Low-intensity pulsed ultrasound for treatment of tibial fractures: an economic evaluation of the TRUST study.

AIMS: This 501-patient, multi-centre, randomised controlled trial sought to establish the effect of low-intensity, pulsed, ultrasound (LIPUS) on tibial shaft fractures managed with intramedullary nailing. We conducted an economic evaluation as part of this trial. PATIENTS AND METHODS: Data for patients' use of post-operative healthcare resources and time taken to return to work were collected and costed using publicly available sources. Health-related quality of life, assessed using the Health Utilities Index Mark-3 (HUI-3), was used to derive quality-adjusted life years (QALYs). Costs and QALYs were compared between LIPUS and control (a placebo device) from a payer and societal perspective using non-parametric bootstrapping. All costs are reported in 2015 Canadian dollars unless otherwise stated. RESULTS: With a cost per device of $3,995, the mean cost was significantly higher for patients treated with LIPUS versus placebo from a payer (mean increase = $3647, 95% confidence interval (CI) $3244 to $4070; p < 0.001) or a societal perspective (mean increase = $3425, 95% CI $1568 to $5283; p < 0.001). LIPUS did not provide a significant benefit in terms of QALYs gained (mean difference = 0.023 QALYs, 95% CI -0.035 to 0.069; p = 0.474). Incremental cost-effectiveness ratios of LIPUS compared with placebo were $155 433/QALY from a payer perspective and $146 006/QALY from a societal perspective. CONCLUSION: At the current price, LIPUS is not cost-effective for fresh tibial fractures managed with intramedullary nailing. Cite this article: Bone Joint J 2017;99-B:1526-32.

The current economic burden of illness of osteoporosis in Canada.

UNLABELLED: We estimate the current burden of illness of osteoporosis in Canada is double ($4.6 billion) our previous estimates ($2.3 billion) due to improved data capture of the multiple encounters and services that accompany a fracture: emergency room, admissions to acute and step-down non-acute institutions, rehabilitation, home-assisted or long-term residency support. INTRODUCTION: We previously estimated the economic burden of illness of osteoporosis-attributable fractures in Canada for the year 2008 to be $2.3 billion in the base case and as much as $3.9 billion. The aim of this study is to update the estimate of the economic burden of illness for osteoporosis-attributable fractures for Canada based on newly available home care and long-term care (LTC) data. METHODS: Multiple national databases were used for the fiscal-year ending March 31, 2011 (FY 2010/2011) for acute institutional care, emergency visits, day surgery, secondary admissions for rehabilitation, and complex continuing care, as well as national dispensing data for osteoporosis medications. Gaps in national data were supplemented by provincial and community survey data. Osteoporosis-attributable fractures for Canadians age 50+ were identified by ICD-10-CA codes. Costs were expressed in 2014 dollars. RESULTS: In FY 2010/2011, the number of osteoporosis-attributable fractures was 131,443 resulting in 64,884 acute care admissions and 983,074 acute hospital days. Acute care costs were $1.5 billion, an 18 % increase since 2008. The cost of LTC was 33.4 times the previous estimate ($31 million versus $1.03 billion) because of improved data capture. The cost for rehabilitation and secondary admissions increased 3.4 fold, while drug costs decreased 19 %. The overall cost of osteoporosis was over $4.6 billion, an increase of 83 % from the 2008 estimate. CONCLUSION: Since the 2008 estimate, new Canadian data on home care and LTC are available which provided a better estimate of the burden of osteoporosis in Canada. This suggests that our previous estimates were seriously underestimated.

Evaluation of a chronic disease management system for the treatment and management of diabetes in primary health care practices in Ontario: an observational study.

BACKGROUND: Computerized chronic disease management systems (CDMSs), when aligned with clinical practice guidelines, have the potential to effectively impact diabetes care. OBJECTIVE: The objective was to measure the difference between optimal diabetes care and actual diabetes care before and after the introduction of a computerized CDMS. METHODS: This 1-year, prospective, observational, pre/post study evaluated the use of a CDMS with a diabetes patient registry and tracker in family practices using patient enrolment models. Aggregate practice-level data from all rostered diabetes patients were analyzed. The primary outcome measure was the change in proportion of patients with up-to-date "ABC" monitoring frequency (i.e., hemoglobin A1c, blood pressure, and cholesterol). Changes in the frequency of other practice care and treatment elements (e.g., retinopathy screening) were also determined. Usability and satisfaction with the CDMS were measured. RESULTS: Nine sites, 38 health care providers, and 2,320 diabetes patients were included. The proportion of patients with up-to-date ABC (12%), hemoglobin A1c (45%), and cholesterol (38%) monitoring did not change over the duration of the study. The proportion of patients with up-to-date blood pressure monitoring improved, from 16% to 20%. Data on foot examinations, retinopathy screening, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and documentation of self-management goals were not available or not up to date at baseline for 98% of patients. By the end of the study, attitudes of health care providers were more negative on the Training, Usefulness, Daily Practice, and Support from the Service Provider domains of the CDMS, but more positive on the Learning, Using, Practice Planning, CDMS, and Satisfaction domains. LIMITATIONS: Few practitioners used the CDMS, so it was difficult to draw conclusions about its efficacy. Simply giving health care providers a potentially useful technology will not ensure its use. CONCLUSIONS: This real-world evaluation of a web-based CDMS for diabetes failed to impact physician practice due to limited use of the system. PLAIN LANGUAGE SUMMARY: Patients and health care providers need timely access to information to ensure proper diabetes care. This study looked at whether a computer-based system at the doctor's office could improve diabetes management. However, few clinics and health care providers used the system, so no improvement in diabetes care was seen.

Estimating the excess costs for patients with incident fractures, prevalent fractures, and nonfracture osteoporosis.

SUMMARY: Based on a population age 50+, significant excess costs relative to matched controls exist for patients with incident fractures that are similar in relative magnitude to other chronic diseases such as stroke or heart disease. Prevalent fractures also have significant excess costs that are similar in relative magnitude to asthma/chronic obstructive pulmonary disease. INTRODUCTION: Cost of illness studies for osteoporosis that only include incident fractures may ignore the long-term cost of prevalent fractures and primary preventive care. We estimated the excess costs for patients with incident fractures, prevalent fractures, and nonfracture osteoporosis relative to matched controls. METHODS: Men and women age 50+ were selected from administrative records in the province of Manitoba, Canada for the fiscal year 2007-2008. Three types of cases were identified: (1) patients with incident fractures in the current year (2007-2008), (2) patients with prevalent fractures in previous years (1995-2007), and (3) nonfracture osteoporosis patients identified by specific pharmacotherapy or low bone mineral density. Excess resource utilization and costs were estimated by subtracting control means from case means. RESULTS: Seventy-three percent of provincial population age 50+ (52 % of all men and 91 % of all women) were included (121,937 cases, 162,171 controls). There were 3,776 cases with incident fracture (1,273 men and 2,503 women), 43,406 cases with prevalent fractures (15,784 men and 27,622 women) and 74,755 nonfracture osteoporosis cases (7,705 men and 67,050 women). All incident fractures had significant excess costs. Incident hip fractures had the highest excess cost: men $44,963 (95 % CI: $38,498-51,428) and women $45,715 (95 % CI: $36,998-54,433). Prevalent fractures (other than miscellaneous or wrist fractures) also had significant excess costs. No significant excess costs existed for nonfracture osteoporosis. CONCLUSION: Significant excess costs exist for patients with incident fractures and with prevalent hip, vertebral, humerus, multiple, and traumatic fractures. Ignoring prevalent fractures underestimate the true cost of osteoporosis.

The burden of illness of osteoporosis in Canada.

UNLABELLED: To update the 1993 burden of illness of osteoporosis in Canada, administrative and community data were used to calculate the 2010 costs of osteoporosis at $2.3 billion in Canada or 1.3% of Canada's healthcare expenditures. Prevention of fractures in high-risk individuals is key to decrease the financial burden of osteoporosis. INTRODUCTION: Since the 1996 publication of the burden of osteoporosis in 1993 in Canada, the population has aged and the management of osteoporosis has changed. The study purpose was to estimate the current burden of illness due to osteoporosis in Canadians aged 50 and over. METHODS: Analyses were conducted using five national administrative databases from the Canadian Institute for Health Information for the fiscal-year ending March 31 2008 (FY 2007/2008). Gaps in national data were supplemented by provincial and community data extrapolated to national levels. Osteoporosis-related fractures were identified using a combination of most responsible diagnosis at discharge and intervention codes. Fractures associated with severe trauma codes were excluded. Costs, expressed in 2010 dollars, were calculated for osteoporosis-related hospitalizations, emergency care, same day surgeries, rehabilitation, continuing care, homecare, long-term care, prescription drugs, physician visits, and productivity losses. Sensitivity analyses were conducted to measure the impact on the results of key assumptions. RESULTS: Osteoporosis-related fractures were responsible for 57,413 acute care admissions and 832,594 hospitalized days in FY 2007/2008. Acute care costs were estimated at $1.2 billion. When outpatient care, prescription drugs, and indirect costs were added, the overall yearly cost of osteoporosis was over $2.3 billion for the base case analysis and as much as $3.9 billion if a proportion of Canadians were assumed to be living in long-term care facilities due to osteoporosis. CONCLUSIONS: Osteoporosis is a chronic disease that affects a large segment of the adult population and results in a substantial economic burden to the Canadian society.

Estimation of the lifetime risk of hip fracture for women and men in Canada.

UNLABELLED: In Canada in 2008, based on current rates of fracture and mortality, a woman or man at age 50 years will have a projected lifetime risk of fracture of 12.1% and 4.6%, respectively, and 8.9% and 6.7% after incorporating declining rates of hip fracture and increases in longevity. INTRODUCTION: In 1989, the lifetime risk of hip fractures in Canada was 14.0% (women) and 5.2% (men). Since then, there have been changes in rates of hip fracture and increased longevity. We update these estimates to 2008 adjusted for these trends, and in addition, we estimated the lifetime risk of first hip fracture. METHODS: We used national administrative data from fiscal year April 1, 2007 to March 31, 2008 to identify all hip fractures in Canada. We estimated the crude lifetime risk of hip fracture for age 50 years to end of life using life tables. We projected lifetime risk incorporating national trends in hip fracture and increased longevity from Poisson regressions. Finally, we removed the percentage of second hip fractures to estimate the lifetime risk of first hip fracture. RESULTS: From April 1, 2007 to March 31, 2008, there were 21,687 hip fractures, 15,742 (72.6%) in women and 5,945 (27.4%) in men. For women and men, the crude lifetime risk was 12.1% (95%CI, 12.1, 12.2%) and 4.6% (95%CI, 4.5, 4.7%), respectively. When trends in mortality and hip fractures were both incorporated, the lifetime risk of hip fracture were 8.9% (95%CI, 2.3, 15.4%) and 6.7% (95%CI, 1.2, 12.2%). The lifetime risks for first hip fracture were 7.3% (95%CI, 0.8, 13.9%) and 6.2% (95%CI, 0.7, 11.7%). CONCLUSIONS: The lifetime risk of hip fracture has fallen from 1989 to 2008 for women and men. Adjustments for trends in mortality and rates of hip fracture with removing second fractures produced non-significant differences in estimates.

Estimating the national wage loss from cancer in Canada.

OBJECTIVES: Using primary and secondary data sources, we set out to estimate the Canadian wage loss from cancer for patients, caregivers, and parents from a patient and a societal perspective. METHODS: First, a multiple-database literature search was conducted to find Canadian-specific direct surveys of wage loss from cancer. Second, estimates for wage loss were generated from the nationally representative Canadian Community Health Survey (CCHS) Cycle 3.1. In addition, both estimates were standardized to derive a friction-period estimate and were extrapolated to produce national annual estimates. RESULTS: The literature search identified six direct surveys that included a total of 1632 patients with cancer. The CCHS Cycle 3.1 included 2287 patients with cancer. Overall, based on the direct surveys, newly diagnosed cancer patients reduced their labour participation in the friction period by 36% ($4,518), and caregivers lost 23% of their workable hours ($2,887). The CCHS estimated that annual household income was 26.5% lower ($4,978) for respondents with cancer as compared with the general population. For the year 2009, results from direct surveys indicated that new cancers in Canada generated a wage loss of $3.18 billion; the CCHS Cycle 3.1 estimate was $2.95 billion. CONCLUSIONS: Wage loss from cancer is a significant economic burden on patients, their families, and society in Canada, with direct surveys and the CCHS providing similar estimates.

Phosphorus reductions following riparian restoration in two agricultural watersheds in Vermont, USA.

Achievement of management goals for Lake Champlain (Vermont/New York, USA and Quebec, Canada) will require significant reductions of phosphorus (P) loads from agriculture, the dominant diffuse source in the basin. Cost-effective P reduction strategies must be based on reliable treatment techniques beyond basic erosion control and animal waste storage practices. The Lake Champlain Basin Agricultural Watersheds National Monitoring Program (NMP) Project evaluates the effectiveness of low-cost livestock exclusion, streambank protection, and riparian restoration practices in reducing concentrations and loads of diffuse-source pollutants from grazing land at the watershed level. Treatment and control watersheds in northwestern Vermont have been monitored since 1994 according to a paired-watershed design. Monitoring includes continuous stream discharge recording, flow-proportional sampling for total P and other pollutants, and documentation of land use and agricultural management activities. Strong statistical calibration between the control and treatment watersheds has been achieved. Landowner participation in the land treatment program was entirely voluntary and all treatments were 100% cost-shared by the project and cooperators. Installation of riparian fencing, alternative water supplies, protected stream crossings, and streambank bioengineering was completed in 1997 at a cost of less than US$40,000. The paired-watershed design was effective in controlling for the influence of extreme variations in precipitation and streamflow over six years of monitoring. Two years of post-treatment data have documented significant reductions in P concentrations and loads from both treated watersheds. Reductions of approximately 20% in mean total P concentration and approximately 20-50% in mean total P load have been observed, with greater reductions occurring in the watershed receiving more extensive treatment. The effectiveness of riparian zone restoration in P reduction tended to be lower during periods of very high runoff, especially outside the growing season.

Risk factors for lyme disease in Chester County, Pennsylvania.

OBJECTIVE: To identify factors associated with increased or decreased risk of infection for Lyme disease in Chester County, Pennyslvania. METHODS: The authors designed an unmatched case-control study involving 294 incident cases reported to the Chester County Health Department in 1998 and 449 controls selected by random digit dialing. All case and control participants were interviewed by telephone. RESULTS: Age is a risk factor for Lyme disease for groups aged 10-19 years old and 50 years or older. Sex was not a risk factor. Incidence of Lyme disease in a rural setting was three times the incidence in an urban setting. Increased risk also was associated with living in single family homes, homes with yards or attached land, woods on the land, signs of tick hosts seen on the land, and homes within 100 feet of woodland. Gardening for more than four hours per week was also a risk factor, but most other outdoor activities were not. Twice as many participants took protective measures against tick bites before outdoor employment than those who merely ventured into the yard or land associated with the home. Only checking for ticks during outdoor activity and the use of repellents prior to outdoor activities outside the yard were unequivocally associated with a reduced risk of Lyme disease. CONCLUSIONS: It is important to increase public awareness about the risk of acquiring Lyme disease from ticks in the immediate environment of the home.

Cloning, expression and N-terminal myristoylation of CpCPK1, a calcium-dependent protein kinase from zucchini (Cucurbita pepo L.).

We have isolated a full-length cDNA clone (CpCDPK1) encoding a calcium-dependent protein kinase (CDPK) gene from zucchini (Cucurbita pepo L.). The predicted amino acid sequence of the cDNA shows a remarkably high degree of similarity to members of the CDPK gene family from Arabidopsis thaliana, especially AtCPK1 and AtCPK2. Northern analysis of steady-state mRNA levels for CpCPK1 in etiolated and light-grown zucchini seedlings shows that the transcript is most abundant in etiolated hypocotyls and overall expression is suppressed by light. As described for other members of the CDPK gene family from different species, the CpCPK1 clone has a putative N-terminal myristoylation sequence. In this study, site-directed mutagenesis and an in vitro coupled transcription/translation system were used to demonstrate that the protein encoded by this cDNA is specifically myristoylated by a plant N-myristoyl transferase. This is the first demonstration of myristoylation of a CDPK protein which may contribute to the mechanism by which this protein is localized to the plasma membrane.

Synthesis and structure of chiral macrocycles containing 2,2'-bipyridine subunits.

A series of macrocyclic receptors has been prepared containing bipyridine groups linked to two amino acids. Variations in both the amino acid and the linking spacer have been made. The structure of the resulting macrocycles has been investigated using 1H NMR spectroscopy and X-ray crystallography. The use of L-valine leads to an open conformation for the macrocycle in which the 2-propyl substituents are directed perpendicular to the plane of the ring leaving the bipyridine and amide groups accessible for binding to a metal or complementary substrate. Proline-based macrocycles take up a twisted arrangement with the linking chain stretched across the face of the bipyridine which takes up a trans conformation. The metal ion binding properties of these derivatives have been investigated and shown to occur only to the valine macrocyles which have the two pyridine rings preorganized for complexation. These macrocycles have also been shown to bind to phenolic hydroxyl groups by using hydrogen-bond donors and acceptors from the amide groups in the linking chain.

Immunological relatedness of high mobility group chromosomal proteins from calf thymus.

The non-histone proteins HMG-1, HMG-2, HMG-3, HMB-8, HMG-14, and HMG-17 (Goodwin, G. H., SANDERS, C., and Johns, E. W. (1973) Eur. J. Biochem. 38, 14) were purified from calf thymus. The apparent molecular weights on polyacrylamide gels run in the presence of sodium dodecyl sulfate of the high mobility group (HMB) proteins were determined. Those for HBG-1 and HMG-2 agreed with the molecular weights determined by sedimentation; that for HMG-17 was anomalously high. Antibodies against HMG-1 were elicited in rabbits. The interaction between HMG-1 and anti-HBG-1 was measured by quantitative precipitation and by the microcomplement fixation technique. Quantitative microcomplement fixation assays revealed that the indices of dissimilarity between HMG-1 and HMG-2, HMG-3, HMG-8, HMG-14, and HMG-17 were 2.0, 1.0, 3.8, 10.0, and 6.1, respectively. These correspond to 6%, 0%, 12%, 20%, and 16% sequence difference between HMG-1 and the other five HMG proteins, although the immunological distance between HMG-1 and HMG-14 may be too large to allow a good correlation between the sequence and the immunological reaction. Antibodies to HMB-1 bind to chromatin purified from calf thymus. Therefore, we suggest that the in situ organization of HMG proteins in chromatin and chromosomes may be studied by serological techniques.