Observational study of medical marijuana as a treatment for treatment-resistant epilepsies.

OBJECTIVES: Medical cannabis formulations with cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC) are widely used to treat epilepsy. We studied the safety and efficacy of two formulations. METHODS: We prospectively observed 29 subjects (12 to 46 years old) with treatment-resistant epilepsies (11 Lennox-Gastaut syndrome; 15 with focal or multifocal epilepsy; three generalized epilepsy) were treated with medical cannabis (1THC:20CBD and/or 1THC:50CBD; maximum of 6 mg THC/day) for ≥24 weeks. The primary outcome was change in convulsive seizure frequency from the pre-treatment baseline to the stable optimal dose phase. RESULTS: There were no significant differences during treatment on stable maximal doses for convulsive seizure frequency, seizure duration, postictal duration, or use of rescue medications compared to baseline. No benefits were seen for behavioral disorders or sleep duration; there was a trend for more frequent bowel movements compared to baseline. Ten adverse events occurred in 6/29 patients, all were transient and most unrelated to study medication. No serious adverse events were related to study medication. INTERPRETATION: Our prospective observational study of two high-CBD/low-THC formulations found no evidence of efficacy in reducing seizures, seizure duration, postictal duration, or rescue medication use. Behavioral disorders or sleep duration was unchanged. Study medication was generally well tolerated. The doses of CBD used were lower than prior studies. Randomized trials with larger cohorts are needed, but we found no evidence of efficacy for two CBD:THC products in treating epilepsy, sleep, or behavior in our population.

Is the prescription right? A review of non-vitamin K antagonist anticoagulant (NOAC) prescriptions in patients with non-valvular atrial fibrillation. Safe prescribing in atrial fibrillation and evaluation of non-vitamin K oral anticoagulants in stroke prevention (SAFE-NOACS) group.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are a major advance for stroke prevention in atrial fibrillation (AF). Use of the vitamin K antagonist (VKA), warfarin, has dropped 40% since 2010 in our institution. There is limited Irish hospital data on NOAC prescribing for stroke prevention. METHOD: Single centre, retrospective observational cohort study of consecutive AF patients at increased risk of stroke and/or awaiting electrical cardioversion. Data on prescribed NOACs from February 2010 till July 2015 was collected from the electronic inpatient record. Appropriateness of prescriptions was based on CHA2DS2-VASC score and accuracy on individual NOAC SPCs. Potential drug interactions and bleeding risk were also quantified. RESULTS: A total of 348 patients AF and increased risk of stroke (CHA2DS2-VASC score > 1 for men and > 2 for women) were studied. Forty-eight percent were female with a mean age 71 ± 18.6 years, 52% of whom were > 75. Mean CHA2DS2-Vasc and HAS-BLED scores were 4.1 ± 1.8 and 1.4 ± 0.8, respectively. Rivaroxaban, dabigatran and apixaban were prescribed to 154 (54.2%), 106 (34.3%) and 41 (13.2%) patients, respectively. 20.4% had inaccurate prescriptions; 92.9% (n = 65) underdosed and 7.1% (n = 5) on inappropriately higher doses. Neither choice of NOAC, age, history of anaemia, previous bleeding or co-prescribed antiplatelets influenced the accuracy of prescription (p = NS), but decreased renal function appeared to do so (p = 0.05). CONCLUSION: Our study highlights significant inaccuracies in NOAC prescribing. Patients commenced on NOACs should be assessed and followed up in a multidisciplinary AF clinic to ensure safe and effective prescribing and stroke prevention.

Cigarette Smoking Impairs the Bioenergetic Immune Response to Mycobacterium tuberculosis Infection.

Smoking is a major risk factor driving the tuberculosis epidemic, and smokers' alveolar macrophages (AM) demonstrate significant immune defects after infection. Recently, macrophage glycolytic reprogramming has emerged as crucial in the early host immune response to Mycobacterium tuberculosis (Mtb) infection. In the present study, we sought to compare baseline metabolic characteristics and the glycolytic response to infection of human AM from smokers and nonsmokers. AM were obtained at bronchoscopy, and extracellular flux analyses were performed to determine baseline metabolic characteristics compared with human monocyte-derived macrophages (MDM). Metabolic characterization of AM from smokers and nonsmokers was performed similarly. After infection with Mtb, differences in glycolytic response were measured by extracellular flux analyses and gene expression analyses and correlated with production of glycolysis-driven IL-1ß and prostaglandin E2. Similar experiments were performed in cigarette smoke extract-treated MDM as an alternative model. At baseline, human AM from nonsmokers have a significantly lower extracellular acidification rate/oxygen consumption rate ratio than MDM (P < 0.05), but they retain substantial glycolytic reserve. Compared with nonsmokers' AM, smokers' AM demonstrate reduced metabolic activity, reduced glycolytic reserve (P = 0.051), and reduced spare respiratory capacity (P < 0.01). After infection with Mtb, smokers' AM have significantly reduced glycolytic response, as measured by extracellular flux analyses (P < 0.05) and glycolytic gene expression analyses. Cigarette smoke extract-treated MDM similarly demonstrate reduced metabolic activity and reserves, as well as impaired glycolytic response to infection. Human AM demonstrate metabolic plasticity that allows glycolytic reprogramming to occur after Mtb infection. In smokers, this metabolic reserve is significantly attenuated, with consequent impairment of the glycolytic response to infection.

Acupuncture, ACC and the Medicines Act.

Acupuncture is covered under the Accident Compensation (Liability to Pay or Contribute to Cost of Treatment) Regulations 2003, and is therefore eligible for Accident Compensation Corporation payments for the treatment of personal injuries. This study searched New Zealand acupuncturists' websites for therapeutic claims that may breach Section 58(1)(a) of the Medicines Act. A search of acupuncturists' websites shows that many claim to be able to treat a wide range of conditions, despite a lack of evidence showing the efficacy of acupuncture in the treatment of those conditions. Practitioners and owners of websites likely to be in breach of the Medicines Act include many committee members from acupuncture's professional bodies.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury.

An important strategy for promoting voluntary movements after motor system injury is to harness activity-dependent corticospinal tract (CST) plasticity. We combine forelimb motor cortex (M1) activation with co-activation of its cervical spinal targets in rats to promote CST sprouting and skilled limb movement after pyramidal tract lesion (PTX). We used a two-step experimental design in which we first established the optimal combined stimulation protocol in intact rats and then used the optimal protocol in injured animals to promote CST repair and motor recovery. M1 was activated epidurally using an electrical analog of intermittent theta burst stimulation (iTBS). The cervical spinal cord was co-activated by trans-spinal direct current stimulation (tsDCS) that was targeted to the cervical enlargement, simulated from finite element method. In intact rats, forelimb motor evoked potentials (MEPs) were strongly facilitated during iTBS and for 10 min after cessation of stimulation. Cathodal, not anodal, tsDCS alone facilitated MEPs and also produced a facilitatory aftereffect that peaked at 10 min. Combined iTBS and cathodal tsDCS (c-tsDCS) produced further MEP enhancement during stimulation, but without further aftereffect enhancement. Correlations between forelimb M1 local field potentials and forelimb electromyogram (EMG) during locomotion increased after electrical iTBS alone and further increased with combined stimulation (iTBS+c-tsDCS). This optimized combined stimulation was then used to promote function after PTX because it enhanced functional connections between M1 and spinal circuits and greater M1 engagement in muscle contraction than either stimulation alone. Daily application of combined M1 iTBS on the intact side and c-tsDCS after PTX (10 days, 27 min/day) significantly restored skilled movements during horizontal ladder walking. Stimulation produced a 5.4-fold increase in spared ipsilateral CST terminations. Combined neuromodulation achieves optimal motor recovery and substantial CST outgrowth with only 27 min of daily stimulation compared with 6h, as in our prior study, making it a potential therapy for humans with spinal cord injury.

The role of a nurse specialist in a modern lung-cancer service.

The delivery of a modern cancer service is dependent on the nurse specialist occupying a central role in the overall pathway. However, there are significant variations in the access to a lung cancer clinical nurse specialist (CNS) across the UK and the USA. In the UK, the lung cancer CNS plays a pivotal role in the delivery of high-quality care and treatment to patients with (presumed) thoracic malignancy. They are in an ideal position to provide holistic care to patients with lung cancer-ensuring that all needs are addressed from the time of initial referral to commencement of definitive treatment or palliative care. In addition the role provides support and advice to people on the increasingly complex treatment options and on survivorship, and plays an essential role in end-of-life care. In the USA, the nurse navigator is a core member of the lung cancer screening programme. In this review the authors provide a transatlantic perspective on the history, current practice and potential future roles for the lung cancer CNS in the UK and nurse navigator in the US.

The movement of oil under non-breaking waves.

The combined effects of wave kinematics, turbulent diffusion, and buoyancy on the transport of oil droplets at sea were investigated in this work using random walk techniques in a Monte Carlo framework. Six hundred oil particles were placed at the water surface and tracked for 500 wave periods. A dimensionless formulation was presented that allowed reporting distances in terms of the wave length and times in terms of the wave period. Stokes' drift was, expectedly, the major mechanism for horizontal transport. It was also found that plumes that have large terminal rise velocities move faster forward but spread less than those that have small terminal rise velocities. The increase in wave slope (or wave steepness) caused an increase in transport and spreading of the plume. Our results supported treating the oil as completely mixed vertically in a layer near the surface. In the horizontal direction, buoyant plumes had spreading coefficients that are essentially constant after about 200 wave periods. But neutrally buoyant plumes had horizontal spreading coefficients that increased with time (for the simulation time of 500 wave periods). Techniques for generalizing the results for a wide range of wave parameters were presented.

Summary results from a pilot study conducted around an oil production platform on the Northwest Shelf of Australia.

The Australian Institute of Marine Science (AIMS) conducted a pilot study around the Harriet A oil production platform on the Northwest Shelf of Australia. We evaluated hepatic ethoxyresorufin-O-deethylase (EROD) activity, fluorescent aromatic compounds (FACs) in bile and immunodetection of CYP1A-like proteins in two Australian tropical fish species, Gold-Spotted Trevally (Carangoides fulvoguttatus) and Bar-Cheeked Coral Trout (Plectropomus maculatus) to assess exposure to petroleum hydrocarbons associated with produced formation water (PFW). Additionally, the incidence of hydrocarbon-degrading bacteria isolated from the liver and bile of all fish captured was examined. Low EROD activity was found in both species, with EROD activity in C. fulvoguttatus showing significant site differences. FACs and CYP1A protein levels in C. fulvoguttatus showed a clear trend in hydrocarbon exposure consistent with hydrocarbon chemistry data: Harriet A>Harriet C>reference site. P. maculatus showed elevated levels of FACs at Harriet A as compared to the reference site and demonstrated detectable levels of CYP1A-like proteins at these two sites. Hydrocarbon-degrading bacteria were found in the liver and bile of both species, yet there was no correlation by sites. Our results demonstrate that C. fulvoguttatus and P. maculatus have potential as indicator species for assessing the effects from exposure to petroleum hydrocarbons. Both FACs and CYP1A are providing warning signs that there is potential for biological effects on fish populations exposed to PFW around the Harriet A production platform.