Rate and reasons for peritoneal dialysis dropout following haemodialysis to peritoneal dialysis switch: a systematic review and meta-analysis.

BACKGROUND: Patient experiences and survival outcomes can be influenced by the circumstances related to dialysis initiation and subsequent modality choices. This systematic review and meta-analysis aimed to explore the rate and reasons for peritoneal dialysis (PD) dropout following haemodialysis (HD) to PD switch. METHOD: This systematic review conducted searches in four databases, including Medline, PubMed, Embase, and Cochrane. The protocol was registered on PROSPERO (study ID: CRD42023405718). Outcomes included factors leading to the switch from HD to PD, the rate and reasons for PD dropout and mortality difference in two groups (PD first group versus HD to PD group). The Critical Appraisal Skills Programme (CASP) checklist and the GRADE tool were used to assess quality. RESULTS: 4971 papers were detected, and 13 studies were included. On meta-analysis, there was no statistically significant difference in PD dropout in the PD first group (OR: 0.81; 95%CI: 0.61, 1.09; I2 = 83%; P = 0.16), however, there was a statistically significant reduction in the rate of mortality (OR: 0.48; 95%CI: 0.25, 0.92; I2 = 73%; P = 0.03) compared to the HD to PD group. The primary reasons for HD to PD switch, included vascular access failure, patient preference, social issues, and cardiovascular disease. Causes for PD dropout differed between the two groups, but inadequate dialysis and peritonitis were the main reasons for PD dropout in both groups. CONCLUSION: Compared to the PD first group, a previous HD history may not impact PD dropout rates for patients, but it could impact mortality in the HD to PD group. The reasons for PD dropout differed between the two groups, with no statistical differences. Psychosocial reasons for PD dropout are valuable to further research. Additionally, establishing a consensus on the definition of PD dropout is crucial for future studies.

Using a Capsular Tension Ring (CTR) Inserter for CTR Explantation in Cases of Posteriorly Dislocated Intraocular Lens-CTR-Capsule Complex.

PURPOSE: Explantation of a dislocated capsular tension ring (CTR) from the vitreous cavity can be challenging, typically requiring a bimanual hand-shake technique or cutting the CTR into segments. We present three cases of dislocated intraocular lens (IOL)-CTR-capsule complexes in which CTRs were explanted efficiently and safely by using a CTR inserter (CTR-I) through a clear corneal incision. METHODS: Retrospective case series. RESULTS: Capsular tension rings were successfully explanted by freeing the eyelet of the CTR from the capsule, engaging it with the CTR-I hook and retracting the CTR into the device's shaft while maintaining the entire IOL-CTR-capsule complex in a safe position behind the iris plane. No complications of the procedure were observed in all three cases. All patients had subsequent uneventful IOL exchange through sutureless scleral fixation during the same surgery. CONCLUSION: The CTR inserter provides a simple and efficient approach to CTR removal from IOL-CTR-capsule complexes dislocated into the vitreous cavity. Greater awareness of this technique among providers is needed.

A phase II dose evaluation pilot feasibility randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

BACKGROUND: Vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (ICU) and associated with worse clinical course. Trials in adult ICU demonstrate rapid restoration of vitamin D status using an enteral loading dose is safe and may improve outcomes. There have been no published trials of rapid normalization of VDD in the pediatric ICU. METHODS: We conducted a multicenter placebo-controlled phase II pilot feasibility randomized clinical trial from 2016 to 2017. We randomized 67 critically ill children with VDD from ICUs in Canada, Chile and Austria using a 2:1 randomization ratio to receive a loading dose of enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or placebo. Participants, care givers, and outcomes assessors were blinded. The primary objective was to determine whether the loading dose normalized vitamin D status (25(OH)D > 75 nmol/L). Secondary objectives were to evaluate for adverse events and assess the feasibility of a phase III trial. RESULTS: Of 67 randomized participants, one was withdrawn and seven received more than one dose of cholecalciferol before the protocol was amended to a single loading dose, leaving 59 participants in the primary analyses (40 treatment, 19 placebo). Thirty-one/38 (81.6%) participants in the treatment arm achieved a plasma 25(OH)D concentration > 75 nmol/L versus 1/18 (5.6%) the placebo arm. The mean 25(OH)D concentration in the treatment arm was 125.9 nmol/L (SD 63.4). There was no evidence of vitamin D toxicity and no major drug or safety protocol violations. The accrual rate was 3.4 patients/month, supporting feasibility of a larger trial. A day 7 blood sample was collected for 84% of patients. A survey administered to 40 participating families showed that health-related quality of life (HRQL) was the most important outcome for families for the main trial (30, 75%). CONCLUSIONS: A single 10,000 IU/kg dose can rapidly and safely normalize plasma 25(OH)D concentrations in critically ill children with VDD, but with significant variability in 25(OH)D concentrations. We established that a phase III multicentre trial is feasible. Using an outcome collected after hospital discharge (HRQL) will require strategies to minimize loss-to-follow-up. CLINICALTRIALS: gov NCT02452762 Registered 25/05/2015.

Global COVID-19 lockdown highlights humans as both threats and custodians of the environment.

The global lockdown to mitigate COVID-19 pandemic health risks has altered human interactions with nature. Here, we report immediate impacts of changes in human activities on wildlife and environmental threats during the early lockdown months of 2020, based on 877 qualitative reports and 332 quantitative assessments from 89 different studies. Hundreds of reports of unusual species observations from around the world suggest that animals quickly responded to the reductions in human presence. However, negative effects of lockdown on conservation also emerged, as confinement resulted in some park officials being unable to perform conservation, restoration and enforcement tasks, resulting in local increases in illegal activities such as hunting. Overall, there is a complex mixture of positive and negative effects of the pandemic lockdown on nature, all of which have the potential to lead to cascading responses which in turn impact wildlife and nature conservation. While the net effect of the lockdown will need to be assessed over years as data becomes available and persistent effects emerge, immediate responses were detected across the world. Thus, initial qualitative and quantitative data arising from this serendipitous global quasi-experimental perturbation highlights the dual role that humans play in threatening and protecting species and ecosystems. Pathways to favorably tilt this delicate balance include reducing impacts and increasing conservation effectiveness.

Advances in dry eye disease treatment.

PURPOSE OF REVIEW: The prevalence and burden of dry eye disease continues to grow at a rapid pace, creating an increased need for new therapies. In a sector once limited to only a handful of treatments, clinicians now have multiple options available for patients who fail traditional therapies. This review summarizes the various treatment options available to clinicians treating complex dry eye disease patients. RECENT FINDINGS: As we better understand the multifactorial mechanisms leading to dry eye disease, treatments increasingly focus on the amelioration of the underlying deficiencies and inflammation, rather than on transient symptomatic relief alone. Most topical medications seek to replace deficient growth factors and/or decrease inflammation on the ocular surface. The majority of new devices and procedures seek to treat meibomian gland dysfunction, with one new device stimulating tear production through utilizing the nasolacrimal reflex pathway. SUMMARY: Clinicians have more options at their disposal in the treatment of dry eye disease than ever before, including topical medications and devices.

Reproducibility of radioactive iodine uptake (RAIU) measurements.

BACKGROUND: Measurement of radioactive iodine uptake (RAIU) is an important aspect of the assessment and treatment of patients with hyperthyroidism. Its uncertainty affects how much of a true change in RAIU can be detected as well as appropriateness of the therapy dosage upon which it is based. In this study, a method of estimating the reproducibility and least significant change (LSC) values for RAIU measurements, and the implications of the values observed are discussed, with emphasis on application to quality assurance initiatives. METHODS: We prospectively studied 36 consecutive patients referred for RAIU measurements. Twenty-four hours after oral administration of 370 kBq of 131 I-NaI in capsule form, RAIU measurements were obtained in duplicate using a thyroid probe uptake system. Assessment of reproducibility was performed using root-mean-square standard deviation. RESULTS: Average difference between duplicated RAIU measurements in our study cohort was -0.1 ± 1.6% and ranged from -4.8% to 3.1%. Reproducibility of probe-based RAIU measurement was calculated to be 1.1% and 95% LSC was 3.2%. CONCLUSION: In our clinic, probe-based RAIU is a reproducible and relatively precise measurement. Using the method we have outlined, each institution can perform reproducibility assessment and compute the LSC of RAIU measurements based on its own staff, iodine isotope, equipment, protocols, and patient population. These values are useful in the assessment of serial change in RAIU, and as more experience is accumulated, can serve as benchmarks to be used in quality assurance initiatives.

Unified theory of whispering gallery multilayer microspheres with single dipole or active layer sources.

The development of a fast and reliable whispering gallery mode (WGM) simulator capable of generating spectra that are comparable with experiment is an important step forward for designing microresonators. We present a new model for generating WGM spectra for multilayer microspheres, which allows for an arbitrary number of concentric dielectric layers, and any number of embedded dipole sources or uniform distributions of dipole sources to be modeled. The mode excitation methods model embedded nanoparticles, or fluorescent dye coatings, from which normalized power spectra with accurate representation of the mode coupling efficiencies can be derived. In each case, the emitted power is expressed conveniently as a function of wavelength, with minimal computational load. The model makes use of the transfer-matrix approach, incorporating improvements to its stability, resulting in a reliable, general set of formulae for calculating whispering gallery mode spectra. In the specific cases of the dielectric microsphere and the single-layer coated microsphere, our model simplifies to confirmed formulae in the literature.

Quantification of the fluorescence sensing performance of microstructured optical fibers compared to multi-mode fiber tips.

Microstructured optical fibers, particularly those with a suspended-core geometry, have frequently been argued as efficient evanescent-field fluorescence-based sensors. However, to date there has not been a systematic comparison between such fibers and the more common geometry of a multi-mode fiber tip sensor. In this paper we make a direct comparison between these two fiber sensor geometries both theoretically and experimentally. Our results confirm that suspended-core fibers provide a significant advantage in terms of total collected fluorescence signal compared to multi-mode fibers using an equivalent experimental configuration.

S-nitrosylation therapy to improve oxygen delivery of banked blood.

From the perspectives of disease transmission and sterility maintenance, the world's blood supplies are generally safe. However, in multiple clinical settings, red blood cell (RBC) transfusions are associated with adverse cardiovascular events and multiorgan injury. Because ∼85 million units of blood are administered worldwide each year, transfusion-related morbidity and mortality is a major public health concern. Blood undergoes multiple biochemical changes during storage, but the relevance of these changes to unfavorable outcomes is unclear. Banked blood shows reduced levels of S-nitrosohemoglobin (SNO-Hb), which in turn impairs the ability of stored RBCs to effect hypoxic vasodilation. We therefore reasoned that transfusion of SNO-Hb-deficient blood may exacerbate, rather than correct, impairments in tissue oxygenation, and that restoration of SNO-Hb levels would improve transfusion efficacy. Notably in mice, administration of banked RBCs decreased skeletal muscle pO2, but infusion of renitrosylated cells maintained tissue oxygenation. In rats, hemorrhage-induced reductions in muscle pO2 were corrected by SNO-Hb-repleted RBCs, but not by control, stored RBCs. In anemic awake sheep, stored renitrosylated, but not control RBCs, produced sustained improvements in O2 delivery; in anesthetized sheep, decrements in hemodynamic status, renal blood flow, and kidney function incurred following transfusion of banked blood were also prevented by renitrosylation. Collectively, our findings lend support to the idea that transfusions may be causally linked to ischemic events and suggest a simple approach to prevention (i.e., SNO-Hb repletion). If these data are replicated in clinical trials, renitrosylation therapy could have significant therapeutic impact on the care of millions of patients.

Q-factor limits for far-field detection of whispering gallery modes in active microspheres.

This paper investigates the Q-factor limits imposed on the far-field detection of the whispering gallery modes of active microspherical resonators. It is shown that the Q-factor measured for a given active microsphere in the far-field using a microscope is significantly lower than that measured using evanescent field collection through a taper. The discrepancy is attributed to the inevitable small asphericity of microspheres that results in mode-splitting which becomes unresolvable in the far-field. Analytic expressions quantifying the Q-factor limits due to small levels of asphericity are subsequently derived.

Method for predicting whispering gallery mode spectra of spherical microresonators.

A full three-dimensional Finite-Difference Time-Domain (FDTD)-based toolkit is developed to simulate the whispering gallery modes of a microsphere in the vicinity of a dipole source. This provides a guide for experiments that rely on efficient coupling to the modes of microspheres. The resultant spectra are compared to those of analytic models used in the field. In contrast to the analytic models, the FDTD method is able to collect flux from a variety of possible collection regions, such as a disk-shaped region. The customizability of the technique allows one to consider a variety of mode excitation scenarios, which are particularly useful for investigating novel properties of optical resonators, and are valuable in assessing the viability of a resonator for biosensing.

Mass spectrometric characterization of methylaluminoxane-activated metallocene complexes.

Electrospray-ionization mass spectrometric studies of poly(methylaluminoxane) (MAO) in the presence of [Cp2 ZrMe2 ], [Cp2 ZrMe(Cl)], and [Cp2 ZrCl2 ] in fluorobenzene (PhF) solution are reported. The results demonstrate that alkylation and ionization are separate events that occur at competitive rates in a polar solvent. Furthermore, there are significant differences in ion-pair speciation that result from the use of metallocene dichloride complexes in comparison to alkylated precursors at otherwise identical Al/Zr ratios. Finally, the counter anions that form are dependent on the choice of precursor and Al/Zr ratio; halogenated aluminoxane anions [(MeAlO)x (Me3 Al)y-z (Me2 AlCl)z Me](-) (z=1, 2, 3…︁) are observed using metal chloride complexes and under some conditions may predominate over their non-halogenated precursors [(MeAlO)x (Me3 Al)y Me](-) . Specifically, this halogenation process appears selective for the anions that form in comparison to the neutral components of MAO. Only at very high Al/Zr ratios is the same "native" anion distribution observed when using [Cp2 ZrCl2 ] when compared with [Cp2 ZrMe2 ]. Together, the results suggest that the need for a large excess of MAO when using metallocene dichloride complexes is a reflection of competitive alkylation vs. ionization, the persistence of unreactive, homodinuclear ion pairs in the case of [Cp2 ZrCl2 ], as well as a change in ion pairing resulting from modification of the anions formed at lower Al/Zr ratios. Models for neutral precursors and anions are examined computationally.

Evaluation of Research Productivity among Academic Glaucoma Specialists Using the Relative Citation Ratio.

PURPOSE: To provide relative citation ratio (RCR) benchmark data for the field of glaucoma. DESIGN: Cross-sectional bibliometric analysis. SUBJECTS: Fellowship-trained glaucoma faculty at Accreditation Council for Graduate Medical Education-accredited institutions. METHODS: Glaucoma faculty were individually indexed using the National Institutes of Health (NIH) iCite website. Publication count, mean RCR score, and weighted RCR score were collected for each author between May and August 2023 and included PubMed-listed articles from 1980 to 2023. Data were compared by sex, career duration, academic rank, and acquisition of a Doctor of Philosophy (PhD). MAIN OUTCOME MEASURES: Total number of publications, mean RCR value, and weighted RCR value. RESULTS: Five hundred twenty-six academic glaucoma specialists from 113 institutions were indexed. These physicians produced highly impactful research with a median publication count of 13 (interquartile range [IQR] 4-38), median RCR of 1.41 (IQR 0.97-1.98), and median weighted RCR of 16.89 (4.80-63.39). Academic rank, career duration, and having a PhD were associated with increased publication count, mean RCR, and weighted RCR. Publication count and weighted RCR differed significantly by sex; however, no difference was observed with mean RCR. CONCLUSIONS: Current academic glaucoma specialists have high mean RCR values relative to the NIH standard RCR value of 1. This benchmark data serve as a more accurate gauge of research impact within the glaucoma community and can be used to inform self, institutional, and departmental evaluations. Additionally, the mean RCR may provide an accurate metric for quantifying research productivity among historically underrepresented groups that are disadvantaged by time-dependent factors such as number of publications. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Evaluation of Research Productivity Among Academic Cornea, External Diseases, and Refractive Surgery Ophthalmologists Using the Relative Citation Ratio.

PURPOSE: The purpose of this study was to provide relative citation ratio (RCR) benchmark data for cornea and external diseases specialists. DESIGN: This is a cross-sectional bibliometric analysis. SUBJECTS: Subjects included were fellowship-trained cornea and external diseases faculty at Accreditation Council for Graduate Medical Education-accredited institutions in the United States. METHODS: Academic specialists were indexed using the National Institutes of Health iCite Web site. Publication count, mean RCR score, and weighted RCR score were obtained between October 2022 and January 2023 by examining PubMed-listed publications from 1980 to 2022. Data were compared by sex, career duration, academic rank, and acquisition of a Doctor of Philosophy. MAIN OUTCOME MEASURES: The main outcome measures were publication count, mean RCR value, and weighted RCR value. RESULTS: The cohort included 602 specialists from 112 Accreditation Council for Graduate Medical Education-accredited institutions. These clinician-scientists produced highly impactful research with a median publication count of 15 (interquartile ranges 4-41), median RCR of 1.4 (interquartile ranges 0.91-1.88), and median-weighted RCR of 20.28 (5.3-66.69). Both academic rank and career length were associated with greater publication count and RCR values. Male sex was also associated with greater publications counts and RCR scores compared with female faculty. Acquisition of a Doctor of Philosophy was associated with greater publication counts and weighted RCR scores but no difference in mean RCR scores. CONCLUSIONS: Academic cornea and external diseases specialists conduct high-impact research, with a median RCR of 1.4, exceeding the NIH standard value of 1. These data provide RCR benchmark data for the field to inform self, institutional, and departmental evaluations. These results also highlight a significant gender disparity in the field necessitating efforts to increase female representation and ensure equal opportunities.

Changes in CpG Methylation of the Vitellogenin 1 Promoter in Adult Male Zebrafish after Exposure to 17α-Ethynylestradiol.

Numerous pharmaceutical and industrial chemicals are classified as endocrine-disrupting chemicals (EDCs) that interfere with hormonal homeostasis, leading to developmental disorders and other pathologies. The synthetic estrogen 17α-ethynylestradiol (EE2) is used in oral contraceptives and other hormone therapies. EE2 and other estrogens are inadvertently introduced into aquatic environments through municipal wastewater and agricultural effluents. Exposure of male fish to estrogens increases expression of the egg yolk precursor protein vitellogenin (Vtg), which is used as a molecular marker of exposure to estrogenic EDCs. The mechanisms behind Vtg induction are not fully known, and we hypothesized that it is regulated via DNA methylation. Adult zebrafish were exposed to either dimethyl sulfoxide or 20 ng/L EE2 for 14 days. Messenger RNA (mRNA) expression and DNA methylation were assessed in male zebrafish livers at 0, 0.25, 0.5, 1, 4, 7, and 14 days of exposure; and those of females were assessed at 13 days (n ≥ 4/group/time point). To test the persistence of any changes, we included a recovery group that received EE2 for 7 days and did not receive any for the following 7 days, in the total 14-day study. Methylation of DNA at the vtg1 promoter was assessed with targeted gene bisulfite sequencing in livers of adult male and female zebrafish. A significant increase in vtg1 mRNA was observed in the EE2-exposed male fish as early as 6 h. Interestingly, DNA methylation changes were observed at 4 days. Decreases in the overall methylation of the vtg1 promoter in exposed males resulted in levels comparable to those in female controls, suggesting feminization. Importantly, DNA methylation levels in males remained significantly impacted after 7 days post-EE2 removal, unlike mRNA levels. These data identify an epigenetic mark of feminization that may serve as an indicator of not only estrogenic exposure but also previous exposure to EE2. Environ Toxicol Chem 2024;43:1547-1556. © 2024 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Enhancing the radiation efficiency of dye doped whispering gallery mode microresonators.

We present a novel form of a Whispering Gallery Mode (WGM) sensor that exploits dye doped polystyrene microspheres, as active resonators, positioned onto the tip of a Microstructured Optical Fiber (MOF) as a means of overcoming the limited Q-factors for small resonators. We show that it is possible to substantially enhance the fluorescence emission of selected WGMs of the microspheres, resulting in an increase of the signal-to-noise ratio of the modes and of the effective Q-factor. This is done by positioning the resonator into one of the holes of a suspended core MOF and matching the resonator diameter with the hole diameter where it sits, effectively breaking the symmetry of the environment surrounding the sphere. Furthermore we demonstrate that using this experimental configuration, the lasing efficiency of the dye-doped microspheres is also significantly enhanced, which also contributes to an enhancement in the observed Q-factor.

An Approach for Evaluating Potential Screening Thresholds Using Biomarker Population Distribution and Analytical Imprecision.

BACKGROUND: A common approach in laboratory medicine is to use a simple but sensitive test to screen samples to identify those that require additional investigation with a more complex and informative method. Selection of screening thresholds can be guided by biomarker distribution in the tested population and the analytical imprecision of the method. METHODS: A simulation using joint probabilities derived from the population distribution for galactose-1-phosphate uridylyltransferase (GALT) activity and the analytical imprecision for the GALT assay was used to estimate the number of samples that would require repeat analysis and the number of samples with possibly false-negative screening determinations due to analytical imprecision. RESULTS: In the case of GALT activity, screening a conservative initial threshold 6 standard deviations from the confirmation threshold can essentially eliminate the chance of a false-negative screening determination due to analytical imprecision. The trade-off is a greater number of samples requiring follow-up testing (n = 222, equivalent to 0.15% of samples annually). CONCLUSIONS: Selection of thresholds in a screening algorithm is informed by estimates of the number of samples that would require repeat testing and the number that could be false negative due to analytical imprecision.

Evaluation of Research Productivity among Academic Vitreoretinal Surgeons Using the Relative Citation Ratio.

PURPOSE: To provide relative citation ratio (RCR) benchmark data for the field of vitreoretinal surgery. DESIGN: Cross-sectional bibliometric analysis. SUBJECTS: Fellowship-trained vitreoretinal faculty at Accreditation Council for Graduate Medical Education-accredited institutions. METHODS: Academic vitreoretinal surgeons were individually indexed using the National Institutes of Health iCite Website. Publication count, mean RCR score, and weighted RCR score were collected for each author between June and July 2022 and included PubMed-listed articles from 1980 to 2022. Data were compared by gender, career duration, academic rank, and acquisition of a Doctor of Philosophy (PhD). MAIN OUTCOME MEASURES: Total number of publications, mean RCR value, and weighted RCR value. RESULTS: Our sample consisted of 677 academic vitreoretinal surgeons from 113 institutions. These physicians produced highly impactful research with a median publication count of 30 (interquartile range [IQR], 11-82), median RCR of 1.78 (IQR, 1.09-3.00), and median weighted RCR of 59.83 (14.31-195.78). Academic rank and career duration were associated with increased publication count, mean RCR, and weighted RCR. Publication count and weighted RCR differed significantly by gender; however, no difference was observed with mean RCR. CONCLUSIONS: Current academic vitreoretinal surgeons have high mean RCR values relative to the National Institutes of Health standard RCR value of 1. This benchmark data serves as a more accurate gauge of research impact within the vitreoretinal community and can be used to inform self, institutional, and departmental evaluations. Additionally, the mean RCR may provide an accurate metric for quantifying research productivity among historically underrepresented groups that are disadvantaged by time-dependent factors, such as number of publications. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.