Comparative effectiveness of common therapies for Wilson disease: A systematic review and meta-analysis of controlled studies

BACKGROUND & AIMS: Wilson disease (WD) is a rare disorder of copper metabolism. The objective of this systematic review is to determine the comparative effectiveness and safety of common treatments of WD. METHODS: We included WD patients of any age or stage and the study drugs D-penicillamine, zinc salts, trientine, and tetrathiomolybdate. The control could be placebo, no treatment, or any other treatment. We included prospective, retrospective, randomized, and non-randomized studies. We searched Medline and Embase via Ovid, the Cochrane Central Register of Controlled Trials, and screened reference lists of included articles. Where possible, we applied random-effects meta-analyses. RESULTS: The 23 included studies reported on 2055 patients and mostly compared D-penicillamine to no treatment, zinc, trientine, or succimer. One study compared tetrathiomolybdate and trientine. Post-decoppering maintenance therapy was addressed in one study only. Eleven of 23 studies were of low quality. When compared to no treatment, D-penicillamine was associated with a lower mortality (odds ratio 0.013; 95% CI 0.0010 to 0.17). When compared to zinc, there was no association with mortality (odds ratio 0.73; 95% CI 0.16 to 3.40) and prevention or amelioration of clinical symptoms (odds ratio 0.84; 95% CI 0.48 to 1.48). Conversely, D-penicillamine may have a greater impact on side effects and treatment discontinuations than zinc. CONCLUSIONS: There are some indications that zinc is safer than D-penicillamine therapy while being similarly effective in preventing or reducing hepatic or neurologic WD symptoms. Study quality was low warranting cautious interpretation of our findings

Consciousness in Neurocritical Care Cohort Study Using fMRI and EEG (CONNECT-ME): Protocol for a Longitudinal Prospective Study and a Tertiary Clinical Care Service

Aims and Objectives: To facilitate individualized assessment of unresponsive patients in the intensive care unit for signs of preserved consciousness after acute brain injury.Background: Physicians and neuroscientists are increasingly recognizing a disturbing dilemma: Brain-injured patients who appear entirely unresponsive at the bedside may show signs of covert consciousness when examined by functional MRI (fMRI) or electroencephalography (EEG). According to a recent meta-analysis, roughly 15% of behaviorally unresponsive brain-injured patients can participate in mental tasks by modifying their brain activity during EEG- or fMRI-based paradigms, suggesting that they are conscious and misdiagnosed. This has major ethical and practical implications, including prognosis, treatment, resource allocation, and end-of-life decisions. However, EEG- or fMRI-based paradigms have so far typically been tested in chronic brain injury. Hence, as a novel approach, CONNECT-ME will import the full range of consciousness paradigms into neurocritical care.Methods: We will assess intensive care patients with acute brain injury for preserved consciousness by serial and multimodal evaluation using active, passive and resting state fMRI and EEG paradigms, as well as state-of-the-art clinical techniques including pupillometry and sophisticated clinical rating scales such as the Coma Recovery Scale-Revised. In addition, we are establishing a biobank (blood, cerebrospinal fluid and brain tissue, where available) to facilitate future genomic and microbiomic research to search for signatures of consciousness recovery.Discussion: We anticipate that this multimodal approach will add vital clinical information, including detection of preserved consciousness in patients previously thought of as unconscious, and improved (i.e., personalized) prognostication of individual patients. Our aim is two-fold: We wish to establish a cutting-edge tertiary care clinical service for unresponsive patients in the intensive care unit and lay the foundation for a fruitful multidisciplinary research environment for the study of consciousness in acute brain injury. Of note, CONNECT-ME will not only enhance our understanding of consciousness disorders in acute brain injury but it will also raise awareness for these patients who, for obvious reasons, have lacked a voice so far.Trial registration: The study is registered with clinicaltrials.org (ClinicalTrials.gov Identifier: NCT02644265)

Potentiometric Surfactant Sensor for Anionic Surfactants Based on 1,3-dioctadecyl-1H-imidazol-3-ium tetraphenylborate

As anionic surfactants are used as cleaning agents, they pose an environmental and health threat. A novel potentiometric sensor for anionic surfactants based on the 1,3-dioctadecyl-1H-imidazol-3-ium tetraphenylborate (DODI–TPB) ionophore is presented. The newly developed approach for DODI–TPB synthesis is faster and simpler than the currently used strategies and follows the green chemistry principles. The DODI–TPB ionophore was characterized by computational and instrumental techniques (NMR, LC–MS, FTIR, elemental analysis) and used to produce a PVC-based DODI–TPB sensor. The sensor showed linear response to dodecylbenzenesulfonate and dodecyl sulfate in concentration ranges of 6.3 × 10−7–3.2 × 10−4 M and 5.9 × 10−7–4.1 × 10−3 M, for DBS and SDS, respectively. The sensor exhibits a Nernstian slope (59.3 mV/decade and 58.3 mV/decade for DBS and SDS, respectively) and low detection limits (7.1 × 10−7 M and 6.8 × 10−7 M for DBS and SDS, respectively). The DODI–TPB sensor was successfully tested on real samples of commercial detergents and the results are in agreement with the referent methods. A computational analysis underlined the importance of long alkyl chains in DODI+ and their C–H∙∙∙π interactions with TPB− for the ionophore formation in solution, thereby providing guidelines for the future design of efficient potentiometric sensors

The 1,3-Dioctadecyl-1H-imidazol-3-ium Based Potentiometric Surfactant Sensor for Detecting Cationic Surfactants in Commercial Products

A low-cost and fast potentiometric surfactant sensor for cationic surfactants, based on the new ion-pair 1,3-dioctadecyl-1H-imidazol-3-ium-tetraphenylborate (DODI-TPB), is presented. The new cationic surfactant DODI-Br was synthesized and characterized by NMR, LC-MS, and elemental analysis, and was used for synthesis of the DODI-TPB ionophore. The DODI-TPB surfactant sensor was obtained by implementation of the ionophore in PVC. The sensor showed excellent response characteristics with near-Nernstian slopes to the cationic surfactants DMIC, CPC, CTAB, and Hyamine 1622. The highest voltage responses were obtained for DMIC and CPC (58.7 mV/decade of activity). DMIC had the lowest detection limit (0.9 × 10−6 M) and the broadest useful linear concentration range (1.8 × 10−6 to 1.0 × 10−4 M). An interference study showed remarkable stability. Potentiometric titration curves for the titration of cationic surfactants (DMIC, CPC, CTAB, and Hyamine 1622), with DDS and TPB used as titrants, showed sigmoidal curves with well-defined inflexion points and a broad signal change. The standard addition method was successfully applied with recovery rates from 98.9 to 101.2 at two concentrations. The amount of cationic surfactant found in disinfectants and antiseptics was in good agreement with the referent two-phase titration method and the surfactant sensor on the market. This new surfactant sensor represents a low-cost alternative to existing methods for cationic surfactant detection