Outcomes for clinical trials involving adults with chronic kidney disease: a multinational Delphi survey involving patients, caregivers and health professionals.

BACKGROUND: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in chronic kidney disease (CKD), which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices. METHODS: This was an online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals who could read English, Spanish or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a Best-Worst Scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically. RESULTS: In total, 1399 participants from 73 countries completed Round 1 of the Delphi survey, including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization and cardiovascular disease (mean difference >0.3). Consensus was based upon the two groups yielding median scores of ≥7 and mean scores >7, and the proportions of both groups rating the outcome as 'critically important' being >50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences. CONCLUSION: Across trials in CKD, the outcomes of highest priority to patients, caregivers and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease and death.

The humanistic burden of immunoglobulin A nephropathy on patients and care-partners in the United States.

PURPOSE: This cross-sectional survey study quantified the humanistic burden of immunoglobulin A nephropathy (IgAN), in terms of physical and mental health-related quality of life (HRQoL) and work productivity, among adults with primary IgAN and their care-partners. METHODS: HRQoL was assessed (01/31/22 - 05/31/23) with validated tools including the KDQoL-36 (with SF-12), GAD-7 (anxiety), PHQ-9 (depression), and WPAI: SHP (work productivity). Participant characteristics and total/domain scores were summarized; selected outcomes were compared to an external, kidney disease-free cohort. RESULTS: 117 adults with IgAN and their care-partner pairs, and one adult without a care-partner, were included. The mean ages of patients and care-partners were 38.0 (SD: 8.6) and 40.2 (11.8) years, respectively; 55.9% and 43.6% were female. Mean physical and mental SF-12 scores for patients were 46.7 (SD: 8.0) and 41.9 (9.2), respectively, and 50.7 (7.3) and 43.7 (10.24) for care-partners. Both SF-12 components for patients, and the mental component for care-givers, were significantly worse compared to the US general population. Among patients, 27.1% had moderate/severe anxiety and 49.2% reported at least moderate depression. Compared to external controls, patients experienced significantly higher severity of anxiety (6.6 vs. 5.4) and depression (8.1 vs. 6.6; both p < 0.0001). Among care-partners, 13.7% experienced moderate anxiety and 37.8% experienced moderate/moderately-severe depression. Among employed individuals, both groups reported IgAN-related absenteeism (8.8-9.4%), presenteeism (25.1-25.9%), and overall work impairment (30.4-30.5%). CONCLUSION: US adults with IgAN and their care partners experience impairments to mental and physical HRQoL and heightened levels of depression and anxiety, underscoring the need for effective IgAN therapies and care-partner support.

The European Kidney Health Alliance (EKHA) and the Decade of the KidneyTM.

The European Kidney Health Alliance (EKHA) is an advocacy organization that defends the case of the kidney patients and the nephrological community at the level of the European Union (EU), and from there, top to bottom, also at the national level of the EU member states and the EU-associated countries. The Decade of the KidneyTM is a global initiative launched by the American Association of Kidney Patients (AAKP) to create greater awareness and organize patient demands for long overdue innovation in kidney care. This article describes the medical and patient burden of kidney disease, the history of EKHA, its major activities and tools for policy action, and the need for innovation of kidney care. We then describe the Decade of the KidneyTM initiative, the rationale behind why EKHA joined this activity to emanate parallel action at the European side, the novel professionalized structure of EKHA, and its immediate targets. The final aim is to align all major stakeholders for an action plan on kidney disease comparable to Europe's successful Beating Cancer Plan, with the additional intent that the EKHA model is applied also by the respective national kidney-related societies to create a broad mobilization at all levels. The ultimate aims are that the EU considers chronic kidney disease (CKD) as a major health and health-economic problem, to consequently have CKD included as a key health research target by the European Commission, and to improve quality of life and outcomes for all kidney patients.

Lessons learned during the war in Ukraine: a report from the Renal Disaster Relief Task Force of the ERA.

People living with kidney disease are among the most vulnerable at times of natural or man-made disasters. In addition to their unpredictable course, armed conflicts impose a major threat given the disruption of infrastructure, sanitation and access to food, water and medical care. The ongoing war in Ukraine has once more demonstrated the importance of preparedness, organization, coordination and solidarity during disasters. People living with kidney disease face serious challenges given their dependence on life-sustaining treatment, irrespective of whether they remain in the war zone or are displaced internally or externally. This especially affects those requiring kidney replacement therapy, dialysis or transplantation, but also patients with other kidney diseases and the medical staff who care for them. Soon after the war started, the European Renal Association assigned a Renal Disaster Relief Task Force dedicated to support the people living with kidney disease and the nephrology community in Ukraine. This report summarizes the major challenges faced, actions taken and lessons learned by this task force. We anticipate that the experience will help to increase preparedness and mitigate the devastating effects of armed conflicts on the kidney community in the future and propose to establish an international collaboration to extend this effort to other parts of the world facing similar challenges.

Distribution, preparedness and management of Ukrainian adult refugees on dialysis-an international survey by the Renal Disaster Relief Task Force of the European Renal Association.

BACKGROUND: Due to the Russian-Ukrainian war, some of the about 10 000 adults requiring dialysis in Ukraine fled their country to continue dialysis abroad. To better understand the needs of conflict-affected dialysis patients, the Renal Disaster Relief Task Force of the European Renal Association conducted a survey on distribution, preparedness and management of adults requiring dialysis who were displaced due to the war. METHODS: A cross-sectional online survey was sent via National Nephrology Societies across Europe and disseminated to their dialysis centers. Fresenius Medical Care shared a set of aggregated data. RESULTS: Data were received on 602 patients dialyzed in 24 countries. Most patients were dialyzed in Poland (45.0%), followed by Slovakia (18.1%), Czech Republic (7.8%) and Romania (6.3%). The interval between last dialysis and the first in the reporting center was 3.1 ± 1.6 days, but was ≥4 days in 28.1% of patients. Mean age was 48.1 ± 13.4 years, 43.5% were females. Medical records were carried by 63.9% of patients, 63.3% carried a list of medications, 60.4% carried the medications themselves and 44.0% carried their dialysis prescription, with 26.1% carrying all of these items and 16.1% carrying none. Upon presentation outside Ukraine, 33.9% of patients needed hospitalization. Dialysis therapy was not continued in the reporting center by 28.2% of patients until the end of the observation period. CONCLUSIONS: We received information about approximately 6% of Ukrainian dialysis patients, who had fled their country by the end of August 2022. A substantial proportion were temporarily underdialyzed, carried incomplete medical information and needed hospitalization. The results of our survey may help to inform policies and targeted interventions to respond to the special needs of this vulnerable population during wars and other disasters in the future.

The European Green Deal and nephrology: a call for action by the European Kidney Health Alliance.

The world faces a dramatic man-made ecologic disaster and healthcare is a crucial part of this problem. Compared with other therapeutic areas, nephrology care, and especially dialysis, creates an excessive burden via water consumption, greenhouse gas emission and waste production. In this advocacy article from the European Kidney Health Alliance we describe the mutual impact of climate change on kidney health and kidney care on ecology. We propose an array of measures as potential solutions related to the prevention of kidney disease, kidney transplantation and green dialysis. For dialysis, several proactive suggestions are made, especially by lowering water consumption, implementing energy-neutral policies, waste triage and recycling of materials. These include original proposals such as dialysate regeneration, dialysate flow reduction, water distillation systems for dialysate production, heat pumps for unit climatization, heat exchangers for dialysate warming, biodegradable and bio-based polymers, alternative power sources, repurposing of plastic waste (e.g. incorporation in concrete), registration systems of ecologic burden and platforms to exchange ecologic best practices. We also discuss how the European Green Deal offers real potential for supporting and galvanizing these urgent environmental changes. Finally, we formulate recommendations to professionals, manufacturers, providers and policymakers on how this correction can be achieved.

Armed conflicts and kidney patients: a consensus statement from the Renal Disaster Relief Task Force of the ERA.

During conflicts, people with kidney disease, either those remaining in the affected zones or those who are displaced, may be exposed to additional threats because of medical and logistical challenges. Acute kidney injury developing on the battlefield, in field hospitals or in higher-level hospital settings is characterized by poor outcomes. People with chronic kidney disease may experience treatment interruptions, contributing to worsening kidney function. Patients living on dialysis or with a functioning graft may experience limitations of dialysis possibilities or availability of immunosuppressive medications, increasing the risk of severe complications including death. When patients must flee, these threats are compounded by unhealthy and insecure conditions both during displacement and/or at their destination. Measures to attenuate these risks may only be partially effective. Local preparedness for overall and medical/kidney-related disaster response is essential. Due to limitations in supply, adjustments in dialysis frequency or dose, switching between hemodialysis and peritoneal dialysis and changes in immunosuppressive regimens may be required. Telemedicine (if possible) may be useful to support inexperienced local physicians in managing medical and logistical challenges. Limited treatment possibilities during warfare may necessitate referral of patients to distant higher-level hospitals, once urgent care has been initiated. Preparation for disasters should occur ahead of time. Inclusion of disaster nephrology in medical and nursing curricula and training of patients, families and others on self-care and medical practice in austere settings may enhance awareness and preparedness, support best practices adapted to the demanding circumstances and prepare non-professionals to lend support.

Hot Air Balloon Fatalities in New Mexico: The Forensic Pathology Experience.

INTRODUCTION: Albuquerque New Mexico is the "hot air balloon capital of the world," with balloons flying throughout the year and during the Albuquerque International Balloon Fiesta. The medical literature regarding morbidity and mortality in hot air balloon accidents is relatively scarce. METHODS: A series of fatal, hot air balloon accidents were identified by querying and analyzing the databases of the Office of the Medical Investigator in New Mexico from 1972 to 2021. RESULTS: Twenty-one lethal cases from 11 hot air balloon accidents were evaluated. Fifty-seven percent of decedents were male, the age range was 29 to 74 years, and all the decedents were White. Causes of death were certified as multiple injuries (52.4%), blunt trauma (42.9%), and electrocution (4.76%). The manner of death was accidental in all cases. Most common autopsy findings were rib fractures (100%), pelvic fractures (81.8%), and subarachnoid hemorrhage (72.7%). October was the month with the most accidents (63.63%), the most common cause was the pilot's failure to maintain clearance from obstacles (14.3%), and the most frequent collision was with power lines (63.6%). CONCLUSIONS: Hot air balloon fatalities are rare, and the patterns of injury resemble those seen in free falls from significant heights with extensive blunt trauma.

High current short pulse driver using a high power diode laser for optoacoustic biomedical imaging techniques.

Optoacoustic biomedical imaging combines the high spatial resolution of the ultrasound imaging with the specificity of the optical absorption spectroscopy techniques. It is being used in various scenarios such as anatomical, functional and molecular imaging. Typically light sources for this imaging technique is based on solid state lasers since they can produce high energy short optical pulses. However, they are bulky, expensive and the imaging speed is limited because their low pulse repetition rate. High power diode lasers (HPDLs) are a promising alternative for imaging small volume absorbers as they are compact, affordable and allow high repetition rates. However, HPDLs provide relative low peak optical power compared to solid state lasers. Therefore, imaging systems based on diode lasers require much longer pulse duration resulting in lower in-depth resolution and optoacoustic conversion efficiency. HPDLs need dedicated fast electronics to generate short optical pulses. In this work, we have designed, built and test a pulsed diode laser driver based on RF power MOSFETs, specifically considering the optimization of the current pulse in order to maximize the optical peak power, achieving current pulses of more than 900 A with a duration of 50 ns. We have studied the operation of a low cost HPDL out of the manufacturers datasheet ratings without noticeable degradation at high current (> 250 A) and short pulse duration (< 60 ns). We have obtained an optical peak power of 750 W and a energy per pulse of 31.2 µJ at 40 ns optical pulse duration. The optoacoustic images obtained in this operation regime shown a clear enhancement respect to the ones obtained in standard operation of the HPDL.

Building a bridge between patients and transplant healthcare professionals - a descriptive study.

This article describes a pathway for collaboration between transplant healthcare professionals and organ recipients. Under the umbrella of the European Society for Organ Transplantation (ESOT) a joint initiative started from three Sections and Committees of ESOT: EDTCO (European Donation and Transplant Coordination Organisation), ETHAP (European Transplant Allied Healthcare Professionals) and ELPAT (Ethical, Legal and Psycho-social Aspects of Transplantation). The formal 'kick-off' of the Advisory Board Meeting of the European Transplant Patient Organisation (ETPO) was during the ESOT congress in 2019. The aim was to produce a series of statements to serve as a path to dialogue between patients and transplant professionals and to define the next steps towards giving a voice to the patient network. To include the patients' perspectives, two surveys have been performed. The results identified the unmet needs and lead to a proposal for future plans. Educational activities have since started leading to a patient learning workstream. All initiatives taken have one purpose: to include patients, give them a voice and build a foundation for collaboration between patients and transplant professionals. ESOT has created a platform for mutual understanding, learning and a collaborative partnership between ETPO and European donation and transplant professionals.

Urodynamic Differences between Complete and Incomplete Spinal Cord Injuries with Neurogenic Detrusor Overactivity.

OBJECTIVE: To analyze if there are urodynamic differences in patients with neurogenic detrusor overactivity (NDO) secondary to spinal cord injury (SCI) depending on whether the SCI is complete or incomplete according to the American Spinal Injury Association (ASIA) classification. METHODS: A retrospective and comparative study was carried out, including 194 patients with suprasacral SCI and NDO. Maximum cystometric capacity (MCC), volume at first involuntary contraction (VIC), compliance, maximum pressure of the detrusor during filling cystometry (MaxDetP), detrusor leak point pressure (LeakDetP) and postvoid residual urine volume (PVR) were analysed. Means were compared with Student t test for independent samples, with statistical significance p < 0.05. RESULTS: SCI was complete (ASIA A) in 51 patients (26.3%) and incomplete (ASIA B-E) in 143 (73.7%). The comparison of means showed significant differences regarding MCC (278.5 ± 102.6 mL in ASIA A vs. 321.6 ± 127.1 mL in ASIA B-E; p = 0. 018) and VIC (161 ± 85.1 and 210 ± 114.4 mL -respectively; p = 0.006). There were no differences regarding MaxDetP (58.8 ± 26.9 vs. 49.3 ± 35.6 cm H2O), LeakDetP (44.6 ± 25.3 vs. 48.3 ± 26.7 cm H2O), PVR (155.3 ± 94.2 vs. 118.5 ± 129.8) or compliance (29.9 ± 25.3 vs. 48.3 ± 26.7 cm H2O). CONCLUSIONS: In our serie incomplete SCI (ASIA B-E) showed differences from complete ones (ASIA A) regarding MCC and VIC, but not regarding LeakDetP, MaxDetP, PVR or compliance.

Inversion of two-flux and four-flux radiative transfer models for determining scattering and absorption coefficients for a suspended particle device.

Intrinsic and extrinsic scattering and absorption coefficients of a suspended particle device (SPD) smart window sample at dark and clear appearance states-without and with applied electrical voltage, respectively-were determined by means of the Maheu, Letoulouzan, and Gouesbet four-flux (intrinsic) and Kubelka-Munk two-flux (extrinsic) radiative transfer models, respectively. Extrinsic values were obtained from fitting to the two-flux model taking into account the predominantly forward scattering of the SPD. As an approximation, the Fresnel reflection coefficients were integrated out to the critical angle of total internal reflection in order to compute diffuse interface reflectances. Intrinsic coefficients were retrieved by adding a new proposed approximation for the average crossing parameter based on the collimated and diffuse light intensities at each interface. This approximation, although an improvement of previous approaches, is not entirely consistent with the two-flux model results. However, it paves the way for further development of methods to solve the inverse problem of the four-flux model.

Adherence to the European Association of Urology Guidelines Regarding the Therapeutic Indications for the Treatment of Urinary Lithiasis: A Spanish Multicenter Study.

INTRODUCTION: Urinary lithiasis involves a major source of morbidity and economic costs. The aim of this study was to evaluate the adherence to the European Association of Urology Guidelines on Urolithiasis with regard to treatment among Spanish urologists. METHODS: A total of 723 patients were included in a prospective study between May 1, 2014, and July 31, 2014. The study involved 8 hospitals responsible of urolithiasis in a geographical area of Spain (Comunidad Valenciana) with approximately 4,500,000 inhabitants. Data were collected about the demographic characteristics of the patients, the characteristics of the stones, and the indicated treatment, in order to analyze the adherence to the clinical guidelines. A 90% threshold was used in concordance with the indications in the guidelines. RESULTS: Adherence to guidelines was poor in chemolysis, distal and ureteral calculi, and >2 cm renal calculi. Adherence was high in <2 cm renal calculi. CONCLUSIONS: In our study, the overall adherence to the clinical guidelines regarding the therapeutic indication for urinary lithiasis has been low. In the case of both renal and ureteral stones, the adherence in small lithiasis has been greater, compared with larger ones. In our survey, a trend has been observed in favor of endoscopic procedures even in large lithiasis.

Analysis of Memory B-Cell Responses Reveals Suboptimal Dosing Schedule of a Licensed Vaccine.

Current guidance recommends that adolescents receive a 2-dose human papillomavirus (HPV) vaccine, whereas young adults and immunocompromised persons receive 3 doses. We examined secondary responses of vaccine-elicited memory B cells (Bmem) in naive women receiving 3 doses of the quadrivalent HPV vaccine to understand the quality of B-cell memory generated by this highly effective vaccine. Unexpectedly, we observed a lower Bmem response rate and magnitude of Bmem responses to the third dose than to a booster dose administered at month 24. Moreover, high titers of antigen-specific serum antibody at vaccination inversely correlated with Bmem responses. As the purpose of additional doses/boosters is to stimulate Bmem to rapidly boost antibody levels, these results indicate the timing of the third dose is suboptimal and lend support to a 2-dose HPV vaccine for young adults. Our findings also indicate more broadly that multidose vaccine schedules should be rationally determined on the basis of Bmem responses.

Capturing Elusive Cobaltacycle Intermediates: A Real-Time Snapshot of the Cp*CoIII -Catalyzed Oxidative Alkyne Annulation.

Despite Cp*CoIII catalysts having emerged as a very attractive alternative to noble transition metals for the construction of heterocyclic scaffolds through C-H activation, the structure of the reactive species remains uncertain. Herein, we report the identification and unambiguous characterization of two long-sought cyclometalated Cp*CoIII complexes that have been proposed as key intermediates in C-H functionalization reactions. The addition of MeCN as a stabilizing ligand plays a crucial role, allowing the access to otherwise highly reactive species. Mechanistic investigations demonstrate the intermediacy of these species in oxidative annulations with alkynes, including the direct observation, under catalytic conditions, of a previously elusive post-migratory insertion seven-membered cobaltacycle.

Elucidating the effect of the nucleophilicity of the silyl group in the reduction of CO2 to CO mediated by silyl-copper(I) complexes.

The reduction of CO2 to CO with silyl-copper(I) complexes bearing various silyl groups has been investigated. The silyl-copper(I) complexes [LSi(X)Cu(IPr)] 2-5 (X = OtBu (2), OH (3), H (4), OC6F5 (5); L = CH{C=CH2}(CMe)(NAr)2, IPr = (CHNAr)2C:, Ar = 2,6-iPr2C6H3) bearing OtBu, OH, H, and OC6F5 as functional groups are readily accessible by the activation of the Cu-O and Cu-H bonds in (IPr)CuX with silylene LSi: (1). These complexes are not readily accessible by the commonly used transmetallation reaction, rendering this methodology rather unique and facile in synthesizing silicon-functionalized silyl-metal complexes. The functional groups at the silicon atoms in compounds 2-5 enable the silyl groups to feature different nucleophilicity, which affords different activities toward CO2 reduction to CO. The silyl moieties of complexes 2 and 3, containing electron-donating groups (i.e., OtBu and OH) at the silicon centers, are more nucleophilic than that of compound 4 and 5, bearing a hydride and the electron-withdrawing group OC6F5 at the silicon centers, respectively. Consistent with this observation, compounds 2 and 3 show higher activity in CO2 reduction to CO compared to compounds 4 and 5, and the latter cases are zero-order reactions with respect to 4 and 5 (4: k = 7.8×10(-6) mol L(-1) s(-1); 5: 2.7×10(-8) mol L(-1) s(-1)). This suggests that the more nucleophilic the silyl moiety in a silyl-copper(I) complex is, the higher is the efficiency in CO2 reduction to CO. In addition, the siloxyl-copper(I) complexes [LSi(X)OCu(IPr)] 6-9 [X = OtBu (6), OH (7), H (8), OC6F5 (9)] were isolated as the products from the corresponding reduction reactions. Complexes 2-4 and 6-8 were characterized by spectroscopic and structural means.

Lead extraction experience with high frequency excimer laser.

BACKGROUND: A higher frequency Excimer laser sheath using an 80-Hz pulse repetitive rate was approved by the Food and Drug Administration in April 2012. We reported our initial clinical experience with a high-frequency Excimer laser sheath and compared it with lower-frequency laser sheaths which have been previously used. METHODS: In this single center, retrospective cohort study, we evaluated patients who underwent lead extraction from December 2008 to May 2013. Those who underwent lead removal without using a laser sheath or with approaches other than subclavian were excluded. Primary endpoints included total laser time, number of pulses, and complications. Data on clinical characteristics, lead type, indications, and outcomes were prospectively collected and analyzed. RESULTS: A total of 427 patients were included in the study (72.6% male; age 67.9 ± 15.23 years). Lower frequency and higher frequency laser sheaths were used in 315 and 112 patients, respectively. A total of 821 leads were removed with 765 leads (93.2%) extracted using the Excimer laser sheath. Lead age was 5.71 ± 4.96 years. Complete extraction was seen in all patients. A higher-frequency laser sheath was associated with a lower laser time and a lower total number of laser pulses even after adjustments for the number of leads, type of leads, and lead age. In the higher frequency group, mortality rate was 0.9% and minor complication rate was 3.6%. CONCLUSIONS: When compared with the lower-frequency laser sheath, the higher-frequency laser sheath requires less laser times and more efficient amount of pulses for lead extraction with comparable success rate. Due to the rarity of major and minor complications, no statistical significance was found between the two groups.

Microplastic presence in dog and human testis and its potential association with sperm count and weights of testis and epididymis.

The ubiquitous existence of microplastics and nanoplastics raises concerns about their potential impact on the human reproductive system. Limited data exists on microplastics within the human reproductive system and their potential consequences on sperm quality. Our objectives were to quantify and characterize the prevalence and composition of microplastics within both canine and human testes and investigate potential associations with the sperm count, and weights of testis and epididymis. Using advanced sensitive pyrolysis-gas chromatography/mass spectrometry, we quantified 12 types of microplastics within 47 canine and 23 human testes. Data on reproductive organ weights, and sperm count in dogs were collected. Statistical analyses, including descriptive analysis, correlational analysis, and multivariate linear regression analyses were applied to investigate the association of microplastics with reproductive functions. Our study revealed the presence of microplastics in all canine and human testes, with significant inter-individual variability. Mean total microplastic levels were 122.63 µg/g in dogs and 328.44 µg/g in humans. Both humans and canines exhibit relatively similar proportions of the major polymer types, with PE being dominant. Furthermore, a negative correlation between specific polymers such as PVC and PET and the normalized weight of the testis was observed. These findings highlight the pervasive presence of microplastics in the male reproductive system in both canine and human testes, with potential consequences on male fertility.