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1.
Pharmaceutics ; 15(7)2023 Jun 29.
Article in English | MEDLINE | ID: mdl-37514038

ABSTRACT

Cystinosis is a severe inherited metabolic storage disease caused by the lysosomal accumulation of cystine. Lifelong therapy with the drug cysteamine bitartrate is necessary. Cysteamine cleaves intralysosomal cystine, and thereafter, it can exit from the organelle. The need for frequent dosing every 6 h and the high prevalence of gastrointestinal side effects lead to poor therapy adherence. The purpose of our study was to improve cysteamine treatment by comparing the efficacy of two cysteamine formulas. This is highly relevant for the long-term outcome of cystinosis patients. The cystine and cysteamine levels of 17 patients taking immediate-release cysteamine (IR-cysteamine/Cystagon®) and 6 patients taking encapsulated delayed-release cysteamine (EC-cysteamine) were analyzed. The EC-cysteamine levels showed a near-ideal pharmacokinetic profile indicative of delayed release (longer Tmax and Tmin), and the corresponding cystine levels showed few fluctuations. In addition, the Cmax of IR-cysteamine was greater, which was responsible for unbearable side effects (e.g., nausea, vomiting, halitosis, lethargy). Treatment with EC-cysteamine improves the quality of life of cystinosis patients because the frequency of intake can be reduced to 2-3 times daily and it has a more favorable pharmacokinetic profile than IR-cysteamine. In particular, cystinosis patients with no access to the only approved delayed-release cysteamine Procysbi® could benefit from a cost-effective alternative.

2.
Orphanet J Rare Dis ; 16(1): 387, 2021 09 14.
Article in English | MEDLINE | ID: mdl-34521447

ABSTRACT

BACKGROUND: Nephropathic cystinosis is a rare and severe metabolic disease leading to an accumulation of cystine in lysosomes which especially harms kidney function. A lifelong therapy with the aminothiol cysteamine can delay the development of end-stage renal disease and the necessity of kidney transplantation. The purpose of our study was to compare the effectiveness of immediate-release and delayed-release cysteamine on cystine and cysteamine levels as well as assessing the onset of adverse effects. METHODS: We retrospectively analysed cystine and cysteamine levels of 17 patients after a single dose of immediate-release cysteamine (Cystagon®, Mylan Pharmaceuticals, Canonsburg, PA and Recordati Pharma GmbH) as well as a single dose of delayed-release cysteamine (Procysbi®; Horizon Pharma USA and Chiesi Farmaceutici S.p.A., Parma, Italy) respectively. Data were collected during a period of three years in the context of optimizing the individual treatment regimens. The dose of DR-cysteamine was reduced to 70% of the equivalent dose of IR-cysteamine. The efficacy of both formulas in depleting white blood cells' cystine levels and their side effects were compared. RESULTS: Immediate (IR)- and delayed-release (DR) cysteamine effectively decreased intracellular cystine levels under the target value of 0.5 nmol cystine/mg protein, while fewer side effects occurred under DR-cysteamine. Mean maximum levels of cysteamine were reached after 60 min with IR-cysteamine and after 180 min with DR-cysteamine. CONCLUSION: A therapy with DR-cysteamine is as effective as IR-cysteamine while less side effects were reported. Our data show that DR-cysteamine should be dosed higher than 70% of the equivalent dose of IR-cysteamine in order to decrease cystine levels over an extended period of time. Moreover, our data suggest increasing the dosing scheme of Procysbi® to three times daily, to prevent a rapid decrease and achieve a steadier decline in cystine levels. Due to the more convenient dosing scheme, DR-cysteamine might ameliorate therapy adherence and improve patients' quality of life.


Subject(s)
Cystinosis , Fanconi Syndrome , Cysteamine/therapeutic use , Cystine , Cystinosis/drug therapy , Fanconi Syndrome/drug therapy , Humans , Quality of Life , Retrospective Studies
3.
Eur Arch Psychiatry Clin Neurosci ; 270(5): 501-511, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31520149

ABSTRACT

There is a need for interventions supporting patients with mental health conditions in coping with stigma and discrimination. A psycho-educational group therapy module to promote stigma coping and empowerment (STEM) was developed and tested for efficacy in patients with schizophrenia or depression. 30 clinical centers participated in a cluster-randomized clinical trial, representing a broad spectrum of mental health care settings: in-patient (acute treatment, rehabilitation), out-patient, and day-hospitals. As randomized, patients in the intervention group clusters/centers received an illness-specific eight sessions standard psychoeducational group therapy plus three specific sessions on stigma coping and empowerment ('STEM'). In the control group clusters the same standard psychoeducational group therapy was extended to 11 sessions followed by one booster session in both conditions. In total, N = 462 patients were included in the analysis (N = 117 with schizophrenia spectrum disorders, ICD-10 F2x; N = 345 with depression, ICD-10 F31.3-F31.5, F32-F34, and F43.2). Clinical and stigma-related measures were assessed before and directly after treatment, as well as after 6 weeks, 6 months, and 12 months (M12). Primary outcome was improvement in quality of life (QoL) assessed with the WHO-QOL-BREF between pre-assessment and M12 analyzed by mixed models and adjusted for pre-treatment differences. Overall, QoL and secondary outcome measures (symptoms, functioning, compliance, internalized stigma, self-esteem, empowerment) improved significantly, but there was no significant difference between intervention and control group. The short STEM module has proven its practicability as an add-on in different settings in routine mental health care. The overall increase in empowerment in both, schizophrenia and depression, indicates patients' treatment benefit. However, factors contributing to improvement need to be explored.The study has been registered in the following trial registers. ClinicalTrials.gov: https://register.clinicaltrials.gov/ Registration number: NCT01655368. DRKS: https://www.drks.de/drks_web/ Registration number: DRKS00004217.


Subject(s)
Adaptation, Psychological , Depressive Disorder/rehabilitation , Empowerment , Mentally Ill Persons/psychology , Outcome Assessment, Health Care , Psychotherapy, Group , Schizophrenia/rehabilitation , Social Stigma , Adult , Female , Humans , Male , Middle Aged , Patient Education as Topic , Quality of Life , Self Concept
4.
J Bone Miner Res ; 32(9): 1789-1801, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28272751

ABSTRACT

The study aimed to estimate excess mortality in patients aged 60 years or older up to 1 year after pelvic fracture compared with a population without pelvic fracture. In this retrospective population-based observational study, we use routine data from a large health insurance in Germany. For each patient with a first pelvic fracture between 2008 and 2010 (n = 5685 cases, 82% female, mean age 80 ± 9 years), about 34 individuals without pelvic fracture (n = 193,159 controls) were frequency matched by sex, age at index date, and index month. We estimated survival probabilities in the first year after the index date separated for cases (further stratified into inpatient/outpatient treated or minor/major pelvic fractures) and controls using Kaplan-Meier curves. Additionally, time-dependent hazard ratios (HRs) measuring excess mortality in 4-week intervals up to 52 weeks were estimated by fitting Cox regression models including adjustment for relevant confounders. Twenty-one percent of cases and 11% of controls died within 1 year. HRs (95% confidence intervals) decreased from 3.9 (3.5-4.5) within the first 4 weeks to 1.4 (1.1-1.9) within weeks 49 to 52 after the index date. After full adjustment, HRs lowered substantially (3.0 [2.6-3.4] and 1.0 [0.8-1.4]) but were still significantly increased up to week 32. Adjusted HRs in women were lower than in men: 2.8 (2.4-3.2) and 1.0 (0.7-1.4) versus 3.8 (2.9-5.0) and 1.2 (0.6-2.3). We found a clear excess mortality among older people in the first 8 months after pelvic fracture even after full adjustment. Excess mortality was higher among men in the beginning as well as for inpatient-treated persons. Absence of excess mortality was noticed for outpatient-treated persons within the first 3 months. When broken down into site-specific data, excess mortality was no longer significant for most pelvic fractures classified as minor. The only exception was fracture of pubis within the first 4 weeks. © 2017 American Society for Bone and Mineral Research.


Subject(s)
Aging , Fractures, Bone/mortality , Pelvic Bones , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Male , Retrospective Studies , Survival Rate , Time Factors
5.
PLoS One ; 10(9): e0139078, 2015.
Article in English | MEDLINE | ID: mdl-26418971

ABSTRACT

Epidemiological data about pelvic fractures are limited. Until today, most studies only analyzed inpatient data. The purpose of this study was to estimate incidence rates of pelvic fractures in the German population aged 60 years or older, based on outpatient and inpatient data. We conducted a retrospective population-based observational study based on routine data from a large health insurance company in Germany. Age and sex-specific incidence rates of first fractures between 2008 and 2011 were calculated. We also standardized incidence rates with respect to age and sex in the German population. Multiple Poisson regression models were used to evaluate the association between the risk of first pelvic fracture as outcome and sex, age, calendar year and region as independent variables. The total number of patients with a first pelvic fracture corresponded to 8,041 and during the study period 5,978 insured persons needed inpatient treatment. Overall, the standardized incidence rate of all first pelvic fractures was 22.4 [95% CI 22.0-22.9] per 10,000 person-years, and the standardized incidence rate of inpatient treated fractures 16.5 [16.1-16.9]. Our adjusted regression analysis confirmed a significant sex (RR 2.38 [2.23-2.55], p < 0.001, men as reference) and age effect (higher risk with increasing age, p < 0.001) on first fracture risk. We found a slight association between calendar year (higher risk in later years compared to 2008, p = 0.0162) and first fracture risk and a further significant association with region (RR 0.92 [0.87-0.98], p = 0.006, Westfalen-Lippe as reference). The observed incidences are considerably higher than incidences described in the international literature, even if only inpatient treated pelvic fractures are regarded. Besides which, non-inclusion of outpatient data means that a relevant proportion of pelvic fractures are not taken into account. Prevention of low energy trauma among older people remains an important issue.


Subject(s)
Hip Fractures/epidemiology , Hospitalization/statistics & numerical data , Pelvic Bones/injuries , Activities of Daily Living , Age Factors , Aged , Aged, 80 and over , Female , Germany/epidemiology , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Sex Factors
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