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Journal of Mass Spectrometry and... Aug 2023Free thyroxine (FT4) measurement is one of the most requested tests in patient care for diagnosing and treating thyroid-related illnesses. Equilibrium dialysis (ED) is...
BACKGROUND
Free thyroxine (FT4) measurement is one of the most requested tests in patient care for diagnosing and treating thyroid-related illnesses. Equilibrium dialysis (ED) is considered the "gold standard" for FT4 measurement; however, several factors have a profound effect on the reliability of FT4 assays and require special consideration.
METHODS
In the current study, we focused on evaluating critical factors that could contribute to reporting errors, such as adsorption of thyroxine (T4) to labware surfaces, stability of serum samples, stock solutions, and calibrator storage conditions, as well as the solvents used to prepare T4 solutions.
RESULTS
The adsorption of T4 in ethanolic solutions and dialysates to labware surfaces can be reduced with the careful selection of pipette tips, test tubes, and 96-well plates. Adding pH modifiers to neat T4 solutions can improve its stability. FT4 in serum samples remains stable after exposure to four freeze-thaw cycles, 5 °C for 18-20 h, or -70 °C for a minimum of three years.
CONCLUSION
The presented study has demonstrated that the loss of analyte due to pre-analytical and analytical factors during operation of the FT4 reference measurement procedure (RMP) can be minimized by careful selection of all labware for sample preparation. It was found that the accuracy and imprecision of FT4 assays can be influenced by different types of dialysis devices, but acceptable alternatives to ED membranes were identified. This study demonstrates approaches to establish a FT4 method that is independent from specific suppliers and addresses critical pre-analytical and analytical factors important for FT4 measurements.
PubMed: 37449264
DOI: 10.1016/j.jmsacl.2023.06.001 -
PloS One 2023Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in... (Clinical Trial)
Clinical Trial
Diffuse midline gliomas (DMG) are the most aggressive brain tumors of childhood and young adults, with documented 2-year survival rates <10%. Treatment failure is due in part to the function of the BBB. Intratumoral microdialysis sampling is an effective tool to determine brain entry of varied agents and could help to provide a better understanding of the relationship of drug permeability to DMG treatment responsivity. This is a non-randomized, single-center, phase 1 clinical trial. Up to seven young adult (18-39 years) patients with recurrent high-grade or diffuse midline glioma will be enrolled with the goal of 5 patients completing the trial over an anticipated 24 months. All patients will take abemaciclib pre-operatively for 4.5 days at twice daily dosing. Patients will undergo resection or biopsy, placement of a microdialysis catheter, and 48 hours of dialysate sampling coupled with timed plasma collections. If intratumoral tumor or brain dialysate sampling concentrations are >10nmol/L, or tumor tissue studies demonstrate CDK inhibition, then restart of abemaciclib therapy along with temozolomide will be administered for maintenance therapy and discontinued with evidence of radiologic or clinical disease progression. The poor survival associated with diffuse midline gliomas underscore the need for improved means to evaluate efficacy of drug delivery to tumor and peritumoral tissue. The findings of this novel study, will provide real-time measurements of BBB function which have the potential to influence future prognostic and diagnostic decisions in such a lethal disease with limited treatment options. Trial registration: Clinicaltrials.gov, NCT05413304. Registered June 10, 2022, Abemaciclib Neuropharmacokinetics of Diffuse Midline Glioma Using Intratumoral Microdialysis.
Topics: Young Adult; Humans; Feasibility Studies; Microdialysis; Clinical Protocols; Dialysis Solutions; Glioma
PubMed: 37682953
DOI: 10.1371/journal.pone.0291068 -
Health (London, England : 1997) Sep 2023Quality of life has become a central value in the provision of healthcare for patients with chronic conditions. This has engendered debates in critical medical sociology...
Quality of life has become a central value in the provision of healthcare for patients with chronic conditions. This has engendered debates in critical medical sociology on the non-neutral effects that valuing health and illness, medical interventions, and health care delivery in terms of quality of life yields. Focusing on the case of nephrology, this paper presents qualitative data collected in Austria of two dialysis units in which nephrologists initiated projects aimed towards 'the improvement of patients' quality of life'. Whereas the first involved nurses supporting patients in the administration of peritoneal dialysis at home, the second implied the provision of treatment and care exclusively focused on a well-being 'in the here and now' to patients. By conceptualising physicians as actors within networks of relations and values enacted in practices, it analyses how in both dialysis units reference to quality of life enabled nephrologists to problematise the provision of standard haemodialysis treatment to multi-morbid, elderly patients, to develop a new treatment protocol, and to interest and enrol others in the provision of healthcare according this new protocol. Valuing medical interventions in terms of quality of life not only leads to a governmentalization of living and an economisation of health. It also allows physicians to articulate a socio-medico-ethical problem - the availability of life-prolonging technologies for a growing population of elderly, multi-morbid patients - and develop solutions locally. What the solutions consist in may fundamentally differ, however.
PubMed: 37772459
DOI: 10.1177/13634593231200128 -
Journal of the American Society of... Sep 2023The optimal choice of vascular access for patients undergoing hemodialysis-arteriovenous fistula (AVF) or arteriovenous graft (AVG)-remains controversial. In a pragmatic... (Observational Study)
Observational Study
SIGNIFICANCE STATEMENT
The optimal choice of vascular access for patients undergoing hemodialysis-arteriovenous fistula (AVF) or arteriovenous graft (AVG)-remains controversial. In a pragmatic observational study of 692 patients, the authors found that among patients who initiated hemodialysis with a central vein catheter (CVC), a strategy that maximized AVF placement resulted in a higher frequency of access procedures and greater access management costs for patients who initially received an AVF than an AVG. A more selective policy that avoided AVF placement if an AVF was predicted to be at high risk of failure resulted in a lower frequency of access procedures and access costs in patients receiving an AVF versus an AVG. These findings suggest that clinicians should be more selective in placing AVFs because this approach improves vascular access outcomes.
BACKGROUND
The optimal choice of initial vascular access-arteriovenous fistula (AVF) or graft (AVG)-remains controversial, particularly in patients initiating hemodialysis with a central venous catheter (CVC).
METHODS
In a pragmatic observational study of patients who initiated hemodialysis with a CVC and subsequently received an AVF or AVG, we compared a less selective vascular access strategy of maximizing AVF creation (period 1; 408 patients in 2004 through 2012) with a more selective policy of avoiding AVF creation if failure was likely (period 2; 284 patients in 2013 through 2019). Prespecified end points included frequency of vascular access procedures, access management costs, and duration of catheter dependence. We also compared access outcomes in all patients with an initial AVF or AVG in the two periods.
RESULTS
An initial AVG placement was significantly more common in period 2 (41%) versus period 1 (28%). Frequency of all access procedures per 100 patient-years was significantly higher in patients with an initial AVF than an AVG in period 1 and lower in period 2. Median annual access management costs were significantly higher among patients with AVF ($10,642) versus patients with AVG ($6810) in period 1 but significantly lower in period 2 ($5481 versus $8253, respectively). Years of catheter dependence per 100 patient-years was three-fold higher in patients with AVF versus patients with AVG in period 1 (23.3 versus 8.1, respectively), but only 30% higher in period 2 (20.8 versus 16.0, respectively). When all patients were aggregated, the median annual access management cost was significantly lower in period 2 ($6757) than in period 1 ($9781).
CONCLUSIONS
A more selective approach to AVF placement reduces frequency of vascular access procedures and cost of access management.
Topics: Humans; Kidney Failure, Chronic; Arteriovenous Shunt, Surgical; Retrospective Studies; Renal Dialysis; Arteriovenous Fistula; Treatment Outcome
PubMed: 37401775
DOI: 10.1681/ASN.0000000000000174 -
Peritoneal Dialysis International :... Mar 2024Overhydration is highly prevalent in patients on peritoneal dialysis (PD), with inappropriately high sodium load supposedly playing a central role in the pathophysiology... (Review)
Review
Overhydration is highly prevalent in patients on peritoneal dialysis (PD), with inappropriately high sodium load supposedly playing a central role in the pathophysiology of the conditions. Recent studies have revealed the novel role of the interstitium as a buffer system for sodium ions, and it has been reported that patients on dialysis, including PD, present increased levels of sodium in the interstitium, such as in subcutaneous tissue and muscle. Hence, therapy for correction of overhydration should target the excess extracellular volume and the excess sodium storage in the interstitium. The ultrafiltrate obtained using the currently available PD solutions is hypo- to isonatric as compared to serum, which is disadvantageous for prompt and efficient sodium removal from the body in patients with overhydration. In contrast, use of low sodium PD solutions is characterised by iso- to hypernatric ultrafiltrate, which may beneficial for reducing sodium storage in the interstitium. Trials of low sodium PD solutions have reported possible clinical merits, for example, decreased blood pressure, reduced dryness of mouth and decreased body water content as assessed using bioimpedance methods. Given these observations and the high prevalence of overhydration in current PD populations, it makes medical sense that low sodium solutions be positioned as the new standard solution in the future. However, for medical safety, that is, to avoid hyponatremia and excessive decreases in blood pressure, further studies are needed to establish the appropriate compositions and applications of low sodium solutions.
Topics: Humans; Peritoneal Dialysis; Dialysis Solutions; Water Intoxication; Renal Dialysis; Sodium
PubMed: 38265014
DOI: 10.1177/08968608231222141 -
Peritoneal Dialysis International :... Sep 2023Incremental peritoneal dialysis (PD), defined as less than Full-dose PD prescription, has several possible merits, including better preservation of residual kidney... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Incremental peritoneal dialysis (PD), defined as less than Full-dose PD prescription, has several possible merits, including better preservation of residual kidney function (RKF), lower peritoneal glucose exposure and reduced risk of peritonitis. The aims of this study were to analyse the association of Incremental and Full-dose PD strategy with RKF and urine volume (UV) decline in patients commencing PD.
METHODS
Incident PD patients who participated in the balANZ randomised controlled trial (RCT) (2004-2010) and had at least one post-baseline RKF and UV measurement was included in this study. Patients receiving <56 L/week and ≥56 L/week of PD fluid at PD commencement were classified as Incremental and Full-dose PD, respectively. An alternative cut-point of 42 L/week was used in a sensitivity analysis. The primary and secondary outcomes were changes in measured RKF and daily UV, respectively.
RESULTS
The study included 154 patients (mean age 57.9 ± 14.1 years, 44% female, 34% diabetic, mean follow-up 19.5 ± 6.6 months). Incremental and Full-dose PD was commenced by 45 (29.2%) and 109 (70.8%) participants, respectively. RKF declined in the Incremental group from 7.9 ± 3.2 mL/min/1.73 m at baseline to 3.2 ± 2.9 mL/min/1.73 m at 24 months ( < 0.001), and in the Full-dose PD group from 7.3 ± 2.7 mL/min/1.73 m at baseline to 3.4 ± 2.8 mL/min/1.73 m at 24 months ( < 0.001). There was no difference in the slope of RKF decline between Incremental and Full-dose PD ( = 0.78). UV declined from 1.81 ± 0.73 L/day at baseline to 0.64 ± 0.63 L/day at 24 months in the Incremental PD group ( < 0.001) and from 1.38 ± 0.61 L/day to 0.71 ± 0.46 L/day in the Full-dose PD group ( < 0.001). There was no difference in the slope of UV decline between Incremental and Full-dose PD ( = 0.18).
CONCLUSIONS
Compared with Full-dose PD start, Incremental PD start is associated with similar declines in RKF and UV.
Topics: Female; Humans; Adult; Middle Aged; Aged; Male; Peritoneal Dialysis; Glomerular Filtration Rate; Dialysis Solutions; Peritoneum; Kidney; Kidney Failure, Chronic
PubMed: 37259236
DOI: 10.1177/08968608231175826 -
Membranes Dec 2023This study presents the possibility of using diffusion dialysis for the separation of inorganic acids (hydrochloric, nitric, and hydrofluoric) and their ferric salts...
This study presents the possibility of using diffusion dialysis for the separation of inorganic acids (hydrochloric, nitric, and hydrofluoric) and their ferric salts whose composition corresponds to that of real spent pickling solutions. At a steady state, the transport properties of three different anion-exchange membranes (Fumasep-FAD, Neosepta-AFN, and Neosepta-AHA) are compared using a continuous counter-current dialyzer. At a constant composition of the solutions (acid concentration 3 mol L and iron concentration 30-40 g L), the effects of volumetric liquid flow rates on the transport rate of H and Fe ions through the membrane are studied. The dialysis process is characterized by the recovery of acids and the rejection of salts. Furthermore, the values of the dialysis coefficients of acids, iron, and the acid/iron separation factors are calculated and compared. The volumetric flow rates of the inlet streams change in limits from 3 × 10 to 6 × 10 m s (from 3 to 6 L h m, relative to the membrane area). A comparison of the tested membranes shows slightly better results for acid recovery, iron rejection, and acid/iron separation factors for the Fumasep-FAD membrane than for the Neosepta-AFN membrane. However, the results obtained show that both of these anion-exchange membranes can be considered good separators for tested mixtures that simulate real spent pickling solutions, and there is a good precondition for using diffusion dialysis for processing these solutions in industrial practice. On the contrary, very low values of acid recovery and the overall dialysis coefficient of acid are found for the Neosepta-AHA membrane in the test range of the volumetric flow rate, and, thus, this membrane is insufficient for the adequate separation of these acids and iron salts.
PubMed: 38248696
DOI: 10.3390/membranes14010006 -
International Journal of Molecular... Aug 2023Patients with end-stage kidney disease (ESKD) suffer from high levels of protein-bound uremic toxins (PBUTs) that contribute to various comorbidities. Conventional...
Patients with end-stage kidney disease (ESKD) suffer from high levels of protein-bound uremic toxins (PBUTs) that contribute to various comorbidities. Conventional dialysis methods are ineffective in removing these PBUTs. A potential solution could be offered by a bioartificial kidney (BAK) composed of porous membranes covered by proximal tubule epithelial cells (PTECs) that actively secrete PBUTs. However, BAK development is currently being hampered by a lack of knowledge regarding the cytocompatibility of the dialysis fluid (DF) that comes in contact with the PTECs. Here, we conducted a comprehensive functional assessment of the DF on human conditionally immortalized PTECs (ciPTECs) cultured as monolayers in well plates, on Transwell inserts, or on hollow fiber membranes (HFMs) that form functional units of a BAK. We evaluated cell viability markers, monolayer integrity, and PBUT clearance. Our results show that exposure to DF did not affect ciPTECs' viability, membrane integrity, or function. Seven anionic PBUTs were efficiently cleared from the perfusion fluid containing a PBUTs cocktail or uremic plasma, an effect which was enhanced in the presence of albumin. Overall, our findings support that the DF is cytocompatible and does not compromise ciPTECs function, paving the way for further advancements in BAK development and its potential clinical application.
Topics: Humans; Renal Dialysis; Uremic Toxins; Kidney Failure, Chronic; Kidney; Kidney Tubules, Proximal; Dialysis Solutions; Toxins, Biological
PubMed: 37569805
DOI: 10.3390/ijms241512435 -
JAMA Internal Medicine May 2024Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, cardiovascular events, and death.
OBJECTIVE
To evaluate a computerized clinical decision support (CDS) system for the management of uncontrolled hypertension in patients with CKD.
DESIGN, SETTING, AND PARTICIPANTS
This multiclinic, randomized clinical trial randomized primary care practitioners (PCPs) at a primary care network, including 15 hospital-based, ambulatory, and community health center-based clinics, through a stratified, matched-pair randomization approach February 2021 to February 2022. All adult patients with a visit to a PCP in the last 2 years were eligible and those with evidence of CKD and hypertension were included.
INTERVENTION
The intervention consisted of a CDS system based on behavioral economic principles and human-centered design methods that delivered tailored, evidence-based recommendations, including initiation or titration of renin-angiotensin-aldosterone system inhibitors. The patients in the control group received usual care from PCPs with the CDS system operating in silent mode.
MAIN OUTCOMES AND MEASURES
The primary outcome was the change in mean systolic blood pressure (SBP) between baseline and 180 days compared between groups. The primary analysis was a repeated measures linear mixed model, using SBP at baseline, 90 days, and 180 days in an intention-to-treat repeated measures model to account for missing data. Secondary outcomes included blood pressure (BP) control and outcomes such as percentage of patients who received an action that aligned with the CDS recommendations.
RESULTS
The study included 174 PCPs and 2026 patients (mean [SD] age, 75.3 [0.3] years; 1223 [60.4%] female; mean [SD] SBP at baseline, 154.0 [14.3] mm Hg), with 87 PCPs and 1029 patients randomized to the intervention and 87 PCPs and 997 patients randomized to usual care. Overall, 1714 patients (84.6%) were treated for hypertension at baseline. There were 1623 patients (80.1%) with an SBP measurement at 180 days. From the linear mixed model, there was a statistically significant difference in mean SBP change in the intervention group compared with the usual care group (change, -14.6 [95% CI, -13.1 to -16.0] mm Hg vs -11.7 [-10.2 to -13.1] mm Hg; P = .005). There was no difference in the percentage of patients who achieved BP control in the intervention group compared with the control group (50.4% [95% CI, 46.5% to 54.3%] vs 47.1% [95% CI, 43.3% to 51.0%]). More patients received an action aligned with the CDS recommendations in the intervention group than in the usual care group (49.9% [95% CI, 45.1% to 54.8%] vs 34.6% [95% CI, 29.8% to 39.4%]; P < .001).
CONCLUSIONS AND RELEVANCE
These findings suggest that implementing this computerized CDS system could lead to improved management of uncontrolled hypertension and potentially improved clinical outcomes at the population level for patients with CKD.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03679247.
Topics: Humans; Female; Male; Hypertension; Decision Support Systems, Clinical; Renal Insufficiency, Chronic; Antihypertensive Agents; Aged; Middle Aged; Primary Health Care
PubMed: 38466302
DOI: 10.1001/jamainternmed.2023.8315 -
Toxins Apr 2024Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement... (Review)
Review
Chronic kidney disease poses a growing global health concern, as an increasing number of patients progress to end-stage kidney disease requiring kidney replacement therapy, presenting various challenges including shortage of care givers and cost-related issues. In this narrative essay, we explore innovative strategies based on in-depth literature analysis that may help healthcare systems face these challenges, with a focus on digital health technologies (DHTs), to enhance removal and ensure better control of broader spectrum of uremic toxins, to optimize resources, improve care and outcomes, and empower patients. Therefore, alternative strategies, such as self-care dialysis, home-based dialysis with the support of teledialysis, need to be developed. Managing ESKD requires an improvement in patient management, emphasizing patient education, caregiver knowledge, and robust digital support systems. The solution involves leveraging DHTs to automate HD, implement automated algorithm-driven controlled HD, remotely monitor patients, provide health education, and enable caregivers with data-driven decision-making. These technologies, including artificial intelligence, aim to enhance care quality, reduce practice variations, and improve treatment outcomes whilst supporting personalized kidney replacement therapy. This narrative essay offers an update on currently available digital health technologies used in the management of HD patients and envisions future technologies that, through digital solutions, potentially empower patients and will more effectively support their HD treatments.
Topics: Humans; Renal Dialysis; Telemedicine; Kidney Failure, Chronic; Patient Care; Patient Participation; Self Care; Digital Health
PubMed: 38787063
DOI: 10.3390/toxins16050211