Microbial Transfer by Intermittent Catheters: An In Vitro Evaluation of Microbial Transfer in Catheter With Variable Protective Features.

PURPOSE: The purpose of this study was to evaluate the effects of various protective features (eg, catheter cap, introducer tip, and catheter sleeve) of hydrophilic intermittent catheters against contamination with urinary tract infection-associated microorganisms using an in vitro model. DESIGN: An in vitro study of microbial transfer. MATERIALS AND METHODS: Gloves were contaminated with uropathogenic microorganisms and used to simulate intermittent catheterization of male anatomical models with and without the protective features present in 5 commercially available hydrophilic catheters. Using this contaminated touch transfer method, both the meatus of the sterile male anatomical models and sterile surgical gloves of an operator were inoculated with a high level of microorganisms (107 and 109 colony-forming units [CFU], respectively). The operator then performed catheterization of the anatomical model. The most relevant segments of the catheter were sampled, and the level of microbial transfer and catheter contamination was quantified. Results from experimental and sample replicates from the 3 microbial species and 5 catheters (sleeved and unsleeved) were analyzed by pair-wise t tests and analysis of variance. RESULTS: Of the 5 commercially available sleeved intermittent catheters evaluated in this study, use of catheters with multiple protective components (ring cap, introducer tip, and catheter sleeve) resulted in significant improvement in protection against contamination with a 25- to 2500-fold lower level of microbial contamination (C1 segment) across all species as compared to catheters protected with only sleeves or un-sleeved catheters. CONCLUSIONS: The combination of a ring cap, protective introducer tip, and protective sleeve provides additional protection when compared to sleeve alone from transferring microbial contamination from the meatus to the advancing catheter. Additional research is needed to determine whether these design features result in fewer urinary tract infections among intermittent catheter users.

A Cross-Sectional Survey Reporting on the Value of Patient-Centered Ostomy Programs: A Smooth Transition After Ostomy Surgery.

PURPOSE: The purpose of the study was to evaluate a postsurgical ostomy patient support program in regard to postsurgical experience, education, skin care, pouching system and accessory use, insurance issues, supplier assistance, hospital readmission status, and the benefit of multiple interactions. DESIGN: Cross-sectional design. SUBJECTS AND SETTING: Potential respondents were randomly selected from a group of adults 18 years or older who underwent ostomy surgery within 6 months prior to survey completion. Nine hundred seventy-one individuals met inclusion criteria, and 297 were selected for analysis, based on having 1 or more program interactions. Data were collected between the second and third quarters of 2020. All participants were residents of the United States. METHODS: Participants were contacted by e-mail containing an invitation to participate in a survey; the e-mail also described the intent of the survey. Survey distribution was conducted by the sponsor and linked to a third-party survey management organization for compilation. The survey questionnaire, developed specifically for the purpose of this study, comprised 73 items that queried demographic and pertinent clinical data, participation in an industry-sponsored patient support program, and their post-hospital discharge experiences including unplanned health care provider visits, emergency department visits, and hospital readmissions. RESULTS: Eighty-three percent (n = 237) of respondents did not have postsurgical ostomy-related emergency department visits, 75% (n = 223) did not have related unplanned physician visits, and 90% (n = 268) did not have related hospitalizations. Participants with 2 or more interactions were more likely to contact a program representative for issues of stoma care, leakage and skin care, ostomy products/accessories, and supplier issues than their single-interaction counterparts. CONCLUSIONS: Study findings suggest that patients with new ostomies benefited from engagement in an industry-sponsored patient support program. The benefit appears to arise from personal interactions and respondents; 2 or more interactions were shown to have greater benefit than a single interaction.

Incidence of urinary tract infection following initiation of intermittent catheterization among patients with recent spinal cord injury in Germany and the Netherlands.

Objective: To assess incidence of urinary tract infection (UTI) among patients with recent spinal cord injury (SCI) who initiated intermittent catheterization (IC).Design: Retrospective chart review.Setting: Two European SCI rehabilitation centers.Participants: Seventy-three consecutive patients with recent SCI who initiated IC.Outcome measures: Incidence of UTI, using six different definitions, each based on microbiology ± symptomatology ± mention of UTI . Rates were expressed in terms of numbers of UTIs per 100 patient-months (PMs). Attention was focused on first-noted UTI during the three-month follow-up, as assessed with each of the six definitions.Results: Fifty-eight percent of patients (n = 33) met ≥1 definitions for UTI during follow-up (rate: 31.5 UTIs per 100 PMs), ranging from 14% (5.3 per 100 PMs; definition requiring bacteriuria, pyuria, and presence of symptoms) to 45% (22.7 per 100 PMs; definition requiring "mention of UTI"). Ten cases were identified using the definition that required bacteriuria, pyuria, and symptoms, whereas definitions that required bacteriuria and either pyuria or symptoms resulted in the identification of 20-25 cases. Median time to UTI ranged from 42 days ("mention of UTI") to 81 days (definition requiring bacteriuria and ≥100 leukocytes/mm3).Conclusion: Depending on definition, 14% to 45% of patients with recent SCI experience UTI within three months of initiating IC. Definitions requiring bacteriuria and either pyuria or symptoms consistently identified about twice as many cases as those that required all three conditions. Standardizing definitions may help improve detection, treatment, and prevention of UTI within this vulnerable population.

Evolving Evidence Supporting Use of Rectal Irrigation in the Management of Bowel Dysfunction: An Integrative Literature Review.

Disorders of bowel function are prevalent, particularly among patients with spinal cord injuries and other neurological disorders. An individual's bowel control significantly impacts quality of life, as predictable bowel function is necessary to actively and independently participate in everyday activities. For many patients with bowel dysfunction, initial lifestyle adjustments and other conservative therapeutic interventions (eg, digital stimulation, oral laxatives, suppositories) are insufficient to reestablish regular bowel function. In addition to these options, rectal irrigation (RI) is a safe and effective method of standard bowel care that has been used for several decades in adults and children suffering from bowel dysfunction associated with neurogenic or functional bowel etiologies. Rectal irrigation is an appropriate option when conservative bowel treatments are inadequate. Unlike surgical options, RI can be initiated or discontinued at any time. This report summarizes the clinical, humanistic, and economic evidence supporting the use of RI in clinical practice, noting features (eg, practical considerations, patient education) that can improve patients' success with RI treatment.

The burden of illness in initiating intermittent catheterization: an analysis of German health care claims data.

BACKGROUND: Intermittent catheterization (IC) is a common medical technique to drain urine from the bladder when this is no longer possible by natural means. The objective of this study was to evaluate the standard of care and the burden of illness in German individuals who perform intermittent catheterization and obtain recommendations for improvement of care. METHODS: A descriptive study with a retrospective, longitudinal cohort design was conducted using the InGef research database from the German statutory health insurance claims data system. The study consisted of individuals with initial IC use in 2013-2015. RESULTS: Within 3 years 1100 individuals with initial IC were identified in the database (~ 19,000 in the German population). The most common IC indications were urologic diseases, spinal cord injury, Multiple Sclerosis and Spina Bifida. Urinary tract infections (UTI) were the most frequent complication occurring 1 year before index (61%) and in follow-up (year 1 60%; year 2 50%). Resource use in pre-index including hospitalizations (65%), length of stay (12.8 ± 20.0 days), physician visits (general practitioner: 15.2 ± 29.1), prescriptions of antibiotics (71%) and healthcare costs (€17,950) were high. Comorbidities, complications, and healthcare resource use were highest 1 year before index, decreasing from first to second year after index. CONCLUSIONS: The data demonstrated that prior to initial catheterization, IC users experienced UTIs and high healthcare utilization. While this demonstrates a potential high burden of illness prior to initial IC, UTIs also decreased over time, suggesting that IC use may have a positive influence. The findings also showed that after the first year of initial catheterization the cost decreased. Further studies are needed to better understand the extent of the burden for IC users compared to non-IC users.

A Patient-Centric Tool to Facilitate Goal Attainment Scaling in Neurogenic Bladder and Bowel Dysfunction: Path to Individualization.

OBJECTIVES: People with neurogenic bladder and/or bowel dysfunction experience diverse challenges that can be difficult to evaluate with standardized outcome measures. Goal attainment scaling (GAS) is an individualized, patient-centric outcome measure that enables patients/caregivers to identify and track their own treatment goals. Because creating goals de novo can be cumbersome, we aimed to develop a neurogenic bladder/bowel dysfunction goal menu to facilitate goal attainment scaling uptake and use. METHODS: We conducted a workshop with 6 expert clinicians to develop an initial menu. Individual interviews with 12 people living with neurogenic bladder and/or bowel dysfunction and 2 clinician panels with 5 additional experts aided us in refining the menu. A thematic framework analysis identified emergent themes for analysis and reporting. RESULTS: Interview participants were adults (median = 36 years, range 25-58), most with spinal cord injury (75%; 9/12). Of 24 goals identified initially, 2 (8%) were not endorsed and were removed, and 3 goals were added. Most participants listed "Impact on Life" goals (eg, Exercise, Emotional Well-Being) among their 5 most important goals (58%; 35/60). Three main themes emerged: challenges posed by incontinence, limitations on everyday life, and need for personalized care. CONCLUSIONS: We developed a clinical outcome assessment tool following a multistep process of representative stakeholder engagement. This patient-centric tool consists of 25 goals specific to people living with neurogenic bladder and/or bowel dysfunction. Asking people what matters most to them can identify important constructs that clinicians might have overlooked.

Postauthorization safety surveillance study of antihaemophilic factor (recombinant) reconstituted in 2 mL sterile water for injection in children with haemophilia A.

INTRODUCTION: Antihaemophilic factor (recombinant) (rAHF; ADVATE® ) is approved for prophylaxis and treatment of bleeding in children and adults with haemophilia A. Reconstitution in 2 mL sterile water for injection instead of 5 mL allows for a 60% reduction in infusion volume and administration time, but could increase the likelihood of hypersensitivity and infusion-related reactions, especially in children. AIM: To assess local tolerability, safety and effectiveness of rAHF 2 mL during routine clinical practice factor VIII (FVIII) replacement (on-demand and prophylaxis) in children with severe (FVIII < 1%) or moderately severe (FVIII 1%-2%) haemophilia A. METHODS: This was a prospective, non-interventional, postauthorization safety surveillance study (NCT02093741). Eligible patients were previously treated with rAHF and had a negative inhibitor test result during ≤10 exposure days prior to study entry. RESULTS: Of 65 patients enrolled (0-11 years of age), 54 and 11 had severe and moderately severe haemophilia A, respectively; 56 patients received prophylaxis, and 11 had ≤50 exposure days, of which 4 had ≤4 exposure days. No patients reported local hypersensitivity reactions, treatment-related adverse events or developed inhibitors. Investigators rated overall effectiveness of rAHF 2 mL prophylaxis as excellent or good. Ninety-four bleeding events in 34 patients were treated. Haemostatic effectiveness was rated as excellent or good for 75.8% of bleeds; 86.2% of bleeds required 1 or 2 infusions. CONCLUSION: In children with severe/moderately severe haemophilia A, no hypersensitivity reactions were reported with rAHF 2 mL treatment, and the safety and effectiveness are consistent with data previously reported for rAHF 5 mL.

Factors influencing health-related quality of life of those in the Netherlands living with an ostomy.

BACKGROUND: this study examined the health-related quality of life (HRQoL) and wellbeing of people in the Netherlands who had undergone ostomy surgery. AIMS: to assess how an ostomy population perceives their HRQoL and determine key stressors that influence HRQoL in this population. METHODS: a cross-sectional survey, including the City of Hope National Medical Center Quality of Life Questionnaire for patients with an ostomy and a Visual Analogue Scale measuring HRQoL, was used to evaluate postsurgical patients. FINDINGS: people with an ostomy in the Netherlands have a generally positive HRQoL, but this may be affected by peristomal skin irritation, experience of leakage on to the peristomal skin and whether their surgery was planned. CONCLUSIONS: access to specialist nurse support and products designed to prevent leakage and prevent skin irritation-two key drivers of HRQoL-may be able to maximise an individual's health status throughout their lifelong journey as a person with an ostomy.

In Their Own Words: Adults' Lived Experiences With Intermittent Catheterization.

PURPOSE: The aim of this study was to identify themes related to barriers and facilitators to the integration of intermittent catheterization (IC) in the daily lives or persons using the form of bladder evacuation. DESIGN: Descriptive, qualitative study. SUBJECTS AND SETTING: A purposive sample of 25 adults from 5 countries (United States, United Kingdom, Germany, France, and the Netherlands) was assembled. All participants had used IC as their primary method of bladder emptying for at least 1 year and, in that time, had used as least 2 different IC products. METHODS: Guided telephone interviews with each participant were conducted by professional staff fluent in each participant's local language as well as trained in qualitative data collection. Interviews were digitally recorded and subsequently transcribed verbatim into English for analysis. We used ATLAS.ti qualitative analysis software (version 7.5.11) to assist with data organization and identification of major themes. Descriptive statistics (eg, mean, standard deviation, or frequency) were used to characterize the sample in terms of sociodemographic and clinical characteristics as collected during the interview. RESULTS: Analysis revealed 9 main themes around individuals' lived experiences of IC: initial fear, urinary tract infection, pain/discomfort, independence, choice, community, life quality, resilience, and acceptance. DISCUSSION: Our results indicate that IC is perceived as a burden by some, but not all, users. The challenge, and opportunity, is to learn more about what has gone right for those who have adapted and to leverage the clinical, practical, psychological, and social factors that enable individuals to integrate IC into the rhythm of their daily lives.

A multinational evaluation assessing the relationship between peristomal skin health and health utility.

BACKGROUND:: irritation to peristomal skin remains one of the most prevalent ostomy-related complications influencing an individual's health status and quality of life. AIMS:: to assess the impact of damaged peristomal skin on the health utility and quality-adjusted life days (QALD) in an international adult ostomy population. METHODS:: a cross-sectional survey incorporating the SF-6D preference-based health utility index was developed to assess a random selection of post-surgical patients. FINDINGS:: health utility decreased with increasing skin irritation among the three geographic groups. The total mean health utility of normal peristomal skin for the three groups dropped incrementally for mild, moderate, and severe irritation. There were no differences in health utility or QALDs between the three country groups. CONCLUSION:: improvement of peristomal skin health is associated with improvements to QALDs. Clinicians, caregivers and patients have the responsibility to address a critical unmet need in skin health through interventions and products designed to support healthy peristomal skin.

Polyethylene Glycol Exposure with Antihemophilic Factor (Recombinant), PEGylated (rurioctocog alfa pegol) and Other Therapies Indicated for the Pediatric Population: History and Safety.

Polyethylene glycol (PEG) is an inert, water soluble polymer, used for decades in pharmaceuticals. Although PEG is considered safe, concerns persist about the potential adverse effects of long-term exposure to PEG-containing therapies, specifically in children, following the introduction of PEGylated recombinant factor products used for the treatment of hemophilia. Given the absence of long-term surveillance data, and to evaluate the potential risk, we estimated PEG exposure in the pediatric population receiving PEGylated therapies with pediatric indications administered intravenously or intramuscularly. We used a range of pediatric weights and doses based on prescribing information (PI) or treatment guidelines. PIs and reporting websites were searched for information about adverse events (AEs). For a child weighing 50 kg on the highest prophylactic dose of a FVIII product, the range of total PEG exposure was 40⁻21,840 mg/year; for factor IX (FIX) products, the range was 13⁻1342 mg/year; and for other products, the range was 383⁻26,743 mg/year, primarily as a derivative excipient. No AE patterns attributable to PEG were found for any of these products, including potential renal, neurological, or hepatic AEs. Our analyses suggest the pediatric population has had substantial exposure to PEG for several decades, with no evidence of adverse consequences.

Nonaminoglycoside compounds induce readthrough of nonsense mutations.

Large numbers of genetic disorders are caused by nonsense mutations for which compound-induced readthrough of premature termination codons (PTCs) might be exploited as a potential treatment strategy. We have successfully developed a sensitive and quantitative high-throughput screening (HTS) assay, protein transcription/translation (PTT)-enzyme-linked immunosorbent assay (ELISA), for identifying novel PTC-readthrough compounds using ataxia-telangiectasia (A-T) as a genetic disease model. This HTS PTT-ELISA assay is based on a coupled PTT that uses plasmid templates containing prototypic A-T mutated (ATM) mutations for HTS. The assay is luciferase independent. We screened approximately 34,000 compounds and identified 12 low-molecular-mass nonaminoglycosides with potential PTC-readthrough activity. From these, two leading compounds consistently induced functional ATM protein in ATM-deficient cells containing disease-causing nonsense mutations, as demonstrated by direct measurement of ATM protein, restored ATM kinase activity, and colony survival assays for cellular radiosensitivity. The two compounds also demonstrated readthrough activity in mdx mouse myotube cells carrying a nonsense mutation and induced significant amounts of dystrophin protein.

Intrinsic mitochondrial dysfunction in ATM-deficient lymphoblastoid cells.

One of the characteristic features of cells from patients with ataxia telangiectasia (A-T) is that they are in a state of continuous oxidative stress and exhibit constitutive activation of pathways that normally respond to oxidative damage. In this report, we investigated whether the oxidative stress phenotype of A-T cells might be a reflection of an intrinsic mitochondrial dysfunction. Mitotracker Red staining showed that the structural organization of mitochondria in A-T cells was abnormal compared to wild-type. Moreover, A-T cells harbored a much larger population of mitochondria with decreased membrane potential (DeltaPsi) than control cells. In addition, the basal expression levels of several nuclear DNA-encoded oxidative damage responsive genes whose proteins are targeted to the mitochondria--polymerase gamma, mitochondrial topoisomerase I, peroxiredoxin 3 and manganese superoxide dismutase--are elevated in A-T cells. Consistent with these results, we found that overall mitochondrial respiratory activity was diminished in A-T compared to wild-type cells. Treating A-T cells with the antioxidant, alpha lipoic acid (ALA), restored mitochondrial respiration rates to levels approaching those of wild-type. When wild-type cells were transfected with ATM-targeted siRNA, we observed a small but significant reduction in the respiration rates of mitochondria. Moreover, mitochondria in A-T cells induced to stably express full-length ATM, exhibited respiration rates approaching those of wild-type cells. Taken together, our results provide evidence for an intrinsic mitochondrial dysfunction in A-T cells, and implicate a requirement for ATM in the regulation of mitochondrial function.

Constitutive phosphorylation of ATM in lymphoblastoid cell lines from patients with ICF syndrome without downstream kinase activity.

Double strand DNA breaks in the genome lead to the activation of the ataxia-telangiectasia mutated (ATM) kinase in a process that requires ATM autophosphorylation at serine-1981. ATM autophosphorylation only occurs if ATM is previously acetylated by Tip60. The activated ATM kinase phosphorylates proteins involved in arresting the cell cycle, including p53, and in repairing the DNA breaks. Chloroquine treatment and other manipulations that produce chromatin defects in the absence of detectable double strand breaks also trigger ATM phosphorylation and the phosphorylation of p53 in primary human fibroblasts, while other downstream substrates of ATM that are involved in the repair of DNA double strand breaks remain unphosphorylated. This raises the issue of whether ATM is constitutively activated in patients with genetic diseases that display chromatin defects. We examined lymphoblastoid cell lines (LCLs) generated from patients with different types of chromatin disorders: Immunodeficiency, Centromeric instability, Facial anomalies (ICF) syndrome, Coffin Lowry syndrome, Rubinstein Taybi syndrome and Fascioscapulohumeral Muscular Dystrophy. We show that ATM is phosphorylated on serine-1981 in LCLs derived from ICF patients but not from the other syndromes. The phosphorylated ATM in ICF cells did not phosphorylate the downstream targets NBS1, SMC1 and H2AX, all of which require the presence of double strand breaks. We demonstrate that ICF cells respond normally to ionizing radiation, ruling out the possibility that genetic deficiency in ICF cells renders activated ATM incapable of phosphorylating its downstream substrates. Surprisingly, p53 was also not phosphorylated in ICF cells or in chloroquine-treated wild type LCLs. In this regard the response to chromatin-altering agents differs between primary fibroblasts and LCLs. Our findings indicate that although phosphorylation at serine-1981 is essential in the activation of the ATM kinase, serine-1981 phosphorylation is insufficient to render ATM an active kinase towards downstream substrates, including p53.