Search

In this interview, Dr. Thomas discusses the relationship between race and copyright. This conversation with Tucker Taylor of the Journal of Copyright in Education and Librarianship covers Dr. Thomas’s path to copyright education as well as her work at Connecting Communities Digital Initiative (CCDI) at the Library of Congress. Dr. Thomas details the interaction of race and copyright, and how it relates to librarianship and education. She also details ideas for librarians and educators to help improve our current situation.

BackgroundProgressive supranuclear palsy is a neurodegenerative disorder associated with tau protein aggregation. Tilavonemab (ABBV-8E12) is a monoclonal antibody that binds to the N-terminus of human tau. We assessed the safety and efficacy of tilavonemab for the treatment of progressive supranuclear palsy.MethodsWe did a phase 2, multicentre, randomised, placebo-controlled, double-blind study at 66 hospitals and clinics in Australia, Canada, France, Germany, Italy, Japan, Spain, and the USA. Participants (aged ≥40 years) diagnosed with possible or probable progressive supranuclear palsy who were symptomatic for less than 5 years, had a reliable study partner, and were able to walk five steps with minimal assistance, were randomly assigned (1:1:1) by interactive response technology to tilavonemab 2000 mg, tilavonemab 4000 mg, or matching placebo administered intravenously on days 1, 15, and 29, then every 28 days through to the end of the 52-week treatment period. Randomisation was done by the randomisation specialist of the study sponsor, who did not otherwise participate in the study. The sponsor, investigators, and participants were unaware of treatment allocations. The primary endpoint was the change from baseline to week 52 in the Progressive Supranuclear Palsy Rating Scale (PSPRS) total score in the intention-to-treat population. Adverse events were monitored in participants who received at least one dose of study drug. Prespecified interim futility criteria were based on a model-based effect size of 0 or lower when 60 participants had completed the 52-week treatment period and 0·12 or lower when 120 participants had completed the 52-week treatment period. This study is registered at ClinicalTrials.gov, number NCT02985879.FindingsBetween Dec 12, 2016, and Dec 31, 2018, 466 participants were screened, 378 were randomised. The study was terminated on July 3, 2019, after prespecified futility criteria were met at the second interim analysis. A total of 377 participants received at least one dose of study drug and were included in the efficacy and safety analyses (2000 mg, n=126; 4000 mg, n=125; placebo, n=126). Least squares mean change from baseline to week 52 in PSPRS was similar in all groups (between-group difference vs placebo: 2000 mg, 0·0 [95% CI -2·6 to 2·6], effect size 0·000, p>0·99; 4000 mg, 1·0 [-1·6 to 3·6], -0·105, p=0·46). Most participants reported at least one adverse event (2000 mg, 111 [88%]; 4000 mg, 111 [89%]; placebo, 108 [86%]). Fall was the most common adverse event (2000 mg, 42 [33%]; 4000 mg, 54 [43%]; placebo, 49 [39%]). Proportions of patients with serious adverse events were similar among groups (2000 mg, 29 [23%]; 4000 mg, 34 [27%]; placebo, 33 [26%]). Fall was the most common treatment-emergent serious adverse event (2000 mg, five [4%]; 4000 mg, six [5%]; placebo, six [5%]). 26 deaths occurred during the study (2000 mg, nine [7%]; 4000 mg, nine [7%]; placebo, eight [6%]) but none was drug related.InterpretationA similar safety profile was seen in all treatment groups. No beneficial treatment effects were recorded. Although this study did not provide evidence of efficacy in progressive supranuclear palsy, the findings provide potentially useful information for future investigations of passive immunisation using tau antibodies for progressive supranuclear palsy.FundingAbbVie Inc.

This study investigated the relationship between spiritual development and cultural reentry adjustment in a group of missionaries. One hundred and two missionaries completed a questionnaire that correlated the Spiritual Assessment [...]

The Five Smooth Stones: Essential Principles for Biblical Ministry. By Robertson McQuilkin. Nashville: B & H, 2007, 223 pp., $14.99. paper. One of the greatest challenges facing every minister is [...]

This article presents an evidence‐based approach to the patient with newly diagnosed Parkinson disease (PD). It includes a discussion of the current understanding of the aetio‐pathogenesis of PD and of clinical features, both motor and non‐motor, that assist the clinician in making this diagnosis. An approach to the management of early stage PD is discussed, including emerging evidence of the benefits of physical exercise in this condition, and issues to consider in the selection of dopaminergic medication. The newly diagnosed patient with PD is often keen to know what the future holds for them, as they face this progressive neurodegenerative condition. While currently available medical therapies are symptomatic, rather than disease‐modifying, in nature, it is hoped that improved understanding of the aetio‐pathogenesis of PD will pave the way for future disease‐modifying therapies. [ABSTRACT FROM AUTHOR]

Parkinson disease (PD) is a complex neurodegenerative disorder that can present heterogeneously with a combination of motor and non-motor symptoms. α-synuclein, a neuronal protein, can undergo aberrant conformational change resulting in the intra-neuronal accumulation of toxic oligomers that form Lewy bodies, the pathological hallmark of PD. There is evidence that pathological α-synuclein exhibits prion-like behaviour in its mode of transmission through the nervous system. The choice of initial dopaminergic treatments should be individually tailored but long term outcomes appear to be equivalent. There is level A evidence supporting the benefit of three different device-assisted therapies in treating troublesome motor fluctuations and dyskinesias. Stem cell transplantation as currently being trialled is predominantly a symptomatic therapy targeting only limited regions of the brain affected by PD, and will need to be proven to be not only as effective but as safe as currently available device-assisted therapies. New modes of treatment including active immunisation against oligomeric α-synuclein and drugs that alter cellular metabolism show some promise. The inability to effectively treat a range of non-motor, non-dopaminergic symptoms remains a major therapeutic challenge. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 66-year-old man who presented to his general practitioner with a half-year history of tremor in his left hand. Tremor is a clinical problem in middle-aged and older patients. It was mentioned that several features of his condition are typical of parkinsonian tremor, which diminishes during limb movement. The man's wife stated that his posture had become more stooped over the past two years.

Parkinson disease (PD) is a multisystem neurodegenerative disorder that affects about 1% of the population over the age of 55 years and has mean age of onset of about 60 years. The Braak hypothesis proposes that the earliest pathological evidence of PD is found in the enteric nervous system, medulla and olfactory bulb, and only subsequently progresses (over years) to the substantia nigra and cortex. Non-motor symptoms, such as constipation, hyposmia and sleep disorders, may precede typical motor features of PD by several years. No treatment has been convincingly shown to slow PD progression (ie, a neuroprotective drug remains elusive). Symptomatic benefit from dopaminergic therapy is usually maintained throughout the course of the disease. The decision as to whether to commence treatment with either levodopa or a dopamine agonist needs to be individually tailored, but long-term outcomes appear to be equivalent. Advanced PD is complicated by the loss of non-dopaminergic neurones, resulting in symptoms that are largely unresponsive to dopaminergic therapy. Treatment with apomorphine, Duodopa or deep-brain stimulation surgery may be beneficial for selected patients with advanced PD. Non-motor symptoms, such as mood disorders, cognitive impairment, autonomic dysfunction and sleep disorders, are responsible for significant morbidity. Management often requires a multidisciplinary approach. [ABSTRACT FROM AUTHOR]

The article examines the case of a patient with dystonia-parkinsonism due to pallidal and nigral necrosis following heroin overdose. The patient has a history of marijuana use, post-traumatic stress disorder, depression and amphetamine-induced psychosis. Examination of the patient revealed right hemichorea and impairment of left-sided fractioned finger movements. It revealed that the evolution from hemichorea to dystonia was owing to acute and subacute effect of pallidal anoxia, respectively.

The article discusses a study which identified and quantified current deficiencies in primary and secondary stroke prevention and possible gains from optimal employment of thrombolysis. The study involved 259 consecutive patients admitted to a tertiary hospital stroke unit from January 24 2006 to January 10 2007 in Adelaide, South Australia. The researchers found that 183 patients had a disabling or fatal stroke, while 135 patients had at least one suboptimally managed risk factor.

The article presents a case study of a 42-year-old man with segmental dystonia from long-term dextromethorphan abuse. The susceptibility of the patient to drug-induced dystonia is investigated. Explored is the association of the spectrum of movement disorders with N-methyl-D-aspartate (NMDA) receptor blockade.

Background Patients with Parkinson disease ( PD) commonly experience motor fluctuations and dyskinesias in response to oral dopaminergic medications. Affected patients may benefit from device-assisted therapy, such as medication infusion or deep brain stimulation surgery. This is the first Australian study of the long-term adherence to apomorphine infusion ( AI) in patients with PD. Aims To assess the adherence to AI in patients with PD in a single centre over a 10-year period and to find the reasons for discontinuation in patients who discontinued AI. Methods This is an observational study of patients with PD treated with AI between 2004 and 2014. Outcome measures included changes in motor function and quality of life following AI, change in dose of other dopaminergic medications following AI, duration of infusion, adverse effects, reasons for cessation of AI and subsequent treatment after cessation. Results Mean duration of AI was 21.65 months. No patient achieved apomorphine monotherapy, and the mean reduction in the levodopa-equivalent dose of other dopaminergic medications after AI was 22.7%. The benefit of AI on motor function and quality of life was rated as 'much improved' or 'better' in 83% of patients. The most common reasons for discontinuation of AI were adverse effects and inadequate motor benefit. Most patients who discontinued AI were subsequently treated with another device-assisted therapy. Conclusion AI is an effective therapy for severe motor response complications in PD, especially in the short and medium term. However, many patients cannot be maintained on AI in the longer term. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 63 years old woman with cerebellar syndrome with seizures, hypomagnesaemia, and pantoprazole. It discusses the symptoms including dizziness, lethargy, and anorexia. It also presents information on the use of proton pump inhibitors, electrocardiogram results, and computed tomography scan results of the chest.

The article discusses the case of a female patient diagnosed with rhabdomyolysis and bilateral peroneal and tibial neuropathies caused by wearing and squatting in tight jeans. Topics discussed include the clinical presentation of the patient which include severe weakness of both ankles and impaired sensation, results of nerve conduction studies and the treatment of the patient intravenous hydration.

A letter to the editor is presented regarding a 64 year old businesswoman presented with treatment-resistant depression and multiple system atrophy (MSA) wherein electroconvulsive therapy (ECT) 3 times per week improved her physical symptoms.

Background: Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI).Methods: We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537.Findings: We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion.Interpretation: Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Progressive supranuclear palsy (PSP) is a neurodegenerative disorder for which there are currently no disease-modifying therapies. The neuropathology of PSP is associated with the accumulation of hyperphosphorylated tau in the brain. We have previously shown that protein phosphatase 2 activity in the brain is upregulated by sodium selenate, which enhances dephosphorylation. Therefore, the objective of this study is to evaluate the efficacy and safety of sodium selenate as a disease-modifying therapy for PSP., Methods and Analysis: This will be a multi-site, phase 2b, double-blind, placebo-controlled trial of sodium selenate. 70 patients will be recruited at six Australian academic hospitals and research institutes. Following the confirmation of eligibility at screening, participants will be randomised (1:1) to receive 52 weeks of active treatment (sodium selenate; 15 mg three times a day) or matching placebo. Regular safety and efficacy visits will be completed throughout the study period. The primary study outcome is change in an MRI volume composite (frontal lobe+midbrain-3rd ventricle) over the treatment period. Analysis will be with a general linear model (GLM) with the MRI composite at 52 weeks as the dependent variable, treatment group as an independent variable and baseline MRI composite as a covariate. Secondary outcomes are change in PSP rating scale, clinical global impression of change (clinician) and change in midbrain mean diffusivity. These outcomes will also be analysed with a GLM as above, with the corresponding baseline measure entered as a covariate. Secondary safety and tolerability outcomes are frequency of serious adverse events, frequency of down-titration occurrences and frequency of study discontinuation. Additional, as yet unplanned, exploratory outcomes will include analyses of other imaging, cognitive and biospecimen measures., Ethics and Dissemination: The study was approved by the Alfred Health Ethics Committee (594/20). Each participant or their legally authorised representative and their study partner will provide written informed consent at trial commencement. The results of the study will be presented at national and international conferences and published in peer-reviewed journals., Trial Registration Number: Australian New Zealand Clinical Trials Registry (ACTRN12620001254987)., Competing Interests: Competing interests: All authors report a grant from the NHMRC to support this study. The authors report the following disclosures outside of this study: LV reports personal fees from Biogen Australia, and research funding from Biogen, Eisai and LMI. AHE reports honoraria for presentations from Merck, Allergan, Ipsen, Teva, UCB, Abbott, AbbVie, STADA, participation in scientific advisory board meetings with Allergan, AbbVie, Ipsen and STADA and shares in GKC and CSL. DD reports consultancy fees from Biogen, Novartis. KLB, CMalpas, CMarotta, IHH, SK, JF, MC, SJGL, ST, JDOS, TK, LC, ML, CMH and DV report no disclosures., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are currently no Australian guidelines to assist clinicians performing deep brain stimulation (DBS) procedures in setting postoperative driving restrictions., Purpose: We aimed to provide recommendations for post-DBS driving restrictions to guide practice in Australia., Methods: A review of current Australian and international driving guidelines, literature regarding the adverse effects of DBS and literature regarding the long-term effect of neurostimulation on driving was conducted using Elton B Stephens Company discovery service-linked databases. Australian neurologists and neurosurgeons who perform DBS were surveyed to gain insight into existing practice., Results: No guidance on driving restrictions following DBS surgery was found, either in existing driving guidelines or in the literature. There was a wide difference seen in the rates of reported adverse effects from DBS surgery. The most serious adverse events (haemorrhage, seizure and neurological dysfunction) were uncommon. Longer term, there does not appear to be any adverse effect of DBS on driving ability. Survey of Australian practitioners revealed a universal acceptance of the need for and use of driving restrictions after DBS but significant heterogeneity in how return to driving is managed., Conclusion: We propose a 6-week driving restriction for private licences and 6-month driving restriction for commercial licences in uncomplicated DBS. We also highlight some of the potential pitfalls and pearls to assist clinicians to modify these recommendations where needed. Ultimately, we hope this will stimulate further examination of this issue in research and by regulatory bodies to provide more robust direction for practitioners performing DBS implantation., Competing Interests: Competing interests: ARC was participating in a movement disorders fellowship in 2019 partially funded by Abbott medical. TK had paid travel to DBS workshop (DBS user group meeting) paid for by Medtronic. NM reports no conflicts of interest. AL reports no conflicts of interest. This article was written by the authors with no input from any outside entity. The editing, recommendations and decision to published were not influenced by any external entity., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A rare extramedullary manifestation of haematological malignancy, myeloid sarcoma is most commonly seen in patients with acute myeloid leukaemia. We report on an adult patient who presented with an atypical phenotype of progressive cranial neuropathy without blood or bone marrow involvement, and in whom obtaining material for pathological diagnosis was made challenging by unusual findings of absent fluorodeoxyglucose-positron emission tomography avidity and involvement of sites not readily accessible to biopsy (orbital apex and cauda equina). The eventual diagnosis was obtained through biopsy of the uterine cervix before being verified on repeat lymph node and cerebrospinal fluid sampling prior to initiation of chemotherapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)