How to assess the risks associated with the usage of a medical device based on predictive modeling: the case of an anemia control model certified as medical device.

Background: The successful application of Machine Learning (ML) to many clinical problems can lead to its implementation as a medical device (MD), which is important to assess the associated risks.

Methods: An anemia control model (ACM), certified as MD, may face adverse events as a result of wrong predictions that are translated into suggestions of doses of erythropoietic stimulating agents to dialysis patients. Risks are assessed as the combination of severity and probability of a given hazard.

Performance of a Predictive Model for Long-Term Hemoglobin Response to Darbepoetin and Iron Administration in a Large Cohort of Hemodialysis Patients.

Anemia management, based on erythropoiesis stimulating agents (ESA) and iron supplementation, has become an increasingly challenging problem in hemodialysis patients. Maintaining hemodialysis patients within narrow hemoglobin targets, preventing cycling outside target, and reducing ESA dosing to prevent adverse outcomes requires considerable attention from caregivers. Anticipation of the long-term response (i.

Computational intelligence for the Balanced Scorecard: studying performance trends of hemodialysis clinics.

Objectives: The Balanced Scorecard (BSC) is a general, widely employed instrument for enterprise performance monitoring based on the periodic assessment of strategic Key Performance Indicators that are scored against preset targets. The BSC is currently employed as an effective management support tool within Fresenius Medical Care (FME) and is routinely analyzed via standard statistical methods. More recently, the application of computational intelligence techniques (namely, self-organizing maps) to BSC data has been proposed as a way to enhance the quantity and quality of information that can be extracted from it.

Use of Self-Organizing Maps for Balanced Scorecard analysis to monitor the performance of dialysis clinic chains.

The Balanced Scorecard (BSC) is a validated tool to monitor enterprise performances against specific objectives. Through the choice and the evaluation of strategic Key Performance Indicators (KPIs), it provides a measure of the past company's outcome and allows planning future managerial strategies. The Fresenius Medical Care (FME) BSC makes use of 30 KPIs for a continuous quality improvement strategy within its dialysis clinics.

Dysregulation of axonal transport and motorneuron diseases.

MNDs (motorneuron diseases) are neurodegenerative disorders in which motorneurons located in the motor cortex, in the brainstem and in the spinal cord are affected. These diseases in their inherited or sporadic forms are mainly characterized by motor dysfunctions, occasionally associated with cognitive and behavioural alterations. Although these diseases show high variability in onset, progression and clinical symptoms, they share common pathological features, and motorneuronal loss invariably leads to muscle weakness and atrophy.

An interdomain interaction of the androgen receptor is required for its aggregation and toxicity in spinal and bulbar muscular atrophy.

Polyglutamine expansion within the androgen receptor (AR) causes spinal and bulbar muscular atrophy (SBMA) and is associated with misfolded and aggregated species of the mutant AR. We showed previously that nuclear localization of the mutant AR was necessary but not sufficient for SBMA. Here we show that an interdomain interaction of the AR that is central to its function within the nucleus is required for AR aggregation and toxicity.

17-AAG increases autophagic removal of mutant androgen receptor in spinal and bulbar muscular atrophy.

Several types of motorneuron diseases are linked to neurotoxic mutant proteins. These acquire aberrant conformations (misfolding) that trigger deleterious downstream events responsible for neuronal dysfunction and degeneration. The pharmacological removal of misfolded proteins might thus be useful in these diseases.

A role of small heat shock protein B8 (HspB8) in the autophagic removal of misfolded proteins responsible for neurodegenerative diseases.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of upper and lower motor neurons. As with other age-dependent neurodegenerative disorders, ALS is linked to the presence of misfolded proteins that may perturb several intracellular mechanisms and trigger neurotoxicity. Misfolded proteins aggregate intracellularly generating insoluble inclusions that are a key neuropathological hallmark of ALS.

Proteasomal and autophagic degradative activities in spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA or Kennedy's disease) is a fatal neurodegenerative disease characterized by the selective loss of motor neurons in the bulbar region of the brain and in the anterior horns of the spinal cord. The disease has been associated to an expansion of a CAG triplet repeat present in the first coding exon of the androgen receptor (AR) gene. SBMA was the first identified member of a large class of neurodegenerative diseases now known as CAG-related diseases, which includes Huntington's disease (HD), several types of spinocerebellar ataxia (SCAs), and dentatorubral and pallidoluysian atrophy (DRPLA).

The small heat shock protein B8 (HspB8) promotes autophagic removal of misfolded proteins involved in amyotrophic lateral sclerosis (ALS).

Several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), are characterized by the presence of misfolded proteins, thought to trigger neurotoxicity. Some familial forms of ALS (fALS), clinically indistinguishable from sporadic ALS (sALS), are linked to superoxide dismutase 1 (SOD1) gene mutations. It has been shown that the mutant SOD1 misfolds, forms insoluble aggregates and impairs the proteasome.

The role of the polyglutamine tract in androgen receptor.

The androgen receptor (AR) is a ligand-activated transcription factor which is responsible for the androgen responsiveness of target cells. Several types of mutations have been found in the AR and linked to endocrine dysfunctions. Surprisingly, the polymorphism involving the CAG triplet repeat expansion of the AR gene, coding for a polyglutamine (PolyGln) tract in the N-terminal transactivation domain of the AR protein, has been involved either in endocrine or neurological disorders.

Mutation of SOD1 in ALS: a gain of a loss of function.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by motoneuron loss. Some familial cases (fALS) are linked to mutations of superoxide dismutase type-1 (SOD1), an antioxidant enzyme whose activity is preserved in most mutant forms. Owing to the similarities in sporadic and fALS forms, mutant SOD1 animal and cellular models are a useful tool to study the disease.