Exploratory Assessment of K-means Clustering to Classify 18F-Flutemetamol Brain PET as Positive or Negative.

RATIONALE: We evaluated K-means clustering to classify amyloid brain PETs as positive or negative. PATIENTS AND METHODS: Sixty-six participants (31 men, 35 women; age range, 52-81 years) were recruited through a multicenter observational study: 19 cognitively normal, 25 mild cognitive impairment, and 22 dementia (11 Alzheimer disease, 3 subcortical vascular cognitive impairment, and 8 Parkinson-Lewy Body spectrum disorder). As part of the neurocognitive and imaging evaluation, each participant had an 18F-flutemetamol (Vizamyl, GE Healthcare) brain PET. All studies were processed using Cortex ID software (General Electric Company, Boston, MA) to calculate SUV ratios in 19 regions of interest and clinically interpreted by 2 dual-certified radiologists/nuclear medicine physicians, using MIM software (MIM Software Inc, Cleveland, OH), blinded to the quantitative analysis, with final interpretation based on consensus. K-means clustering was retrospectively used to classify the studies from the quantitative data. RESULTS: Based on clinical interpretation, 46 brain PETs were negative and 20 were positive for amyloid deposition. Of 19 cognitively normal participants, 1 (5%) had a positive 18F-flutemetamol brain PET. Of 25 participants with mild cognitive impairment, 9 (36%) had a positive 18F-flutemetamol brain PET. Of 22 participants with dementia, 10 (45%) had a positive 18F-flutemetamol brain PET; 7 of 11 participants with Alzheimer disease (64%), 1 of 3 participants with vascular cognitive impairment (33%), and 2 of 8 participants with Parkinson-Lewy Body spectrum disorder (25%) had a positive 18F-flutemetamol brain PET. Using clinical interpretation as the criterion standard, K-means clustering (K = 2) gave sensitivity of 95%, specificity of 98%, and accuracy of 97%. CONCLUSIONS: K-means clustering may be a powerful algorithm for classifying amyloid brain PET.

Exposure to Anticholinergic and Sedative Drugs and Healthcare Costs in Older Patients with Neurocognitive Disorders.

BACKGROUND: Literature supports an increasing number of older patients living with neurocognitive disorders alongside with their annual worldwide costs. Therapeutic management of behavioral and psychological symptoms includes the use of anticholinergic and sedative drugs for which significant exposure is negatively associated with clinical outcomes. OBJECTIVE: The aim of this study was to assess the healthcare costs differences related to an increase in the exposure to anticholinergic and sedative drugs in older patients with neurocognitive disorder. METHODS: A longitudinal study was conducted during 3 years on 1,604 participants of the MEMORA cohort linked with both regional public health insurance and hospital discharge databases between 2012 and 2017. Direct medical and non-medical costs were included. Exposure to anticholinergic and sedative drugs was measured by the drug burden index (DBI). RESULTS: Costs difference associated with a DBI≥0.5 were + 338€ (p < 0.001). After adjustment on comorbidities, NCD stage, cognitive impairment, functional limitation, polypharmacy, and sociodemographic characteristics, a DBI≥0.5 was found to be an independent predictor of an increase of total healthcare costs by 22%(p < 0.001). CONCLUSION: Anticholinergic and sedative drugs have a substantial economic burden among older patients with neurocognitive disorder. More studies are required to assess the clinical and economic impact of an efficient strategy based on the reduction of the exposure to anticholinergic and sedative drugs and the promotion of non-pharmacological interventions.

Challenges of introducing new biomarker products for neuropsychiatric disorders into the market.

There are many challenges associated with the discovery and development of serum-based biomarkers for psychiatric disorders such as schizophrenia. Here, we review these challenges from the point of view of psychiatrists, general practitioners, the regulatory agencies, and biomarker scientists. There is a general opinion in psychiatric medicine that improvements over the current subjective tests are essential. Despite this, there is a reluctance to accept that peripheral molecules can do the job any better. In addition, psychiatrists find it difficult to accept that peripheral molecules, such as those found in blood, can reflect what is happening in the brain. However, the regulatory health authorities now consider biomarkers as important for the future of drug development and have called for efforts to modernize methods, tools, and techniques for the purpose of developing more efficient and safer drugs. We also describe here the development of the first ever molecular blood test for schizophrenia, and its reception in the market place, as a case in point.

Withdrawal of penicillamine from zinc sulphate-penicillamine maintenance therapy in Wilson's disease: promising, safe and cheap.

BACKGROUND: Penicillamine, once considered the cornerstone of treatment for Wilson disease (WD), is rather expensive and toxic, and often causes neurological worsening. Zinc sulphate, aiming at the treatment of free-copper toxicosis, has emerged as effective, safe and cheap alternative. AIM: To assess the effect of withdrawal of penicillamine from maintenance treatment with penicillamine and zinc sulphate. PATIENTS AND METHODS: 45 patients of WD (M:F: 28:17; age at diagnosis: 13.5+/-63 years), on both penicillamine (P) and zinc sulphate (Zn), couldn't continue penicillamine due to financial constraints. Their clinical data, disability and impairment scores (Schwab and England (S&E) score, Neurological Symptom Score (NSS), and Chu staging) and follow-up data of patients maintained only on zinc sulphate were recorded. RESULTS: Majority of patients (84.4%) had neuropsychiatric manifestations. The mean duration of treatment with penicillamine (P) and zinc sulphate (P+Zn), before stopping penicillamine, was 107.4+/-67.3 months. 40 patients improved variably, while the rest didn't. They received only zinc sulphate for 27.2+/-8.5 months (range: 12 to 34) and 44 patients (97.7%) remained status quo or improved marginally. Only one patient reported worsening in dysarthria. Their disability and impairment scores during combination (penicillamine and zinc sulphate) and Zn alone were: Chu (1.3+/-0.5 vs. 1.5+/-1.9; p=0.4), NSS (1.8+/-3.1 vs. 1.5+/-2.3; p=0.03) and S&E (96.4+/-5.6 vs. 98.6+/-3.5; p=0.03). There were no adverse effects. CONCLUSIONS: Withdrawal of penicillamine from zinc sulphate/penicillamine maintenance therapy for patients with Wilson's disease was effective, safe and economic, for almost all patients. This retrospective study reiterates that zinc sulphate may be used as a preferred mode of treatment for patients with Wilson's disease.