Computational pathology definitions,best practices,and recommendations for regulatory guidance: a white paper from the Digital Pathology Association

In this white paper, experts from the Digital Pathology Association (DPA) define terminology and concepts in the emerging field of computational pathology, with a focus on its application to histology images analyzed together with their associated patient data to extract information. This review offers a historical perspective and describes the potential clinical benefits from research and applications in this field, as well as significant obstacles to adoption. Best practices for implementing computational pathology workflows are presented. These include infrastructure considerations, acquisition of training data, quality assessments, as well as regulatory, ethical, and cyber-security concerns. Recommendations are provided for regulators, vendors, and computational pathology practitioners in order to facilitate progress in the field. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Physical activity as a risk factor for amyotrophic lateral sclerosis-findings from three large European cohorts

Journal of Neurology -     

Hydroxyapatite coating does not improve uncemented stem survival after total hip arthroplasty!: An analysis of 116,069 THAs in the Nordic Arthroplasty Register Association (NARA) database

ResultsUnadjusted 10-year survival with the endpoint revision of any component for any reason was 92.1% (CI: 91.8–92.4). Unadjusted 10-year survival with the endpoint stem revision due to aseptic loosening varied between the stem brands investigated and ranged from 96.7% (CI: 94.4–99.0) to 99.9% (CI: 99.6–100). Of the stem brands with the best survival, stems with and without HA coating were found. The presence of HA coating was not associated with statistically significant effects on the adjusted risk of stem revision due to aseptic loosening, with an HR of 0.8 (CI: 0.5–1.3; p = 0.4). The adjusted risk of revision due to infection was similar in the groups of THAs using HA-coated and non-HA-coated stems, with an HR of 0.9 (CI: 0.8–1.1; p = 0.6) for the presence of HA coating. The commonly used Bimetric stem (n = 25,329) was available both with and without HA coating, and the adjusted risk of stem revision due to aseptic loosening was similar for the 2 variants, with an HR of 0.9 (CI: 0.5–1.4; p = 0.5) for the HA-coated Bimetric stem.InterpretationUncemented HA-coated stems had similar results to those of uncemented stems with porous coating or rough sand-blasted stems. The use of HA coating on stems available both with and without this surface treatment had no clinically relevant effect on their outcome, and we thus question whether HA coating adds any value to well-functioning stem designs.Hydroxyapatite (HA) is thought to improve early implant ingrowth and long-term stability in bone (Overgaard et al. 1997), and many stems intended for uncemented total hip arthroplasty (THA) are thus manufactured with HA coating. Several uncemented stems are only available with HA coating. Some HA-coated stems have excellent long-term outcomes in terms of the risk of revision, both for any reason and due to aseptic loosening (Capello et al. 2003, Shah et al. 2009). Registry data from Norway and Finland also indicate that certain HA-coated stems have excellent survivorship up to 10 years (Eskelinen et al. 2006, Hallan et al. 2007, Makela et al. 2008).On the other hand, a number of studies on stem survival in the setting of randomized trials or smaller observational studies have failed to show beneficial effects of HA coating on clinical outcome and implant survival when compared to alternatives such as porous coating and sand-blasted rough surfaces (McPherson et al. 1995, Tanzer et al. 2001, Kim et al. 2003, Parvizi et al. 2004, Sanchez-Sotelo et al. 2004). Meta-analyses that have pooled data from randomized or cohort studies have come to the conclusion that there is “[…] no clinically beneficial effect to the addition of HA to porous coating alone in primary uncemented hip arthroplasty” (Gandhi et al. 2009, Li et al. 2013). In addition, a Danish registry analysis found that the use of HA coating does not reduce the risk of stem revision (Paulsen et al. 2007). Furthermore, a comparison of 4,772 uncemented Bimetric stems with or without HA coating implanted between 1992 and 2009 did not reveal any difference in survival between the 2 variants (Lazarinis et al. 2011).HA was initially introduced as an implant coating to speed up and facilitate ongrowth and ingrowth of bone and thereby improve fixation, based on comprehensive preclinical and promising clinical documentation (Geesink et al. 1987, Bauer et al. 1991, Overgaard et al. 1997, Karrholm et al. 1998). Later on, concerns were raised due to findings of delamination and generation of HA particles originating from the coating with the potential to trigger osteolysis, acceleration of polyethylene wear, and subsequent implant loosening (Bloebaum and Dupont 1993, Morscher et al. 1998, Lazarinis et al. 2010). Today, there is renewed interest in HA coatings due to possible properties as a carrier for agents aimed at preventing infection (Ghani et al. 2012). Theoretical arguments for and against the use of HA coating can therefore be found. Given the renewed interest in uncemented stems—instigated by favorable outcomes after uncemented stem fixation in younger patients—the question of whether HA coating is beneficial or not is highly relevant (Eskelinen et al. 2006, Hooper et al. 2009, Swedish Hip Arthroplasty Register 2011). We therefore investigated uncemented stems with and without HA coating that are in frequent use in the Nordic countries, regarding early and long-term survival.     

Urgent neurology out-patient referrals from primary health care physicians

We retrospectively analysed patients seen in a rapid referral clinic to identify those with abnormalities genuinely requiring urgent assessment, and to evaluate the impact of the clinic on routine services. After advertising the availability of the service, 25% of telephone referrals from primary-care physicians led to identification of patients considered suitable for urgent evaluation. We assessed 350 patients over an 18-month period. After neurological review, relevant abnormalities were identified in 73%, and 33% were considered to have warranted urgent assessment. In addition, 74% required radiological evaluation and 14% had a neurophysiological procedure; 19.4% were admitted on the same day, 13% underwent CSF analysis and 34% required some form of therapeutic intervention. In retrospect, patients with a clinical history of > 11 days rarely warranted urgent referral. Visual failure and diplopia provided the highest correlation with patients deemed to require urgent assessment, and syncope and headache the lowest. Despite the number of patients reviewed, no effect was demonstrated on waiting times for standard out-patient review.      

Respiratory insufficiency in neuronopathic and neuropathic disorders

Twenty-nine patients with a neuronopathic or neuropathic disorder were referred for assessment of respiratory insufficiency between 1978 and 1994. Diagnoses included spinal muscular atrophy (6), chronic idiopathic demyelinating neuropathy (4), Vialetto-van Laere syndrome (3), hereditary motor and sensory neuropathy (3) and a miscellaneous group (5). We also describe seven patients with Guillain-Barre syndrome (GBS) who required long-term ventilatory support for over 6 months to 7 years after the initial illness. Respiratory insufficiency occurred as a consequence of respiratory muscle weakness, impaired bulbar function and restrictive lung defects. In some groups presentation was with progressive nocturnal hypoventilation culminating in acute respiratory failure. Five patients with GBS or chronic idiopathic demyelinating neuropathy were weaned from ventilatory support up to 18 months after the initial illness. The remaining 24 patients required continuous or nocturnal ventilatory support using intermittent positive-pressure ventilation (13), negative pressure ventilation (4), nasal-mask-delivered intermittent positive-pressure ventilation (4), nasal-mask-delivered continuous positive-pressure ventilation (3), mouthpiece-assisted ventilation by day (2) and rocking bed (1). None have been weaned from support after a period of ventilation ranging from one month to 10 years. Eight patients have subsequently died.