HostSeq: a Canadian whole genome sequencing and clinical data resource.

HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

The Canadian Neuromuscular Disease Registry 2010-2019: A Decade of Facilitating Clinical Research Througha Nationwide, Pan-NeuromuscularDisease Registry.

We report the recruitment activities and outcomes of a multi-disease neuromuscular patient registry in Canada. The Canadian Neuromuscular Disease Registry (CNDR) registers individuals across Canada with a confirmed diagnosis of a neuromuscular disease. Diagnosis and contact information are collected across all diseases and detailed prospective data is collected for 5 specific diseases: Amyotrophic Lateral Sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), Myotonic Dystrophy (DM), Limb Girdle Muscular Dystrophy (LGMD), and Spinal Muscular Atrophy (SMA). Since 2010, the CNDR has registered 4306 patients (1154 pediatric and 3148 adult) with 91 different neuromuscular diagnoses and has facilitated 125 projects (73 academic, 3 not-for-profit, 3 government, and 46 commercial) using registry data. In conclusion, the CNDR is an effective and productive pan-neuromuscular registry that has successfully facilitated a substantial number of studies over the past 10 years.

Comparison of custom and prefabricated orthoses in the initial treatment of proximal plantar fasciitis.

Fifteen centers for orthopaedic treatment of the foot and ankle participated in a prospective randomized trial to compare several nonoperative treatments for proximal plantar fasciitis (heel pain syndrome). Included were 236 patients (160 women and 76 men) who were 16 years of age or older. Most reported duration of symptoms of 6 months or less. Patients with systemic disease, significant musculoskeletal complaints, sciatica, or local nerve entrapment were excluded. We randomized patients prospectively into five different treatment groups. All groups performed Achilles tendon- and plantar fascia-stretching in a similar manner. One group was treated with stretching only. The other four groups stretched and used one of four different shoe inserts, including a silicone heel pad, a felt pad, a rubber heel cup, or a custom-made polypropylene orthotic device. Patients were reevaluated after 8 weeks of treatment. The percentages improved in each group were: (1) silicone insert, 95%; (2) rubber insert, 88%; (3) felt insert, 81%; (4)stretching only, 72%; and (5) custom orthosis, 68%. Combining all the patients who used a prefabricated insert, we found that their improvement rates were higher than those assigned to stretching only (P = 0.022) and those who stretched and used a custom orthosis (P = 0.0074). We conclude that, when used in conjunction with a stretching program, a prefabricated shoe insert is more likely to produce improvement in symptoms as part of the initial treatment of proximal plantar fasciitis than a custom polypropylene orthotic device.

Chronic disorders of the Achilles tendon: results of conservative and surgical treatments.

We reviewed our results of nonoperative and operative treatment of chronic Achilles tenosynovitis to further define outcomes and treatment parameters. Forty-one patients presented with an average of 14 weeks of Achilles tendon symptoms. All patients received nonsurgical treatment initially, and 21 patients (51%) recovered after an average of 18 weeks of therapy. Three additional patients improved after brisement of the tendon/peritenon interspace. Seventeen of 41 patients eventually underwent soft tissue tenolysis and/or excision of degenerative tendon cysts. Those patients who responded to nonoperative therapy tended to be younger (average age, 33 years) than those who had degenerative tendon changes requiring surgery (average age, 48 years). All surgical patients were able to return to unrestricted activity after 31 weeks (range, 27-48 weeks). We believe 4 to 6 months of nonsurgical therapy is appropriate for middle aged patients or athletes with chronic Achilles tenosynovitis. Those that fail this treatment will improve with a limited debridement of diseased tissue without excessive soft tissue dissection of the tendon.

Nurse practitioners as leaders in a quality health care delivery system.

Access to health care is often difficult for people infected with the human immunodeficiency virus (HIV). This article explores the role of the nurse practitioner (NP) within a self-directed, multidisciplinary framework, attending to the needs of a large population infected with HIV and acquired immunodeficiency syndrome (AIDS). The role of the NP is examined through the concepts of case management, primary care, multidisciplinary teams, consultation, and patient advocacy. A model is presented that describes the interaction between external stimuli and the central foci, with the NP being the orchestrator of the dynamic flow of communication. Positive consumer and professional outcomes will be identified as a result of the success of this model. It can serve as a framework for future health care delivery systems that provide cost-effective, accessible, continuous, quality health care.

Treatment of chronic heel pain by surgical release of the first branch of the lateral plantar nerve.

Sixty-nine heels (53 patients) with chronic heel pain had a surgical release of the first branch of the lateral plantar nerve. The average duration of heel-pain symptoms was 23 months (range, six months to eight years). No patient had less than six months of conservative treatment before surgery. The average duration of preoperative conservative treatment was 14 months. Forty-four patients (83%) had taken nonsteroidal antiinflammatory agents. Sixty-three heels (91%) had used heel cups and/or orthoses. Fifty-nine heels (86%) had received one or more injections of a steroid preparation. Thirty-four heels had developed pain initially during a sports activity. Postoperatively, 61 heels (89%) had excellent or good results; 57 heels (83%) had complete resolution of pain. The average follow-up period was 49 months. In general, heel pain resolves with conservative treatment. In recalcitrant cases, however, entrapment of the first branch lateral plantar nerve should be suspected. Surgical release of this nerve can be expected to provide excellent relief of pain and facilitate return to normal activity.

Pine stilbene synthase cDNA, a tool for probing environmental stress.

Stilbene synthase cDNAs were isolated from a pine (Pinus sylvestris) cDNA library. Poly(A)+RNA required for the preparation was obtained from young seedlings challenged with Botrytis cinerea. A full-length cDNA encoding pinosylvin-forming stilbene synthase was sequenced, and the deduced amino acid sequence was compared with sequences of resveratrol-forming stilbene synthases. The cDNA coding for the key enzyme of pinosylvin formation is a valuable tool for detecting early effects of environmental stress in pine needles.

Chronic heel pain. Treatment rationale.

Chronic heel pain needs a treatment rationale. Most heel pain responds to conservative treatment. When surgery is done, the surgeon must be aware of the anatomy and especially the nerves about the heel that can cause pain. The author's experience is presented.

The history of carpal tunnel syndrome.

Carpal tunnel syndrome is the most frequently diagnosed, best understood and most easily treated entrapment neuropathy. During the first half of the 20th century, however, most patients with carpal tunnel syndrome were diagnosed as having compression of either the brachial plexus or thenar nerve motor branch of the median nerve. As late as 1950, only twelve patients with operative release of the transverse carpal ligament for idiopathic carpal tunnel syndrome had been reported. The delay in accurate anatomical localization of this compressive neuropathy can be attributed both to the confusion caused by the diverse manifestations of median nerve compression in the carpal tunnel, and to some interesting developments that altered early investigations in this area.

Results of treatment of severe carpal-tunnel syndrome without internal neurolysis of the median nerve.

Thirty-three hands (twenty-nine patients) had a release of the carpal tunnel without internal neurolysis for severe carpal-tunnel syndrome. All of the hands had increased values for two-point discrimination or thenar atrophy, or both. Twenty-three (89 per cent) of the twenty-six hands that had increased values for two-point discrimination and twenty-six (87 per cent) of the thirty hands that had an elevated result on Semmes-Weinstein testing had normal values at follow-up. Nine (90 per cent) of the ten hands that had weakness of the thenar muscles (grade-3 strength or less) regained grade-4 or 5 strength. Thirteen (65 per cent) of the twenty hands that had thenar atrophy regained normal muscle bulk. Eighteen (62 per cent) of the twenty-nine patients had complete resolution of symptoms and signs of compression of the median nerve. No significant difference was found between the results in this series of patients and those in a previously reported similar group of patients who were treated by release of the carpal tunnel combined with internal neurolysis of the median nerve.

In vivo growth plate stimulation in various capacitively coupled electrical fields.

The right proximal tibial growth plates of adolescent New Zealand white rabbits were stimulated with various capacitively coupled electrical fields. Capacitor plates attached to plastic jigs placed over the proximal tibiae were connected to function generators which supplied sine wave signals of 60 kHz frequency and various voltages (2.5, 5, 10, and 20 V peak-to-peak). At 0 h and at 48 h, each animal was labeled with intravenously injected oxytetracycline. For the next 48 h, each right proximal tibial growth plate was stimulated with one of the above electrical signals. At the end of the 48 h of stimulation, the animals were sacrificed, and the tibiae were excised; histological sections of the proximal growth plate in each tibia were made, and the distance the labels moved away from the bone-cartilage junction down into the metaphysis was measured under fluorescent microscopy. Results indicate that the rabbit growth plate can be consistently stimulated to statistically significant accelerated growth in a capacitively coupled electrical field. A dose-response effect was noted, with 5 V peak-to-peak exhibiting maximum growth acceleration. Thus, the application of the proper capacitively coupled electrical field significantly stimulated the rabbit growth plate at voltage and current levels that are safe for human use.

Fluorinated phenytoin anticonvulsant analogs.

Six ring-fluorinated phenytoin analogs were synthesized, and their anticonvulsant activity in the maximal electroshock seizure and subcutaneous pentylenetetrazol assays was determined. 5-(4-Fluorophenyl)-5-phenylhydantoin, 5-(3-fluorophenyl)-5-phenylhydantoin, and 5,5-bis(4-fluorophenyl)hydantoin were active in the maximal electroshock seizure assay. The compounds were much less potent than phenytoin but showed an extremely long duration of action.