Kidney failure amongst Irish Travellers.

BACKGROUND: The occurrence of Kidney Failure with Replacement Therapy (KFRT) amongst Irish Travellers has not been well described. This study aims to determine the burden of KFRT amongst the Irish Traveller population and identify determinants of health amongst this cohort which may differ from the general population in Ireland. METHODS: This retrospective cohort study included self-identifying Irish Travellers with KFRT registered in the National Kidney Disease Clinical Patient Management System between 1995 and 2022. KFRT was defined as Chronic Kidney Disease stage 5 (CKD G5) treated by dialysis or CKD G1-G5 after transplantation. The primary outcome measure was the prevalence of KFRT in Irish Travellers. Secondary exploratory outcomes included age at diagnosis, family history, biopsy diagnosis, kidney replacement therapy (KRT) modality, time to initiation of KRT, primary vascular access used, and time to receive a kidney transplant. RESULTS: Four of six Irish hospital groups participated in the study. A total of 38 patients were identified as Irish Travellers with KFRT, with a crude prevalence rate of KFRT of 0.12% (CI 0.084-0.161, 95%) or 11.9 per 10,000 Irish Travellers. The mean age for diagnosis of kidney disease was 43 (SD, 20.8) and at commencement of KRT was 45 (SD, 20.9) years. A biopsy-proven diagnosis was provided in 24%. Twenty-two per cent was diagnosed with polycystic kidney disease or congenital anomalies of the kidney and urinary tract. The predominant modality for KRT was haemodialysis (89%), with central venous catheters being the most common initial vascular access (79%). Kidney transplants occurred in 45% of those studied, with a mean waiting time of 1.96 (SD, 1.6) years. CONCLUSIONS: The Irish Traveller community have similar prevalence of KFRT when compared to the national prevalence, with a short time interval from diagnosis to commencement of KRT. They are less likely to avail of home therapies but have comparable wait times to the national waiting time to receive a kidney transplant.

Cardiologist Evaluation and Approval Was the Primary Predictor of Kidney Transplant Candidacy and Transplantation Among Patients With Reduced Left Ventricular Ejection Fraction.

End-stage kidney disease patients with concomitant heart failure (HF) with reduced ejection fraction are often denied kidney transplantation. The aims of this study were to explore factors predictive of suitability for kidney transplant and to assess cardiovascular outcomes in patients with impaired left ventricular ejection fraction (LVEF) after transplant. Methods: We evaluated 109 consecutive adults with LVEF ≤40% at the time of initial kidney transplant evaluation between 2013 and 2018. Posttransplant cardiovascular outcomes were defined as nonfatal myocardial infarction (MI), admission for HF, cardiovascular death, and all-cause mortality. Results: A cardiologist participated in kidney transplant evaluation for 87% of patients and was present at 49% of transplant selection conferences. Twenty-four patients (22%) were denied by a cardiologist for kidney transplant' and 59 (54%) were denied by the selection committee, of whom 43 were because of cardiovascular risk. Forty-two (38%) patients were approved for kidney transplant. On univariate analysis, the variables associated with denial for kidney transplant included cardiologist denial, higher cardiac troponin T, prior coronary intervention, cardiovascular event, positive stress study, lower ejection fraction, and lower VO2 max (all P < 0.05). Cardiologist denial was the most significant predictor of denial for kidney transplant in different multivariate models. At a median follow-up of 15 mo, 5 (5%) suffered nonfatal MI, 13 (12%) were hospitalized for HF exacerbation, and 17 (16%) died. Only 22 patients, 52% of those approved, underwent kidney transplant. After kidney transplant, there was 1 death, 1 nonfatal MI, and 3 hospitalizations for HF. Median LVEF improved from 38% before listing to 55% posttransplant. Conclusions: Cardiologist denial was the primary predictor of rejection for kidney transplant. Despite careful selection, prevalence of cardiovascular events and mortality after kidney transplant was 23%. There is need for a structured multidisciplinary approach for patients with impaired LVEF.

What Works to Improve and Manage Fecal Incontinence in Care Home Residents Living With Dementia? A Realist Synthesis of the Evidence.

The prevalence of fecal incontinence (FI) in care homes is estimated to range from 30% to 50%. There is limited evidence of what is effective in the reduction and management of FI in care homes. Using realist synthesis, 6 potential program theories of what should work were identified. These addressed clinician-led support, assessment, and review; the contribution of teaching and support for care home staff on how to reduce and manage FI; addressing the causes and prevention of constipation; how cognitive and physical capacity of the resident affects outcomes; how the potential for recovery, reduction, and management of FI is understood by those involved; and how the care of people living with dementia and FI is integral to the work patterns of the care home and its staff. Dementia was a known risk factor for fecal incontinence (FI), but how it affected uptake of different interventions or the dementia specific continence and toileting skills staff require, were not addressed in the literature. There was a lack of dementia-specific evidence on continence aids. Most care home residents with FI will be doubly incontinent; there is, therefore, limited value in focusing solely on FI or single causes, such as constipation. Medical and nursing support for continence care is an important resource, but it is unhelpful to create a distinction between what is continence care and what is personal or intimate care. Prompted toileting is an approach that may be particularly beneficial for some residents. Valuing the intimate and personal care work unqualified and junior staff provide to people living with dementia and reinforcement of good practice in ways that are meaningful to this workforce are important clinician-led activities. Providing dementia-sensitive continence care within the daily work routines of care homes is key to helping to reduce and manage FI for this population.

Pleomorphic xanthoastrocytomas: institutional experience of 18 patients.

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade glioma (World Health Organization Grade II) that most often presents in the first two decades of life. We summarize and present our institutional experience in the management of these tumors. All patients managed for PXA at the University of California San Francisco were retrospectively identified through chart review. Patient demographics, tumor characteristics, management, and follow-up were extracted using medical records. Primary endpoints were overall (OS) and progression-free survival (PFS). In total, nineteen patients were treated for PXA from 1993-2011. Clinical data were available for analysis in 18 patients. Median OS was 209.0 months after date of surgery, with both 5 year and 10 year survival rates of 94%. In this patient cohort, tumor grade (p=0.07), age (p=0.32), and extent of resection (p=0.58) did not predict OS. The majority of tumors (78%) recurred. Median PFS was 21.7 months, with 5 year and 10 year recurrence-free rates of 28% and 22%. On univariate analysis, tumor grade (p=0.01), but not age (p=0.51), size (p=0.30), or extent of resection (p=0.21), was the only covariate predictive of PFS. In patients presenting with higher tumor grade, however, earlier recurrence was demonstrated. Furthermore, the majority of recurrences (36%) occurred within the first 6 months post-operatively, which indicates the need to closely follow patients for that time.

Modern treatment of 84 newly diagnosed craniopharyngiomas.

There is debate regarding the appropriate treatment for craniopharyngiomas, which often present symptomatically given their proximity to critical brain structures, and pose significant surgical challenges. The goal of this study is to identify which patient and tumor characteristics are associated with specific preoperative symptoms, surgical complications, patient outcomes, and tumor recurrence in order to guide craniopharyngioma treatment. We retrospectively identified 84 patients with newly diagnosed craniopharyngiomas treated at our institution from 1986-2010. We used binary logistic regression and survival analysis to determine the effect of several variables (including sex, age, tumor size, location, surgical approach, and extent of resection) on preoperative symptoms and postoperative outcomes, including complication rates and tumor recurrence. Age and tumor location were associated with increased rates of preoperative symptoms, with children being more likely than adults to present with endocrine dysfunction, and intraventricular tumors being more likely than extraventricular tumors to present with headaches and hydrocephalus. A transcranial surgical approach was associated with 1.5 times higher rate of surgical complications than transsphenoidal surgery, while only intraventricular tumor location was associated with a poorer patient outcome. The main factor significantly associated with tumor recurrence was extent of resection. We conclude that intraventricular tumor location is most highly correlated with preoperative symptoms. If feasible, transsphenoidal approaches are preferred, as they result in fewer surgical complications, and gross total resections are optimal because they lead to lower rates of recurrence. When gross total resection is not possible, we favor multimodal treatment approaches.

Adjuvant radiotherapy for atypical and malignant meningiomas: a systematic review.

Atypical meningiomas (AMs) and malignant meningiomas (MMs) are tumors with a lower incidence and poorer prognosis than benign meningiomas. The role of radiotherapy as an adjuvant to surgical resection, especially for AMs, is incompletely defined. In this study, the English-language literature was systematically reviewed for studies that reported tumor characteristics, treatment parameters, and clinical outcomes after adjuvant radiotherapy for AM and MM, including overall survival, progression-free survival, and/or time to recurrence or mortality. Clinical outcomes were further assessed in the context of resection status, timing of administration, and radiation dose. Outcomes after stereotactic radiosurgery were also examined. Treatment toxicity and other potential prognostic or confounding factors were appraised. Ten and 11 studies for AM and MM, respectively, met the inclusion criteria. The median 5-year progression-free survival and overall survival after adjuvant radiotherapy were 54.2% and 67.5%, respectively, for AM and 48% and 55.6% for MM. The complication rates were 11.1% for AM and 5.1% for MM. Incomplete resection and radiation dose <50 Gy conferred significantly poorer 5-year progression-free survival. Most studies were unable to demonstrate a statistically significant prognostic benefit for adjuvant radiotherapy in AM. In conclusion, adjuvant radiotherapy significantly improved local control of AMs and MMs, especially after subtotal resection. Study limitations, including inadequate statistical power, may underlie the studies' inability to demonstrate a statistically significant benefit for adjuvant radiotherapy in AM. Because these tumors preferentially recur within 5 years of surgical resection, future studies should define whether early adjuvant therapy should become part of the standard treatment paradigm for completely excised tumors.

The prognostic implications of Hyam's subtype for patients with Kadish stage C esthesioneuroblastoma.

Esthesioneuroblastoma (EN) is a rare sinonasal tumor with varied aggressiveness and potential for intracranial invasion. EN is staged anatomically with radiographic evaluation using the Kadish staging system (stages A, B, and C) and histologically by using Hyam's criteria (grades 1-4). Here we show that despite radiographic evidence of aggressive features, the prognosis of patients with Kadish stage C EN is best predicted by tumor histology using Hyam's criteria. We retrospectively analyzed patients with EN with Kadish stage C who were evaluated and treated at our institution between 1995 and 2009. Clinical information was collected using patient medical records, imaging, and review of pathological specimens. Twenty patients with Kadish stage C EN were identified with mean age of 51 years (31-70 years) with a median follow-up of 41.4 months (1.3-175 months). Upon pathological review, 44.4% of patients had low-grade (1/2) and 55.6% had high-grade (3/4) histology. About 37.5% of patients with low-grade EN had undergone gross total resection (GTR) and the remaining 62.5% had GTR and adjuvant radiation, whereas 50% of patients with high-grade ER had undergone GTR, 20% had undergone GTR and adjuvant radiation, and 30% had been treated with a subtotal resection (STR) and adjuvant radiation. The 5-year and 10-year survival in patients with low-grade EN was 86% in comparison to 56% and 28% with high-grade EN, respectively. In patients with low-grade EN, the 2-year progression free survival (PFS) was 86% and the 5-year PFS was 65% in comparison to 73% and 49% in patients with high-grade EN, respectively. The patient's tumor histology (Hyam's criteria) appeared to be the best way of predicting the prognosis and for selecting patients for adjuvant radiotherapy.

The methadone epidemic: methadone-related deaths on the rise in Vermont.

The prevalence of methadone-related overdose deaths is increasing worldwide and has been a topic of recent debate. Methadone-related deaths, to this point, have not been systematically reviewed in the state of Vermont. All of the methadone-related fatalities from 2001 to 2006 (total, 76 cases), which were examined by the Vermont Office of the Chief Medical Examiner were retrospectively reviewed. The mean age of the decedents was 36 years (range, 16-74 years), and 72% were male. The manners of death were classified as follows: 84% accident, 12% undetermined, and 4% suicide. The mean level of methadone was 457 ng/mL (range, 50-3793 ng/mL). The substances causing death were determined to be methadone alone in 26 (34%), methadone with only other prescribed medications in 29 (38%), methadone with only illicit drugs (excluding tetrahydrocannabinol) in 13 (17%), methadone with both illicit and prescribed medications in 5 (7%), and methadone with ethanol in 3 (4%). The methadone was obtained by illegal diversion (sale, gift, or theft) in 67% of cases. In the remaining cases (33%), the methadone was obtained by physician's prescription for chronic pain (60%), acute pain or injury (8%), methadone maintenance therapy for heroin dependence (8%), and unknown reasons (24%). The number of overdose deaths has increased 4-fold from 2001 (17 deaths) to 2006 (79 deaths). The proportion of methadone-related deaths has increased by 300% from 2001 (0.6% of reported deaths, 12% of overdose deaths) to 2006 (3% of reported deaths, 37% of overdose deaths). Methadone maintenance therapy for heroin dependence in our population comprises an insignificant number of the methadone-related deaths (3% of the decedents). In Vermont, the populations most at risk are those taking methadone for chronic pain and those obtaining diverted methadone for abuse. Education of clinicians regarding the increasing number of methadone-related deaths, the potential for abuse and diversion, and the pharmacokinetics of methadone may help halt this epidemic and reduce the number of fatalities from this drug.

Chiral purity assay for Flindokalner using tandem mass spectrometry: method development, validation, and benchmarking.

The present work demonstrates the application and validation of a mass spectrometry method for quantitative chiral purity determination. The particular compound analyzed is Flindokalner, a Bristol-Myers Squibb drug candidate for post-stroke neuroprotection. Chiral quantification of Flindokalner was achieved using tandem mass spectrometry (MS/MS) and the kinetic method, a gas phase method used for thermochemical and chiral determinations. The MS/MS method was validated and benchmarked against two separate chromatographic techniques, chiral high performance liquid chromatography with ultra-violet detection (LC/UV) and achiral high performance liquid chromatography with circular dichroism detection (LC/CD). The chiral purity determination of Flindokalner using MS/MS proved to be rapid (3 min run time for each sample) and to have accuracy and precision comparable to the chiral LC/UV and achiral LC/CD methods. This method represents an alternative to commonly used chromatographic techniques as a means of chiral purity determination and is particularly useful in rapid screening experiments.