.

#1884 Slowing kidney disease with weight loss: a randomised controlled feasibility study (SLOW-CKD Feasibility Study)

Abstract Background and Aims Obesity is a modifiable risk factor for chronic kidney (CKD) and progression to kidney failure. Low energy diets (LEDs) (800 to 1000 kcal/day) are an established weight management strategy and have demonstrated the ability to facilitate 10 to 15 kg weight loss and induce diabetes remission. However, the use of LEDs in adults with CKD is limited and there have been no randomised controlled trials (RCT) exploring their use. Before initiating a definitive trial, there is first a need to assess feasibility and safety. The primary aim of this study was to test the feasibility, acceptability and safety of a low energy diet and weight management program in individuals with obesity and CKD. Method The SLOW-CKD Feasibility Study, a 6-month multi-centre RCT in kidney outpatient clinics in Brisbane Australia, targeted adults with stages 1-3 CKD and a body mass index (BMI) ≥ 30 kg m2 with proteinuria (urinary albumin to creatinine ratio &amp;gt;3 mg/mmol). Participants wererandomised (1:1). The LED group followed a 3-month LED (800-1000 kcal/day) with meal replacements and low-calorie foods, with fortnightly dietitian support. Following this, participants entered a 3-month weight maintenance phase,emphasising healthy eating and commencing a physical activity program guided by an exercise physiologist. The usual care group was offered weight loss support through the kidney clinic, involving referral to a dietitian or weight loss program if agreeable. Primary outcomes included safety (study related serious adverse events [SAEs] and adverse events [aEs]) and feasibility (recruitment rate, retention rate, target weight loss). Secondary outcomes explored changes in anthropometry and clinical measures, patient-reported outcomes, and participant experiences through semi-structured interviews. Pre-defined safety and feasibility outcome criteria are presented in Table 1. Results Overall, 49 participants consented to participate (mean age 52.4 ± 3.8 years, 57% male). The incidence of SAEs was low and comparable between the two groups. There were two SAEs in the LED group (hypoglycaemia and acute kidney injury both requiring hospital admission) and one in the control (hypoglycaemia requiring hospital admission). The most common AE was hyperkalaemia with three episodes (&amp;gt;6.0 mmol/L) in each group. Two of the three feasibility criteria were met deeming the intervention feasible—see Table 1. Mean weight loss for the initial 3-month study period was 10.6 kg ± 5.1 kg in the LED group and 0.7 kg ± 4.3 for the usual care group (p = &amp;lt;0.00). Conclusion Our findings provide important preliminary evidence that LEDs are relatively safe, feasible, and demonstrate promising efficacy as a treatment option for obesity in adults with CKD. A definitive RCT exploring the use of LEDs to improve clinical outcomes and slow progression of CKD is warranted.

App-Based Mental Training to Reduce Atrial Fibrillation-Related Symptoms After Pulmonary Vein Isolation: MENTAL AF Trial.

Even after atrial fibrillation (AF) catheter ablation, many patients still experience relevant symptom burden. The objective of the MENTAL AF trial was to determine whether app-based mental training (MT) during the 3 months following pulmonary vein isolation reduces AF-related symptoms. Patients scheduled for pulmonary vein isolation were enrolled and randomized 1:1 to either app-based MT or usual care. Of 174 patients, 76 in the MT and 75 in the usual care group were included in the final analysis. The intervention was delivered by a daily 10-minute app-based MT. The primary outcome was the intergroup difference of the mean AF6 sum score, an AF-specific questionnaire, during the 3-month study period. Secondary outcomes included quality-of-life measures such as the AFEQT (Atrial Fibrillation Effect on Quality of Life). Mean age (SD) was 61 (8.7) years and 61 (41%) were women. The mean AF6 sum score over the study period was 8.9 (6.9) points in the MT group and 12.5 (10.1) in the usual care group (P=0.011). This referred to a reduction in the AF6 sum score compared with baseline of 75% in MT and 52% for usual care (P<0.001). The change in the AFEQT Global Score was 22.6 (16.3) and 15.7 (22.1), respectively; P=0.026. MENTAL AF showed that app-based MT as an adjunctive treatment tool following pulmonary vein isolation was feasible. App-based MT was found to be superior to standard care in reducing AF-related symptom burden and improving health-related quality of life. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04067427.

Identifying and managing treatment resistance early with the integration of a clozapine clinic within an early intervention for psychosis service.

Despite being the most effective antipsychotic medication for treatment-resistant psychosis, clozapine is often under-utilized with long delays to initiation. This study aimed to determine whether the integration of a clozapine clinic within an early intervention for psychosis service resulted in a change in the rate and time to initiation of clozapine, the number of trials of different antipsychotic medications prior to clozapine, community initiation and discontinuation rates. A clozapine clinic was established in the Early Psychosis Prevention and Intervention Centre in Melbourne. This was a pre- and post-evaluation study design. The 'clozapine clinic' cohort included those who commenced on clozapine from 01 January 2016 to 30 June 2018. Prior to the clozapine clinic, 24 young people commenced clozapine over the 30-month period compared to 36 in the clozapine clinic cohort (RR = 1.30, 95% CI: 0.75-2.28, p = .32). In the pre-clozapine clinic cohort, 4.6% of all those with a first episode of psychosis were commenced on clozapine compared to 6% in the clozapine clinic cohort. Prior to the clozapine clinic, the median time to the commencement of clozapine was 72 weeks (IQR: 38, 87), compared to 53.5 weeks (IQR: 38, 81.5) in the clozapine clinic (Z = -0.86, p = .393). The mean number of different antipsychotic medications prior to commencing clozapine remained stable at 3.2 (SD ± 1.1) in both cohorts (t = -0.20, p = .841). There was a lower rate of discontinuation in the clozapine clinic (43.5% vs. 14.7%, HR = 0.30, 95% CI: 0.09-0.98, p = .046). While this study was underpowered and there are limitations to the naturalistic study design, the findings lend support to the integration of a clozapine clinic within early intervention for psychosis services.

In vivo evaluation of hyaluronic acid–polyethylene glycol amended PMMA bone cement for orthopaedic application

The utilization of polymethyl methacrylate (PMMA) bone cement is employed for the purpose of stabilizing fractured vertebral bodies. The existence of a mechanical imbalance in hard polymethylmethacrylate (PMMA) bone cement has the potential to increase the likelihood of a fracture occurring in the neighbouring vertebral body. In order to reduce potential difficulties, the primary goal of this study is to investigate the potential benefits of increasing PMMA bone cement’s bioactivity and lowering its elastic modulus. The incorporation of a 10% volume fraction of hyaluronic acid (HyA) and polyethylene glycol (PEG) into the bone cement led to an improvement in the bioactivity and decreasing of elastic modulus of polymethylmethacrylate (PMMA). The integration of HyPE gel phase presents several advantages over pure PMMA bone cement, including enhanced setting parameters, improved degradability, and increased biocompatibility. The gel phase is additionally accountable for a reduction in the elastic modulus of polymethylmethacrylate (PMMA) bone cement. In addition, the existence of a porous structure that arises from the degradation of the HyPE gel phase delivers a significant amount of room, thereby enhancing the process of bone regeneration when implanted in the femur of rabbits. The utilization of HyPE in PMMA has been shown through comprehensive µ-CT analysis to enhance bone formation, thereby promoting osteointegration at the implantation site. Furthermore, the histological analysis demonstrated the existence of osteogenic activity in the PMMA polyethylene glycol supplemented with 10% HyA and 10% PEG after a 2-month period subsequent to implantation.