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As medication adherence represents a critical challenge in healthcare, pill and medication dispensers have gained increasing attention as potential solutions to promote adherence and improve patient outcomes. Following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) methodology, we carried out a systematic literature review on papers indexed in Scopus and PubMed, which present solutions for pill or medication dispensers. Given the importance of user acceptance for these solutions, the research questions of the survey are driven by a human-centered perspective. We first provide an overview of the different solutions, classifying them according to their stage of development. We then analyze each solution considering its hardware/software architecture. Finally, we review the characteristics of user interfaces designed for interacting with pill and medication dispensers and analyze the involvement of different types of users in dispenser management. On the basis of this analysis, we draw findings and indications for future research that are aimed to provide insights to healthcare professionals, researchers, and designers who are interested in developing and using pill and medication dispensers., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2024.)

We report the analysis of 1 year of data from the first cohort of 15 patients enrolled in an open-label, first-in-human, dose-escalation phase I study (ClinicalTrials.gov: NCT03282760, EudraCT2015-004855-37) to determine the feasibility, safety, and tolerability of the transplantation of allogeneic human neural stem/progenitor cells (hNSCs) for the treatment of secondary progressive multiple sclerosis. Participants were treated with hNSCs delivered via intracerebroventricular injection in combination with an immunosuppressive regimen. No treatment-related deaths nor serious adverse events (AEs) were observed. All participants displayed stability of clinical and laboratory outcomes, as well as lesion load and brain activity (MRI), compared with the study entry. Longitudinal metabolomics and lipidomics of biological fluids identified time- and dose-dependent responses with increased levels of acyl-carnitines and fatty acids in the cerebrospinal fluid (CSF). The absence of AEs and the stability of functional and structural outcomes are reassuring and represent a milestone for the safe translation of stem cells into regenerative medicines., Competing Interests: Declaration of interests S.P. is founder, CSO, and shareholder (>5%) of CITC Ltd. and Chair of the Scientific Advisory Board at ReNeuron plc., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

A 43-year-old female patient diagnosed with chronic progressive external ophthalmoplegia (CPEO) because of mitochondrial myopathy documented by muscle biopsy is presented. The chief complaints were represented by blepharoptosis and ophthalmoplegia. The muscle biopsy was evaluated by histology, using the appropriate histochemical and histoenzimological stains. Ragged red fibers with Gomori trichrome stain were seen, which showed cytochrome c oxydase deficiency and abnormal succinate dehydrogenase staining in around 20% of muscle fibres. Electron microscopy was also performed which demonstrated abnormal, hyperplastic, pleomorphic, and hypertrophic mitochondria, characterized by paracrystalline inclusions arranged in parallel rows ("parking-lot" inclusions), consisting of rectangular arrays of mitochondrial membranes in a linear or grid-like pattern. In conclusion, mitochondrial myopathy was definitely diagnosed. Although molecular analysis, which was subsequently carried out, failed to reveal mutations in the mitochondrial DNA or in selected nuclear genes, the pathologic diagnosis was not changed. The differential diagnosis of CPEO with other forms of ocular myopathies as well as the possible association of CPEO with systemic syndromes is discussed. Ophtalmologists and medical internists should always suspect CPEO when dealing with patients affected by ocular myopathy, either in its pure form or in association with other myopathic or systemic signs.

Background: There is only one small single-center study on the reliability of the diagnosis of focal dystonia. The aim of this study was to assess the inter-rater reliability of dystonia diagnosis among neurologists with different professional experience., Methods: Twenty-nine adults (18 with dystonia, 9 with other movement disorders, and 2 healthy controls) were videotaped while undergoing neurological examination and during the process of collecting information on the history of their condition. Each case was diagnosed by 35 blind raters (12 general neurologists, 21 neurology residents, and 2 experts in movement disorders) from different hospitals. Sensitivity and specificity were calculated confronting raters with the gold standard (the caring physician). Inter-rater agreement was measured by the Kappa statistic., Results: Specificity and sensitivity were 95.2 and 66.7%, 76.3 and 75.2%, 84.6 and 71.6% for experts, general neurologists, and residents, respectively. Kappa values on dystonia diagnosis ranged from 0.30 to 0.46. The agreement was moderate for experts and residents (0.40-0.60) and fair for general neurologists (0.20-0.40). Kappas were the highest among experts for cranial and laryngeal dystonia (0.61-1), but not for cervical dystonia (0.37)., Conclusions: The diagnosis of dystonia is difficult and only partially mirrors a physician's background., (© 2014 S. Karger AG, Basel.)

Background: Primary focal or segmental dystonia is a rare clinical condition including early-onset dystonia, which has the tendency to generalize, and late-onset dystonia, which may be focal or segmental. The prevalence of late-onset dystonia ranges from 30 to 7,320 cases per million, but no data are available in Italy., Methods: A service-based study was conducted in the period 1 January 2001 through 31 December 2002 in the administrative district of Foggia, southern Italy (population 541,653). Cases were traced through hospital discharge diagnosis, botulinum toxin services, day hospital access, ear, nose and throat, ophthalmology and orthopedic surgery specialists, and territorial outpatient services. Inclusion criteria were age 17 years or older, residency in the study area and a diagnosis of primary focal/segmental dystonia., Results: A total of 69 patients were included, giving a crude prevalence of 127.4 per 1,000,000 (women: 146.4; men: 107.0; age 18-34 years: 39.2; 35-54 years: 98.7; 55-74 years: 273.6; 75+ years: 163.3). The standardized rate was 137.5 (95% confidence interval 107.0-174.6). Blepharospasm was the commonest clinical condition (prevalence 68.2), followed by cervical dystonia (prevalence 44.8)., Conclusion: The prevalence of primary focal or segmental dystonia in Italy is in keeping with several other reports, but is lower than in studies performed in northern Europe, Minnesota, USA, and Japan. The difference in our results may be mostly explained by misdiagnosis, underascertainment of cases and a fairly limited observation period., (2009 S. Karger AG, Basel.)

The occurrences of factor V Leiden mutation (Arg506Gln) and antiphospholipid antibodies (APA) in migraine patients have been reported, but the findings are controversial. We investigated the presence of factor V Leiden and the serum level of anticardiolipin antibodies (aCL) in a consecutive series of 70 migraine patients (47 women; mean age, 34.1 years). Of these, 40 patients had migraine with aura. A matched sample of 70 healthy people was considered as the control group. Heterozygous genotype for factor V Leiden mutation was detected in 4 (5.7%) migraine patients (of which 2 had migraine with aura) and in 2 (2.8%) subjects of the control group. Although proportionally more migraine patients harbored the factor V Leiden mutation, this difference was not statistically significant, perhaps due to the small number of patients involved. We found normal serum levels of aCL in all migraine patients. Further studies and a long-term follow-up are warranted to determine the significance of this genetic abnormality in migraine.

The excitability of the motor cortex to magnetic stimulation was evaluated in seven patients with cerebellar lesions (six patients with a unilateral lesion) and in 20 control subjects. Magnetic motor threshold was defined at rest. In all but one of the patients with a hemicerebellar lesion the threshold was higher in the motor cortex contralateral to the impaired hemicerebellum and the right/left threshold asymmetry was clearly greater than normal. In the patient with a lesion involving both cerebellar hemispheres the magnetic threshold was above the normal limit on both sides. The latencies of motor responses were normal in all patients. This increase in the magnetic threshold of the motor cortex functionally related to the impaired hemicerebellum suggests the existence of a facilitating tonic action of the cerebellum on central motor circuits that might act at the cortical, or spinal level, or both.