Media and technology usage and attitudes in emergency department patients.

Introduction: Digital health technologies are increasingly being used in emergency medicine, many of which utilize smartphones and computers. Patient willingness to use these modalities is an important factor in successful implementation. Therefore, this study aimed to assess emergency department (ED) patients' use of and attitudes towards technology. Methods: This was a pooled sub-analysis of ED patients (≥18 years old) that were enrolled in two studies evaluating the ED patient experience in response to novel technological interventions. Participants completed the Media and Technology Usage and Attitudes Scale (MTUAS) that assessed computer and smartphone ownership; frequency of use of phone calls, texting, email, and smartphones; and anxiety and dependence attitudes on these technologies. Results: One hundred and forty-four participants completed the survey. Mean age was 47.2 years (SD 17.94); 61.8% were female; and 61.1% were white. There was high usage of smartphones (93.1%) and computers (74.3%). Participants most frequently used phone calling and texting and least commonly used email. Participants had a positive attitude (mean 3.9/5, SD 0.68) towards the use of these technologies. Discussion: ED patients reported high ownership of smartphones and computers, had a positive attitude towards their use, and had varying frequency with which they used different technologies. Future studies can use this information to inform the development of digital health interventions that utilize technologies that patients find most acceptable.

Prognostic impact of baseline tumour immune infiltrate on disease-free survival in patients with completely resected, BRAFv600 mutation-positive melanoma receiving adjuvant vemurafenib.

BACKGROUND: We conducted a retrospective exploratory analysis to evaluate the effects of baseline tumour immune infiltrate on disease-free survival (DFS) outcomes in patients with fully resected stage IIC-IIIC melanoma receiving adjuvant vemurafenib monotherapy or placebo in the BRIM8 study. PATIENTS AND METHODS: BRIM8 was a phase III, international, double-blind, randomised, placebo-controlled study. Eligible patients with BRAFV600 mutation-positive, completely resected melanoma were randomly assigned to oral vemurafenib (960 mg twice daily) or matching placebo for 52 weeks. The primary end point was DFS. The association of CD8+ T-cell infiltration and programmed death ligand 1 (PD-L1) expression with DFS, as measured by immunohistochemistry, was explored retrospectively. RESULTS: Four hundred ninety-eight patients were randomly assigned to receive adjuvant vemurafenib (n = 250) or placebo (n = 248); tumour samples were available for biomarker analysis for approximately 60% of patients. In the pooled biomarker population, placebo-treated patients with <1% CD8+ T cells in the tumour centre had shorter median DFS than those with ≥1% CD8+ T cells (7.7 versus 47.8 months). DFS benefit from vemurafenib versus placebo was greater in patients with <1% CD8+ T cells [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.34-0.92) than in patients with ≥1% CD8+ T cells (HR 0.77; 95% CI 0.48-1.22). Likewise, median DFS was shorter among placebo-treated patients with <5% versus ≥5% PD-L1+ immune cells (IC) in the tumour (7.2 versus 47.8 months). A greater DFS benefit with vemurafenib versus placebo was observed in patients with <5% PD-L1+IC (HR 0.36; 95% CI 0.24-0.56) than in patients with ≥5% PD-L1+IC (HR 0.99; 95% CI 0.58-1.69). CONCLUSIONS: The presence of CD8+ T cells and PD-L1+IC are favourable prognostic factors for DFS. Treatment with adjuvant vemurafenib may overcome the poor DFS prognosis associated with low CD8+ T-cell count or PD-L1 expression. CLINICALTRIALS. GOV IDENTIFIER: NCT01667419.

Transforming growth factor-beta administration modifies cyclosporine A-induced bone loss.

Cyclosporine A (CsA), a potent immunosuppressant used in transplantation, induces increased formation with excess resorption in the rat with resultant osteopenia. These findings are confirmed in the human model. Transforming growth factor-beta (TGF-beta) is reported to be involved in the coupling of bone formation with resorption and in vivo and in vitro stimulates osteoblasts, and in vitro inhibits osteoclasts. CsA stimulates secretion of TGF-beta1 in humans, which, while improving immunosuppression, may also contribute to renal toxicity. This study was performed determine whether exogenously administered TGF-beta would modify the bone effects of CsA. Male Sprague-Dawley rats, 6 months of age, were randomized to receive: TGF-beta and CsA vehicle (group A); TGF-beta 5 microg/kg three times per week and CsA vehicle (group B); TGF-beta vehicle and CsA 10 mg/kg (group C); or TGF-beta 5 microg/kg three times per week and CsA 10 mg/kg (group D). These were compared with control over 28 days. CsA, but not TGF-beta, increased serum 1,25(OH)(2)D levels throughout the study. CsA increased osteocalcin (BGP), but TGF-beta negated this effect. Histomorphometry confirmed the known effects of CsA, whereas TGF-beta alone had no effect. However, in combination, TGF-beta blocked CsA's effect and increased osteoblast recruitment and activity, as reflected by increased percent mineralizing surface, percent osteoid perimeter, bone formation rate (bone volume referent), and activation frequency. Thus, it appears as if TGF-beta administration may have potential in modulating the deleterious bone effects of CsA.

Effect of the interaction of parathyroid hormone and cyclosporine a on bone mineral metabolism in the rat.

Cyclosporine A (CsA) induces high turnover osteopenia in the rat and there is evidence for this in humans. Recent studies suggest that increases in parathyroid hormone (PTH) may be involved in posttransplantation bone loss. However, human studies are difficult to interpret since transplant patients usually receive a cocktail of immunosuppressants and have underlying disease. Our aim was to try to resolve the influence of the absence or presence of PTH on CsA-induced bone disease. Male Sprague Dawley rats aged 7-9 months, either sham operated or parathyroidectomized (PTX), were randomly divided into vehicle and CsA groups. All PTX rats were given oral calcium supplementation ad libitum. The rats were divided into groups: basal, sham/vehicle, sham/CsA, PTX/vehicle, and PTX/CsA. Serial biochemistry was performed 0, 14, and 28 days after the start of the experimental period; bone histomorphometry was performed 28 days after the start of the experimental period. Statistical analysis consisted of group comparisons and factorial analyses. The results showed that CsA alone produced a high turnover osteopenia consistent with previous studies. In the PTX animals there was an increase in bone mass. PTX also decreased osteoblast activity and recruitment, and serum 1,25OH2D levels. Serum levels of osteocalcin (BGP) were unaffected by PTX. The combination group (PTX/CsA) did not differ statistically from the controls in most of the histomorphometric parameters measured, with the exception of reduced mineral apposition and bone formation rates, reflecting the effects of PTX. Serum BGP and 1,25OH2D levels did not differ, but PTH was reduced from the control. Explanations for these results are (1) CsA and PTX exert their effects via separate mechanisms, negating each other; (2) in the absence of PTH, CsA managed to cause bone loss, and thus PTH may not be essential for CsA-induced bone loss; or (3) the profound accelerated bone loss produced by CsA in normal rats requires PTH. These findings may help explain the discrepancies found in clinical studies where bone loss occurs with either elevated or normal PTH levels.

Immunosuppressant use without bone loss--implications for bone loss after transplantation.

Cyclosporine A (CsA) is associated with posttransplantation bone disease. Immunosuppressant drugs such as sirolimus (SRL), which are more potent and less deleterious than CsA, are being developed. Previous experiments have shown that SRL although immunosuppressive, is relatively bone sparing. The use of low doses of CsA and SRL in combination has displayed in vivo synergism. This study was initiated to examine the effect of low-dose CsA and SRL on bone metabolism, thereby hopefully providing a bone sparing immunosuppressive regimen for transplant recipients. One hundred and nineteen rats were divided into groups: basal, vehicle, CsA high dose, CsA low dose, SRL low dose, and combination low-dose CsA and SRL. The basal group was killed on day 0 for histomorphometry. The experimental groups were weighed and bled on days 0, 28, 56, and 84 and were killed on day 84 for histomorphometry. Serial assays for blood urea nitrogen (BUN), creatinine, and osteocalcin were performed. Osteocalcin was raised on days 28 and 56 in the high dose CsA group. Histomorphometry showed osteopenia with high-dose CsA. Low-dose CsA was relatively bone sparing, while low-dose SRL and combined low-dose CsA did not cause bone loss. In conclusion, the synergistic combination of low-dose CsA and SRL has the potential of providing both bone sparing and immunosuppressive benefits.

Radiation safety program outcomes as indicated by regulatory compliance activities from 1988 to 1997 in Texas.

Occupational radiation protection programs rarely encounter readily observable workplace injuries or illnesses, so upper management must rely on different indicators of relative performance. In many cases, the number of violations, complaints, and reported incidents is used. As with reported workplace injury and illness data, violation, complaint, and incident data provide only a crude indication of a radiation protection program's overall effectiveness. Even so, it is important to recognize that tangible program outcome measures such as these often dictate management decisions. Hence, safety professionals should have access to baseline violation, complaint, and incident trend data so that more informed preventive strategies can be put into place where possible. To assess the outcomes of radiation protection programs in Texas, data from regulatory compliance activities for a 10-y period, inclusive of calendar years 1988 to 1997, were assembled, summarized, and independently verified. For licensees of radioactive material, the ten most frequently cited violations represented 64% of the total issued during the study period. For registrants of radiation producing devices, the ten most frequently cited violations accounted for 73% of the total. A particular emphasis on proper recordkeeping is evident, and should be noted by any internal radiation protection quality assurance programs. Regardless of the permit type, the vast majority of violations issued were classified as low severity. Licensees were found to be involved in approximately 73% of the incidents recorded, with overexposures and badge overexposures representing the largest identifiable types. Registrants were found to be involved in approximately 57% of the complaints recorded, with the largest identifiable issue being concerns about health care provider qualifications or performance. Although this study was limited to a single state, the results can be of benefit to both quality assurance programs and professional health physics training courses by objectively identifying the areas commonly found to be deficient.

Interferon-alpha, unlike interferon-gamma, does not cause bone loss in the rat.

Interferons (IFN) are a group of related glycoproteins. IFN-gamma, in vitro, has been shown to inhibit resorption; however, an in vivo experiment showed that it had the opposite effect, resulting in bone loss that was comparable to that caused by cyclosporine A. IFN-alpha has numerous clinical applications but is used most extensively in the treatment of chronic hepatitis B and chronic hepatitis C. Research into the effects of IFN-alpha on bone mineral metabolism has been very sparse, and the majority of studies reflect in vitro models. Like IFN-gamma, there exists discordance between in vitro and in vivo studies on IFN-alpha. Both in vivo and in vitro studies demonstrate that IFN-alpha decreases bone resorption, whereas osteoblasts may or may not be affected in vivo. This study was designed to provide information on the in vivo effects of IFN-alpha in the rat model, because we feel that, given its widespread clinical use, this is an extremely important issue. Rats were given low dose IFN-alpha (1.6 x 10(6) IU/m2), intermediate dose IFN-alpha (5.35 x 10(6) IU/m2), and high dose IFN-alpha (30 x 10(6) IU/m2) three times per week for 28 days. Serum osteocalcin (bone gla protein, or BGP) and parathyroid hormone (PTH) were measured serially and, after double labeling, the bones were examined histomorphometrically. IFN-alpha did not alter any of the histomorphometric parameters measured and did not affect PTH. However, it produced a disparate BGP response. Low dose IFN-alpha resulted in a statistically significant increase in serum BGP on days 14 and 28, whereas intermediate and high doses of IFN-alpha did not. Overall, these results provide no evidence of a deleterious effect of IFN-alpha on bone metabolism and confirm the limited clinical study.

Improved strategies for diagnosis and treatment of osteoporosis.

OBJECTIVE: Osteoporosis is a silent epidemic that afflicts millions of postmenopausal women around the world. Osteoporosis places an enormous economic burden on society, including significant morbidity and mortality. Because of the increasing numbers of patients with osteoporosis, primary care physicians have become the front line for the diagnosis and treatment of this condition. Thus, the primary care provider should be able to diagnose osteoporosis in both asymptomatic and symptomatic women, perform a thorough workup to exclude secondary causes of osteoporosis, and optimally prevent and treat osteoporosis using the various forms of pharmacologic and nonpharmacologic therapies. DESIGN: Review of current literature and articles dealing with pathophysiology, diagnosis, and treatment of osteoporosis. RESULTS: Diagnostic and therapeutic modalities can reduce the incidence of fractures. CONCLUSIONS: The diagnosis and treatment of osteoporosis has greatly improved but needs further efforts to prevent the disease.

The proliferative response to platelet-derived growth factor of smooth muscle cells isolated from synthetic vascular grafts in a canine model.

OBJECTIVE: Previous studies on graft healing have shown increased platelet-derived growth factor (PDGF) production in graft segments versus native aortic segments. The purpose of this study was to characterize the proliferative response of graft smooth muscle cells (SMCs) to PDGF. METHODS: Thoracoabdominal grafts were implanted in beagles. SMCs were harvested from the graft and the proximal and distal aortas. Basal proliferation was assessed with growth curves in primary culture. The proliferative response to PDGF then was compared with [3H]thymidine uptake studies and cell counts. Finally, PDGF receptors were characterized with radio-labeled ligand binding assays. RESULTS: The growth curves showed that the graft SMCs entered log-phase growth 2 days earlier than did the aortic SMCs. Stimulation of quiescent early-passage graft SMCs with PDGF (10 ng/mL) resulted in a 1.7 +/- 0.1-fold increase in [3H]thymidine incorporation, which was significantly less than that of the SMCs from both the proximal aorta (11.8 +/- 3.0) and the distal aorta (10. 2 +/- 1.9; P <.5). Similarly, the 1.1 +/- 0.1-fold increase in graft SMC cell number was significantly less than the increases for both proximal (2.8 +/- 0.5) and distal (2.9 +/- 0.8) aortic SMCs (P <.5). Binding studies on quiescent first-passage cells showed fewer PDGF receptors available for binding in the graft SMCs (185 +/- 70 fmol/million cells) as compared with both the proximal (419 +/- 147 fmol/million cells) and the distal (387 +/- 112 fmol/million cells) aortas (P <.5). Binding affinity was similar for the three groups. CONCLUSION: Graft SMCs exist in a chronic proliferative state but exhibit a decreased proliferative response to PDGF and have fewer receptors available for binding PDGF than do aortic SMCs in vitro.

Mycophenolate mofetil: a promising new immunosuppressant that does not cause bone loss in the rat.

BACKGROUND: Posttransplantation bone disease is a well-described phenomenon; among its etiology is immunosuppressant-induced bone disease. Mycophenolate mofetil (MMF) has emerged as a promising new immunosuppressant. Our study was designed to investigate the effect of MMF on in vivo bone mineral metabolism. METHODS: Twenty-four 6-month-old male Sprague-Dawley rats were randomized into two groups to receive either MMF vehicle daily for 28 days or 30 mg/kg MMF daily for 28 days. The serum was assayed for osteocalcin and 1,25-dihydroxy vitamin D3. Subsequent to double-labeling, the right tibiae were removed on day 28 for histomorphometry. RESULTS: MMF suppressed bone gla protein (osteocalcin) levels on days 14 and 28 (P < 0.05). Except for percentage osteoid perimeter, there was no difference in bone histomorphometry between the two groups. CONCLUSION: In this relatively short-term study, MMF did not cause osteopenia in the rat model, but the suppressed bone gla protein merits further study.

Staff knowledge, attitudes and practices in public sector primary care of diabetes in Cape Town.

OBJECTIVE: To audit staff knowledge, attitudes and practices in the interest of improved public sector primary care for diabetics. DESIGN: External audit using face-to-face, private, questionnaire-based interviews. SETTING: Twelve public sector ambulatory health centres in Cape Town. SUBJECTS: Non-specialist, principal staff members (N = 35)-12 doctors, 10 primary health care nurses (PHCNs), 7 registered nurses (RNs) and 6 staff nurses (SNs). RESULTS: Staff members were long-standing employees (mean-doctors 6 years, PHCNs 8 years, RNs 5 years, SNs 12 years). Few had post-basic training (doctors 25%, PHCNs 20%, RNs 26%, SNs 83%). Knowledge of chronic diabetic complications was adequate, e.g. diabetic eye disease was mentioned by 100% of staff. There were gaps in knowledge of pathophysiology and of signs and symptoms of diabetic emergencies, e.g. < 33% knew control of hypertension to be important in the prevention of diabetic nephropathy. Knowledge of appropriate care of patients with hypoglycaemia (94% mentioned glucose administration) was better than that of hyperglycaemia (69% mentioned intravenous fluids). Problems were reported in inter-staff communication within (approximately 50%) and between (approximately 75%) disciplines by doctors, PHCNs and RNs. Staff/patient communication problems were reported by approximately 75% of staff. Solutions suggested by staff included meetings between staff members and with management, in-service training programmes and appointment systems for patients. Despite logistic, organisational and communication-related problems, most staff enjoy and believe in the value of their work. CONCLUSIONS: This study reveals deficiencies in in-service training with consequent gaps in knowledge and practice. Recommendations that would lead to improved quality of care and increased staff and patient satisfaction have been given.

Inhibition of smooth muscle cell proliferation and migration in vitro by antisense oligonucleotide to c-myb.

PURPOSE: Smooth muscle cell (SMC) migration and proliferation are prominent features of intimal hyperplasia. Previous studies have shown that inhibition of c-myb inhibits arterial SMC proliferation. Our goal was to evaluate the effect of an antisense oligonucleotide targeted to c-myb on the proliferation and migration of SMC explanted from synthetic vascular grafts. METHODS: SMCs were enzymatically removed from aortas and Dacron grafts explanted from dogs (n = 5). For proliferation studies, quiescent SMCs were incubated with either 0.0, 0.5, 5.0, or 10.0 microM antisense (GTGTCGGGGTCTCCGGGC) or sense (GCCCGGAGACCCCGACAC) oligonucleotides to c-myb. Proliferation was measured after 24 hours by incorporation of [3H]thymidine. Migration was assessed 24 hours after a razor injury. RESULTS: Antisense to c-myb consistently inhibited proliferation and migration of both native aortic and graft SMCs in a dose-dependent fashion. At a concentration of 10 microM antisense oligonucleotide, aortic and graft SMC proliferation rates were 32% +/- 20% and 56% +/- 9% of control samples, respectively. At 25 microM antisense, the number of migrating aortic and graft SMCs decreased to 41.9% +/- 26.8% and 51.9% +/- 34.1% of control samples, respectively. CONCLUSIONS: Our results suggest that antisense oligonucleotides to c-myb may be useful in the inhibition of SMC proliferation and migration associated with development of intimal hyperplasia.

Group processes of decision making for hospital-based technology assessment committees.

There are a variety of group-judgment methods to resolve controversial issues in health care. Meta-analysis and group judgment methods such as consensus conferences are attempts to bring diverse elements of information together for synthesis. Leape notes that a significant body of literature exists regarding the techniques used to elicit opinions from groups. Organizational structures and functions of groups vary in terms of the natures of interactions among group members and the manners in which final conclusions are reached and expressed. The introduction of the process of technology assessment into the hospital setting introduces a problem inherent in the introduction of somewhat academic processes into the operational real world of interpersonal relations, administrative and medical staff interactions, staff costs, and institutional priorities. Hospital administrative processes are based on the committee approach. Medical staff credentialing, drug formularies, and administrative policies are all developed, approved, and implemented through committees. It would seem logical that if technology assessment is to be effective in the hospital setting, then those same group decision processes inherent in committees should be used in technology assessment. Relatedly, if technology assessment is to be successful in the hospital setting, then how can the limited resources of hospital-based staff be best utilized to carry through the assessment of elected technologies? This paper discusses group decision processes, particularly as they relate to technology assessment. The processes of particular interest are those that focus on group interactions rather than theory-based decision processes. The purpose for the paper is to provide to clinical engineering management and senior hospital management background information to use in the formulation of the operating parameters of a hospital-based technology assessment committee.

Increasing physician acceptance of technology assessment through a focused training program.

This paper presents the framework for a one-semester course to give physicians a better understanding of the core concepts of technology assessment, using medical instrumentation technology as a vehicle to stimulate the discussion of technology assessment and its applications. An assessment matrix has been developed as an organizational tool to identify issues in assessment to be addressed under each topic and to identify those issues that are of key importance to particular technologies. At the end of the class, the physician-student should be able to identify major types of medical instrumentation and the instrument's principal application(s), to identify the techniques of technology assessment, and to analyze the economic, ethical, and legal issues that are applicable to instrumentation.

Thrombolytic therapy in an isolated limb.

Intraoperative thrombolytic therapy is a useful adjunct to balloon catheter thromboembolectomy for treatment of acute embolism or thrombosis, but the technique is frequently limited by incomplete thrombolysis and systemic hemorrhage. In an attempt to improve results and reduce complications of conventional thrombolytic therapy, urokinase was infused into a limb that was isolated with a tourniquet. This isolated limb perfusion technique was initially developed in an animal model and subsequently used for limb salvage in patients who failed thromboembolectomy. The animal model demonstrated that a fibrinolytic state could be achieved and isolated to the extremity, even when using extremely high dose (20,000 to 50,000 IU/kg) of thrombolytic agents. The fibrinogen level was unmeasurable and the prothrombin, partial thromboplastin, and thrombin times were significantly prolonged in the isolated limb (p < 0.001), whereas no changes occurred in these parameters in the systemic circulation. In seven patients, streptokinase (27,000 to 200,000 IU) and urokinase (150,000 to 300,000 IU) were infused into isolated extremities after thrombectomy alone had failed to restore blood flow. All extremities showed improved perfusion after thrombolytic therapy and five remained viable 6 months after treatment. There were no systemic bleeding complications despite two patients having undergone major operations within 6 days. Tourniquet isolation of the limb can achieve extremely high concentrations of thrombolytic drugs while reducing the potential for systemic fibrinolysis and allows lysis of previously inaccessible thrombus.

ICD implantation via thoracoscopy without the need for sternotomy or thoracotomy.

After development of the technique in mongrel dogs, implantable cardioverter defibrillator (ICD) patch and sensing lead implantation was attempted via thoracoscopy, without sternotomy or thoracotomy, in three patients. Two large titanium mesh defibrillator patches and two "screw-in" epicardial sensing leads were applied without difficulty in each of two patients. In a third patient, satisfactory placement of the defibrillator patches could not be achieved via thoracoscopy, necessitating thoracotomy. Defibrillation threshold (DFT), cardioversion energy requirement (CER), and rate and morphology signals in those patients with successful thoracoscopic implantation were comparable to those achieved by open technique. We conclude that ICD patch and sensing lead implantation via thoracoscopy is feasible.