Chaperone Therapy in Fabry Disease Weidemann, Frank; Jovanovic, Ana; Herrmann, Ken ...
International journal of molecular sciences,
02/2022, Volume:
23, Issue:
3
Journal Article
Peer reviewed
Open access
Fabry disease is an X-linked lysosomal multisystem storage disorder induced by a mutation in the alpha-galactosidase A (GLA) gene. Reduced activity or deficiency of alpha-galactosidase A (AGAL) leads ...to escalating storage of intracellular globotriaosylceramide (GL-3) in numerous organs, including the kidneys, heart and nerve system. The established treatment for 20 years is intravenous enzyme replacement therapy. Lately, oral chaperone therapy was introduced and is a therapeutic alternative in patients with amenable mutations. Early starting of therapy is essential for long-term improvement. This review describes chaperone therapy in Fabry disease.
Fabry disease (FD) is a rare lysosomal storage disease associated with glycolipid accumulation that impacts multiple physiological systems. We conducted a systematic literature review (SLR) to ...characterize the humanistic (quality of life QoL) and economic burden of FD.
Searches were conducted in the Embase, MEDLINE
, and MEDLINE
In-Process databases from inception to January 19, 2022. Conference abstracts of specified congresses were manually searched. Additional searches were performed in the Cochrane and ProQuest databases for the humanistic SLR and the National Health Service Economic Evaluations Database for the economic SLR. Studies of patients with FD of any sex, race, and age, and published in the English language were included. There was no restriction on intervention or comparator. For the humanistic SLR, studies that reported utility data, database/registry-based studies, questionnaires/surveys, and cohort studies were included. For the economic SLR, studies reporting economic evaluations or assessing the cost of illness and resource use were included.
Of the 1363 records identified in the humanistic search, 36 studies were included. The most commonly used QoL assessments were the 36-item Short-Form Health Survey (n = 16), EQ-5D questionnaire descriptive system or visual analog scale (n = 9), and the Brief Pain Inventory (n = 8). Reduced QoL was reported in patients with FD compared with healthy populations across multiple domains, including pain, physical functioning, and depressive symptoms. Multiple variables-including sex, age, disease severity, and treatment status-impacted QoL. Of the 711 records identified in the economic burden search, 18 studies were included. FD was associated with high cost and healthcare resource use. Contributors to the cost burden included enzyme replacement therapy, healthcare, and social care. In the seven studies that reported health utility values, lower utility scores were generally associated with more complications (including cardiac, renal, and cerebrovascular morbidities) and with classical disease in males.
FD remains associated with a high cost and healthcare resource use burden, and reduced QoL compared with healthy populations. Integrating information from QoL and economic assessments may help to identify interventions that are likely to be of most value to patients with FD.
Background/Aim. There is a constant increase in the need to use third-party reproductive cells among couples who are unable to conceive with their own reproductive cells or in order to prevent the ...passing of an existing hereditary genetic disorder to the child. The aim of the study was to present a theoretical overview and perform a practical analysis of the use of social marketing strategies using the first technique of analyzing the attitudes of potential donors of reproductive cells in the Republic of Serbia (RS) in the interest of adapting to the target group. Methods. Empirical research in this study, in which both women and men from the RS participated, was based on a questionnaire about people?s willingness to be potential reproductive cell donors and about having information on the donation of reproductive cells. The data in this paper were obtained during 2021, and the questionnaire was focused on a particular population group. The questionnaire was sent to people aged 20 to 34 years who could become potential donors of reproductive cells. In the research, 201 women and men from the RS participated. The first part of the questionnaire was tested for internal consistency, which was tested by Cronbach?s alpha coefficient calculation (?). Values of ? lower than 0.5 indicate that the questionnaire possesses unacceptable conistency. Results. A total of 57% of participants were in-formed about reproductive cell donation through the Internet, 29% by friends and family, and 11% of them were informed by doctors. Only 32% of participants were fully informed, and 25.1% were partially informed about the donation of reproductive material in the RS. Forty-three percent of participants were not informed about the donation of re-productive material. Most of the participants (54%) said they would maybe donate their reproductive material if they had more information, 20% would donate in any case, and 26% would refuse to donate reproductive material. Conclusion. The target group of potential donors of reproductive cells is present in the RS. In addition to the analysis of attitudes, further planning and implementation measures for the promotion of donation could have an influence on raising awareness about the lack of reproductive material and increase the recruitment of gamete donors.
Fabry disease is a rare, progressive X-linked lysosomal storage disorder. It is caused by mutations in the GLA gene resulting in deficiency of alpha-galactosidase A (alpha-Gal A), leading to ...peripheral neuropathy, cardiovascular disease, stroke, end-stage renal disease, gastrointestinal disorders and premature death. Given the long-term nature of disease progression, trials in Fabry disease are often not powered to capture these clinical events. Clinical measures such as estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI) are often captured instead. eGFR and LVMI are believed to be associated with long-term Fabry disease clinical events of interest, but the precise relationships are unclear. We aimed to identify published literature exploring the link between eGFR/LVMI and long-term clinical events in Fabry disease. A comprehensive literature search was conducted in EmbaseR and MEDLINER (using Embase.com), and a targeted literature review was conducted. Studies reporting a quantitative relationship between eGFR and/or LVMI and clinical events in Fabry disease were extracted, and narrative synthesis was conducted to understand these predictive relationships. Eight studies, consisting of seven patient-level retrospective analyses plus one prospective cohort study, met the inclusion criteria. Seven of these studies reported eGFR and six reported LVMI, with five reporting both. All studies presented results for either a composite measure including a range of key Fabry disease clinical events, or a composite outcome that included at least one key Fabry disease clinical event. All studies employed Cox proportional hazards survival modelling. The studies consistently reported that eGFR and LVMI are predictors of key clinical events in Fabry disease, with the findings remaining consistent regardless of the therapy received by patients in the studies. The evidence identified suggests that eGFR and LVMI outcomes may be appropriate indicators for long-term clinical events in Fabry disease, and all identified papers implied the same directional relationship. However, additional research is needed to further understand the specific details of these relationships and to quantify them.
Objective
Transcultural adaptation and validation of FACIT-TS-PS questionnaire to Serbian language.
Methods
Standard forward and backward translation from English to Serbian language was performed. ...Pilot testing of FACIT-TS-PS was conducted on 12 patients with a confirmed diagnosis of malignant tumor. The study included 154 patients with malignant disease. The Questionnaire of Patient Satisfaction was used as a validated tool to evaluate concurrent validity of FACIT-TS-PS questionnaire. Reproducibility was tested on 30 subjects who answered the questionnaire for the second time two weeks later.
Results
Three FACIT-TS-PS subscales (Physician Communication, Treatment Staff Communication and Nurse Communication) demonstrated satisfactory construct validity using Cronbach’s alpha, the remaining two subscales (Technical Competence and Confidence & Trust) showed high ceiling effect. Treatment Staff Communication subscale showed large floor effect. Concurrent validity was demonstrated by correlation with the two dimensions of the Questionnaire of Patient Satisfaction. Satisfactory reproducibility was demonstrated on 30 patients who filled the questionnaire for the second time two weeks after initial interview.
Conclusion
The Serbian version of FACIT-TS-PS with the omission of Treatment Staff Communication subscale could be used as a valid instrument to assess patient and treatment satisfaction in chronically ill patients in the Serbian population. Omission of Treatment Staff Communication subscale is necessary because it contains questions not relevant for patients in Serbian healthcare system.
OBJECTIVE: In health, the rise in glucose after lunch is less if breakfast is eaten. We evaluated the second-meal effect in type 2 diabetes. RESEARCH DESIGN AND METHODS: Metabolic changes after lunch ...in eight obese type 2 diabetic subjects were compared on 3 days: breakfast eaten, no breakfast, and no breakfast but intravenous arginine 1 h before lunch. RESULTS: Despite comparable insulin levels, the rise in plasma glucose after lunch was considerably less if breakfast had been eaten (0.68 ± 1.49 vs. 12.32 ± 1.73 vs. 7.88 ± 1.03 mmol · h⁻¹ · l⁻¹; P < 0.0001). Arginine administration almost halved the lunch rise in plasma glucose (12.32 ± 1.73 vs. 7.88 ± 1.03 mmol · h⁻¹ · l⁻¹). The plasma free fatty acid concentration at lunchtime directly related to plasma glucose rise after lunch (r = 0.67, P = 0.0005). CONCLUSIONS: The second-meal effect is preserved in type 2 diabetes. Premeal administration of a nonglucose insulin secretagogue results in halving the postprandial glucose rise and has therapeutic potential.
Transcultural adaptation and validation of the FACT-C questionnaire to Serbian language.
The study included 131 patients with colorectal cancer. Translation included standard forward and backward ...translation from original language to Serbian and back. Pilot testing of the questionnaire was conducted on 10 patients with diagnosed colorectal cancer. The questionnaires EORTC-QLQ-C30 and DASS will be used as validated tools to evaluate validity of examined, FACT-C questionnaire.
The FACT-C demonstrated satisfactory construct validity using Cronbach's alpha. Satisfactory concurrent validity was demonstrated using correlations with EORTC-QLQ-C30 and DASS questionnaires. High reproducibility was demonstrated using repeated questionnaires on 30 patients two weeks after the first interview.
The Serbian version of the FACT-C was demonstrated to have satisfactory applicability, reliability and validity in Serbian patients with colorectal cancer. It can be considered as a valid colorectal cancer specific health related quality of life tool for the Serbian population.
Enzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are ...dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations.
We conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients.
Clinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes.
ERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment.
•This article provides a systematic review of the available clinical evidence on ERT in adult male Fabry patients.•The patient population heterogeneity highlights the need for standardized reporting and population-specific guidelines.•ERT may slow down progression of cardiac and renal disease and has a positive effect on other outcomes.•Treatment effects can be optimized when ERT is started as early as possible before the onset of major organ damage.•Consolidated evidence suggests a dose effect of ERT.•Therapeutic goals for the treatment of Fabry disease with ERT help advance disease management.
Fabry disease is a rare, X-linked inherited lysosomal storage disorder, that manifests as a heterogeneous disease with renal, cardiac and nervous system involvement. The most common pain experienced ...by people with Fabry disease are episodes of neuropathic pain reported in up to 80% of classical hemizygous male patients and up to 65% of heterozygous female patients. No clear consensus exists within UK clinical practice for the assessment and management of pain in Fabry disease based on agreed clinical practice and clinical experience. Here we describe a modified Delphi initiative to establish expert consensus on management of pain in Fabry disease in the UK clinical setting.
Delphi panel members were identified based on their demonstrated expertise in managing adult or paediatric patients with Fabry disease in the UK and recruited by an independent third-party administrator. Ten expert panellists agreed to participate in two survey rounds, during which they remained anonymous to each other. Circulation of the questionnaires, and collection and processing of the panel's responses were conducted between September 2021 and December 2021. All questions required an answer.
The Delphi panel reached a consensus on 21 out of 41 aspects of pain assessment and management of pain in Fabry disease. These encompassed steps in the care pathway from the goals of therapy through to holistic support, including the use of gabapentin and carbamazepine as first-line analgesic medications for the treatment of neuropathic pain in Fabry disease, as well as the proactive management of symptoms of anxiety and/or depression associated with Fabry pain.
The consensus panel outcomes reported here have highlighted strengths in current UK clinical practice, along with unmet needs for further research and agreement. This consensus is intended to prompt the next steps towards developing clinical guidelines.
The number of people suffering from constant tinnitus is ever-increasing and has spread to all age groups, including adolescents. The etiology of tinnitus is multifactorial, but dietary factors have ...been rarely investigated. The purpose of this study is to examine the relationship between dietary factors and constant tinnitus among adolescents from an urban environment. A population-oriented cross-sectional study was carried out during the 2019/2020 school year in 12 Belgrade secondary schools. There were 1287 school children aged from 15 to 19 years who participated in the study. There were 1003 respondents who completed a questionnaire on tinnitus (response rate 77.9%; 31% male). We used the standardized Tinnitus Screener questionnaire and a food frequency questionnaire specially designed for this study and adapted to Serbian adolescents. A logistic regression analysis revealed a strong negative correlation between fresh vegetables and fruits and tinnitus presence. On the other hand, the risk of constant tinnitus increased with the increased intake of white bread, carbonated beverages, and fast food. In conclusion, we show that fresh fruit and vegetable intakes may be negatively related to tinnitus frequency, while sweetened sodas, fast food, and white bread may raise the odds for tinnitus.
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