Novel approaches in diabetic nephropathy

Dit proefschrift laat zien dat het carnosinase-1 gen (CNDP1) voorspellend is voor het risico op eindstadium nierfalen bij patiënten met type 1 diabetes. In tegenstelling tot de bevindingen van cross-sectionele studies bij patiënten met type 2 diabetes, blijkt de homozygote variant voor het laagste aantal leucines (5L-5L) in het CNDP1 gen niet te beschermen tegen achteruitgang van nierfunctie bij patiënten met type 2 diabetes. Vrouwen met 5L-5L lijken een verhoogd risico op cardiovasculaire mortaliteit te hebben vergeleken met vrouwen met andere varianten. Deze bevinding kan van invloed zijn geweest op de resultaten van cross-sectionele studies. Prospectief onderzoek is noodzakelijk om een beter inzicht te krijgen in de rol van het CNDP1 gen bij diabetische nefropathie. De rol van ACE I/D SNP als genetische risicofactor voor het ontwikkelen van albuminurie bij patiënten met type 2 diabetes kunnen aantonen. Een recent beschreven SNP in het CCR2 (CCR2 V64I) is echter niet voorspellend gebleken voor het risico op het ontstaan van albuminurie. Analyse van eiwitten en collageenfragmenten in de urine (urine-proteomics) is een bruikbare diagnostische methode voor diabetische nefropathie in vroeg stadium. Hierdoor is het in de toekomst wellicht mogelijk om patiënten met diabetes en een verhoogd risico op nefropathie tijdig te behandelen. De laatste conclusie van dit proefschrift luidt dat er geen bewijs is voor het gebruik van benfotiamine (een vitamine B1 derivaat) bij patiënten met type 2 diabetes, omdat het niet leidt tot vermindering van albuminurie of andere markers van nierschade

On Healing HeARTs: A Saudi Woman Perspective on the Experience of Baby Loss, Art, and Compassion

The dissertation, “On Healing HeARTs: A Saudi Woman’s Perspective on the Experience of Baby Loss,” investigates how Shia Saudi bereaved mothers create meaning and make sense of their experience of baby loss. It explores the importance of art and compassion in the healing process. Using a multi-method design that includes art-based methods and autoethnography, I narrate my own experience of baby loss. The study relies on theories of sense-making and constructivism to interpret my findings. Looking at the experience from a unique cultural lens enables the readers and health providers to comprehend how certain cultural factors contribute to both the suffering and healing process. The study expands previous research and contributes to the body of knowledge of communication studies by exploring a fundamental component of the human condition: death. Four themes emerged from the research: continuing bonds, loss as an opportunity for growth, living a new normal, and identity reconstruction. I argue that art and compassion have the potential to help women in their healing process. The project contributes to family and health communication by advocating for the importance of compassion and expressive arts to facilitate the healing process, while addressing a taboo topic: the experience of baby death and loss. The study has the potential to advance women’s health and patient-centered communication by exploring the bereavement experiences of women from the East. The project aims to challenge and change the status quo of lacking compassion through highlighting the importance of empowerment, meaning-making, connection, identity reconstruction, and emotional expression for bereaved women to bring comfort and facilitate healing. The research was funded by fellowships from the University of Denver’s Communication Department in 2020 and 2021

Alpha Lipoic Acid for Symptomatic Peripheral Neuropathy in Patients with Diabetes: A Meta-Analysis of Randomized Controlled Trials

Objective. We performed a systematic review of the literature to evaluate the effects of alpha lipoic acid for symptomatic peripheral neuropathy in patients with diabetes mellitus. Research design and methods. The databases MEDLINE and EMBASE were searched using the key words “lipoic acid”, “thioctic acid”, “diabet∗”, and the MeSH-terms “thioctic acid” and “diabetes mellitus”. Randomised controlled trials using the TSS score as the outcome measure were selected and assessed for their methodological quality. Study selection and quality assessment were performed independently by three observers. Results. Overall, the pooled standardized mean difference estimated from all trials revealed a reduction in TSS scores of −2.26 (CI: −3.12 to −1.41; P = 0.00001) in favour of alpha lipoic acid administration. Subgroup analyses of oral administration (−1.78 CI: −2.45 to −1.10; P = 0.00001) and intravenous administration (−2.81 CI: −4.16 to −1.46; P = 0.0001) confirmed the robustness of the overall result. Conclusions. When given intravenously at a dosage of 600 mg/day over a period of 3 weeks, alpha lipoic acid leads to a significant and clinically relevant reduction in neuropathic pain (grade of recommendation A). It is unclear if the significant improvements seen after 3–5 weeks of oral administration at a dosage of >600 mg/day are clinically relevant

Multicentric validation of proteomic biomarkers in urine specific for diabetic nephropathy

Background: Urine proteome analysis is rapidly emerging as a tool for diagnosis and prognosis in disease states. For diagnosis of diabetic nephropathy (DN), urinary proteome analysis was successfully applied in a pilot study. The validity of the previously established proteomic biomarkers with respect to the diagnostic and prognostic potential was assessed on a separate set of patients recruited at three different European centers. In this case-control study of 148 Caucasian patients with diabetes mellitus type 2 and duration >= 5 years, cases of DN were defined as albuminuria >300 mg/d and diabetic retinopathy (n = 66). Controls were matched for gender and diabetes duration (n = 82). Methodology/Principal Findings: Proteome analysis was performed blinded using high-resolution capillary electrophoresis coupled with mass spectrometry (CE-MS). Data were evaluated employing the previously developed model for DN. Upon unblinding, the model for DN showed 93.8% sensitivity and 91.4% specificity, with an AUC of 0.948 (95% CI 0.898-0.978). Of 65 previously identified peptides, 60 were significantly different between cases and controls of this study. In <10% of cases and controls classification by proteome analysis not entirely resulted in the expected clinical outcome. Analysis of patient's subsequent clinical course revealed later progression to DN in some of the false positive classified DN control patients. Conclusions: These data provide the first independent confirmation that profiling of the urinary proteome by CE-MS can adequately identify subjects with DN, supporting the generalizability of this approach. The data further establish urinary collagen fragments as biomarkers for diabetes-induced renal damage that may serve as earlier and more specific biomarkers than the currently used urinary albumin

Vertical R1 margins are not always associated with residual neoplasia after endoscopic resection of Barrett's neoplasia:a nationwide cohort with dedicated pathology reassessment

BACKGROUND: To evaluate the proportion of patients with residual neoplasia after endoscopic resection (ER) for Barrett's neoplasia with confirmed tumor-positive vertical resection margin (R1v).METHODS: Retrospective cohort study including all patients treated with ER for Barrett's neoplasia with histologically documented R1v since 2008 in the Dutch Barrett Expert Centers. R1v was defined as cancer cells touching the vertical resection margin and Rx as not assessable margins. Reassessment of R1v specimen was performed by experienced pathologists until consensus was reached regarding vertical margins.RESULTS: 101/110 included patients had macroscopically complete resections (T1a n=17, T1b n=84), of which 99/101 (98%) ER specimens were reassessed. Reassessment confirmed R1v in 74 (75%) patients and found Rx in 16% and R0 in 9%. Presence of residual neoplasia could be assessed in 66/74 patients during endoscopic reassessment (n=52) and/or in the surgical resection specimen (n=14), of whom 33/66 (50%)had residual neoplasia. Residual neoplasia detected during endoscopy was always endoscopically visible and biopsies from a normal appearing ER-scar did not detect additional neoplasia. Twenty-five patients with no residual neoplasia during endoscopic reassessment underwent endoscopic follow-up for median 37 months(IQR 12-50), in which 4 developed a local recurrence(16.0%), all detected as visible abnormalities.CONCLUSIONS: Histological evaluation of ER margins appears challenging as 75% of documented R1v cases were confirmed during reassessment. After ER with R1v, 50% of the patients had no residual neoplasia. Endoscopic reassessment 8-12 weeks after ER seems accurately able to detect residual neoplasia and help to determine the most appropriate strategy for patients with R1v.</p

Comparison of Methods for Renal Risk Prediction in Patients with Type 2 Diabetes (ZODIAC-36)

BACKGROUND: Patients with diabetes are at high risk of death prior to reaching end-stage renal disease, but most models predicting the risk of kidney disease do not take this competing risk into account. We aimed to compare the performance of Cox regression and competing risk models for prediction of early- and late-stage renal complications in type 2 diabetes. METHODS: Patients with type 2 diabetes participating in the observational ZODIAC study were included. Prediction models for (micro)albuminuria and 50% increase in serum creatinine (SCr) were developed using Cox regression and competing risk analyses. Model performance was assessed by discrimination and calibration. RESULTS: During a total follow-up period of 10 years, 183 out of 640 patients (28.6%) with normoalbuminuria developed (micro)albuminuria, and 22 patients (3.4%) died without developing (micro)albuminuria (i.e. experienced the competing event). Seventy-nine out of 1,143 patients (6.9%) reached the renal end point of 50% increase in SCr, while 219 (19.2%) died without developing the renal end point. Performance of the Cox and competing risk models predicting (micro)albuminuria was similar and differences in predicted risks were small. However, the Cox model increasingly overestimated the risk of increase in SCr in presence of a substantial number of competing events, while the performance of the competing risk model was quite good. CONCLUSIONS: In this study, we demonstrated that, in case of substantial numbers of competing events, it is important to account for the competing risk of death in renal risk prediction in patients with type 2 diabetes

The Important Role of Optometrist and Qualified Nursing in Primary Healthcare for Eye Care

The use of evidence-based practice is essential for delivering high-quality care, ensuring patient satisfaction, and making efficient use of limited healthcare resources. Nevertheless, there have been reports of inconsistency in the administration of evidence-based eye care. To enhance our comprehension of the obstacles and enablers to delivering optometric care, it is necessary to recognize the significant role that optometrists play in providing primary eye care. This narrative study sought to identify the provision of eye care services by optometrists and measures that could enhance the delivery of eye care in primary care settings, alongside certified nursing. In the field of optometry, similar to other healthcare professions like nursing, there has been a broadening of the optometrist\u27s responsibilities in primary eye care. This includes taking on tasks such as prescription medication, which was previously done by general practitioners. Within the field of optometry, this expanded responsibility entails overseeing eye diseases that do not necessitate treatment or monitoring in secondary healthcare settings, which were historically referred to. Nevertheless, any expanded responsibility necessitates educational assistance