A wearable platform for closed-loop stimulation and recording of single-neuron and local field potential activity in freely moving humans.

Advances in technologies that can record and stimulate deep brain activity in humans have led to impactful discoveries within the field of neuroscience and contributed to the development of novel therapies for neurological and psychiatric disorders. Further progress, however, has been hindered by device limitations in that recording of single-neuron activity during freely moving behaviors in humans has not been possible. Additionally, implantable neurostimulation devices, currently approved for human use, have limited stimulation programmability and restricted full-duplex bidirectional capability. In this study, we developed a wearable bidirectional closed-loop neuromodulation system (Neuro-stack) and used it to record single-neuron and local field potential activity during stationary and ambulatory behavior in humans. Together with a highly flexible and customizable stimulation capability, the Neuro-stack provides an opportunity to investigate the neurophysiological basis of disease, develop improved responsive neuromodulation therapies, explore brain function during naturalistic behaviors in humans and, consequently, bridge decades of neuroscientific findings across species.

GPs' decisions about prescribing end-of-life anticipatory medications: a qualitative study.

BACKGROUND: GPs have a central role in decisions about prescribing anticipatory medications to help control symptoms at the end of life. Little is known about GPs' decision-making processes in prescribing anticipatory medications, how they discuss this with patients and families, or the subsequent use of prescribed drugs. AIM: To explore GPs' decision-making processes in the prescribing and use of anticipatory medications for patients at the end of life. DESIGN AND SETTING: A qualitative interview study with GPs working in one English county. METHOD: Semi-structured interviews were conducted with a purposive sample of 13 GPs. Interview transcripts were analysed inductively using thematic analysis. RESULTS: Three themes were constructed from the data: something we can do, getting the timing right, and delegating care while retaining responsibility. Anticipatory medications were a tangible intervention GPs felt they could offer patients approaching death (something we can do). The prescribing of anticipatory medications was recognised as a harbinger of death for patients and their families. Nevertheless, GPs preferred to discuss and prescribe anticipatory medications weeks before death was expected whenever possible (getting the timing right). After prescribing medications, GPs relied on nurses to assess when to administer drugs and keep them updated about their use (delegating care while retaining responsibility). CONCLUSION: GPs view anticipatory medications as key to symptom management for patients at the end of life. The drugs are often presented as a clinical recommendation to ensure patients and families accept the prescription. GPs need regular access to nurses and rely on their skills to administer drugs appropriately. Patients' and families' experiences of anticipatory medications, and their preferences for involvement in decision making, warrant urgent investigation.

Planning for an uncertain future in progressive neurological disease: a qualitative study of patient and family decision-making with a focus on eating and drinking.

BACKGROUND: Dysphagia and other eating and drinking difficulties are common in progressive neurological diseases. Mealtimes can become a major source of difficulty and anxiety for patients and their families. Decisions about eating, drinking and care can become challenging as disease progresses, and the person in question loses the capacity to participate in decisions about their own care. We sought to investigate how patients and their family members make decisions about their future care as their condition deteriorates, with a particular focus on mealtimes, eating and drinking. METHODS: Longitudinal qualitative in-depth interviews were undertaken with patients and their family members (N = 29) across a range of disease groups, including: dementia, Parkinson's Disease, Huntington's Disease, Progressive Supranuclear Palsy, Motor Neurone Disease, Multiple Sclerosis. Patients had varying degrees of eating and drinking difficulties, and levels of decision-making capacity. Interviews were 'participant led' and undertaken in the patients' own homes or a place of their choosing. Follow-up interviews were three months to one year later depending upon disease trajectory. Interviews were audio recorded and analysed in NVivo using a Thematic Analysis approach. RESULTS: Twenty-nine participants were interviewed between 2015 and 2017. Two key themes emerged from the analysis: 1) Health Literacy: the extent to which patients and relatives appeared to know about the condition and its treatment. Patients and their family members varied in their ability to speak and communicate about their condition and prognosis. 2) Planning style: the extent to which participants appeared to value involvement in advance care-planning. Patients and their family members varied in the way in which they made decisions: some preferred to 'take each day as it comes', while others wished to plan extensively for the future. CONCLUSIONS: Issues with eating and drinking are often overlooked. Clinicians need to understand both the patient's level of health literacy and their style of planning before communicating with patients and their families about these sensitive issues.

Between "the best way to deliver patient care" and "chaos and low clinical value": General Practitioners' and Practice Managers' views on data sharing.

OBJECTIVE: In the UK, General Practitioners and Practice Managers are key to enabling health information exchange (typically referred to as 'data sharing'). This study aimed to survey GPs and PMs for familiarity, engagement with and perceptions of patient data sharing. METHODS: Cross-sectional survey. All 107 general practices in England's second largest Clinical Commissioning Group, Cambridgeshire & Peterborough CCG. Descriptive statistics; hierarchical logistic regression; thematic analysis. RESULTS: 405 (64%) responses were received - from 338 (62%) GPs and 67 (71%) PMs. Familiarity and engagement were highest for local frail elderly and end of life care projects (>76% had used). The greatest difference in use concerned the now suspended national care.data initiative: PMs had odds of reporting use 75 times higher than GP partners (95% CI 27-211). Patient confusion was the most pronounced challenge and improved coordination the most pronounced expected benefit. Frequency of discussions with patients varied with IT competence (OR 4.2 for most competent users relative to least, 95% CI 1.7-10.7) and clinical system (OR 0.3, 95% CI 0.1-0.5). Patient reservations were reported more frequently by respondents who rated their IT competence as highest (OR 3.3, 95% CI 1.5-7.6), perceived more data sharing challenges (OR for a 1-point increase in challenges perception score 3.4, 95% CI 2.1-5.6) and by PMs (relative to GP partners, OR 18.0, 95% CI 7.9-41.3). CONCLUSIONS: Familiarity with and use of data sharing projects was high among GPs and PMs. Both their individual and organisational characteristics were associated with the reported frequency of discussions and patients' responses. Improved awareness of the impact of provider characteristics and attitudes on patients' decisions about data sharing may enhance the equity and autonomy of those decisions.

Systems biology analysis of Drosophila in vivo screen data elucidates core networks for DNA damage repair in SCA1.

DNA damage repair is implicated in neurodegenerative diseases; however, the relative contributions of various DNA repair systems to the pathology of these diseases have not been investigated systematically. In this study, we performed a systematic in vivo screen of all available Drosophila melanogaster homolog DNA repair genes, and we tested the effect of their overexpression on lifespan and developmental viability in Spinocerebellar Ataxia Type 1 (SCA1) Drosophila models expressing human mutant Ataxin-1 (Atxn1). We identified genes previously unknown to be involved in CAG-/polyQ-related pathogenesis that function in multiple DNA damage repair systems. Beyond the significance of each repair system, systems biology analyses unraveled the core networks connecting positive genes in the gene screen that could contribute to SCA1 pathology. In particular, RpA1, which had the largest effect on lifespan in the SCA1 fly model, was located at the hub position linked to such core repair systems, including homologous recombination (HR). We revealed that Atxn1 actually interacted with RpA1 and its essential partners BRCA1/2. Furthermore, mutant but not normal Atxn1 impaired the dynamics of RpA1 in the nucleus after DNA damage. Uptake of BrdU by Purkinje cells was observed in mutant Atxn1 knockin mice, suggesting their abnormal entry to the S-phase. In addition, chemical and genetic inhibitions of Chk1 elongated lifespan and recovered eye degeneration. Collectively, we elucidated core networks for DNA damage repair in SCA1 that might include the aberrant usage of HR.

Misdiagnosis of late-onset Lyme arthritis by inappropriate use of Borrelia burgdorferi immunoblot testing with synovial fluid.

The primary objective of this study was to determine whether patients with putative late-onset Lyme arthritis based upon synovial fluid Borrelia burgdorferi IgM and IgG immunoblot testing offered by commercial laboratories satisfied conventional criteria for the diagnosis of Lyme arthritis. Secondary objectives included assessing the prior duration and responsiveness of associated antibiotic therapy. We conducted a retrospective analysis of 11 patients referred to an academic medical center infectious disease clinic during the years 2007 to 2009 with a diagnosis of Lyme disease based upon previously obtained synovial fluid B. burgdorferi immunoblot testing. Ten of the 11 (91%) patients with a diagnosis of late-onset Lyme arthritis based upon interpretation of synovial fluid B. burgdorferi immunoblot testing were seronegative and did not satisfy published criteria for the diagnosis of late-onset Lyme arthritis. None of the 10 patients had a clinical response to previously received antibiotics despite an average course of 72 days. Diagnosis of Lyme arthritis should not be based on synovial fluid B. burgdorferi immunoblot testing. This unvalidated test does not appear useful for the diagnosis of Lyme disease, and this study reinforces the longstanding recommendation to use B. burgdorferi immunoblot testing only on serum samples and not other body fluids. Erroneous interpretations of "positive" synovial fluid immunoblots may lead to inappropriate antibiotic courses and delays in diagnosis of other joint diseases.

Increasing incidence of iliopsoas abscesses with MRSA as a predominant pathogen.

OBJECTIVES: Iliopsoas abscesses (IPAs) are rare infections involving purulence within the muscles of the iliopsoas compartment, seldom due to Methicillin-resistant Staphylococcus aureus (MRSA) historically. This study was designed to evaluate the clinical characteristics and outcomes of patients with IPAs. METHODS: A retrospective analysis of the demographics, clinical presentation, microbiologic data and treatment modalities among patients with IPAs from 1993 to 2007 at The Johns Hopkins Hospital was performed. RESULTS: Among 61 patients with IPAs, infection rates increased from 0.5 cases/10,000 admissions (1993-2004) to 6.5 cases/10,000 admissions (2005-2007) (P < 0.001). An adjacent infectious focus was identified in 80% of patients, from skeletal (48%), intra-abdominal (23%), vascular (5%), genitourinary (3%), and cutaneous sources (2%). During 2005-2007, MRSA became a predominant pathogen, accounting for 25% of all cases and 37% of cases with a definitive microbiologic diagnosis (P = 0.006). Patients with IPAs >2 cm were more likely to undergo drainage, with trends toward longer hospitalizations, longer antibiotic courses, and increased odds of securing a definitive microbiologic diagnosis. CONCLUSIONS: Since 2005, rates of IPA have dramatically increased, with MRSA now the leading cause of infection. Knowledge of common pathogens should guide antimicrobial therapy including empiric coverage for MRSA in institutions with similar populations, especially if culture data are not available.