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.

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.

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.

Real-world effectiveness of ribociclib in metastatic breast cancer patients: Does dose affect survival?

Introduction: Real-world data are critical to demonstrate the reproducibility of evidence and external generalizability of randomized clinical trials. The purpose of this study was to assess real-world security profile and management of adverse events (AEs) presented with ribociclib for the treatment of HR + /HER2- metastatic breast cancer (MBC). Our secondary objective was to provide real-world effectiveness of this treatment (measured with progression-free survival (PFS)) and to confirm the hypothesis that dose reductions are not related with disease progression. Material and methods: Observational retrospective study evaluating all females with MBC treated with ribociclib. Study period: January 2017 to September 2019. Follow-up was done until November 2021. Response was assessed through the PFS according to RECIST1.1 and National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) was used to classify AEs. Results: The most common AE was any grade neutropenia, documented in 37 of 53 patients (69.8%) during the course of treatment. By the end of the follow-up period, overall median PFS with ribociclib therapy was 27.3 months (95% confidence interval (CI) 20.8-71.8 months). In total, 50 patients (94.4%) initiated ribociclib at 600 mg dose, 28 patients (58%) required dose reductions. PFS of patients receiving ribociclib as first-line treatment was 28 (95% CI 15-41 months). Conclusions: Our results from patients treated in real-world clinical settings indicate that ribociclib is safe and their AEs are manageable with active monitoring, temporal suspension of treatment and dose reduction. Furthermore, our results indicate that dose reduction of ribociclib is not associated with a loss of efficacy.

Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays.

INTRODUCTION: Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. METHODS: In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aß42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aß42/p-tau ratio. RESULTS: All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aß42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94). DISCUSSION: Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD. HIGHLIGHTS: Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts.

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.

Convergent and discriminative validity of the Frail-VIG index with the EQ-5D-3L in people cared for in primary health care.

BACKGROUND: The Frail-VIG frailty index has been developed recently. It is an instrument with a multidimensional approach and a pragmatic purpose that allows rapid and efficient assessment of the degree of frailty in the context of clinical practice. Our aim was to investigate the convergent and discriminative validity of the Frail-VIG frailty index with regard to EQ-5D-3L value. METHODS: We carried out a cross-sectional study in two Primary Health Care (PHC) centres of the Catalan Institute of Health (Institut Català de la Salut), Barcelona (Spain) from February 2017 to January 2019. Participants in the study were all people included under a home care programme during the study period. No exclusion criteria were applied. We used the EQ-5D-3L to measure Health-Related Quality of Life (HRQoL) and the Frail-VIG index to measure frailty. Trained PHC 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 and multiple linear regression analyses. RESULTS: Four hundred and twelve participants were included in this study. Frail-VIG score and EQ-5D-3L value were negatively correlated (r = - 0.510; P < 0.001). Non-frail people reported a substantially better HRQoL than people with moderate and severe frailty. EQ-5D-3L value declined significantly as the Frail-VIG index score increased. CONCLUSIONS: Frail-VIG index demonstrated a convergent validity with the EQ-5D-3L value. Its discriminative validity was optimal, as their scores showed an excellent capacity to differentiate between people with better and worse HRQoL. These findings provide additional pieces of evidence for construct validity of the Frail-VIG index.

Health related quality of life utility weights for economic evaluation through different stages of chronic kidney disease: a systematic literature review.

BACKGROUND: A Task Force from the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) provides recommendations on how to systematically identify and appraise health state utility (HSU) weights for cost-effectiveness analyses. We applied these recommendations to conduct a systematic review (SR) to identify HSU weights for different stages of chronic kidney disease (CKD), renal replacement therapy (RRT) and complications. METHODS: MEDLINE® and Embase were searched for interventional and non-interventional studies reporting HSU weights for patients with CKD stages 1-5 or RRT. As per ISPOR Task Force Guidance, study quality criteria, applicability for Health Technology Assessment (HTA) and generalisability to a broad CKD population were used to grade studies as either 1 (recommended), 2 (to be considered if there are no data from grade 1 studies) or 3 (not recommended). RESULTS: A total of 17 grade 1 studies were included in this SR with 51 to 1767 participants, conducted in the UK, USA, Canada, China, Spain, and multiple-countries. Health related quality of life (HRQL) instruments used in the studies included were EQ-5D-3L (10 studies), SF-6D (4 studies), HUI2/HUI3 (1 study), and combinations (2 studies). Although absolute values for HSU weights varied among instruments, HSU weights decreased with CKD severity in a consistent manner across all instruments. CONCLUSIONS: This SR identified HSU weights for a range of CKD states and showed that HRQL decreases with CKD progression. Data were available to inform cost-effectiveness analysis in CKD in a number of geographies using instruments acceptable by HTA agencies.

Efficacy and safety of anticoagulation in non-malignant portal vein thrombosis in patients with liver cirrhosis.

BACKGROUND AND AIM: Treatment for portal vein thrombosis (PVT) is not well established. Nevertheless, anticoagulation therapy can seemingly be used as first-line therapy. However, there are limited data on the role of this treatment in patients with PVT and cirrhosis. We sought to assess the safety and efficacy of anticoagulation therapy in a series of patients with non-malignant PVT and liver cirrhosis. METHODS: We analyzed the data of 32 patients with cirrhosis and PVT between March 2009 and September 2015. All patients received anticoagulation treatment. PVT was diagnosed within the context of biannual hepatocellular carcinoma screening in these patients. RESULTS: Recanalisation was achieved in 23 patients: complete in 17 patients (53.1%) and partial in 6 patients (18.7%). The median time for achieving a complete response was 7 months (95% CI: 6-8). We did not discover any risk factors associated with repermeation (partial or complete). None of the patients presented with thrombosis progression while receiving anticoagulation. Nine patients who achieved complete recanalisation and stopped anticoagulation therapy suffered rethrombosis (52%). There were no differences between the patients who achieved complete or partial recanalisation (35%) and those who did not (33%) in relation to the onset of hepatic events during follow-up. Three patients (9%) presented with bleeding complications: two variceal bleeding episodes and one brain hemorrhage. CONCLUSIONS: In cirrhotic patients with non-malignant PVT, anticoagulation therapy led to partial or complete recanalisation in 70% of patients, with a broad safety profile. Due to the existing rethrombosis rate, long-term anticoagulation should be considered.

Eficiencia en la prescripción enfermera en Andalucía. Un paso atrás en el sistema sanitario tras anulación por Real Decreto.

OBJECTIVES: To analyse the efficiency of nurse prescription of the health products inherent to their care work, in Andalusia, Spain, between the years 2009-2015. To also analyse the discussions by the Medical Colleges Organisation and the Ministry of Health, Social Services and Equality, before the draft bill on nurse prescription and their outcome. DESIGN: Scoping review. DATA SOURCE: Main bibliographic databases of Latin-American, Spanish, and foreign languages were reviewed, including, Fundación Index, Doyma, and Medline Library. Google Scholar was also used with the same search terms, adding to limit the search the term "Andalusia": "prescription nurse" AND "efficiency" OR "Andalusia". Another search was conducted in the grey literature using the same criteria in the Andalusian Health Service (SAS) web site. It was complemented with an interview with the care director of the SAS. DATA EXTRACTION: A total of 617 articles were found, of which 20 were selected. In the grey literature, 52 documents were found, of which 4 were used. RESULTS: Few studies were found on the efficiency in nurse prescription in Andalusia, although they are as strong as the data provided by the Andalusian Health Care Directorate on the health products inherent in their profession. After modification of Royal Decree 954/2015, and under pressure from the Medical Colleges Organisation, it leaves the competence of prescription nurse exclusively to the medical indication, who diagnoses and prescribes and eliminates it without argument scientifically endorsed. CONCLUSIONS: We corroborate the incorporation of efficiency in the Health System through the nurse prescription, and the rupture with the Royal Decree 954/2015. The allegations of the Medical Colleges Organisation are without argument.

High efficacy and safety of triple therapy in HCV genotype 1 and moderate fibrosis: a multicenter study of clinical practice in Spain.

BACKGROUND AND RATIONAL: Telaprevir-based therapy (TBT) has been extensively evaluated in clinical trials. So we designed a study to compare the efficacy and safety of TBT between patients with moderate fibrosis and those suffering from advanced fibrosis in clinical practice. A multicenter observational and ambispective study was conducted. It included 582 patients with chronic hepatitis C genotype 1, 214 with fibrosis F2, and 368 with F3/F4 (F3: 148; F4: 220). RESULTS: The mean patient age was 55 years, 67% male. Type of prior response was 22% naïve, 57% relapsers, and 21% partial/null responders, 69% had high viral load (> 800,000 IU/mL). HCV genotypes were 1a (19%), 1b (69%), and 1 (12%), respectively. Sixty-five percent were non-CC IL28B genotype. Week-12 sustained virologic response (SVR12) was significantly higher among F2-naïve patients (78%) compared with F3/F4-naïve patients (60%; p = 0.039) and among F2 non-responders (67%) compared with F3/F4 non-responders (42%; p = 0.014). SVR12 among relapsers was remarkably high in both groups (F2:89% vs. F3/F4:78%). Severe anemia and thrombocytopenia were more frequent among patients with F3/F4 than those with F2 (p < 0.01). Overall, 132 patients (22%) discontinued treatment: 58 due to adverse effects, 42 due to the stopping-rule, and 32 due to breakthrough. Premature discontinuation was more frequent among patients with F3/F4 (p = 0.028), especially due to breakthrough (p < 0.001). CONCLUSIONS: This multicenter study demonstrates high efficacy and an acceptable safety profile with regard to TBT in F2-patients in clinical practice.

[Empowerment and power: their relationship in the proces of caring for the chronically ill in primary care]. / Empoderamiento y poder: su vinculación en el proceso de cuidar al enfermo crónico en atención primaria.

The concepts of "power" and "empowerment" are used in various disciplines, both political and social. Now are these terms frequently in the field of health. Our goal is to know its meaning as a synonym of expressions: "energy", "force", "domain", "vigour", "power", "capacity", "authority" and "control", which have been always within our practice nurse's own lexicon. Semantically analyzing them will help us in the understanding of its nuance. The literature review facilitates their understanding and allows us to link these words within the management of care. In this way we can propose diagnoses, interventions and outcomes specifically related to these concepts, which will help us optimize the efficiency in the management of care plans. The purpose of various collective nurses from different institutions is that the person is able to not generate dependencies and have the option of choosing your own lifestyle according to their culture and environment, independently or with the help. Generate knowledge is to generate power. The person should be educated and informed, to be expert and active and taking action to help control and minimize the progression of your health problem chronic and its possible complications. We are in the process of reformulation of the health system, whether it is private or public, and is necessary to know the power of the various actors involved in the management of the care to us. Each of these main actors--person ill, family/caregiver or nurse--has to know what is his role in this process.

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.

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.

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.

Projecting the economic burden of chronic kidney disease at the patient level (Inside CKD): a microsimulation modelling study.

Background: The growing burden of chronic kidney disease (CKD) places substantial financial pressures on patients, healthcare systems, and society. An understanding of the costs attributed to CKD and kidney replacement therapy (KRT) is essential for evidence-based policy making. Inside CKD maps and projects the economic burden of CKD across 31 countries/regions from 2022 to 2027. Methods: A microsimulation model was developed that generated virtual populations using national demographics, relevant literature, and renal registries for the 31 countries/regions included. Patient-level country/region-specific cost data were extracted via a pragmatic local literature review and under advisement from local experts. Direct cost projections were generated for diagnosed CKD (by age, stage 3a-5), KRT (by modality), cardiovascular complications (heart failure, myocardial infarction, stroke), and comorbidities (hypertension, type 2 diabetes). Findings: For the 31 countries/regions, Inside CKD projected that annual direct costs (US$) of diagnosed CKD and KRT would increase by 9.3% between 2022 and 2027, from $372.0 billion to $406.7 billion. Annual KRT-associated costs were projected to increase by 10.0% from $169.6 billion to $186.6 billion between 2022 and 2027. By 2027, patients receiving KRT are projected to constitute 5.3% of the diagnosed CKD population but contribute 45.9% of the total costs. Interpretation: The economic burden of CKD is projected to increase from 2022 to 2027. KRT contributes disproportionately to this burden. Earlier diagnosis and proactive management could slow disease progression, potentially alleviating the substantial costs associated with later CKD stages. Data presented here can be used to inform healthcare resource allocation and shape future policy. Funding: AstraZeneca.

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.