Understanding falls in progressive supranuclear palsy

IntroductionProgressive supranuclear palsy (PSP) is characterized by frequent falls which worsen with disease progression, causing substantial morbidity and mortality. Few studies have investigated which factors contribute to falls in PSP, and all have involved few participants, thus lacking necessary statistical power. The aim of this study was to identify clinical parameters most significantly associated with increasing falls in PSP, using the largest sample of patients to date.MethodsComprehensive clinical data were collected from 339 not demented PSP patients meeting the NINDS-SPSP criteria, who were divided into two groups – Infrequent Fallers (IF; n = 118) with rare falls, and Frequent Fallers (FF; n = 221) who fell occasionally to multiple times a day. Of 198 clinical parameters, we hypothesized 38 to be correlated with an increasing risk of falls. These 38 parameters were analyzed via univariate regression analysis to determine the strength of their association with fall frequency. Unit odds ratios identified the magnitude with which each parameter resulted in an increasing risk of falls.ResultsTwenty-five of 38 parameters analyzed were significantly associated with fall frequency based on univariate analysis. Symptom duration, clinical measures of disease severity, and several motoric and oculomotor clinical parameters were associated with FF. Examined cognitive parameters and slowing of vertical saccades were not.ConclusionsThe clinical parameters identified as associated with increased frequency of falls improve our understanding of why they occur and may help identify not demented PSP patients at risk for increasing falls.     

Guiding axes for drug safety management of pharmacovigilance centres during the COVID-19 era

International Journal of Clinical Pharmacy - The COVID-19 pandemic presents several challenges to the organisation and workflow of pharmacovigilance centres as a result of the massive increase in...     

Mitochondrial respiration as a target for neuroprotection and cognitive enhancement

This paper focuses on brain mitochondrial respiration as a therapeutic target for neuroprotection and cognitive enhancement. We propose that improving brain mitochondrial respiration is an important future direction in research and treatment of Alzheimer's disease (AD) and other conditions associated with cognitive impairment and neurodegeneration. The central thesis is that supporting and improving brain mitochondrial respiration constitutes a promising neurotherapeutic principle, with potential applications in AD as well as in a wide variety of neuropsychological conditions. We propose three different interventional approaches to improve brain mitochondrial respiration based on (a) pharmacology, (b) photobiomodulation and (c) nutrition interventions, and provide detailed examples for each type of intervention. First, low-dose USP methylene blue is described as a pharmacological intervention that can successfully increase mitochondrial respiration and result in memory enhancement and neuroprotection. Second, transcranial low-level light/laser therapy with near-infrared light is used to illustrate a photobiomodulation intervention with similar neurometabolic mechanisms of action as low-dose methylene blue. Finally, a nutrition intervention to improve mitochondrial respiration is proposed by increasing ketone bodies in the diet. The evidence discussed for each intervention supports a fundamental neurotherapeutic strategy based on improving oxidative energy metabolism while at the same time reducing the pro-oxidant tendencies of the nervous system. Targeting brain mitochondrial respiration with these three types of interventions is proposed as part of a holistic neurotherapeutic approach to improve brain energy metabolism and antioxidant defenses. This strategy represents a promising new bioenergetics direction for treatment of AD and other neuropsychological disorders featuring cognitive impairment and neurodegeneration.     

Osteonecrosis of the metatarsal head with exuberant periostitis

Idiopathic necrosis of the metatarsal head is unusual in adulthood. We report five cases of an atypical necrosis of the metatarsal head with a solid periosteal reaction in adults. Different imaging features are reported and diagnosis difficulties are highlighted.     

Do neighborhoods matter differently for movers and non-movers? Analysis of weight gain in the longitudinal dallas heart study

The few available population-based longitudinal studies examining the link between change in neighborhood condition and weight change to date have only examined neighborhood changes generated by residential mobility. Applying a difference-in-difference analytic framework to data from the Dallas Heart Study (DHS), a multi-ethnic, population-based cohort in Dallas County, TX, we evaluated the relationship between changes in neighborhood condition and weight change for both movers and non-movers over an approximate seven-year follow-up period. We employed a novel measure of neighborhood condition based on property appraisal data to capture temporally consistent measures of change in neighborhood condition regardless of residential mobility. We observed an inverse relationship between weight change and change in neighborhood condition which was more pronounced for non-movers (1.9 fewer kilograms gained per 1-standard deviation improvement in neighborhood condition) than for movers (1.5 fewer kilograms gained per 1-standard deviation improvement in neighborhood condition).     

Role of dyslipidemia in ischemic stroke patients treated in the telestroke network

PurposeThe relationship between the telestroke technology and clinical risk factors in a dysplipidemic ischemic stroke population and neurologic outcomes is not fully understood. This issue was investigated in this study.Patients and methodsWe analyzed retrospective data collected from a regional stroke registry to identify demographic and clinical risk factors in patients with improving (NIHSS ​≤ ​7) or worsening (NIHSS ​> ​7) neurologic outcome in dyslipidemic ischemic stroke population. We used logistic multivariate models to identify independent predictors of improving or worsening outcome based on dyslipidemia disease status in ischemic stroke patients.ResultsIn the adjusted analysis for dyslipidemic ischemic stroke population, cholesterol reducer use (odd ratio; [OR] ​= ​0.393, 95% confidence interval [CI], 0.176–0.879, P ​= ​0.023) and direct admission (OR ​= ​0.435, 95% CI, 0.199–0.953, P ​= ​0.037) were more likely to be associated with neurologic improvement and no clinical or demographic factors were associated with poor neurologic outcome in dyslipidemic ischemic stroke patients treated in the telestroke network.For the ischemic stroke population without dyslipidemia, increasing age (OR ​= ​1.070, 95% CI, 1.031–1.109, P ​< ​0.001), coronary artery disease (OR ​= ​3.633, 95% CI, 1.307–10.099, P ​= ​0.013), history of drug or alcohol abuse (OR ​= ​6.548, 95% CI, 1.106–38.777, P ​= ​0.038), and improvement in ambulatory outcome (OR ​= ​2.880, 95% CI, 1.183–7.010, P ​= ​0.020) were associated with worsening neurological functions, while being Caucasian (OR ​= ​0.294, 95% CI, 0.098–0.882, P ​= ​0.029) was associated with improving neurologic functions.ConclusionDemographic and clinical risk factors among the dysplipidemic ischemic stroke population in the telestroke network were not associated with worsening neurologic functions.     

The significance of HOXB7 and IL17RB serum levels in prognosis of hormonally dependent breast cancer: A pilot study

PurposeImproved prognostication of a patient's outcome could allow for personalized treatment decisions in breast cancer. Homeobox B7 (HOXB7) and interleukin 17 receptor B (IL17RB) are proteins reportedly involved in the development of hormonal therapy resistance. Their prognostic value was previously investigated in tumor tissue but recent mass spectrometric detection of HOXB7 and IL17RB proteins in serum has prompted us to perform the first prognostic evaluation of their serum levels.Patients and methodsThe study included 81 premenopausal breast cancer patients that received adjuvant hormonal therapy. The median follow-up period was 61 months. HOXB7 and IL17RB serum protein levels were measured by quantitative sandwich ELISA and prognostically evaluated by Cox proportional hazards regression analysis.ResultsHOXB7 protein was detected in 96.3% and IL17RB in 33.3% of serum samples. Higher levels of serum HOXB7 significantly associated with favorable disease outcome by prognosticating distant (by HR ​= ​0.04; P ​= ​0.001) and local recurrence (by HR ​= ​0.03, P ​= ​0.001). The recurrence rates in the HOXB7^high and HOXB7^low subgroups of patients (cut-off 81.5 ​pg/mL) were 0% and 17%, respectively. Serum IL17RB levels did not significantly associate with either local or distant events. The multivariate analysis highlighted estrogen receptor, histological grade, nodal status and HOXB7 as independent prognostic parameters.ConclusionsOur findings validate the previous mass-spectrometry data by showing that HOXB7 and IL17RB cellular proteins are detectable in serum by a standard ELISA assay. Furthermore, we show that HOXB7 serum levels are the relevant prognosticator of response to hormonal therapy.