Clinical Outcomes in Patients with CKD and Rapid or Non-rapid eGFR Decline: A Report from the DISCOVER CKD Retrospective Cohort.

INTRODUCTION: This analysis examined the baseline characteristics and clinical outcomes of patients with chronic kidney disease (CKD) and rapid or non-rapid estimated glomerular filtration rate (eGFR) decline, using retrospective data from DISCOVER CKD (ClinicalTrials.gov, NCT04034992). METHODS: Data (2008-2020) were extracted from UK Clinical Practice Research Datalink, US TriNetX, US Limited Claims and Electronic Health Record Dataset, and Japan Medical Data Vision. Patients with CKD (two consecutive eGFR measures < 75 mL/min/1.73 m2 recorded 90-730 days apart) were included. Rapid eGFR decline was defined as an annual decline of > 4 mL/min/1.73 m2 at 2 years post-index; non-rapid eGFR decline was defined as an annual decline of ≤ 4 mL/min/1.73 m2. Clinical outcomes assessed included all-cause mortality, kidney outcomes (composite risk of kidney failure [progression to CKD stage 5] or > 50% eGFR decline, and kidney failure alone), cardiovascular events-including major adverse cardiovascular events (MACE; non-fatal myocardial infarction/stroke and cardiovascular death)-and all-cause hospitalization. RESULTS: Across databases, rapid eGFR decline occurred in 13.7% of 804,237 eligible patients. Mean annual eGFR decline ranged between - 6.21 and - 6.86 mL/min/1.73 m2 in patients with rapid eGFR decline versus between - 0.11 and - 0.77 mL/min/1.73 m2 in patients with non-rapid eGFR decline. Rapid eGFR decline was associated with increased comorbidity burden and medication prescriptions. Across databases, the composite risk of kidney failure or > 50% decline in eGFR was significantly greater in patients with rapid versus non-rapid eGFR decline (P < 0.01); all-cause mortality, kidney failure alone, MACE, and all-cause hospitalization each significantly increased in two databases (P < 0.01-0.05). CONCLUSION: Understanding patient factors associated with rapid eGFR decline in patients with CKD may help identify individuals who would benefit from proactive management to minimize the risk of adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04034992.

Incorporating gendered analysis and flexibility in heavy work investment studies: a systematic literature review.

Introduction: Significant impacts of heavy work investment on employee well-being and organizational performance have prompted its increasing importance as a research topic. The findings about good or evil of these repercussions are nonetheless inconclusive. The intersection of Heavy Work Investment construct with gender has not been explicitly addressed by previous literature review and research. Besides, the relevance of flexibility for women, as one of the key factors for successful work-family balance management, still remains to be analyzed. Methods: A literature review on Heavy Work Investment was conducted using the SPAR-4-SLR protocol, wherein 83 articles were selected from a pool of 208 previously identified works. Bibliometric and content analysis techniques were employed, including co-word analysis, to evaluate research production, impact, and trends in the gender perspective within Heavy Work Investment. Results: As a result, a strategic diagram illustrates thematic topics, providing a clear understanding of the field's structure and evolution. Six thematic groups were identified, around work-family conflict as the central theme. Discussion: The explicit consideration of a gender perspective in literature involves nuanced differences regarding the conclusions of studies with a broader focus. First, the emerging prominence of studies on China and Japan becomes clear with gender as the specific focus of the review, aiming to clarify the experiences women face in more traditional societies with a more decisive division of roles. Second, there is a shift in interest regarding the analysis of Job Demands and Job Resources. Despite the apparent decline in interest in the former, the focus in gender literature clearly shifts toward the side of Job Resources, showing potential for the future. It could be understood that in a context of talent war and employee retention efforts, priority is given to better understanding of facilitating individual and organizational factors for work-life balance, especially for women. Future research areas are identified, including gender differences in organizational support and the impact of flexible work on the work-life balance, providing valuable insights for academia, practitioners, and organizations. The need for more comprehensive cross-cultural and gender research is also made clear.

[Convergent and discriminative validity of the Frail-VIG index with the Pfeiffer test in people cared for in home care]. / Validez convergente y discriminativa del índice Frágil-VIG con el test de Pfeiffer en personas atendidas en atención domiciliaria.

INTRODUCTION: The Frail-VIG index-and the Pfeiffer test are measurements used in Primary Care for assessment frailty and the cognitive impairment screening. The Frail-VIG index is a multidimensional instrument that allows a rapid assessment of the degree of frailty in the context of clinical practice. OBJECTIVE: Our aim was to investigate the convergent and discriminative validity of the Frail-VIG index with regard to Pfeiffer test value. DESIGN: A cross-sectional study. SITE: Two urban Primary Health Care centres of the Catalan Institute of Health, Barcelona (Spain). PARTICIPANTS: All people included under a home care programme during the year 2018. No exclusion criteria were applied. MAIN MEASUREMENTS: We used the Frail-VIG index to measure frailty and the Pfeiffer test to cognitive impairment screening. Trained nurses administered both instruments during face-to-face assessments in a participant's home during usual care. The relationships between both instruments were examined using Pearson's correlation coefficient. RESULTS: A total of 412 participants were included. Frail-VIG score and Pfeiffer test value were moderately correlated (r=0.564; P<0.001). Non-frail people had a lower risk of developing cognitive impairment than moderate to severe frail people. The value of the Pfeiffer test increased significantly as the Frail-VIG index score also increased. CONCLUSIONS: Frail-VIG index demonstrated a convergent validity with the Pfeiffer test. Its discriminative validity was optimal, as their scores showed an excellent capacity to differentiate between people with a higher and lower risk of developing cognitive impairment. These findings provide additional pieces of evidence for construct validity of the Frail-VIG index.

The long-term effects of dapagliflozin in chronic kidney disease: a time-to-event analysis.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) presents a significant clinical and economic burden to healthcare systems worldwide, which increases considerably with progression towards kidney failure. The DAPA-CKD trial demonstrated that patients with or without type 2 diabetes (T2D) who were treated with dapagliflozin experienced slower progression of CKD versus placebo. Understanding the effect of long-term treatment with dapagliflozin on the timing of kidney failure beyond trial follow-up can assist informed decision-making by healthcare providers and patients. The study objective was therefore to extrapolate the outcome-based clinical benefits of treatment with dapagliflozin in patients with CKD via a time-to-event analysis using trial data. METHODS: Patient-level data from the DAPA-CKD trial were used to parameterise a closed cohort-level partitioned survival model that predicted time-to-event for key trial endpoints (kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure). Data were pooled with a subpopulation of the DECLARE-TIMI 58 trial to create a combined CKD population spanning a range of CKD stages; a parallel survival analysis was conducted in this population. RESULTS: In the DAPA-CKD and pooled CKD populations, treatment with dapagliflozin delayed time to first event for kidney failure, all-cause mortality, sustained decline in kidney function, and hospitalisation for heart failure. Attenuation of CKD progression was predicted to slow the time to kidney failure by 6.6 years (dapagliflozin: 25.2, 95%CI: 19.0-31.5; standard therapy: 18.5, 95%CI: 14.7-23.4) in the DAPA-CKD population. A similar result was observed in the pooled CKD population with an estimated delay of 6.3 years (dapagliflozin: 36.0, 95%CI: 31.9-38.3; standard therapy: 29.6, 95%CI: 25.5-34.7). CONCLUSION: Treatment with dapagliflozin over a lifetime time horizon may considerably delay the mean time to adverse clinical outcomes for patients who would go on to experience them, including those at modest risk of progression.

Discrepancies in Electronic Medical Prescriptions Found in a Hospital Emergency Department: A Prospective Observational Study.

The medication in an electronic prescribing system (EPS) does not always match the patient's actual medication. This prospective study analyzes the discrepancies (any inconsistency) between medication prescribed using an EPS and the medication revised by the clinical pharmacist upon admission to the observation area of the emergency department (ED). Adult patients with multimorbidity and/or polypharmacy were included. The pharmacist used multiple sources to obtain the revised medication list, including patient/carer interviews. A total of 1654 discrepancies were identified among 1131 patients. Of these patients, 64.5% had ≥1 discrepancy. The most common types of discrepancy were differences in posology (43.6%), commission (34.7%), and omission (20.9%). Analgesics (11.1%), psycholeptics (10.0%), and diuretics (8.9%) were the most affected. Furthermore, 52.5% of discrepancies affected medication that was high-alert for patients with chronic illnesses and 42.0% of medication involved withdrawal syndromes. Discrepancies increased with the number of drugs (ρ = 0.44, p < 0.01) and there was a difference between non-polypharmacy patients, polypharmacy ones and those with extreme polypharmacy (p < 0.01). Those aged over 75 years had a higher number of prescribed medications and discrepancies occurred more frequently compared with younger patients. The number of discrepancies was larger in women than in men. The EPS medication record requires verification from additional sources, including patient and/or carer interviews.

Dapagliflozin in chronic kidney disease: cost-effectiveness beyond the DAPA-CKD trial.

Background: The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial enrolled patients with estimated glomerular filtration rate 25-75 mL/min/1.73 m2 and urine albumin-to-creatinine ratio >200 mg/g. The Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial enrolled patients with type 2 diabetes, a higher range of kidney function and no albuminuria criterion. The study objective was to estimate the cost-effectiveness of dapagliflozin in a broad chronic kidney disease population based on these two trials in the UK, Spain, Italy and Japan. Methods: We adapted a published Markov model based on the DAPA-CKD trial but to a broader population, irrespective of urine albumin-to-creatinine ratio, using patient-level data from the DAPA-CKD and DECLARE-TIMI 58 trials. We sourced cost and utility inputs from literature and the DAPA-CKD trial. The analysis considered healthcare system perspectives over a lifetime horizon. Results: Treatment with dapagliflozin was predicted to attenuate disease progression and extend projected life expectancy by 0.64 years (12.5 versus 11.9 years, undiscounted) in the UK, with similar estimates in other settings. Clinical benefits translated to mean quality-adjusted life year (QALY; discounted) gains between 0.45 and 0.68 years across countries. Incremental cost-effectiveness ratios in the UK, Spain, Italy and Japan ($10 676/QALY, $14 479/QALY, $7771/QALY and $13 723/QALY, respectively) were cost-effective at country-specific willingness-to-pay thresholds. Subgroup analyses suggest dapagliflozin is cost-effective irrespective of urinary albumin-to-creatine ratio and type 2 diabetes status. Conclusion: Treatment with dapagliflozin may be cost-effective for patients across a wider spectrum of estimated glomerular filtration rates and albuminuria than previously demonstrated, with or without type 2 diabetes, in the UK, Spanish, Italian and Japanese healthcare systems.

Glucose-lowering treatment pathways of individuals with chronic kidney disease and type 2 diabetes according to the Kidney Disease: Improving Global Outcomes 2012 risk classification.

AIMS: To describe treatment pathways for key glucose-lowering therapies in individuals with chronic kidney disease (CKD) and type 2 diabetes (T2D) using retrospective data from DISCOVER CKD (NCT04034992). METHODS: Data were extracted from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics data (2008-2020) and the US integrated Limited Claims and Electronic Health Records Database (LCED; 2012-2019). Eligible individuals were aged ≥18 years with CKD, identified by two consecutive estimated glomerular filtration rate (eGFR) measures (15-<75 mL/min/1.73 m2 ; 90-730 days apart; index date was the second measurement) and T2D. Chronological treatment pathways for glucose-lowering therapies prescribed on or after CKD index to end of follow-up were computed. Median time and proportion of overall follow-up time on treatment were described for each therapy by database and by eGFR and urinary albumin-to-creatinine ratio (UACR) categories. RESULTS: Of 36,951 and 4339 eligible individuals in the CPRD and LCED, respectively, median baseline eGFR was 67.8 and 64.9 mL/min/1.73 m2 ; 64.2 and 63.9% received metformin prior to index; and median (interquartile range) time on metformin during follow-up was 917 (390-1671) and 454 (192-850) days (accounting for ~75% of follow-up time in both databases). The frequency of combination treatment increased over time. There were trends towards decreased metformin prescriptions with decreasing eGFR and increasing UACR within each eGFR category. CONCLUSIONS: Individuals with CKD and T2D had many combinations of therapies and substantial follow-up time on therapy. These results highlight opportunities for improved CKD management.

Medication delivery errors in outpatients with percutaneous endoscopic gastrostomy: effect on tube feeding replacement.

Patients with enteral access usually receive oral drugs via feeding tubes and correct drug administration remains a challenge. The aim of this study was to identify common medication delivery errors (MDEs) in outpatients with percutaneous endoscopic gastrostomy (PEG) and evaluate their association with the need for tube replacement due to deterioration or clogging. A 2-year retrospective study that comprised adult outpatients with a placed/replaced PEG tube and whose electronic medical record included home medication was carried out. Treatment with medication that should not be crushed and administered through an enteral feeding tube was considered an MDE. We included 269 patients and 213 MDEs (20% of oral prescriptions) were detected in 159. Ninety-two percent of the medications associated with MDEs could be substituted by appropriate formulations. Tube replacement due to obstruction was needed in 85 patients. MDEs were associated with increased risk for tube replacement (OR 2.17; 95% CI 1.10-4.27). Omeprazole enteric-coated capsules were associated with the greatest risk (OR 2.24; 95% CI 1.01-4.93). PEG outpatients are highly exposed to MDEs, leading to a significant increase in the odds of tube replacement, mainly when treated with omeprazole. The use of appropriate alternative therapies would prevent unnecessary adverse events.

Daytime-Restricted Feeding Ameliorates Oxidative Stress by Increasing NRF2 Transcriptional Factor in the Rat Hippocampus in the Pilocarpine-Induced Acute Seizure Model.

Seizure-mediated oxidative stress is a crucial mechanism in the pathophysiology of epilepsy. This study evaluated the antioxidant effects of daytime-restricted feeding (DRF) and the role of the Nrf2 signaling pathway in a lithium-pilocarpine model seizure model that induces status epilepticus (SE). We performed a lipoperoxidation assay and dihydroethidium fluorescence to measure oxidative stress markers in the hippocampus (malondialdehyde and reactive oxygen species). The protein content of Nrf2 and its downstream protein SOD2 was evaluated using Western blotting. The cellular distribution of the Nrf2 and SOD2 proteins in the pyramidal cell layer of both the CA1 and CA3 hippocampal subfields and astrocytes (GFAP marker) were quantified using immunofluorescence and immunohistochemistry, respectively. Our results indicate that DRF reduced the malondialdehyde levels and the production of reactive oxygen species. Furthermore, a significant increase in Nrf2 and SOD2 protein content was observed in animals subjected to restrictive diet. In addition, DRF increased the relative intensity of the Nrf2 fluorescence in the perinuclear and nuclear compartments of pyramidal neurons in the CA1 subfield. Nrf2 immunoreactivity and the astrocyte marker GFAP also increased their colocalization under DRF conditions. Additionally, SOD2 immunoreactivity was increased in CA1 pyramidal neurons but not in the CA3 region. Our findings suggest that DRF partially prevents oxidative stress by increasing the Nrf2 transcriptional factor and the SOD2 enzyme during the development of SE.

Translating the efficacy of dapagliflozin in chronic kidney disease to lower healthcare resource utilization and costs: a medical care cost offset analysis.

AIMS: Dapagliflozin was approved for use in patients with chronic kidney disease (CKD) based on results of the DAPA-CKD trial, demonstrating attenuation of CKD progression and reduced risk of cardio-renal outcomes and all-cause mortality (ACM) versus placebo, in addition to standard therapy. The study objective was to assess the potential medical care cost offsets associated with reduced rates of cardio-renal outcomes across 31 countries and regions. MATERIALS AND METHODS: A comparative cost-determination framework estimated outcome-related costs of dapagliflozin plus standard therapy versus standard therapy alone over a 3-year horizon based on the DAPA-CKD trial. Incidence rates of end-stage kidney disease (ESKD), hospitalizations for heart failure (HHF), acute kidney injury (AKI), and ACM were estimated for a treated population of 100,000 patients. Associated medical care costs for non-fatal events were calculated using sources from a review of publicly available data specific to each considered setting. RESULTS: Patients treated with dapagliflozin plus standard therapy experienced fewer incidents of ESKD (7,221 vs 10,767; number needed to treat, NNT: 28), HHF (2,370 vs 4,684; NNT: 43), AKI (4,110 vs. 5,819; NNT: 58), and ACM (6,383 vs 8,874; NNT: 40) per 100,000 treated patients versus those treated with standard therapy alone. Across 31 countries/regions, reductions in clinical events were associated with a 33% reduction in total costs, or a cumulative mean medical care cost offset of $264 million per 100,000 patients over 3 years. LIMITATIONS AND CONCLUSIONS: This analysis is limited by the quality of country/region-specific data available for medical care event costs. Based on the DAPA-CKD trial, we show that treatment with dapagliflozin may prevent cardio-renal event incidence at the population level, which could have positive effects upon healthcare service delivery worldwide. The analysis was restricted to outcome-associated costs and did not consider the cost of drug treatments and disease management.

Chronic kidney disease (CKD) has a high clinical, economic, and societal burden and it affects approximately 8-16% of the global population. The progressive nature of CKD may lead to complications, co-morbidities, and mortality, costing healthcare systems millions and consuming a large proportion of healthcare resources. Dapagliflozin, a sodium-glucose co-transporter-2 inhibitor, has been demonstrated to slow CKD progression and reduce cardio-renal complications, as demonstrated in the DAPA-CKD trial. With the emergence of dapagliflozin as a treatment for CKD, it is important for clinicians and healthcare providers to understand how effective treatment can positively affect short-term healthcare service delivery and associated costs. This medical care cost offset modelling analysis considers a scalable population of 100,000 patients in 31 countries/regions worldwide. The analysis estimates treatment with dapagliflozin plus standard therapy to be offset by a 33% reduction in costs associated with key cardio-renal outcomes, translating to an average $264 million in cost offsets per 100,000 treated patients. This modelling analysis of pivotal trial data shows dapagliflozin could have considerable benefits to healthcare systems worldwide that are under strain from the rising burden of CKD.

Research on missed nursing care during the COVID-19 pandemic: A scoping review.

BACKGROUND: Missed nursing care is defined as care that is delayed, partially completed, or not completed at all. The scenario created by the COVID-19 pandemic may have influenced multifactorial determinants related to the care environment, nursing processes, internal processes, and decision-making processes, increasing missed nursing care. AIM: This scoping review aimed to establish the quantity and type of research undertaken on missed nursing care during the COVID-19 pandemic. METHODS: This review was conducted following the Joanna Briggs Institute methodology for scoping reviews. We searched CINAHL, MEDLINE, Scopus, two national and regional databases, two dissertations and theses databases, a gray literature database, two study registers, and a search engine from November 1, 2019, to March 23, 2023. We included quantitative, qualitative, and mixed studies carried out in all healthcare settings that examined missed nursing care during the COVID-19 pandemic. Language restrictions were not applied. Two independent reviewers conducted study selection and data extraction. Disagreements between the reviewers were resolved through discussion or with an additional reviewer. RESULTS: We included 25 studies with different designs, the most common being acute care cross-sectional survey designs. Studies focused on determining the frequency and reasons for missed nursing care and its influence on nurses and organizational outcomes. LINKING EVIDENCE TO ACTION: Missed nursing care studies during the COVID-19 pandemic were essentially nurses-based prevalence surveys. There is an urgent need to advance the design and development of longitudinal and intervention studies, as well as to broaden the focus of research beyond acute care. Further research is needed to determine the impact of missed nursing care on nursing-sensitive outcomes and from the patient's perspective.

Global Economic Burden Associated with Chronic Kidney Disease: A Pragmatic Review of Medical Costs for the Inside CKD Research Programme.

INTRODUCTION: Chronic kidney disease (CKD) is a progressive disease of growing prevalence, posing serious concerns for global public health. While the economic burden of CKD is substantial, data on the cost of CKD is limited, despite growing pressures on healthcare systems. In this review, we summarise the available evidence in 31 countries and regions and compile a library of costing methodology and estimates of CKD management and disease-associated complications across 31 countries/regions within the Inside CKD programme. METHODS: We collected country/region-specific CKD costs via a pragmatic rapid literature review of local literature and engagement with local experts. We extracted cost data and definitions from identified sources for CKD stages G3a-5, kidney failure with replacement therapy by modality, covering haemodialysis, peritoneal dialysis, and kidney transplants, and disease-associated complications in local currency, converted to United States dollars (USD) and inflated to 2022. RESULTS: Annual direct costs associated with CKD management rose by an average factor of 4 in each country/region upon progression from stage G3a to G5. Mean annual costs per patient increased considerably more from early stages versus dialysis (stage G3a, mean: $3060 versus haemodialysis, mean: $57,334; peritoneal dialysis, mean: $49,490); with estimates for annual costs of transplant also substantially higher (incident: $75,326; subsequent: $16,672). The mean annual per patient costs of complications were $18,294 for myocardial infarction, $8463 for heart failure, $10,168 for stroke and $5975 for acute kidney injury. Costing definitions varied widely in granularity and/or definition across all countries/regions. CONCLUSION: Globally, CKD carries a significant economic burden, which increases substantially with increasing disease severity. We identified significant gaps in published costs and inconsistent costing definitions. Cost-effective interventions that target primary prevention and disease progression are essential to reduce CKD burden. Our results can be used to guide cost collection and facilitate better comparisons across countries/regions to inform healthcare policy.

Budget Impact Analysis of Expanding Gliflozin Coverage in the CKD Population: A French Perspective.

INTRODUCTION: Gliflozins have historically been indicated for type 2 diabetes in France. However, their efficacy has recently been demonstrated in heart failure and chronic kidney disease (CKD), with positive recommendations by Haute Autorité de Santé for gliflozin therapies in these indications. The study objective was to investigate the 5-year budget impact associated with the introduction of gliflozins in addition to standard therapy in people with CKD and elevated albuminuria, regardless of diabetes status, from the perspective of the French healthcare system. METHODS: A budget impact model was developed to estimate the 5-year implications of incorporating gliflozins in the treatment of patients with CKD in France, using efficacy data from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial. Direct medical costs associated with drug acquisition and management, treatment-related adverse events, dialysis and kidney transplantation, and adverse clinical outcomes were considered. Market share forecasts were estimated from historical data and expert opinions. Event rates were derived from trial data, while cost data were sourced from published estimates. RESULTS: The introduction of gliflozins was estimated to be cost saving compared to the no gliflozins scenario, with an expected cumulative 5-year budget impact of -€650 million, driven by slowed disease progression in patients treated with gliflozins, with fewer patients cumulatively progressing to end-stage kidney disease (84,526 vs. 92,062). This, in addition to fewer hospitalisations for heart failure and deaths from any cause, led to substantial medical care cost offsets (kidney-related: - €894 million; hospitalisation for heart failure: - €14.3 million; end-of-life care: - €17.3 million) to the additional drug acquisition (€273 million) and treatment-related adverse events costs (€2.98 million). CONCLUSION: In concert with early diagnosis and proactive management of CKD, the expansion of the gliflozin indications into the French CKD population presents the opportunity to reduce the substantial burden associated with cardio-renal complications which outweighs the additional cost of the new treatment. INFOGRAPHIC.

Normal Pressure Hydrocephalus Following Cranial Radiation: Identification of Shunting Responders.

BACKGROUND: We examined cognitive, brain MRI, and lumbar infusion test (LIT) features to identify predictors of response to ventriculoperitoneal shunting (VPS) in long-term cancer survivors with suspected normal pressure hydrocephalus (NPH) following cranial radiotherapy (RT). METHODS: Patients who completed cranial RT at least 2 years before with clinically suspected NPH and an Evans' index (EI) ≥ 0.30 underwent a cognitive and a cerebrospinal fluid (CSF) volumetric (MRI) analysis (n = 36). For those in whom VPS was placed (n = 14), we explored whether adding a CSF volumetric analysis to classical MRI and LIT (Tap Test) features would better identify VPS responders. RESULTS: Nearly 80% exhibited cognitive impairment. The CSF volume at NPH diagnoses was significantly larger in the group of VPS responders (p = 0.04). The addition of CSF volume to NPH diagnoses increased accuracy to 93%, with a positive and negative predictive value of 91% and 100%, respectively. CONCLUSION: The addition of a quantitative MRI analysis of CSF volume to classical MRI and LIT NPH criteria, along with a high clinical suspicion of NPH, may help to identify VPS responders, thus improving the clinical management and prognosis of long-term survivors.

NEURONORMA Cognitive Battery Associations with Cerebrospinal Fluid Amyloid-ß and Tau Levels in the Continuum of Alzheimer's Disease.

BACKGROUND: Neuropsychological assessments are essential to define the cognitive profile and contribute to the diagnosis of Alzheimer's disease (AD). The progress in knowledge about the pathophysiological process of the disease has allowed conceptualizing AD through biomarkers as a biological continuum that encompasses different clinical stages. OBJECTIVE: To explore the association between cerebrospinal fluid (CSF) biomarkers of AD and cognition using the NEURONORMA battery, in a sample of cognitively unimpaired (CU), mild cognitive impaired (MCI), and mild dementia of the Alzheimer type (DAT) subjects, and to characterize the cognitive profiles in MCI subjects classified by A/T/N system. METHODS: 42 CU, 35 MCI, and 35 mild DAT were assessed using the NEURONORMA battery. Core AD biomarkers [amyloid-ß42 (Aß42) peptide, total tau (t-tau), and phosphorylated tau 181 (p-tau181)] proteins were measured in CSF. Correlation coefficients, multivariate regression, and effect sizes were calculated. We explored the age- and education-adjusted cognitive profiles by A/T/N variants within the MCI group. RESULTS: Cognitive outcomes were directly associated with CSF Aß42 and inversely with CSF tau measures. We found differences in both biomarkers and cognitive outcomes comparing all pairs except for CSF measures between cognitively impaired groups. The highest effect size was in memory tasks and biomarkers ratios. Lower performances were in memory and executive domains in MCI subjects with AD pathology (A+T+N±) compared to those with normal levels of AD biomarkers (A- T- N). CONCLUSION: This study provides further evidence of the validity of Spanish NEURONORMA cognitive battery to characterize cognitive impairment in the AD pathological continuum.

Health Care Resource Utilization and Related Costs of Patients With CKD From the United States: A Report From the DISCOVER CKD Retrospective Cohort.

Introduction: It is well established that chronic kidney disease (CKD) results in a significant burden on patients' health and health care providers. However, detailed estimates of the health care resource utilization (HCRU) of CKD are limited, particularly those which consider severity, comorbidities, and payer type. This study aimed to bridge this evidence gap by reporting contemporary HCRU and costs in patients with CKD across the US health care providers. Methods: Cost and HCRU estimates of CKD and reduced kidney function without CKD (estimated glomerular filtration rate [eGFR]: 60-75 and urine albumin-to-creatinine ratio [UACR]: <30) were derived for US patients included in the DISCOVER CKD cohort study, using linked inpatient and outpatient data from the limited claims-EMR data set (LCED) and TriNetX database. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using UACR and eGFR. Results: Overall health care costs ranged from $26,889 (A1) to $42,139 (A3), and from $28,627 (G2) to $42,902 (G5) per patient per year (PPPY), demonstrating a considerable early disease burden which continued to increase with declining kidney function. The PPPY costs of later stage CKD were particularly notable for patients with concomitant heart failure ($50,191 [A3]) and those covered by commercial payers ($55,735 [A3]). Conclusions: Health care costs and resource use associated with CKD and reduced kidney function pose a substantial burden across health care systems and payers, increasing in line with CKD progression. Early CKD screening, particularly of UACR, paired with proactive disease management may provide both an improvement to patient outcomes and a significant HCRU and cost saving to health care providers.

The Role of Expert Opinion in Projecting Long-Term Survival Outcomes Beyond the Horizon of a Clinical Trial.

INTRODUCTION: Clinical trials often have short follow-ups, and long-term outcomes such as survival must be extrapolated. Current extrapolation methods often produce a wide range of survival values. To minimize uncertainty in projections, we developed a novel method that incorporates formally elicited expert opinion in a Bayesian analysis and used it to extrapolate survival in the placebo arm of DAPA-CKD, a phase 3 trial of dapagliflozin in patients with chronic kidney disease (NCT03036150). METHODS: A summary of mortality data from 13 studies that included DAPA-CKD-like populations and training on elicitation were provided to six experts. An elicitation survey was used to gather the experts' 10- and 20-year survival estimates for patients in the placebo arm of DAPA-CKD. These estimates were combined with DAPA-CKD mortality and general population mortality (GPM) data in a Bayesian analysis to extrapolate long-term survival using seven parametric distributions. Results were compared with those from standard frequentist approaches (with and without GPM data) that do not incorporate expert opinion. RESULTS: The group expert-elicited estimate for 20-year survival was 31% (lower estimate, 10%; upper estimate, 40%). In the Bayesian analysis, the 20-year extrapolated survival across the seven distributions was 14.9-39.1%, a range that was 2.4- and 1.6-fold smaller than those produced by the frequentist methods (0.0-56.9% without and 0.0-39.2% with GPM data). CONCLUSIONS: Using expert opinion in a Bayesian analysis provided a robust method for extrapolating long-term survival in the placebo arm of DAPA-CKD. The method could be applied to other populations with limited survival data.

Ten-year experience of bone SBRT in breast cancer: analysis of predictive factors of effectiveness.

PURPOSE: Data on the benefit of stereotactic body radiation therapy (SBRT) in patients with breast cancer (BC) and bone metastases remain limited. The purpose of this study is to report our 10-year experience of bone SBRT, analyzing toxicity and prognostic factors for local control (LC); progression-free survival, and overall survival (OS). METHODS/PATIENTS: We analyzed all spine and non-spine bone SBRT performed in patients with BC during the 2012-2022 period at our institution. Treatments carried out with ablative intent in stereotactic conditions with dose/fraction ≥ 5 Gy in 5 or fewer sessions were considered. Demographic, treatment, and toxicity data were recorded according to CTCAEv4. Risk factors were assessed through univariate and multivariate analysis by Cox regression. RESULTS: 60 bone SBRT treatments were performed during the study period. 75% were spine SBRT and 25% were non-spine SBRT (median BED4Gy was 80 Gy4). The median age was 52.5 years (34-79). The median tumor volume was 2.9 cm3 (0.5-39.4). The median follow-up was 32.4 months (1.2-101.7). 1 and 2 years LC were 92.9 and 86.6%, respectively. 1 and 2 years OS were 100 and 90.6%, respectively. Multivariate analysis (MVA) associated volume of the treated lesion ≥ 13 cm3 with worse LC (p = 0.046; HR 12.1, 95%CI = 1.1-140.3). In addition, deferring SBRT > 3 months after lesion diagnosis to prioritize systemic treatment showed a significant benefit, improving the 2 years LC up to 96.8% vs. 67.5% for SBRT performed before this period (p = 0.031; HR 0.1, 95%CI = 0.01-0.8). Hormonal receptors, the total number of metastases, and CA15-3 value were significantly associated with OS in MVA. During follow-up, three non-spine fractures (5%) were observed. CONCLUSIONS: According to our data, bone SBRT is a safe and effective technique for BC. Upfront systemic treatment before SBRT offers a benefit in LC. Therefore, SBRT should be considered after prior systemic treatment in this population.

Extrapolated longer-term effects of the DAPA-CKD trial: a modelling analysis.

BACKGROUND: The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial assessed dapagliflozin versus placebo, in addition to standard therapy, in patients with chronic kidney disease (CKD) and albuminuria, and was terminated prematurely due to overwhelming efficacy. The study objective was to model the long-term clinical outcomes of DAPA-CKD beyond the trial follow-up. METHODS: A Markov model extrapolated event incidence per 1000 patients and CKD progression rates for patients receiving dapagliflozin or placebo over a 10-year time horizon. We derived treatment-specific CKD stage transition matrices using DAPA-CKD trial data. We extrapolated relevant efficacy endpoints using parametric survival equations for all-cause mortality and generalized estimating equations for recurrent events. RESULTS: When extrapolated over a 10-year period, patients randomized to dapagliflozin spent more time in CKD stages 1-3 and less in stages 4-5 than placebo [0.65 (95% CrI 0.41, 0.90) and -0.23 (95% CrI -0.45, 0.00) years per patient, respectively]. Dapagliflozin prevented an estimated 83 deaths and 51 patients initiating kidney replacement therapy per 1000 patients over 10 years. Predicted rates of hospitalized heart failure and abrupt declines in kidney function were reduced (19 and 39 estimated events per 1000 patients, respectively). CONCLUSIONS: Adding dapagliflozin to standard therapeutic management of CKD is expected to have long-term cardiorenal benefit beyond what has been demonstrated in the DAPA-CKD trial, with patients predicted to live longer with fewer complications.