Geriatric Assessment in Advanced Kidney Disease Brown, Edwina Anne; Farrington, Ken
Clinical journal of the American Society of Nephrology,
07/2019, Letnik:
14, Številka:
7
Journal Article
The absence of accepted patient-centered outcomes in research can limit shared decision-making in peritoneal dialysis (PD), particularly because PD-related treatments can be associated with ...mortality, technique failure, and complications that can impair quality of life. We aimed to identify patient and caregiver priorities for outcomes in PD, and to describe the reasons for their choices.
Patients on PD and their caregivers were purposively sampled from nine dialysis units across Australia, the United States, and Hong Kong. Using nominal group technique, participants identified and ranked outcomes, and discussed the reasons for their choices. An importance score (scale 0-1) was calculated for each outcome. Qualitative data were analyzed thematically.
Across 14 groups, 126 participants (81 patients, 45 caregivers), aged 18-84 (mean 54, SD 15) years, identified 56 outcomes. The ten highest ranked outcomes were PD infection (importance score, 0.27), mortality (0.25), fatigue (0.25), flexibility with time (0.18), BP (0.17), PD failure (0.16), ability to travel (0.15), sleep (0.14), ability to work (0.14), and effect on family (0.12). Mortality was ranked first in Australia, second in Hong Kong, and 15th in the United States. The five themes were serious and cascading consequences on health, current and impending relevance, maintaining role and social functioning, requiring constant vigilance, and beyond control and responsibility.
For patients on PD and their caregivers, PD-related infection, mortality, and fatigue were of highest priority, and were focused on health, maintaining lifestyle, and self-management. Reporting these patient-centered outcomes may enhance the relevance of research to inform shared decision-making.
Introduction. Little is known about physical symptoms in peritoneal dialysis (PD) Patients. This study aims to determine the prevalence of symptoms (general and abdominal) in PD patients. Methods. A ...cross-sectional study, with subsequent followup, using an author-designed 21 symptoms questionnaire (15 nonabdominal and 6 abdominal). Each symptom was assessed on a scale 0–3 for severity (none–severe) and frequency (never–every day). Results. We studied 41 patients, mean age 60±15 years, 56% male, 19.5% diabetics, and 51.5% on APD. Mean number of symptoms was 9.5±3.9 and total symptoms score was 28.5±12 with abdominal scores of 6.4±4.8. Most frequent symptoms were lack of energy, itching, cramps, poor sleep, and loss of appetite. A second evaluation in 20 patients disclosed no statistical difference between the first and second assessments, or between subgroups. Cramps were the only symptoms which decreased over time (P=0.120). Lack of energy did not correlate with haemoglobin, neither did itching with phosphate level. Conclusions. Physical symptoms are frequent and troublesome; they relate to advanced kidney disease and not specifically to PD. Symptoms remain stable over time and do not appear to relate to dialysis parameter markers.
Cyathostomins are the most important and common parasitic nematodes of horses, with > 50 species known to occur worldwide. The frequent and indiscriminate use of anthelmintics has resulted in the ...development of anthelmintic resistance (AR) in horse nematodes. In this study we assessed the efficacy of commonly used anthelmintics against cyathostomins in Australian thoroughbred horses.
Two drug efficacy trials per farm were conducted on two thoroughbred horse farms in the state of Victoria, Australia. In the first trial, the horses on Farm A were treated with single and combinations of anthelmintics, including oxfendazole (OFZ), abamectin (ABM), abamectin and morantel (ABM + MOR), moxidectin (MOX) and oxfendazole and pyrantel (OFZ + PYR), at the recommended doses, whereas the horses on Farm B only received MOX, at the recommended dose. The faecal egg count reduction test (FECRT) was used to determine the efficacy and egg reappearance period (ERP) of anthelmintics. Based on the results of the first trial, the efficacies of MOX and a combination of ABM + MOR were reassessed to confirm their activities against cyathostomins.
Of the five anthelmintic products tested on Farm A, resistance against OFZ, ABM and OFZ + PYR was found, with efficacies of - 41% (- 195% lower confidence limit LCL), 73% (60% LCL) and 82% (66% LCL) at 2 weeks post-treatment, respectively. The FECRT showed high efficacies of MOX and ABM + MOR (100%) at 2 week post-treatment and shortened ERPs for these anthelmintics (ABM + MOR: 4 weeks; MOX: 5 weeks). Resistance to MOX was found on Farm B, with a reduced efficacy of 90% (70% LCL) and 89% (82% LCL) at 2 weeks post-treatment in trials one and two, respectively.
This study provides the first evidence of MOX- and multidrug-resistant (ABM and combinations of anthelmintics) cyathostomins in Australia and indicates the need for continuous surveillance of the efficacy of currently effective anthelmintics and large-scale investigations to assess the ERP for various anthelmintics.
miRNA malfunction causes spinal motor neuron disease Haramati, Sharon; Chapnik, Elik; Sztainberg, Yehezkel ...
Proceedings of the National Academy of Sciences - PNAS,
07/2010, Letnik:
107, Številka:
29
Journal Article
Recenzirano
Odprti dostop
Defective RNA metabolism is an emerging mechanism involved in ALS pathogenesis and possibly in other neurodegenerative disorders. Here, we show that microRNA (miRNA) activity is essential for ...long-term survival of postmitotic spinal motor neurons (SMNs) in vivo. Thus, mice that do notprocess miRNAin SMNs exhibit hallmarks of spinal muscular atrophy (SMA), including sclerosis of the spinal cord ventral horns, aberrant end plate architecture, and myofiber atrophy with signs of denervation. Furthermore, a neurofilament heavy subunit previously implicated in motor neuron degeneration is specifically up-regulated in miRNA-deficient SMNs. We demonstrate that the heavy neurofilament subunit is a target of miR-9, a miRNA that is specifically down-regulated in a genetic model of SMA. These data provide evidence for miRNA function in SMN diseases and emphasize the potential role of miR-9–based regulatory mechanisms in adult neurons and neurodegenerative states.
Strongyloides westeri is found in the small intestine of young horses, mainly in foals up to about 16 weeks of age. The main source of infection for foals is through transmammary transmission, and ...foals can develop acute diarrhoea, weakness, dermatitis and respiratory signs. The epidemiology of S. westeri in Australia is largely unknown. Further, molecular techniques have never been employed for detection of S. westeri in horses. This pilot study aimed to assess the utility of a molecular phylogenetic method for the detection of S. westeri in the faeces of foals.
Faecal samples were collected from a foal of less than 2 months of age, and eggs of Strongyloides sp. were detected using the modified McMaster technique. DNA was extracted from purified eggs, and a partial fragment of the small subunit of the nuclear ribosomal DNA (18S) was characterised using polymerase chain reaction, DNA sequencing and phylogenetic methods.
Microscopic examination of faeces revealed small ellipsoidal eggs typical of Strongyloides sp. The 18S sequence generated by PCR in this study revealed 98.4% identity with that of a reference sequence of S. westeri available from GenBank. Phylogenetic analyses revealed a polyphyletic clustering of S. westeri sequences.
This is the first study reporting the detection of DNA of Strongyloides sp. in faeces of a foal using a molecular phylogenetic approach targeting the variable region of 18S rDNA. It is anticipated that this study will allow future molecular epidemiological studies on S. westeri in horses.
Cyathostomins are the most common and highly prevalent parasites of horses worldwide. Historically, the control of cyathostomins has mainly relied on the routine use of anthelmintic products. ...Increasing reports on anthelmintic resistance (AR) in cyathostomins are concerning. A potential method proposed for detecting emerging AR in cyathostomins has been estimating the egg reappearance period (ERP). This paper reviews the data available for the ERP of cyathostomins against the three major classes of anthelmintics, macrocyclic lactones, tetrahydropyrimidines, and benzimidazoles. Published peer-reviewed original research articles were obtained from three databases (PubMed, CAB Direct and Web of Science) and were evaluated for their inclusion in a systematic review. Subsets of articles were then subjected to a review of ERP data. A total of 54 (of 134) studies published between 1972 and 2022 met the criteria for inclusion in the systematic review. Until the beginning of 2022, there was no agreed definition of the ERP; eight definitions of ERP were identified in the literature, complicating the comparison between studies. Additionally, potential risk factors for the shortening of the ERP, including previous anthelmintic use and climate, were frequently not described. Reports of shortened ERP for moxidectin and ivermectin are frequent: 20 studies that used comparable ERP definitions reported shortened moxidectin and ivermectin ERPs of 35 and 28 days, respectively. It is unclear whether the ERPs of these anthelmintics reduced to such levels are due to the development of AR or some biological factors related to horses, cyathostomin species, and/or the environment. The ERPs for other anthelmintics, such as fenbendazole and pyrantel, were frequently not reported due to established resistance against these drugs. Future research in horses is required to understand the mechanism(s) behind the shortening of ERP for cyathostomins. Based on this systematic review, we propose recommendations for future ERP studies.
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•Is the egg reappearance period (ERP) an early indicator of anthelmintic resistance?•A summary of cyathostomins ERP for equine registered anthelmintics from 1972 to 2022.•Recent developments on the definition of ERP.•Proposed recommendations for future ERP studies.