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Biomedical subjects

Stephen Hall

Publications and source records attributed to Stephen Hall.

12 recordsLinked to original sources

Rituximab for the treatment of the skin manifestations of dermatomyositis: a report of 3 cases.

Three patients suffering from classic dermatomyositis (juvenile and adult-onset) with prominent recalcitrant skin manifestations are described. All patients demonstrated good control of muscle symptoms on immunosuppressive medications, but their cutaneous disease persisted despite treatment with at least 4 different systemic treatments and topical agents. They were given rituximab, a monoclonal anti-CD20 antibody, achieving a response with minimal side effects. We document our experience with this medication for the cutaneous lesions of dermatomyositis.

Adolescent↗

Therapeutic efficacy and safety of chaperonin 10 in patients with rheumatoid arthritis: a double-blind randomised trial.

BACKGROUND: Chaperonin 10 (heat shock protein 10, XToll) has anti-inflammatory properties related to the inhibition of Toll-like receptor signalling pathways. Our aim was to establish whether chaperonin 10 is safe and effective in the treatment of rheumatoid arthritis. METHODS: In this randomised, double-blind, multicentre study, 23 patients with moderate to severe active rheumatoid arthritis receiving disease-modifying antirheumatic drugs were randomly allocated to three treatment groups receiving intravenous chaperonin 10 twice weekly for 12 weeks at doses of 5 mg (n=8), 7.5 mg (8), or 10 mg (7). The primary outcomes were change in disease activity score (DAS28) and improvement of core disease measures (American College of Rheumatology response score) from baseline to week 12. All analyses were done by intention to treat. This study is registered with the Australian Clinical Trials Registry, number ACTRNO12606000041550. FINDINGS: Primary endpoint measures improved from day 14 in all groups and continued to improve to day 84. By end of study, a 20% improvement of core disease measures was seen in six (86%, 95% CI 43-100), a 50% improvement in four (57%, 14-86), and a 70% improvement in two (29%, 0-57) patients given the highest dose of chaperonin 10. Clinical remission (as defined by a DAS28 <2.6) was achieved in three (13%) of 23 patients. Three individuals dropped out during the study: one in the 5 mg group (rheumatoid arthritis not controlled), one in the 7.5 mg group (adverse event), and one in the 10 mg group (lost to follow-up). The most common adverse events were exacerbation of rheumatoid arthritis (both during and after the study) and upper respiratory tract infection. Only one adverse event was judged to be of severe intensity. INTERPRETATION: Chaperonin 10 seems to be well tolerated and efficacious in treatment of the symptoms of rheumatoid arthritis, at least in the short term.

Adult↗

Functional health literacy of patients with rheumatoid arthritis attending a community-based rheumatology practice.

OBJECTIVE: To determine the health literacy of patients with rheumatoid arthritis (RA) attending community-based rheumatology practice. METHODS: Eighty patients were administered the Test of Functional Health Literacy in Adults (TOFHLA), a 50-item reading comprehension and 17-item numerical ability test (score 0-100); the Rapid Estimate of Adult Literacy in Medicine (REALM), which asks participants to read aloud 66 words of varying difficulty (score 0-66); and the Test of Reading Comprehension (TORCH), which asks participants to read a short text and then fill in the gaps of another version by using one or more of their own words (score 1-9). RESULTS: The study group included 60 women (75%), mean age (SD) 60.29 (15.02) years, median duration of RA 8 years (range 0.3-39). Nineteen of 80 (24%) had completed or= 11 years. TOFHLA and REALM scores ranged from 39-100 and 41-66 respectively. Scores for 8 patients (10%) indicated they would have difficulty reading and interpreting health texts and struggle with most currently available patient education materials. Of those who attempted the TORCH, 8/65 (12%) scored low or below average and 23/65 (35%) scored average compared with students completing 9th grade. All 3 literacy tests were significantly correlated with education level, but use of educational level alone as a measure of literacy would have misclassified more than 10% as health literate/illiterate. CONCLUSION: A significant number of patients with RA have limited health literacy and may not understand even simple written instructions or prescription labels.

Adult↗

Cancer Care Ontario's computerized physician order entry system: a province-wide patient safety innovation.

More than one-third of all women and men in Canada will develop cancer during their lifetimes. Cancer patients typically require complex chemotherapy regimens, specific to their type and stage of disease, to slow or stop cancer cells from growing, multiplying, or spreading to other parts of the body. Despite the complexity of managing medication regimens for cancer patients and the associated risks to patient safety, current medical oncology practice throughout most of Canada is still to use paper-based tools, policies and procedures. To increase patient safety by reducing prescription errors and to offer clinical decision support to medical oncologists across the province, Cancer Care Ontario (CCO) developed and implemented Canada's first, cancer-specific computerized physician order entry (CPOE) system. This e-health innovation is currently in use in 11 cancer centres, and represents the largest ambulatory oncology CPOE implementation in Canada, with a 100% implementation success rate, and greater than 90% physician adoption. This paper describes the critical success factors in the design and implementation of CCO's CPOE system, including Web-based training and ease of administration to maximize physician adoption, incorporating point-of-care access to clinical practice guidelines into the tool, and the use of CPOE data to monitor and increase access to anti-cancer drugs and patient safety.

Cancer Care Facilities↗

Using cancer registry data for survival studies: the example of the Ontario Cancer Registry.

BACKGROUND AND OBJECTIVES: The Ontario Cancer Registry (OCR) is a population-based tumor registry created to provide data for epidemiologic research and for cancer surveillance. Recently it has been used for health services research. The objective of this project was to assess the quality of the OCR data that is used in survival analysis. METHODS AND DESIGN: Clinical information for 898 patients with squamous carcinoma of the head and neck including index tumor site, date of diagnosis, vital status, date of death, and cause of death from a prospective database at the Kingston Regional Cancer Center is compared to the same data elements in the OCR for the same patients. RESULTS: There is no statistically significant difference in disease-specific survival between the information from the two databases (log rank P = .89). The OCR captured and correctly assigned index tumor site for 81.4% (detection rate). The site assignment was accurate 90.9% of the time (confirmation rate), there was agreement on vital status (dead vs. alive) for all but one patient, and there was excellent agreement on date of death. However, cause of death (cancer vs. noncancer) based on death certificates had a 31% error rate. CONCLUSION: Researchers can be confident in the survival analysis generated from data in this registry, but need to be aware of potential sources of error.

Carcinoma, Squamous Cell↗

Pharmacokinetic interactions between indinavir plus ritonavir and calcium channel blockers.

BACKGROUND: Hypertension is an important modifiable cardiac risk factor in human immunodeficiency virus (HIV)-infected patients. Calcium channel blockers are substrates of cytochrome P450 3A and are commonly prescribed for hypertension. We evaluated potential bidirectional pharmacokinetic interactions between calcium channel blockers and coadministered indinavir and ritonavir. METHODS: Healthy HIV- seronegative subjects received 120 mg diltiazem daily or 5 mg amlodipine daily for days 1 to 7 and 20 to 26. All subjects received 100 mg ritonavir and 800 mg indinavir every 12 hours on days 8 to 26. Twenty-four-hour pharmacokinetic collection was performed on days 7 and 26, with 12-hour collection on day 19. RESULTS: Indinavir plus ritonavir increased the median amlodipine area under the curve from 0 to 24 hours (AUC) by 89.8%, from 122 to 230 ng.h/mL (n = 18, P < .0001), and increased the median diltiazem AUC by 26.5%, from 800 to 1060 ng.h/mL (n = 13, P = .06). Of 13 subjects, 2 (15%) had greater than 4-fold increases in diltiazem AUC. Desacetyldiltiazem AUC increased by 102.2% (P = .001), and desmethyldiltiazem AUC decreased by 27.4% (P = .01). Neither amlodipine nor diltiazem affected steady-state AUCs of the protease inhibitors. No serious cardiovascular adverse effects were observed. CONCLUSIONS: Indinavir plus ritonavir increases the AUCs of both amlodipine and diltiazem, which may result in an increased response. If coadministration is indicated, amlodipine or diltiazem should be initiated at low doses with careful titration to response and side effects.

Adolescent↗

Muscle involvement in mixed connective tissue disease.

Muscle disease has been recognized as a common feature of mixed connective tissue disease (MCTD) since its first description in 1972. In the absence of clinical trials that are directed specifically at the myositis of MCTD, patients should be treated in the manner that is recommended for other forms of myositis. Myositis of MCTD may have a better prognosis than other forms of myositis.

Autoantibodies↗

A comparison of magnetic resonance imaging, sonography, and radiography of the hand in patients with early rheumatoid arthritis.

OBJECTIVE: As therapy for rheumatoid arthritis (RA) becomes more effective, more sensitive imaging methods are required to assess disease activity and joint damage. We compared magnetic resonance imaging (MRI), sonography, and radiography for assessment of disease activity for the detection of bony erosions. METHODS: Forty-six patients with newly diagnosed RA (onset within 2 years) received clinical and laboratory assessment followed by radiographs, sonography, and MRI of the right hand at baseline and at 6 months according to a standardized protocol. We determined the presence of edema, synovitis, effusions, tendon fluid, tendon thickening, and size in the same way by MRI and sonography. The intra- and interreader reliability of MRI and radiographs and predictors of MRI erosions at 6 month followup were also examined. RESULTS: At baseline, 39 (85%), 14 (30%), and 17 (37%) patients had erosions identified on MRI, sonography, and radiography, respectively. Over time, the percentage of patients with erosions increased to 91% for MRI, 41% for sonography, and 48% for radiography. The absolute number of erosions increased from 177 to 239 erosions for MRI, from 30 to 43 for sonography, and from 38 to 73 for radiographs. The intra- and interreader reliability for the assessment of erosions and synovitis on MRI was acceptable (intrareader ICC of 0.60 and 0.90; interreader ICC of 0.77 and 0.89, respectively). CONCLUSION: MRI appears to be the most sensitive modality for erosive disease compared with sonography and radiography. Sonography detected more joint and tendon sheath effusions than MRI in this study and therefore may have a role in the assessment of disease activity.

Adult↗

Kb-R7943 prevents acute, atrial fibrillation-induced shortening of atrial refractoriness in anesthetized dogs.

BACKGROUND: To test the hypothesis that Ca2+ influx via Na+/Ca2+ exchange (NCX) underlies atrial fibrillation (AF)-induced shortening of atrial effective refractory period (AERP), we examined the potential of KB-R7943 (KB), a selective inhibitor of Ca2+-influx mode NCX, to attenuate this effect. METHODS AND RESULTS: Studies were performed in 41 isoflurane-anesthetized dogs. In sinus rhythm dogs, peak AERP changes resulting from intravenous KB infusion ranged from (mean+/-SEM) 4.4+/-0.4% (1 mg/kg) to 14.8+/-2.6% (5 mg/kg; ED50=1.9 mg/kg). AERP was maximally prolonged between 5 and 10 minutes after beginning of KB infusion and returned to baseline values within 30 minutes thereafter. Rapid atrial pacing-induced AF reversibly shortened AERP (P<0.001) in 5 dogs, averaging 14.9+/-2.1% after 90 minutes of AF. Both the time course and magnitude of mean AERP changes in 5 AF dogs receiving 5 mg/kg KB were indistinguishable from those in 5 sinus rhythm dogs receiving an equivalent KB dose (P>0.05). We measured cardiac tissue and arterial plasma KB concentrations produced by intravenous infusion (1 mg x kg(-1) x min(-1)) of 5 mg/kg KB. Plasma drug concentration peaked at the end of KB infusions (30.86+/-3.26 nmol/L; n=4 dogs) and declined to 0.56+/-0.19 nmol/L after 100 minutes. The cardiac tissue-to-plasma drug concentration gradient averaged approximately 40 at 100 minutes after start of KB infusion. KB at concentrations achieved in vivo irreversibly blocked NCX-mediated Ca2+ influx in isolated canine right atrial myocytes by approximately 60%, but had no significant effect on NCX-dependent Ca2+ extrusion. CONCLUSION: NCX-mediated Ca2+ influx plays an important role in acute, AF-induced AERP shortening.

Acute Disease↗