Prolonged disorders of consciousness: identification using the UK FIM + FAM and cohort analysis of outcomes from a UK national clinical database.

PURPOSE: 1: To determine whether Total UK FIM + FAM scores can identify patients in VS/MCS. 2: Using the identified cut-off points, to examine outcomes from specialist rehabilitation. METHODS: Part 1: Retrospective analysis of a consecutive clinical cohort (n = 388) presenting to a single specialist PDOC evaluation programme 2007-2021. FIM + FAM scores were analysed by PDOC diagnosis to define cut-off points for vegetative (VS) and minimally conscious states (MCS). Part 2: Multicentre cohort analysis of prospectively-collected clinical outcomes data from the UK Rehabilitation Outcomes Collaborative database of adults in PDOC registered 2011-2020 (n = 2384 in 68 centres). RESULTS: Cut-off points of ≤31 and 32-35 in FIM + FAM total scores respectively identified patients in VS/MCS-Minus and MCS-Plus. Approximately 365 PDOC patients are admitted to specialist rehabilitation units in England each year. By discharge, 43% have emerged into consciousness and demonstrate a wide range of disability. A few reached full independence, but the majority remained severely dependent. Nevertheless, those who emerged generated mean net life-time savings of over £436,000 (£400 million for this cohort). CONCLUSION: In absence of a dedicated PDOC registry, FIM + FAM scores can identify patients in VS/MCS at population level. Identifying those who emerge and providing timely rehabilitation generates cost-savings well-exceeding the cost of the evaluation/rehabilitation programme.Implications for rehabilitationThe UK National Health Service currently collects no systematic data to identify patients in PDOC, so we have no accurate information on how many patients there are, where they are managed or what their outcomes are.In the absence of more direct data, total FIM + FAM scores of < =31 and 32-35 respectively can be used to identify patients in vegetative and minimally conscious states.Of the 365 or so patients admitted to specialist rehabilitation units per year, 43% emerge into consciousness leaving about 150 patients per year in PDOC states that are likely to be permanent.Identifying those who emerge and providing timely rehabilitation generates cost-savings that pay for the entire PDOC evaluation/rehabilitation programme many times over.

Automated Diabetes Case Identification Using Electronic Health Record Data at a Tertiary Care Facility.

OBJECTIVE: To develop and validate a phenotyping algorithm for the identification of patients with type 1 and type 2 diabetes mellitus (DM) preoperatively using routinely available clinical data from electronic health records. PATIENTS AND METHODS: We used first-order logic rules (if-then-else rules) to imply the presence or absence of DM types 1 and 2. The "if" clause of each rule is a conjunction of logical and, or predicates that provides evidence toward or against the presence of DM. The rule includes International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes, outpatient prescription information, laboratory values, and positive annotation of DM in patients' clinical notes. This study was conducted from March 2, 2015, through February 10, 2016. The performance of our rule-based approach and similar approaches proposed by other institutions was evaluated with a reference standard created by an expert reviewer and implemented for routine clinical care at an academic medical center. RESULTS: A total of 4208 surgical patients (mean age, 52 years; males, 48%) were analyzed to develop the phenotyping algorithm. Expert review identified 685 patients (16.28% of the full cohort) as having DM. Our proposed method identified 684 patients (16.25%) as having DM. The algorithm performed well-99.70% sensitivity, 99.97% specificity-and compared favorably with previous approaches. CONCLUSION: Among patients undergoing surgery, determination of DM can be made with high accuracy using simple, computationally efficient rules. Knowledge of patients' DM status before surgery may alter physicians' care plan and reduce postsurgical complications. Nevertheless, future efforts are necessary to determine the effect of first-order logic rules on clinical processes and patient outcomes.

VHA-19 is essential in Caenorhabditis elegans oocytes for embryogenesis and is involved in trafficking in oocytes.

There is an urgent need to develop new drugs against parasitic nematodes, which are a significant burden on human health and agriculture. Information about the function of essential nematode-specific genes provides insight to key nematode-specific processes that could be targeted with drugs. We have characterized the function of a novel, nematode-specific Caenorhabditis elegans protein, VHA-19, and show that VHA-19 is essential in the germline and, specifically, the oocytes, for the completion of embryogenesis. VHA-19 is also involved in trafficking the oocyte receptor RME-2 to the oocyte plasma membrane and is essential for osmoregulation in the embryo, probably because VHA-19 is required for proper eggshell formation via exocytosis of cortical granules or other essential components of the eggshell. VHA-19 may also have a role in cytokinesis, either directly or as an indirect effect of its role in osmoregulation. Critically, VHA-19 is expressed in the excretory cell in both larvae and adults, suggesting that it may have a role in osmoregulation in C. elegans more generally, probably in trafficking or secretion pathways. This is the first time a role for VHA-19 has been described.

Minireview: the role of the vacuolar ATPase in nematodes.

The vacuolar ATPase enzyme complex (V-ATPase) pumps protons across membranes, energised by hydrolysis of ATP. It is involved in many physiological processes and has been implicated in many different diseases. While the broader functions of V-ATPases have been reviewed extensively, the role of this complex in nematodes specifically has not. Here, the essential role of the V-ATPase in nematode nutrition, osmoregulation, synthesis of the cuticle, neurobiology and reproduction is discussed. Based on the requirement of V-ATPase activity, or components of the V-ATPase, for these processes, the potential of the V-ATPase as a drug target for nematode parasites, which cause a significant burden to human health and agriculture, is also discussed. The V-ATPase has all the characteristics of a suitable drug target against nematodes, however the challenge will be to develop a high-throughput assay with which to test potential inhibitors.