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1.  Airport metal detector activation is rare after posterior spinal fusion in children with scoliosis 
Since the September 11, 2001 terrorist attacks on the World Trade Center in New York City, travel security has become an ever-increasing priority in the United States. Frequent parent and patient inquiry and recent literature reports have generated interest in the impact of heightened security measures on patients with orthopaedic implants, and have indicated increasing rates of metal detector triggering. There are no reports to date, however, evaluating children and adolescents who have undergone posterior spinal fusion for scoliosis, so responses to patient and parent inquiries are not data-driven. The purpose of this study is to determine the frequency of airport metal detector triggering by patients who have had posterior-only spinal fusion and to characterise any potential predictors of metal detector activation.
A cross-sectional study was performed by interviewing 90 patients who underwent posterior-only spinal fusion for a diagnosis of juvenile or adolescent idiopathic scoliosis and have travelled by air in the past year. Demographic, clinical and surgical instrumentation data were collected and evaluated, along with patients’ reports of airport metal detector triggering and subsequent screening procedures.
Five patients with stainless steel instrumentation (5.6 % of the cohort) triggered an airport walkthrough metal detector, and an additional five patients who did not trigger an airport detector triggered a handheld detector at a different venue. All patients who triggered an airport metal detector had stainless steel instrumentation implanted prior to 2008, and no patient with titanium instrumentation triggered any detector in any venue. All trigger events required subsequent screening procedures, even when an implant card was presented.
In this cohort of children and adolescents with posterior spinal instrumentation, airport walkthrough metal detector triggering was a rare event. Therefore, we advise patients and families with planned posterior scoliosis fusions using titanium instrumentation that airport detection risk is essentially non-existent, and only rare for those with planned stainless steel instrumentation. We no longer issue implant cards postoperatively, as these did not prevent further screening procedures in this cohort.
Level of evidence
Prognostic level 2. Study design: cross-sectional.
PMCID: PMC3886360  PMID: 24432117
Adolescent idiopathic scoliosis; Spinal instrumentation; Hardware; Stainless steel; Titanium; Air travel; Metal detector; Security screening
2.  Early Pandemic Influenza (2009 H1N1) in Ho Chi Minh City, Vietnam: A Clinical Virological and Epidemiological Analysis 
PLoS Medicine  2010;7(5):e1000277.
Rogier van Doorn and colleagues analyze the initial outbreak, attempts at containment, and establishment of community transmission of pandemic H1N1 influenza in Ho Chi Minh City, Vietnam.
To date, little is known about the initial spread and response to the 2009 pandemic of novel influenza A (“2009 H1N1”) in tropical countries. Here, we analyse the early progression of the epidemic from 26 May 2009 until the establishment of community transmission in the second half of July 2009 in Ho Chi Minh City (HCMC), Vietnam. In addition, we present detailed systematic viral clearance data on 292 isolated and treated patients and the first three cases of selection of resistant virus during treatment in Vietnam.
Methods and Findings
Data sources included all available health reports from the Ministry of Health and relevant health authorities as well as clinical and laboratory data from the first confirmed cases isolated at the Hospital for Tropical Diseases in HCMC. Extensive reverse transcription (RT)-PCR diagnostics on serial samples, viral culture, neuraminidase-inhibition testing, and sequencing were performed on a subset of 2009 H1N1 confirmed cases. Virological (PCR status, shedding) and epidemiological (incidence, isolation, discharge) data were combined to reconstruct the initial outbreak and the establishment of community transmission. From 27 April to 24 July 2009, approximately 760,000 passengers who entered HCMC on international flights were screened at the airport by a body temperature scan and symptom questionnaire. Approximately 0.15% of incoming passengers were intercepted, 200 of whom tested positive for 2009 H1N1 by RT-PCR. An additional 121 out of 169 nontravelers tested positive after self-reporting or contact tracing. These 321 patients spent 79% of their PCR-positive days in isolation; 60% of PCR-positive days were spent treated and in isolation. Influenza-like illness was noted in 61% of patients and no patients experienced pneumonia or severe outcomes. Viral clearance times were similar among patient groups with differing time intervals from illness onset to treatment, with estimated median clearance times between 2.6 and 2.8 d post-treatment for illness-to-treatment intervals of 1–4 d, and 2.0 d (95% confidence interval 1.5–2.5) when treatment was started on the first day of illness.
The patients described here represent a cross-section of infected individuals that were identified by temperature screening and symptom questionnaires at the airport, as well as mildly symptomatic to moderately ill patients who self-reported to hospitals. Data are observational and, although they are suggestive, it is not possible to be certain whether the containment efforts delayed community transmission in Vietnam. Viral clearance data assessed by RT-PCR showed a rapid therapeutic response to oseltamivir.
Please see later in the article for the Editors' Summary
Editors' Summary
Every year, millions of people catch influenza—a viral infection of the airways—and about half a million people die as a result. These yearly seasonal epidemics occur because small but frequent changes in the influenza virus mean that the immune response produced by infection with one year's virus provides only partial protection against the next year's virus. Sometimes, however, a very different influenza virus emerges to which people have virtually no immunity. Such viruses can start global epidemics (pandemics) and can kill millions of people. Consequently, when the first case of influenza caused by a new virus called pandemic A/H1N1 2009 (2009 H1N1, swine flu) occurred in March 2009 in Mexico, alarm bells rang. National and international public health agencies quickly issued advice about how the public could help to control the spread of the virus and, as the virus spread, some countries banned flights from affected regions and instigated screening for influenza-like illness at airports. However, despite everyone's efforts, the virus spread rapidly and on June 11, 2009 the World Health Organization (WHO) declared that an influenza pandemic was underway.
Why Was This Study Done?
To date, little is known about the spread of and response to 2009 H1N1 in tropical countries. In this study, therefore, the researchers investigate the early progression of the 2009 H1N1 pandemic in Ho Chi Minh City, Vietnam, and the treatment of infected patients. On April 27, 2009, when WHO announced that human-to-human transmission of 2009 H1N1 was occurring, the Vietnamese Ministry of Health mandated airport body temperature scans and symptom questionnaire screening of travelers arriving in Vietnam's international airports. Suspected cases were immediately transferred to in-hospital isolation, screened for virus using a sensitive test called PCR, and treated with the anti-influenza drug oseltamivir if positive. The first case of 2009 H1N1 infection in Vietnam was reported on May 31, 2009 in a student who had returned from the US on May 26, 2009, and, despite these efforts to contain the infection, by the second half of July the virus was circulating in Ho Chi Minh City (community transmission).
What Did the Researchers Do and Find?
The researchers used reports from the Ministry of Health and relevant health authorities and clinical and laboratory data for people infected with 2009 H1N1 and isolated in hospital to reconstruct the initial outbreak and the establishment of community transmission in Ho Chi Minh City. Between April 27 and July 24 2009, three-quarters of a million passengers arriving in the city on international flights were screened at the airport. 200 passenger tested positive for 2009 H1N1 as did 121 nontravelers who were identified during this period after self-reporting illness or through contact tracing. The infected individuals spent 79% of the days when they tested positive for 2009 H1N1 by PCR (days when they were infectious) in isolation; 60% of their PCR-positive days were spent in isolation and treatment. Importantly, travelers and nontravelers spent 10% and 42.2%, respectively, of their potentially infectious time in the community. None of the patients became severely ill but 61% experienced an influenza-like illness. Finally, the average time from starting treatment to clearance of the virus was between 2.6 and 2.8 days for patients who began treatment 1 to 4 days after becoming ill; for those who started treatment on the first day of illness, the average virus clearance time was 2.0 days.
What Do These Findings Mean?
These findings, although limited by missing data, suggest that the strict containment measures introduced early in the 2009 H1N1 pandemic in Ho Chi Minh City may have reduced the circulation of infected people in the community. This reduction in circulation might have delayed the onset of community transmission, suggest the researchers, but because the study was observational, this possibility cannot be proven. However, importantly, these findings show that the containment measures were unable to prevent the eventual establishment of pandemic influenza in Vietnam, presumably because many imported cases were not detected by airport screening. Finally, these findings suggest that in Vietnam, as in other countries, 2009 H1N1 causes a mild disease and that this disease responds quickly to treatment with oseltamivir whenever treatment is started in relation to the onset of illness.
Additional Information
Please access these Web sites via the online version of this summary at
The US Centers for Disease Control and Prevention provides information about influenza for patients and professionals, including specific information on H1N1 influenza and how to prevent its spread, a US government website, provides information on H1N1, avian, and pandemic influenza
The World Health Organization provides information on seasonal influenza and has detailed information on H1N1 influenza (in several languages); the WHO Representative Office in Vietnam provides an overview of the current 2009 H1N1 situation in Vietnam
The UK Health Protection Agency provides information on pandemic influenza and on H1N1 influenza
Wikipedia has a timeline of the 2009 H1N1 pandemic (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC2872648  PMID: 20502525
3.  Rationing of total knee replacement: a cost-effectiveness analysis on a large trial data set 
BMJ Open  2012;2(1):e000332.
Many UK primary care trusts have recently introduced eligibility criteria restricting total knee replacement (TKR) to patients with low pre-operative Oxford Knee Scores (OKS) to cut expenditure. We evaluate these criteria by assessing the cost-effectiveness of TKR compared with no knee replacement for patients with different baseline characteristics from an NHS perspective.
The cost-effectiveness of TKR in different patient subgroups was assessed using regression analyses of patient-level data from the Knee Arthroplasty Trial, a large, pragmatic randomised trial comparing knee prostheses.
34 UK hospitals.
2131 osteoarthritis patients undergoing TKR.
Interventions and outcome measures
Costs and quality-adjusted life years (QALYs) observed in the Knee Arthroplasty Trial within 5 years of TKR were compared with conservative assumptions about the costs and outcomes that would have been accrued had TKR not been performed.
On average, primary TKR and 5 years of subsequent care cost £7458 per patient (SD: £4058), and patients gained an average of 1.33 (SD: 1.43) QALYs. As a result, TKR cost £5623/QALY gained. Although costs and health outcomes varied with age and sex, TKR cost <£20 000/QALY gained for patients with American Society of Anaesthesiologists grades 1–2 who had baseline OKS <40 and for American Society of Anaesthesiologists grade 3 patients with OKS <35, even with highly conservative assumptions about costs and outcomes without TKR. Body mass index had no significant effect on costs or outcomes. Restricting TKR to patients with pre-operative OKS <27 would inappropriately deny a highly cost-effective treatment to >10 000 patients annually.
TKR is highly cost-effective for most current patients if the NHS is willing to pay £20 000–£30 000/QALY gained. At least 97% of TKR patients in England have more severe symptoms than the thresholds we have identified, suggesting that further rationing by OKS is probably unjustified.
Trial registration number
ISRCTN 45837371.
Article summary
Article focus
We assess the cost-effectiveness of total knee replacement (TKR) compared with no knee replacement for patients with different baseline characteristics from a NHS perspective.
In particular, we assess the appropriateness of eligibility criteria recently introduced by many UK primary care trusts, which restrict TKR to patients with low (ie, poor) pre-operative Oxford Knee Scores (OKS) to cut expenditure.
Key messages
We find TKR to be highly cost-effective, costing £5623 per quality-adjusted life year gained for the average patient.
TKR costs <£20 000 per quality-adjusted life year gained for healthy patients with OKS of <40 or <35 for patients who have other conditions restricting their daily activities.
We find no evidence to support the criteria for restricting access to TKR that have been proposed by some primary care trusts and calculate that restricting TKR to those patients with pre-operative OKS of 26 or less would deny a highly cost-effective treatment to >10 000 patients/year.
Strengths and limitations of this study
This is the first study assessing how the cost-effectiveness of TKR varies with OKS and the first assessing the clinical/economic implications of the newly introduced rationing criteria.
Analyses are based on patient-level data from a large pragmatic trial with detailed prospective collection of utilities, baseline characteristics and all major knee-related NHS resource use, including revisions and ambulatory care.
Our study makes several highly conservative assumptions: in particular, assuming that patients would have accrued no knee-related costs and remained at baseline utility without TKR. Furthermore, the Knee Arthroplasty Trial sample included only 37 patients with pre-operative OKS >35. As result, TKR may be also cost-effective for some patients with OKS above 39.
PMCID: PMC3269047  PMID: 22290396
4.  Prosthetic metal implants and airport metal detectors 
Metal detectors have been present in airports and points of departure for some time. With the introduction of heightened security measures in response to fears of an increased threat of terrorism, they may become more prevalent in other public locations. The aim of this study was to ascertain which prosthetic devices activated metal detector devices used for security purposes.
A range of prosthetic devices used commonly in orthopaedic and plastic surgery procedures were passed through an arch metal detector at Birmingham Airport in the UK. Additionally, each item was passed under a wand detector. Items tested included expandable breast prostheses, plates used in wrist and hand surgery, screws, K-wires, Autosuture™ ligation clips and staples.
No prostheses were detected by the arch detector. The expandable implants and wrist plates were the only devices detected by passing the wand directly over them. No device was detected by the wand when it was under cover of the axillary soft tissue. Screws, K-wires, Autosuture™ clips and staples were not detected under any of the study conditions.
Although unlikely to trigger a detector, it is possible that an expandable breast prosthesis or larger plate may do so. It is therefore best to warn patients of this so they can anticipate detection and further examination.
PMCID: PMC4165247  PMID: 23827294
Hand implants; Breast implants; Metal detector; Detection
5.  Total Knee Replacement 
Executive Summary
The aim of this review was to assess the effectiveness, in terms of pain reduction and functional improvement, and costing of total knee replacement (TKR) for people with osteoarthritis for whom less invasive treatments (such as physiotherapy, analgesics, anti-inflammatory drugs, intra-articular steroids, hyaluronic acids, and arthroscopic surgery) have failed.
Clinical Need
Osteoarthritis affects an estimated 10% to 12% of Canadian adults. The therapeutic goals of osteoarthritis treatment are to improve joint mobility and reduce pain. Stepwise treatment options include exercise, weight loss, physiotherapy, analgesics, anti-inflammatory drugs, intra-articular steroids and hyaluronic acids, arthroscopic surgery, and, in severe cases, total joint replacement with follow-up rehabilitation. These treatments are delivered by a range of health care professionals, including physiotherapists, occupational therapists, family physicians, internists, rheumatologists, and orthopedic surgeons. TKR is an end-of-line treatment for patients with severe pain and functional limitations. More women than men undergo knee replacement, and most patients are between 55 and 84 years old.
The Technology
TKR is a surgical procedure in which an artificial joint or prosthesis replaces a damaged knee joint. The primary indication for TKR is pain, followed by functional limitation. Usually, a person’s daily activities must be substantially affected by pain and functional limitations for him or her to be considered a candidate for TKR.
There are 3 different types of knee replacement prostheses. Non-constrained prostheses use the patient’s ligaments and muscles to provide the stability for the prosthesis. Semi-constrained prostheses provide some stability for the knee and do not rely entirely on the patient’s ligaments and muscles to provide the stability. Constrained prostheses are for patients whose ligaments and muscles are not able to provide stability for the knee prosthesis.
The most common risks and complications associated with TKR are deep venous thrombosis, infection, stiffness, loosening, and osteolysis. To prevent deep venous thrombosis, patients are treated with heparin prophylactically and/or given support stockings to wear. Patients are also given antibiotics for 24 hours after surgery to minimize the risk of infection. Stiffness is another associated complication. In most patients, it can be avoided by keeping the knee moving in the days and weeks following surgery.
The National Institutes of Health in the United States concluded that the indications for TKR should include the following: radiological evidence of joint damage, moderate to severe persistent pain that is not adequately relieved by nonsurgical management, and clinically significant functional limitation resulting in diminished quality of life.
Review Strategy
In March 2005, the following databases were searched: Cochrane Library International Agency for Health Technology Assessment (first quarter 2005), Cochrane Database of Systematic Reviews (first quarter 2005), Cochrane Central Register of Controlled Trials (first quarter 2005), MEDLINE (1966 to March 2005), MEDLINE In-Process and Other Non-indexed Citations (1966 to March 14, 2005), and EMBASE (1980 to 2005 week 9). The Medical Advisory Secretariat also searched Medscape on the Internet for recent reports on trials that were unpublished but that were presented at international conferences. In addition, the Web site Current Controlled Trials ( was searched for ongoing trials investigating TKR or unicompartmental knee replacement.
No studies were identified that compared TKR to an alternative treatment. Several studies have been reported that compare preoperative measurement scores on targeted measures of functioning and pain to postoperative measurement scores in patients undergoing various TKR procedures.
In order for the Medical Advisory Secretariat to measure the effectiveness of TKR and to compare the effectiveness of TKR across studies, effect sizes were calculated in studies that reported the standard deviations of the preoperative and postoperative measurement scores. Percent change was also calculated. For this review, a 20% improvement in outcome score was defined as the minimal clinically important difference.
Summary of Findings
Overall, patients who undergo TKR surgery for osteoarthritis have substantial improvements in terms of reduction of pain and improvement of function. A comparison of the mean effect score and the percent change in 19 studies that reported preoperative and postoperative outcome scores for patients who had TKR showed that the procedure is effective. The 19 studies included patients of various ages and used a variety of prostheses and techniques to implant the device. TKR was effective in all of the studies. The revision rates ranged from 0% to 13% in the studies that reported at least 5 years of follow-up.
As for the factors that predict TKR outcomes, a variety of factors have been evaluated, including obesity, age, gender, prosthesis design, and surgical techniques; however, none of these have been shown to predict outcomes (pain or function) consistently across studies. However, the regression analyses identified accounted for only 12% to 27% of the variance, indicating that over 70% of the variance in the outcomes of TKR is unexplained.
In terms of the timing of TKR surgery, 2 studies found that the severity of osteoarthritis does not predict outcome, but 1 study was found that higher functioning patients had significantly less pain and better function up to 2 years after surgery compared with lower functioning patients. It is important to note that the patients in the low and high function groups were evenly matched on comorbid conditions.
Unicompartmental knee replacement surgery seems to be as effective as TKR surgery for people who meet the indications for it. This is a subset of people who have osteoarthritis of the knee, because for unicompartmental knee replacement to be indicated, only 1 (usually the medial) compartment of the knee can be affected. Patients who undergo this kind of surgery seem to have shorter hospital stays and faster recovery times than do patients who have TKR surgery.
There is substantial evidence to indicate that TKR effectively reduces pain and improves function.
PMCID: PMC3382388  PMID: 23074478
6.  Physiotherapy Rehabilitation After Total Knee or Hip Replacement 
Executive Summary
The objective of this health technology policy analysis was to determine, where, how, and when physiotherapy services are best delivered to optimize functional outcomes for patients after they undergo primary (first-time) total hip replacement or total knee replacement, and to determine the Ontario-specific economic impact of the best delivery strategy. The objectives of the systematic review were as follows:
To determine the effectiveness of inpatient physiotherapy after discharge from an acute care hospital compared with outpatient physiotherapy delivered in either a clinic-based or home-based setting for primary total joint replacement patients
To determine the effectiveness of outpatient physiotherapy delivered by a physiotherapist in either a clinic-based or home-based setting in addition to a home exercise program compared with a home exercise program alone for primary total joint replacement patients
To determine the effectiveness of preoperative exercise for people who are scheduled to receive primary total knee or hip replacement surgery
Clinical Need
Total hip replacements and total knee replacements are among the most commonly performed surgical procedures in Ontario. Physiotherapy rehabilitation after first-time total hip or knee replacement surgery is accepted as the standard and essential treatment. The aim is to maximize a person’s functionality and independence and minimize complications such as hip dislocation (for hip replacements), wound infection, deep vein thrombosis, and pulmonary embolism.
The Therapy
The physiotherapy rehabilitation routine has 4 components: therapeutic exercise, transfer training, gait training, and instruction in the activities of daily living. Physiotherapy rehabilitation for people who have had total joint replacement surgery varies in where, how, and when it is delivered. In Ontario, after discharge from an acute care hospital, people who have had a primary total knee or hip replacement may receive inpatient or outpatient physiotherapy. Inpatient physiotherapy is delivered in a rehabilitation hospital or specialized hospital unit. Outpatient physiotherapy is done either in an outpatient clinic (clinic-based) or in the person’s home (home-based). Home-based physiotherapy may include practising an exercise program at home with or without supplemental support from a physiotherapist.
Finally, physiotherapy rehabilitation may be administered at several points after surgery, including immediately postoperatively (within the first 5 days) and in the early recovery period (within the first 3 months) after discharge. There is a growing interest in whether physiotherapy should start before surgery. A variety of practises exist, and evidence regarding the optimal pre- and post-acute course of rehabilitation to obtain the best outcomes is needed.
Review Strategy
The Medical Advisory Secretariat used its standard search strategy, which included searching the databases of Ovid MEDLINE, CINHAL, EMBASE, Cochrane Database of Systematic Reviews, and PEDro from 1995 to 2005. English-language articles including systematic reviews, randomized controlled trials (RCTs), non-RCTs, and studies with a sample size of greater than 10 patients were included. Studies had to include patients undergoing primary total hip or total knee replacement, aged 18 years of age or older, and they had to have investigated one of the following comparisons: inpatient rehabilitation versus outpatient (clinic- or home-based therapy) rehabilitation, land-based post-acute care physiotherapy delivered by a physiotherapist compared with patient self-administered exercise and a land-based exercise program before surgery. The primary outcome was postoperative physical functioning. Secondary outcomes included the patient’s assessment of therapeutic effect (overall improvement), perceived pain intensity, health services utilization, treatment side effects, and adverse events
The quality of the methods of the included studies was assessed using the criteria outlined in the Cochrane Musculoskeletal Injuries Group Quality Assessment Tool. After this, a summary of the biases threatening study validity was determined. Four methodological biases were considered: selection bias, performance bias, attrition bias, and detection bias. A meta-analysis was conducted when adequate data were available from 2 or more studies and where there was no statistical or clinical heterogeneity among studies. The GRADE system was used to summarize the overall quality of evidence.
Summary of Findings
The search yielded 422 citations; of these, 12 were included in the review including 10 primary studies (9 RCTs, 1 non-RCT) and 2 systematic reviews.
The Medical Advisory Secretariat review included 2 primary studies (N = 334) that examined the effectiveness of an inpatient physiotherapy rehabilitation program compared with an outpatient home-based physiotherapy program on functional outcomes after total knee or hip replacement surgery. One study, available only as an abstract, found no difference in functional outcome at 1 year after surgery (TKR or THR) between the treatments. The other study was an observational study that found that patients who are younger than 71 years of age on average, who do not live alone, and who do not have comorbid illnesses recover adequate function with outpatient home-based physiotherapy. However results were only measured up to 3 months after surgery, and the outcome measure they used is not considered the best one for physical functioning.
Three primary studies (N = 360) were reviewed that tested the effectiveness of outpatient home-based or clinic-based physiotherapy in addition to a self-administered home exercise program, compared with a self-administered exercise program only or in addition to using another therapy (phone calls or continuous passive movement), on postoperative physical functioning after primary TKR surgery. Two of the studies reported no difference in change from baseline in flexion range of motion between those patients receiving outpatient or home-based physiotherapy and doing a home exercise program compared with patients who did a home exercise program only with or without continuous passive movement. The other study reported no difference in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) scores between patients receiving clinic-based physiotherapy and practising a home exercise program and those who received monitoring phone calls and did a home exercise program after TKR surgery.
The Medical Advisory Secretariat reviewed two systematic reviews evaluating the effects of preoperative exercise on postoperative physical functioning. One concluded that preoperative exercise is not effective in improving functional recovery or pain after TKR and any effects after THR could not be adequately determined. The other concluded that there was inconclusive evidence to determine the benefits of preoperative exercise on functional recovery after TKR. Because 2 primary studies were added to the published literature since the publication of these systematic reviews the Medical Advisory Secretariat revisited the question of effectiveness of a preoperative exercise program for patients scheduled for TKR ad THR surgery.
The Medical Advisory Secretariat also reviewed 3 primary studies (N = 184) that tested the effectiveness of preoperative exercise beginning 4-6 weeks before surgery on postoperative outcomes after primary TKR surgery. All 3 studies reported negative findings with regard to the effectiveness of preoperative exercise to improve physical functioning after TKR surgery. However, 2 failed to show an effect of the preoperative exercise program before surgery in those patients receiving preoperative exercise. The third study did not measure functional outcome immediately before surgery in the preoperative exercise treatment group; therefore the study’s authors could not document an effect of the preoperative exercise program before surgery. Regarding health services utilization, 2 of the studies did not find significant differences in either the length of the acute care hospital stay or the inpatient rehabilitation care setting between patients treated with a preoperative exercise program and those not treated. The third study did not measure health services utilization.
These results must be interpreted within the limitations and the biases of each study. Negative results do not necessarily support a lack of treatment effect but may be attributed to a type II statistical error.
Finally, the Medical Advisory Secretariat reviewed 2 primary studies (N = 136) that examined the effectiveness of preoperative exercise on postoperative functional outcomes after primary THR surgery. One study did not support the effectiveness of an exercise program beginning 8 weeks before surgery. However, results from the other did support the effectiveness of an exercise program 8 weeks before primary THR surgery on pain and functional outcomes 1 week before and 3 weeks after surgery.
Based on the evidence, the Medical Advisory Secretariat reached the following conclusions with respect to physiotherapy rehabilitation and physical functioning 1 year after primary TKR or THR surgery:
There is high-quality evidence from 1 large RCT to support the use of home-based physiotherapy instead of inpatient physiotherapy after primary THR or TKR surgery.
There is low-to-moderate quality evidence from 1 large RCT to support the conclusion that receiving a monitoring phone call from a physiotherapist and practising home exercises is comparable to receiving clinic-based physiotherapy and practising home exercises for people who have had primary TKR surgery. However, results may not be generalizable to those who have had THR surgery.
There is moderate evidence to suggest that an exercise program beginning 4 to 6 weeks before primary TKR surgery is not effective.
There is moderate evidence to support the effectiveness of an exercise program beginning 8 weeks before surgery to improve physical functioning 3 weeks after THR surgery.
PMCID: PMC3382414  PMID: 23074477
7.  Utilisation of primary total knee joint replacements across socioeconomic status in the Barwon Statistical Division, Australia, 2006–2007: a cross-sectional study 
BMJ Open  2012;2(5):e001310.
There are few Australian data that examine the association between total knee joint replacement (TKR) utilisation and socioeconomic status (SES). This study examined TKR surgeries with a diagnosis of osteoarthritis (OA) performed for residents of Barwon Statistical Division (BSD) for 2006–2007.
BSD, South-eastern Victoria, Australia
All patients who underwent a TKR for OA, 2006–2007, and whose residential postcode was identified as within the BSD of Australia, and for whom SES data were available, were eligible for inclusion.
Primary outcome measure
Primary TKR data ascertained from the Australian Orthopaedic Association National Joint Replacement Registry. Residential addresses were matched with the Australian Bureau of Statistics census data, and the Index of Relative Socioeconomic Disadvantage was used to determine SES, categorised into quintiles whereby quintile 1 indicated the most disadvantaged and quintile 5 the least disadvantaged. Age-specific and sex-specific rates of TKR utilisation per 1000 person-years were reported for 10-year age bands.
Females accounted for 62.7% of the 691 primary TKR surgeries performed during 2006–2007. The greatest utilisation rates of TKR in males was 7.6 observed in those aged >79 years, and in 10.2 in females observed in those aged 70–79 years. An increase in TKR was observed for males in SES quintile four compared to quintile 1 in which the lowest utilisation which was observed (p=0.04). No differences were observed in females across SES quintiles.
Further investigation is warranted on a larger scale to examine the role that SES may play in TKR utilisation, and to determine whether any social disparities in TKR utilisation reflect health system biases or geographic differences.
PMCID: PMC3488757  PMID: 23035014
8.  Assessing the adequacy of procedure-specific consent forms in orthopaedic surgery against current methods of operative consent 
This is an audit of patient understanding following their consent for orthopaedic procedures and uses information on new Orthoconsent forms endorsed by the British Orthopaedic Association as the set standard. The objectives were to: (i) assess whether patients& understanding of knee arthroscopy (KA) and total knee replacement (TKR) at the point of confirming their consent reaches the set standard; and (ii) to ascertain whether issuing procedure-specific Orthoconsent forms to patients can improve this understanding.
This was a prospective audit using questionnaires consisting of 26 (for KA) or 35 (for TKR) questions based on the appropriate Orthoconsent form in a department of orthopaedic surgery within a UK hospital. Participants were 100 patients undergoing KA and 60 patients undergoing TKR between February and July 2008. Participants were identified from sequential operating lists and all had capacity to give consent. During the first audit cycle, consent was discussed with the patient and documented on standard yellow NHS Trust approved generic consent forms. During the second audit cycle, patients were additionally supplied with the appropriate procedure-specific consent form downloaded from which they were required to read at home and sign on the morning of surgery.
Knee arthroscopy patients consented with only the standard yellow forms scored an average of 56.7%, rising to 80.5% with use of Orthoconsent forms. Similarly, total knee replacement patients& averages rose from 57.6% to 81.6%.
Providing patients with an Orthoconsent form significantly improves knowledge of their planned procedure as well as constituting a more robust means of information provision and consent documentation.
PMCID: PMC3080073  PMID: 20412675
Informed consent; Consent documentation; Orthopaedic surgery; Audit; 
9.  Hip and knee replacement patients prefer pen-and-paper questionnaires 
Bone & Joint Research  2013;2(11):238-244.
Electronic forms of data collection have gained interest in recent years. In orthopaedics, little is known about patient preference regarding pen-and-paper or electronic questionnaires. We aimed to determine whether patients undergoing total hip (THR) or total knee replacement (TKR) prefer pen-and-paper or electronic questionnaires and to identify variables that predict preference for electronic questionnaires.
We asked patients who participated in a multi-centre cohort study investigating improvement in health-related quality of life (HRQoL) after THR and TKR using pen-and-paper questionnaires, which mode of questionnaire they preferred. Patient age, gender, highest completed level of schooling, body mass index (BMI), comorbidities, indication for joint replacement and pre-operative HRQoL were compared between the groups preferring different modes of questionnaire. We then performed logistic regression analyses to investigate which variables independently predicted preference of electronic questionnaires.
A total of 565 THR patients and 387 TKR patients completed the preference question. Of the THR patients, 81.8% (95% confidence interval (CI) 78.4 to 84.7) preferred pen-and-paper questionnaires to electronic questionnaires, as did 86.8% (95% CI 83.1 to 89.8) of TKR patients. Younger age, male gender, higher completed level of schooling and higher BMI independently predicted preference of electronic questionnaires in THR patients. Younger age and higher completed level of schooling independently predicted preference of electronic questionnaires in TKR patients.
The majority of THR and TKR patients prefer pen-and-paper questionnaires. Patients who preferred electronic questionnaires differed from patients who preferred pen-and-paper questionnaires. Restricting the mode of patient-reported outcome measures to electronic questionnaires might introduce selection bias.
Cite this article: Bone Joint Res 2013;2:238–44.
PMCID: PMC3834769  PMID: 24203164
Health-related quality of life; Total hip replacement; Total knee replacement; Patient-reported outcome measure; PROM; Questionnaire mode
10.  Current techniques in total knee replacement: results of a national survey. 
A postal questionnaire was sent to all Fellows of the British Orthopaedic Association to obtain a census of total knee replacement (TKR) preferences in the United Kingdom; 1162 questionnaires were sent and 721 replies received. There were 92 Fellows who had retired or filled in the forms incorrectly, and 32 no longer perform TKR. Thus, 597 responded correctly, giving a 62% response rate. This gives an extrapolated total of 34,677 TKRs being implanted per year in the UK, with an average of 34.3 being performed by each surgeon per year. Only 9% perform more than 90 per year. There were 41 different prostheses in current use among the respondents to our questionnaire, of which five prostheses constituted 61% of the total. Cemented prostheses were used by 95.2%. Resurfacing of the patella was always carried out by 32%, while 19% never resurface it; the most common reason for doing so being patellofemoral arthropathy at operation. Intramedullary alignment was used for the femoral component in 86%, 76% preferred extramedullary alignment for the tibial component. Regarding cementing technique, 43% use pulsatile lavage, 9% used a cement gun, 88% dry the bone and 56% seal the hole made by the femoral alignment device in the femur before cementing. All components were cemented simultaneously by 65% and one at a time by 31%. Metal-backed tibial prostheses are now used by 98% of surgeons, modular tibial components being preferred by 80%. Metal-backed patellar components were used by 13%. An onlay type of patella was preferred by 51%. This survey highlights the great diversity of surgical practice in the UK, which may reflect uncertainty regarding best practice in total knee replacement.
PMCID: PMC2502847  PMID: 8943636
11.  Metal-on-Metal Total Hip Resurfacing Arthroplasty 
Executive Summary
The objective of this review was to assess the safety and effectiveness of metal on metal (MOM) hip resurfacing arthroplasty for young patients compared with that of total hip replacement (THR) in the same population.
Clinical Need
Total hip replacement has proved to be very effective for late middle-aged and elderly patients with severe degenerative diseases of the hips. As indications for THR began to include younger patients and those with a more active life style, the longevity of the implant became a concern. Evidence suggests that these patients experience relatively higher rates of early implant failure and the need for revision. The Swedish hip registry, for example, has demonstrated a survival rate in excess of 80% at 20 years for those aged over 65 years, whereas this figure was 33% by 16 years in those aged under 55 years.
Hip resurfacing arthroplasty is a bone-conserving alternative to THR that restores normal joint biomechanics and load transfer. The technique has been used around the world for more than 10 years, specifically in the United Kingdom and other European countries.
The Technology
Metal-on-metal hip resurfacing arthroplasty is an alternative procedure to conventional THR in younger patients. Hip resurfacing arthroplasty is less invasive than THR and addresses the problem of preserving femoral bone stock at the initial operation. This means that future hip revisions are possible with THR if the initial MOM arthroplasty becomes less effective with time in these younger patients. The procedure involves the removal and replacement of the surface of the femoral head with a hollow metal hemisphere, which fits into a metal acetabular cup.
Hip resurfacing arthroplasty is a technically more demanding procedure than is conventional THR. In hip resurfacing, the femoral head is retained, which makes it much more difficult to access the acetabular cup. However, hip resurfacing arthroplasty has several advantages over a conventional THR with a small (28 mm) ball. First, the large femoral head reduces the chance of dislocation, so that rates of dislocation are less than those with conventional THR. Second, the range of motion with hip resurfacing arthroplasty is higher than that achieved with conventional THR.
A variety of MOM hip resurfacing implants are used in clinical practice. Six MOM hip resurfacing implants have been issued licences in Canada.
Review Strategy
A search of electronic bibliographies (OVID Medline, Medline In-Process and Other Non-Indexed Citations, Embase, Cochrane CENTRAL and DSR, INAHTA) was undertaken to identify evidence published from Jan 1, 1997 to October 27, 2005. The search was limited to English-language articles and human studies. The literature search yielded 245 citations. Of these, 11 met inclusion criteria (9 for effectiveness, 2 for safety).
The result of the only reported randomized controlled trial on MOM hip resurfacing arthroplasty could not be included in this assessment, because it used a cemented acetabular component, whereas in the new generation of implants, a cementless acetabular component is used. After omitting this publication, only case series remained.
Summary of Findings
Health Outcomes
The Harris hip score and SF-12 are 2 measures commonly used to report health outcomes in MOM hip resurfacing arthroplasty studies. Other scales used are the Oxford hip score and the University of California Los Angeles hip score.
The case series showed that the mean revision rate of MOM hip resurfacing arthroplasty is 1.5% and the incidence of femoral neck fracture is 0.67%. Across all studies, 2 cases of osteonecrosis were reported. Four studies reported improvement in Harris hip scores. However, only 1 study reported a statistically significant improvement. Three studies reported improvement in SF-12 scores, of which 2 reported a significant improvement. One study reported significant improvement in UCLA hip score. Two studies reported postoperative Oxford hip scores, but no preoperative values were reported.
None of the reviewed studies reported procedure-related deaths. Four studies reported implant survival rates ranging from 94.4% to 99.7% for a follow-up period of 2.8 to 3.5 years. Three studies reported on the range of motion. One reported improvement in all motions including flexion, extension, abduction-adduction, and rotation, and another reported improvement in flexion. Yet another reported improvement in range of motion for flexion abduction-adduction and rotation arc. However, the author reported a decrease in the range of motion in the arc of flexion in patients with Brooker class III or IV heterotopic bone (all patients were men).
Safety of Metal-on-Metal Hip Resurfacing Arthroplasty
There is a concern about metal wear debris and its systemic distribution throughout the body. Detectable metal concentrations in the serum and urine of patients with metal hip implants have been described as early as the 1970s, and this issue is still controversial after 35 years.
Several studies have reported high concentration of cobalt and chromium in serum and/or urine of the patients with metal hip implants. Potential toxicological effects of the elevated metal ions have heightened concerns about safety of MOM bearings. This is of particular concern in young and active patients in whom life expectancy after implantation is long.
Since 1997, 15 studies, including 1 randomized clinical trial, have reported high levels of metal ions after THR with metal implants. Some of these studies have reported higher metal levels in patients with loose implants.
Adverse Biological Effects of Cobalt and Chromium
Because patients who receive a MOM hip arthroplasty are shown to be exposed to high concentrations of metallic ions, the Medical Advisory Secretariat searched the literature for reports of adverse biological effects of cobalt and chromium. Cobalt and chromium make up the major part of the metal articulations; therefore, they are a focus of concern.
Risk of Cancer
To date, only one study has examined the incidence of cancer after MOM and polyethylene on metal total hip arthroplasties. The results were compared to that of general population in Finland. The mean duration of follow-up for MOM arthroplasty was 15.7 years; for polyethylene arthroplasty, it was 12.5 years. The standardized incidence ratio for all cancers in the MOM group was 0.95 (95% CI, 0.79–1.13). In the polyethylene on metal group it was 0.76 (95% CI, 0.68–0.86). The combined standardized incidence ratio for lymphoma and leukemia in the patients who had MOM THR was 1.59 (95% CI, 0.82–2.77). It was 0.59 (95% CI, 0.29–1.05) for the patients who had polyethylene on metal THR. Patients with MOM THR had a significantly higher risk of leukemia. All patients who had leukemia were aged over than 60 years.
Cobalt Cardiotoxicity
Epidemiological Studies of Myocardiopathy of Beer Drinkers
An unusual type of myocardiopathy, characterized by pericardial effusion, elevated hemoglobin concentrations, and congestive heart failure, occurred as an epidemic affecting 48 habitual beer drinkers in Quebec City between 1965 and 1966. This epidemic was directly related the consumption of a popular beer containing cobalt sulfate. The epidemic appeared 1 month after cobalt sulfate was added to the specific brewery, and no further cases were seen a month after this specific chemical was no longer used in making this beer. A beer of the same name is made in Montreal, and the only difference at that time was that the Quebec brand of beer contained about 10 times more cobalt sulphate. Cobalt has been added to some Canadian beers since 1965 to improve the stability of the foam but it has been added in larger breweries only to draught beer. However, in small breweries, such as those in Quebec City, separate batches were not brewed for bottle and draught beer; therefore, cobalt was added to all of the beer processed in this brewery.
In March 1966, a committee was appointed under the chairmanship of the Deputy Minister of Health for Quebec that included members of the department of forensic medicine of Quebec’s Ministry of Justice, epidemiologists, members of Food and Drug Directorate of Ottawa, toxicologists, biomedical researchers, pathologists, and members of provincial police. Epidemiological studies were carried out by the Provincial Ministry of Health and the Quebec City Health Department.
The association between the development of myocardiopathy and the consumption of the particular brand of beer was proven. The mortality rate of this epidemic was 46.1% and those who survived were desperately ill, and recovered only after a struggle for their lives.
Similar cases were seen in Omaha (Nebraska). The epidemic started after a cobalt additive was used in 1 of the beers marketed in Nebraska. Sixty-four patients with the clinical diagnosis of alcoholic myocardiopathy were seen during an 18-month period (1964–1965). Thirty of these patients died. The first patient became ill within 1 month after cobalt was added to the beer, and the last patient was seen within 1 month of withdrawal of cobalt.
A similar epidemic occurred in Minneapolis, Minnesota. Between 1964 and 1967, 42 patients with acute heart failure were admitted to a hospital in Minneapolis, Minnesota. Twenty of these patients were drinking 6 to 30 bottles per day of a particular brand of beer exclusively. The other 14 patients also drank the same brand of beer, but not exclusively. The mortality rate from the acute illness was 18%, but late deaths accounted for a total mortality rate of 43%. Examination of the tissue from these patients revealed markedly abnormal changes in myofibrils (heart muscles), mitochondria, and sarcoplasmic reticulum.
In Belgium, a similar epidemic was reported in 1966, in which, cobalt was used in some Belgian beers. There was a difference in mortality between the Canadian or American epidemic and this series. Only 1 of 24 patients died, 1.5 years after the diagnosis. In March 1965, at an international meeting in Brussels, a new heart disease in chronic beer drinkers was described. This disease consists of massive pericardial effusion, low cardiac output, raised venous pressure, and polycythemia in some cases. This syndrome was thought to be different from the 2 other forms of alcoholic heart disease (beriberi and a form characterized by myocardial fibrosis).
The mystery of the above epidemics as stated by investigators is that the amount of cobalt added to the beer was below the therapeutic doses used for anemia. For example, 24 pints of Quebec brand of beer in Quebec would contain 8 mg of cobalt chloride, whereas an intake of 50 to 100 mg of cobalt as an antianemic agent has been well tolerated. Thus, greater cobalt intake alone does not explain the occurrence of myocardiopathy. It seems that there are individual differences in cobalt toxicity. Other features, like subclinical alcoholic heart disease, deficient diet, and electrolyte imbalance could have been precipitating factors that made these patients susceptible to cobalt’s toxic effects.
In the Omaha epidemic, 60% of the patients had weight loss, anorexia, and occasional vomiting and diarrhea 2 to 6 months before the onset of cardiac symptoms. In the Quebec epidemic, patients lost their appetite 3 to 6 months before the diagnosis of myocardiopathy and developed nausea in the weeks before hospital admission. In the Belgium epidemic, anorexia was one of the most predominant symptoms at the time of diagnosis, and the quality and quantity of food intake was poor. Alcohol has been shown to increase the uptake of intracoronary injected cobalt by 47%. When cobalt enters the cells, calcium exits; this shifts the cobalt to calcium ratio. The increased uptake of cobalt in alcoholic patients may explain the high incidence of cardiomyopathies in beer drinkers’ epidemics.
As all of the above suggest, it may be that prior chronic exposure to alcohol and/or a nutritionally deficient diet may have a marked synergistic effect with the cardiotoxicity of cobalt.
MOM hip resurfacing arthroplasty has been shown to be an effective arthroplasty procedure as tested in younger patients.
However, evidence for effectiveness is based only on 7 case series with short duration of follow-up (2.8–3.5 years). There are no RCTs or other well-controlled studies that compare MOM hip resurfacing with THR.
Revision rates reported in the MOM studies using implants currently licensed in Canada (hybrid systems, uncemented acetabular, and cemented femoral) range from 0.3% to 3.6% for a mean follow-up ranging from 2.8 to 3.5 years.
Fracture of femoral neck is not very common; it occurs in 0.4% to 2.2% of cases (as observed in a short follow-up period).
All the studies that measured health outcomes have reported improvement in Harris Hip and SF-12 scores; 1 study reported significant reduction in pain and improvement in function, and 2 studies reported significant improvement in SF-12 scores. One study reported significant improvement in UCLA Hip scores.
Concerns remain on the potential adverse effects of metal ions. Longer-term follow-up data will help to resolve the inconsistency of findings on adverse effects, including toxicity and carcinogenicity.
Ontario-Based Economic Analysis
The device cost for MOM ranges from $4,300 to $6,000 (Cdn). Traditional hip replacement devices cost about $2,000 (Cdn). Using Ontario Case Costing Initiative data, the total estimated costs for hip resurfacing surgery including physician fees, device fees, follow-up consultation, and postsurgery rehabilitation is about $15,000 (Cdn).
Cost of Total Hip Replacement Surgery in Ontario
MOM hip arthroplasty is generally recommended for patients aged under 55 years because its bone-conserving advantage enables patients to “buy time” and hence helps THRs to last over the lifetime of the patient. In 2004/2005, 15.9% of patients who received THRs were aged 55 years and younger. It is estimated that there are from 600 to 1,000 annual MOM hip arthroplasty surgeries in Canada with an estimated 100 to 150 surgeries in Ontario. Given the increased public awareness of this device, it is forecasted that demand for MOM hip arthroplasty will steadily increase with a conservative estimate of demand rising to 1,400 cases by 2010 (Figure 10). The net budget impact over a 5-year period could be $500,000 to $4.7 million, mainly because of the increasing cost of the device.
Projected Number of Metal-on-Metal Hip Arthroplasty Surgeries in Ontario: to 2010
PMCID: PMC3379532  PMID: 23074495
12.  Airport sentinel surveillance and entry quarantine for dengue infections following a fever screening program in Taiwan 
BMC Infectious Diseases  2012;12:182.
Dengue has not reached an endemic status in Taiwan; nevertheless, we have implemented a fever screening program at airports for the early detection of febrile passengers with a dengue infection. This study is intended to assess the performance of the airport screening procedures for dengue infection.
We analyzed data from the national surveillance system of the Taiwan Centers for Disease Control. We included the imported dengue cases reported by sentinel airports and clinics as well as the domestic cases from 2007–2010.
Approximately 44.9% (95%CI: 35.73-54.13%) of the confirmed imported dengue cases with an apparent symptom (febrile) in the viremic stage were detected via the airport fever screening program, with an estimated positive predictive value of 2.36% (95% CI: 0.96- 3.75%) and a negative predictive value > 99.99%. Fluctuations in the number of the symptomatic imported dengue cases identified in the airports (X) were associated with the total number of imported dengue cases (Y) based on a regression analysis of a biweekly surveillance (i.e., n = 104, R2X:Y = 0.61, P < 0.005). Additionally, the fluctuating patterns in the cumulative numbers of the imported dengue cases (X) with a 1–2 month lead time (t) was in parallel with that of the domestic dengue cases (Y) based on a consecutive 4-year surveillance (i.e., n = 48, R2X(t-1):Y = 0.22, R2X(t-2):Y = 0.31, P < 0.001) from 2007–2010.
A moderate sensitivity of detecting dengue at the airports examined in this study indicated some limitations of the fever screening program for the prevention of importation. The screening program could assist in the rapid triage for self-quarantine of some symptomatic dengue cases that were in the viremic stage at the borders and contribute to active sentinel surveillance; however, the blocking of viral transmission to susceptible populations (neighbors or family) from all of the viremic travelers, including those with or without symptoms, is critical to prevent dengue epidemics. Therefore, the reinforcement of mosquito bite prevention and household vector control in dengue-endemic or dengue-competent hotspots during an epidemic season is essential and highly recommended.
PMCID: PMC3462143  PMID: 22867003
Imported dengue; Asymptomatic viremia; Dengue-competent hotspots
13.  Revision Rates after Primary Hip and Knee Replacement in England between 2003 and 2006 
PLoS Medicine  2008;5(9):e179.
Hip and knee replacement are some of the most frequently performed surgical procedures in the world. Resurfacing of the hip and unicondylar knee replacement are increasingly being used. There is relatively little evidence on their performance. To study performance of joint replacement in England, we investigated revision rates in the first 3 y after hip or knee replacement according to prosthesis type.
Methods and Findings
We linked records of the National Joint Registry for England and Wales and the Hospital Episode Statistics for patients with a primary hip or knee replacement in the National Health Service in England between April 2003 and September 2006. Hospital Episode Statistics records of succeeding admissions were used to identify revisions for any reason. 76,576 patients with a primary hip replacement and 80,697 with a primary knee replacement were included (51% of all primary hip and knee replacements done in the English National Health Service). In hip patients, 3-y revision rates were 0.9% (95% confidence interval [CI] 0.8%–1.1%) with cemented, 2.0% (1.7%–2.3%) with cementless, 1.5% (1.1%–2.0% CI) with “hybrid” prostheses, and 2.6% (2.1%–3.1%) with hip resurfacing (p < 0.0001). Revision rates after hip resurfacing were increased especially in women. In knee patients, 3-y revision rates were 1.4% (1.2%–1.5% CI) with cemented, 1.5% (1.1%–2.1% CI) with cementless, and 2.8% (1.8%–4.5% CI) with unicondylar prostheses (p < 0.0001). Revision rates after knee replacement strongly decreased with age.
Overall, about one in 75 patients needed a revision of their prosthesis within 3 y. On the basis of our data, consideration should be given to using hip resurfacing only in male patients and unicondylar knee replacement only in elderly patients.
Jan van der Meulen and colleagues show that about one in 75 patients with a primary hip or knee replacement needed a revision of their prosthesis within 3 years.
Editors' Summary
Though records show attempts to replace a hip date back to 1891, it was not till the 1960s before total hip replacements were successfully performed, and the 1970s before total knee replacements were carried out. These procedures are some of the most frequently performed surgical operations, with a total of 160,00 total hip and knee replacement procedures carried out in England and Wales and about half a million in the US in 2006. Hip and knee replacements are most commonly used as a treatment for severe arthritis once other approaches, such as pain relief medications, have failed. A total hip replacement involves replacing the head of the femur (the thigh bone) with an artificial component, typically metal; the socket into which the new femur head will insert is also replaced with artificial components. In an alternative procedure, resurfacing, rather than replacing the entire joint, the diseased surfaces are replaced with metal components. This procedure may be better suited to patients with less severe disease, and is also thought to result in quicker recovery. The techniques for hip and knee replacement can also be divided into those where a cement is used to position the metal implant into the bone (cemented) versus those where cement is not used (cementless).
Why Was This Study Done?
To date, little evidence has been available to compare patient outcomes following hip or knee replacement with the many different types of techniques and prostheses available. National registries have been established in a number of countries to try to collect data in order to build the evidence base for evaluating different types of prosthesis. Specifically, it is important to find out if there are any important differences in revision rates (how often the hip replacement has to be re-done) following surgery using the different techniques. In England and Wales, the National Joint Registry (NJR) has collected data on patient characteristics, types of prostheses implanted, and the type of surgical procedures used, since its initiation in April 2003.
What Did the Researchers Do and Find?
The researchers linked the records of the NJR and the Hospital Episode Statistics (HES) for patients treated by the NHS in England who had undergone a primary hip and knee replacement between April 2003 and September 2006. The HES database contains records of all admissions to NHS hospitals in England, and allowed the researchers to more accurately identify revisions of procedures that were done on patients in the NJR database.
They identified 327,557 primary hip or knee replacement procedures performed during that time period, but only 167,076 could be linked between the two databases.
76,576 patients in the linked database had undergone a primary hip replacement. The overall revision rate was 1.4% (95% confidence interval [CI] 1.2%–1.5%) at 3 years, with the lowest revision rates experienced by patients who had cemented prostheses. Women were found to have higher revision rates after hip resurfacing, and the revision rate was about twice as high in patients who had had a hip replacement for other indications than osteoarthritis. A patient's age did not appear to affect revision rates after hip surgery.
80,697 patients in the linked database had undergone a primary knee replacement. The overall revision rate was 1.4% (95% CI 1.3%–1.6%) at three years, again with the lowest rates of replacement experienced by patients who had cemented prostheses. Revision rates after knee replacement strongly decreased with age.
What Do These Findings Mean?
Overall, about one in 75 patients required a revision of their joint replacement, which is considered low, and cemented hip or knee prosthesis had the lowest revision rates. Post hip replacement, the highest revision rate was in patients who had undergone hip resurfacing, especially women. Following knee replacement, the highest revision rate was in patients who had undergone unicondylar prosthesis. However, in this study patients were only followed up for three years after the initial knee replacement, and it's possible that different patterns regarding the success of these differing techniques may emerge after longer follow-up. Importantly, this study was entirely observational, and data were collected from patients who had been managed according to routine clinical practice (rather than being randomly assigned to different procedures). Substantial differences in the age and clinical characteristics of patients receiving the different procedures were seen. As a result, it's not possible to directly draw conclusions on the relative benefits or harms of the different procedures, but this study provides important benchmark data with which to evaluate future performance of different procedures and types of implant.
Additional Information.
Please access these Web sites via the online version of this summary at
The website of the British Orthopaedic Association contains information for patients and surgeons
The website of the National Institute for Health and Clinical Excellence contains guidance on hip prostheses
Information is available from the US National Institutes of Health (Medline) on hip replacement, including interactive tutorials and information about rehabilitation and recovery
Medline also provides similar resources for knee replacement
The NHS provides information for patients on hip and knee replacement, including questions patients might ask, real stories, and useful links
The National Joint Registry provides general information about joint replacement, as well as allowing users to download statistics on the data it has collected on the numbers of procedures carried out in the UK
PMCID: PMC2528048  PMID: 18767900
14.  Total or Partial Knee Arthroplasty Trial - TOPKAT: study protocol for a randomised controlled trial 
Trials  2013;14:292.
In the majority of patients with osteoarthritis of the knee the disease originates in the medial compartment. There are two fundamentally different approaches to knee replacement for patients with unicompartmental disease: some surgeons feel that it is always best to replace both the knee compartments with a total knee replacement (TKR); whereas others feel it is best to replace just the damaged component of the knee using a partial or unicompartment replacement (UKR). Both interventions are established and well-documented procedures. Little evidence exists to prove the clinical and cost-effectiveness of either management option. This provides an explanation for the high variation in treatment of choice by individual surgeons for the same knee pathology.
The aim of the TOPKAT study will be to assess the clinical and cost effectiveness of TKRs compared to UKRs in patients with medial compartment osteoarthritis.
The design of the study is a single layer multicentre superiority type randomised controlled trial of unilateral knee replacement patients. Blinding will not be possible as the surgical scars for each procedure differ.
We aim to recruit 500 patients from approximately 28 secondary care orthopaedic units from across the UK including district general and teaching hospitals. Participants will be randomised to either UKR or TKR. Randomisation will occur using a web-based randomisation system. The study is pragmatic in terms of implant selection for the knee replacement operation. Participants will be followed up for 5 years. The primary outcome is the Oxford Knee Score, which will be collected via questionnaires at 2 months, 1 year and then annually to 5 years. Secondary outcomes will include cost-effectiveness, patient satisfaction and complications data.
Trial registration
Current Controlled Trials ISRCTN03013488; Identifier: NCT01352247
PMCID: PMC3848560  PMID: 24028414
Medial compartment osteoarthritis; Total knee replacement; Unicompartmental knee replacement; Equipoise; Expertise
15.  Relationship between cutting errors and learning curve in computer-assisted total knee replacement 
International Orthopaedics  2009;34(5):655-662.
Computer-assisted total knee replacement (TKR) has been shown to improve radiographic alignment. Continuous feedback from the navigation system allows accurate adjustment of the bone cuts, thus reducing errors. The aim of this study was to determine the impact of experience both with computer navigation and knee replacement surgery on the frequency of errors in intraoperative bone cuts and implant alignment. Three homogeneous patient groups undergoing computer assisted TKR were included in the study. Each group was treated by one of three surgeons with varying experience in computer-aided and knee replacement surgery. Surgeon A had extensive experience in knee replacement and computer-assisted surgery. Surgeon B was an experienced knee replacement surgeon. A general orthopaedic surgeon with limited knee replacement surgery experience performed all surgeries in group C. The cutting errors and the number of re-cuts were determined intraoperatively. The complications and mean surgical time were collected for each group. The postoperative frontal femoral component angle, frontal tibial component angle, hip–knee–ankle angle and component slopes were evaluated. The results showed that the number of cutting errors were lowest for TKR performed by the surgeon with experience in navigation. This difference was statistically significant when compared to the general orthopaedic surgeon. A statistically significant superior result was achieved in final mechanical axis alignment for the surgeon experienced in computer-guided surgery compared to the other two groups (179.3° compared to 178.9° and 178.1°). However, the total number of outliers was similar, with no statistically significant differences among the three surgeons. Experience with navigation significantly reduced the surgical time.
PMCID: PMC2903159  PMID: 19513711
16.  Comparison of ISO Standard and TKR Patient Axial Force Profiles during the Stance Phase of Gait 
Preclinical endurance testing of total knee replacements (TKRs) is performed using International Organization for Standardization (ISO) load and motion protocols. The standards are based on data from normal subjects and may not sufficiently mimic in vivo implant conditions. In this study, a mathematical model was used to calculate the axial force profile of 30 TKR patients with two current implant types, 22 with NexGen and eight with Miller-Galante II Cruciate-Retaining TKRs, and statistically compare the axial force specified by the ISO standard to the TKR patients. Significant differences were found between the axial forces of both groups of TKR patients and the ISO standard at local maxima and minima points in the first half of stance. The force impulse (area under the axial force curve, representing cumulative loading) was smaller for the ISO standard than the TKR patients, but only for those with NexGen implants. Waveform analysis using the coefficient of multiple correlation showed that the ISO and TKR patient axial force profiles were similar. The combined effect of ISO standard compressive load and motion differences from TKR patients could explain some of the differences between the wear scars on retrieved tibial components and those tested in total joint simulators.
PMCID: PMC3384520  PMID: 22558837
Total Knee Replacement; knee axial force; wear testing; mathematical modeling; standardized testing protocol
17.  The Level of Europium-154 Contaminating Samarium-153-EDTMP Activates the Radiation Alarm System at the US Homeland Security Checkpoints 
Case Reports in Oncology  2009;2(2):157-161.
153Sm-EDTMP is a radiopharmaceutical composed of EDTMP (ethylenediamine-tetramethylenephosphonate) and Samarium-153 [1]. 153Sm-EDTMP has an affinity for skeletal tissue and concentrates in areas with increased bone turnover; thus, it is successfully used in relieving pain related to diffuse bone metastases [1]. The manufacturing process of 153Sm-EDTMP leads to contamination with 154Eu (Europium-154) [2]. A previous study only alluded to the retention of 154Eu in the bones after receiving treatment with 153Sm-EDTMP [2]. Activation of the alarm at security checkpoints after 153Sm-EDTMP therapy has not been previously reported. Two out of 15 patients who received 153Sm-EDTMP at Roger Maris Cancer Center (Fargo, N. Dak., USA) activated the radiation activity sensors while passing through checkpoints; one at a US airport and the other while crossing the American-Canadian border. We assume that the 154Eu which remained in the patients’ bones activated the sensors.
In order to investigate this hypothesis, we obtained the consent from 3 of our 15 patients who received 153Sm-EDTMP within the previous 4 months to 2 years, including the patient who had activated the radiation alarm at the airport. The patients were scanned with a handheld detector and a gamma camera for energies from 511 keV to 1.3 MeV.
All three patients exhibited identical spectral images, and further analysis showed that the observed spectra are the result of 154Eu emissions.
Depending on the detection thresholds and windows used by local and federal authorities, the remaining activity of 154Eu retained in patients who received 153Sm-EDTMP could be sufficient enough to increase the count rates above background levels and activate the sensors. At Roger Maris Cancer Center, patients are now informed of the potential consequences of 153Sm-EDTMP therapy prior to initiating treatment. In addition, patients treated with 153Sm-EDTMP at Roger Maris Cancer Center receive laminated cards stating the date and the dose of treatment, as well as a statement that the holder may activate the alarm at the security checkpoints.
PMCID: PMC2918865  PMID: 20740180
Samarium-153-EDTMP; Europium-154; Bone metastases; Radiation alarm
18.  Lower limb orthopaedic surgery results in changes to coagulation and non-specific inflammatory biomarkers, including selective clinical outcome measures 
With an aging society and raised expectations, joint replacement surgery is likely to increase significantly in the future. The development of postoperative complications following joint replacement surgery (for example, infection, systemic inflammatory response syndrome and deep vein thrombosis) is also likely to increase. Despite considerable progress in orthopaedic surgery, comparing a range of biological markers with the ultimate aim of monitoring or predicting postoperative complications has not yet been extensively researched. The aim of this clinical pilot study was to test the hypothesis that lower limb orthopaedic surgery results in changes to coagulation, non-specific markers of inflammation (primary objective) and selective clinical outcome measures (secondary objective).
Test subjects were scheduled for elective total hip replacement (THR) or total knee replacement (TKR) orthopaedic surgery due to osteoarthritis (n = 10). Platelet counts and D-dimer concentrations were measured to assess any changes to coagulation function. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured as markers of non-specific inflammation. Patients were monitored regularly to assess for any signs of postoperative complications, including blood transfusions, oedema (knee swelling), wound infection, pain and fever.
THR and TKR orthopaedic surgery resulted in similar changes of coagulation and non-specific inflammatory biomarkers, suggestive of increased coagulation and inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in an increase in platelet (P = 0.013, THR) and D-dimer (P = 0.009, TKR) concentrations. Evidence of increased inflammation was demonstrated by an increase in CRP and ESR (P ≤ 0.05, THR and TKR). Four patients received blood transfusions (two THR and two TKR patients), with maximal oedema, pain and aural temperatures peaking between days 1 and 3 postoperatively, for both THR and TKR surgery. None of the patients developed postoperative infections.
The most noticeable changes in biological markers occur during days 1 to 3 postoperatively for both THR and TKR surgery, and these may have an effect on such postoperative clinical outcomes as oedema, pyrexia and pain. This study may assist in understanding the postoperative course following lower limb orthopaedic surgery, and may help clinicians in planning postoperative management and patient care.
PMCID: PMC3832226  PMID: 24206644
Coagulation; Inflammation; Orthopaedic surgery
19.  Internet-Based Device-Assisted Remote Monitoring of Cardiovascular Implantable Electronic Devices 
Executive Summary
The objective of this Medical Advisory Secretariat (MAS) report was to conduct a systematic review of the available published evidence on the safety, effectiveness, and cost-effectiveness of Internet-based device-assisted remote monitoring systems (RMSs) for therapeutic cardiac implantable electronic devices (CIEDs) such as pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. The MAS evidence-based review was performed to support public financing decisions.
Clinical Need: Condition and Target Population
Sudden cardiac death (SCD) is a major cause of fatalities in developed countries. In the United States almost half a million people die of SCD annually, resulting in more deaths than stroke, lung cancer, breast cancer, and AIDS combined. In Canada each year more than 40,000 people die from a cardiovascular related cause; approximately half of these deaths are attributable to SCD.
Most cases of SCD occur in the general population typically in those without a known history of heart disease. Most SCDs are caused by cardiac arrhythmia, an abnormal heart rhythm caused by malfunctions of the heart’s electrical system. Up to half of patients with significant heart failure (HF) also have advanced conduction abnormalities.
Cardiac arrhythmias are managed by a variety of drugs, ablative procedures, and therapeutic CIEDs. The range of CIEDs includes pacemakers (PMs), implantable cardioverter-defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices. Bradycardia is the main indication for PMs and individuals at high risk for SCD are often treated by ICDs.
Heart failure (HF) is also a significant health problem and is the most frequent cause of hospitalization in those over 65 years of age. Patients with moderate to severe HF may also have cardiac arrhythmias, although the cause may be related more to heart pump or haemodynamic failure. The presence of HF, however, increases the risk of SCD five-fold, regardless of aetiology. Patients with HF who remain highly symptomatic despite optimal drug therapy are sometimes also treated with CRT devices.
With an increasing prevalence of age-related conditions such as chronic HF and the expanding indications for ICD therapy, the rate of ICD placement has been dramatically increasing. The appropriate indications for ICD placement, as well as the rate of ICD placement, are increasingly an issue. In the United States, after the introduction of expanded coverage of ICDs, a national ICD registry was created in 2005 to track these devices. A recent survey based on this national ICD registry reported that 22.5% (25,145) of patients had received a non-evidence based ICD and that these patients experienced significantly higher in-hospital mortality and post-procedural complications.
In addition to the increased ICD device placement and the upfront device costs, there is the need for lifelong follow-up or surveillance, placing a significant burden on patients and device clinics. In 2007, over 1.6 million CIEDs were implanted in Europe and the United States, which translates to over 5.5 million patient encounters per year if the recommended follow-up practices are considered. A safe and effective RMS could potentially improve the efficiency of long-term follow-up of patients and their CIEDs.
In addition to being therapeutic devices, CIEDs have extensive diagnostic abilities. All CIEDs can be interrogated and reprogrammed during an in-clinic visit using an inductive programming wand. Remote monitoring would allow patients to transmit information recorded in their devices from the comfort of their own homes. Currently most ICD devices also have the potential to be remotely monitored. Remote monitoring (RM) can be used to check system integrity, to alert on arrhythmic episodes, and to potentially replace in-clinic follow-ups and manage disease remotely. They do not currently have the capability of being reprogrammed remotely, although this feature is being tested in pilot settings.
Every RMS is specifically designed by a manufacturer for their cardiac implant devices. For Internet-based device-assisted RMSs, this customization includes details such as web application, multiplatform sensors, custom algorithms, programming information, and types and methods of alerting patients and/or physicians. The addition of peripherals for monitoring weight and pressure or communicating with patients through the onsite communicators also varies by manufacturer. Internet-based device-assisted RMSs for CIEDs are intended to function as a surveillance system rather than an emergency system.
Health care providers therefore need to learn each application, and as more than one application may be used at one site, multiple applications may need to be reviewed for alarms. All RMSs deliver system integrity alerting; however, some systems seem to be better geared to fast arrhythmic alerting, whereas other systems appear to be more intended for remote follow-up or supplemental remote disease management. The different RMSs may therefore have different impacts on workflow organization because of their varying frequency of interrogation and methods of alerts. The integration of these proprietary RM web-based registry systems with hospital-based electronic health record systems has so far not been commonly implemented.
Currently there are 2 general types of RMSs: those that transmit device diagnostic information automatically and without patient assistance to secure Internet-based registry systems, and those that require patient assistance to transmit information. Both systems employ the use of preprogrammed alerts that are either transmitted automatically or at regular scheduled intervals to patients and/or physicians.
The current web applications, programming, and registry systems differ greatly between the manufacturers of transmitting cardiac devices. In Canada there are currently 4 manufacturers—Medtronic Inc., Biotronik, Boston Scientific Corp., and St Jude Medical Inc.—which have regulatory approval for remote transmitting CIEDs. Remote monitoring systems are proprietary to the manufacturer of the implant device. An RMS for one device will not work with another device, and the RMS may not work with all versions of the manufacturer’s devices.
All Internet-based device-assisted RMSs have common components. The implanted device is equipped with a micro-antenna that communicates with a small external device (at bedside or wearable) commonly known as the transmitter. Transmitters are able to interrogate programmed parameters and diagnostic data stored in the patients’ implant device. The information transfer to the communicator can occur at preset time intervals with the participation of the patient (waving a wand over the device) or it can be sent automatically (wirelessly) without their participation. The encrypted data are then uploaded to an Internet-based database on a secure central server. The data processing facilities at the central database, depending on the clinical urgency, can trigger an alert for the physician(s) that can be sent via email, fax, text message, or phone. The details are also posted on the secure website for viewing by the physician (or their delegate) at their convenience.
Research Questions
The research directions and specific research questions for this evidence review were as follows:
To identify the Internet-based device-assisted RMSs available for follow-up of patients with therapeutic CIEDs such as PMs, ICDs, and CRT devices.
To identify the potential risks, operational issues, or organizational issues related to Internet-based device-assisted RM for CIEDs.
To evaluate the safety, acceptability, and effectiveness of Internet-based device-assisted RMSs for CIEDs such as PMs, ICDs, and CRT devices.
To evaluate the safety, effectiveness, and cost-effectiveness of Internet-based device-assisted RMSs for CIEDs compared to usual outpatient in-office monitoring strategies.
To evaluate the resource implications or budget impact of RMSs for CIEDs in Ontario, Canada.
Research Methods
Literature Search
The review included a systematic review of published scientific literature and consultations with experts and manufacturers of all 4 approved RMSs for CIEDs in Canada. Information on CIED cardiac implant clinics was also obtained from Provincial Programs, a division within the Ministry of Health and Long-Term Care with a mandate for cardiac implant specialty care. Various administrative databases and registries were used to outline the current clinical follow-up burden of CIEDs in Ontario. The provincial population-based ICD database developed and maintained by the Institute for Clinical Evaluative Sciences (ICES) was used to review the current follow-up practices with Ontario patients implanted with ICD devices.
Search Strategy
A literature search was performed on September 21, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from 1950 to September 2010. Search alerts were generated and reviewed for additional relevant literature until December 31, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search.
Inclusion Criteria
published between 1950 and September 2010;
English language full-reports and human studies;
original reports including clinical evaluations of Internet-based device-assisted RMSs for CIEDs in clinical settings;
reports including standardized measurements on outcome events such as technical success, safety, effectiveness, cost, measures of health care utilization, morbidity, mortality, quality of life or patient satisfaction;
randomized controlled trials (RCTs), systematic reviews and meta-analyses, cohort and controlled clinical studies.
Exclusion Criteria
non-systematic reviews, letters, comments and editorials;
reports not involving standardized outcome events;
clinical reports not involving Internet-based device assisted RM systems for CIEDs in clinical settings;
reports involving studies testing or validating algorithms without RM;
studies with small samples (<10 subjects).
Outcomes of Interest
The outcomes of interest included: technical outcomes, emergency department visits, complications, major adverse events, symptoms, hospital admissions, clinic visits (scheduled and/or unscheduled), survival, morbidity (disease progression, stroke, etc.), patient satisfaction, and quality of life.
Summary of Findings
The MAS evidence review was performed to review available evidence on Internet-based device-assisted RMSs for CIEDs published until September 2010. The search identified 6 systematic reviews, 7 randomized controlled trials, and 19 reports for 16 cohort studies—3 of these being registry-based and 4 being multi-centered. The evidence is summarized in the 3 sections that follow.
1. Effectiveness of Remote Monitoring Systems of CIEDs for Cardiac Arrhythmia and Device Functioning
In total, 15 reports on 13 cohort studies involving investigations with 4 different RMSs for CIEDs in cardiology implant clinic groups were identified in the review. The 4 RMSs were: Care Link Network® (Medtronic Inc,, Minneapolis, MN, USA); Home Monitoring® (Biotronic, Berlin, Germany); House Call 11® (St Jude Medical Inc., St Pauls, MN, USA); and a manufacturer-independent RMS. Eight of these reports were with the Home Monitoring® RMS (12,949 patients), 3 were with the Care Link® RMS (167 patients), 1 was with the House Call 11® RMS (124 patients), and 1 was with a manufacturer-independent RMS (44 patients). All of the studies, except for 2 in the United States, (1 with Home Monitoring® and 1 with House Call 11®), were performed in European countries.
The RMSs in the studies were evaluated with different cardiac implant device populations: ICDs only (6 studies), ICD and CRT devices (3 studies), PM and ICD and CRT devices (4 studies), and PMs only (2 studies). The patient populations were predominately male (range, 52%–87%) in all studies, with mean ages ranging from 58 to 76 years. One study population was unique in that RMSs were evaluated for ICDs implanted solely for primary prevention in young patients (mean age, 44 years) with Brugada syndrome, which carries an inherited increased genetic risk for sudden heart attack in young adults.
Most of the cohort studies reported on the feasibility of RMSs in clinical settings with limited follow-up. In the short follow-up periods of the studies, the majority of the events were related to detection of medical events rather than system configuration or device abnormalities. The results of the studies are summarized below:
The interrogation of devices on the web platform, both for continuous and scheduled transmissions, was significantly quicker with remote follow-up, both for nurses and physicians.
In a case-control study focusing on a Brugada population–based registry with patients followed-up remotely, there were significantly fewer outpatient visits and greater detection of inappropriate shocks. One death occurred in the control group not followed remotely and post-mortem analysis indicated early signs of lead failure prior to the event.
Two studies examined the role of RMSs in following ICD leads under regulatory advisory in a European clinical setting and noted:
– Fewer inappropriate shocks were administered in the RM group.
– Urgent in-office interrogations and surgical revisions were performed within 12 days of remote alerts.
– No signs of lead fracture were detected at in-office follow-up; all were detected at remote follow-up.
Only 1 study reported evaluating quality of life in patients followed up remotely at 3 and 6 months; no values were reported.
Patient satisfaction was evaluated in 5 cohort studies, all in short term follow-up: 1 for the Home Monitoring® RMS, 3 for the Care Link® RMS, and 1 for the House Call 11® RMS.
– Patients reported receiving a sense of security from the transmitter, a good relationship with nurses and physicians, positive implications for their health, and satisfaction with RM and organization of services.
– Although patients reported that the system was easy to implement and required less than 10 minutes to transmit information, a variable proportion of patients (range, 9% 39%) reported that they needed the assistance of a caregiver for their transmission.
– The majority of patients would recommend RM to other ICD patients.
– Patients with hearing or other physical or mental conditions hindering the use of the system were excluded from studies, but the frequency of this was not reported.
Physician satisfaction was evaluated in 3 studies, all with the Care Link® RMS:
– Physicians reported an ease of use and high satisfaction with a generally short-term use of the RMS.
– Physicians reported being able to address the problems in unscheduled patient transmissions or physician initiated transmissions remotely, and were able to handle the majority of the troubleshooting calls remotely.
– Both nurses and physicians reported a high level of satisfaction with the web registry system.
2. Effectiveness of Remote Monitoring Systems in Heart Failure Patients for Cardiac Arrhythmia and Heart Failure Episodes
Remote follow-up of HF patients implanted with ICD or CRT devices, generally managed in specialized HF clinics, was evaluated in 3 cohort studies: 1 involved the Home Monitoring® RMS and 2 involved the Care Link® RMS. In these RMSs, in addition to the standard diagnostic features, the cardiac devices continuously assess other variables such as patient activity, mean heart rate, and heart rate variability. Intra-thoracic impedance, a proxy measure for lung fluid overload, was also measured in the Care Link® studies. The overall diagnostic performance of these measures cannot be evaluated, as the information was not reported for patients who did not experience intra-thoracic impedance threshold crossings or did not undergo interventions. The trial results involved descriptive information on transmissions and alerts in patients experiencing high morbidity and hospitalization in the short study periods.
3. Comparative Effectiveness of Remote Monitoring Systems for CIEDs
Seven RCTs were identified evaluating RMSs for CIEDs: 2 were for PMs (1276 patients) and 5 were for ICD/CRT devices (3733 patients). Studies performed in the clinical setting in the United States involved both the Care Link® RMS and the Home Monitoring® RMS, whereas all studies performed in European countries involved only the Home Monitoring® RMS.
3A. Randomized Controlled Trials of Remote Monitoring Systems for Pacemakers
Two trials, both multicenter RCTs, were conducted in different countries with different RMSs and study objectives. The PREFER trial was a large trial (897 patients) performed in the United States examining the ability of Care Link®, an Internet-based remote PM interrogation system, to detect clinically actionable events (CAEs) sooner than the current in-office follow-up supplemented with transtelephonic monitoring transmissions, a limited form of remote device interrogation. The trial results are summarized below:
In the 375-day mean follow-up, 382 patients were identified with at least 1 CAE—111 patients in the control arm and 271 in the remote arm.
The event rate detected per patient for every type of CAE, except for loss of atrial capture, was higher in the remote arm than the control arm.
The median time to first detection of CAEs (4.9 vs. 6.3 months) was significantly shorter in the RMS group compared to the control group (P < 0.0001).
Additionally, only 2% (3/190) of the CAEs in the control arm were detected during a transtelephonic monitoring transmission (the rest were detected at in-office follow-ups), whereas 66% (446/676) of the CAEs were detected during remote interrogation.
The second study, the OEDIPE trial, was a smaller trial (379 patients) performed in France evaluating the ability of the Home Monitoring® RMS to shorten PM post-operative hospitalization while preserving the safety of conventional management of longer hospital stays.
Implementation and operationalization of the RMS was reported to be successful in 91% (346/379) of the patients and represented 8144 transmissions.
In the RM group 6.5% of patients failed to send messages (10 due to improper use of the transmitter, 2 with unmanageable stress). Of the 172 patients transmitting, 108 patients sent a total of 167 warnings during the trial, with a greater proportion of warnings being attributed to medical rather than technical causes.
Forty percent had no warning message transmission and among these, 6 patients experienced a major adverse event and 1 patient experienced a non-major adverse event. Of the 6 patients having a major adverse event, 5 contacted their physician.
The mean medical reaction time was faster in the RM group (6.5 ± 7.6 days vs. 11.4 ± 11.6 days).
The mean duration of hospitalization was significantly shorter (P < 0.001) for the RM group than the control group (3.2 ± 3.2 days vs. 4.8 ± 3.7 days).
Quality of life estimates by the SF-36 questionnaire were similar for the 2 groups at 1-month follow-up.
3B. Randomized Controlled Trials Evaluating Remote Monitoring Systems for ICD or CRT Devices
The 5 studies evaluating the impact of RMSs with ICD/CRT devices were conducted in the United States and in European countries and involved 2 RMSs—Care Link® and Home Monitoring ®. The objectives of the trials varied and 3 of the trials were smaller pilot investigations.
The first of the smaller studies (151 patients) evaluated patient satisfaction, achievement of patient outcomes, and the cost-effectiveness of the Care Link® RMS compared to quarterly in-office device interrogations with 1-year follow-up.
Individual outcomes such as hospitalizations, emergency department visits, and unscheduled clinic visits were not significantly different between the study groups.
Except for a significantly higher detection of atrial fibrillation in the RM group, data on ICD detection and therapy were similar in the study groups.
Health-related quality of life evaluated by the EuroQoL at 6-month or 12-month follow-up was not different between study groups.
Patients were more satisfied with their ICD care in the clinic follow-up group than in the remote follow-up group at 6-month follow-up, but were equally satisfied at 12- month follow-up.
The second small pilot trial (20 patients) examined the impact of RM follow-up with the House Call 11® system on work schedules and cost savings in patients randomized to 2 study arms varying in the degree of remote follow-up.
The total time including device interrogation, transmission time, data analysis, and physician time required was significantly shorter for the RM follow-up group.
The in-clinic waiting time was eliminated for patients in the RM follow-up group.
The physician talk time was significantly reduced in the RM follow-up group (P < 0.05).
The time for the actual device interrogation did not differ in the study groups.
The third small trial (115 patients) examined the impact of RM with the Home Monitoring® system compared to scheduled trimonthly in-clinic visits on the number of unplanned visits, total costs, health-related quality of life (SF-36), and overall mortality.
There was a 63.2% reduction in in-office visits in the RM group.
Hospitalizations or overall mortality (values not stated) were not significantly different between the study groups.
Patient-induced visits were higher in the RM group than the in-clinic follow-up group.
The TRUST Trial
The TRUST trial was a large multicenter RCT conducted at 102 centers in the United States involving the Home Monitoring® RMS for ICD devices for 1450 patients. The primary objectives of the trial were to determine if remote follow-up could be safely substituted for in-office clinic follow-up (3 in-office visits replaced) and still enable earlier physician detection of clinically actionable events.
Adherence to the protocol follow-up schedule was significantly higher in the RM group than the in-office follow-up group (93.5% vs. 88.7%, P < 0.001).
Actionability of trimonthly scheduled checks was low (6.6%) in both study groups. Overall, actionable causes were reprogramming (76.2%), medication changes (24.8%), and lead/system revisions (4%), and these were not different between the 2 study groups.
The overall mean number of in-clinic and hospital visits was significantly lower in the RM group than the in-office follow-up group (2.1 per patient-year vs. 3.8 per patient-year, P < 0.001), representing a 45% visit reduction at 12 months.
The median time from onset of first arrhythmia to physician evaluation was significantly shorter (P < 0.001) in the RM group than in the in-office follow-up group for all arrhythmias (1 day vs. 35.5 days).
The median time to detect clinically asymptomatic arrhythmia events—atrial fibrillation (AF), ventricular fibrillation (VF), ventricular tachycardia (VT), and supra-ventricular tachycardia (SVT)—was also significantly shorter (P < 0.001) in the RM group compared to the in-office follow-up group (1 day vs. 41.5 days) and was significantly quicker for each of the clinical arrhythmia events—AF (5.5 days vs. 40 days), VT (1 day vs. 28 days), VF (1 day vs. 36 days), and SVT (2 days vs. 39 days).
System-related problems occurred infrequently in both groups—in 1.5% of patients (14/908) in the RM group and in 0.7% of patients (3/432) in the in-office follow-up group.
The overall adverse event rate over 12 months was not significantly different between the 2 groups and individual adverse events were also not significantly different between the RM group and the in-office follow-up group: death (3.4% vs. 4.9%), stroke (0.3% vs. 1.2%), and surgical intervention (6.6% vs. 4.9%), respectively.
The 12-month cumulative survival was 96.4% (95% confidence interval [CI], 95.5%–97.6%) in the RM group and 94.2% (95% confidence interval [CI], 91.8%–96.6%) in the in-office follow-up group, and was not significantly different between the 2 groups (P = 0.174).
The CONNECT trial, another major multicenter RCT, involved the Care Link® RMS for ICD/CRT devices in a15-month follow-up study of 1,997 patients at 133 sites in the United States. The primary objective of the trial was to determine whether automatically transmitted physician alerts decreased the time from the occurrence of clinically relevant events to medical decisions. The trial results are summarized below:
Of the 575 clinical alerts sent in the study, 246 did not trigger an automatic physician alert. Transmission failures were related to technical issues such as the alert not being programmed or not being reset, and/or a variety of patient factors such as not being at home and the monitor not being plugged in or set up.
The overall mean time from the clinically relevant event to the clinical decision was significantly shorter (P < 0.001) by 17.4 days in the remote follow-up group (4.6 days for 172 patients) than the in-office follow-up group (22 days for 145 patients).
– The median time to a clinical decision was shorter in the remote follow-up group than in the in-office follow-up group for an AT/AF burden greater than or equal to 12 hours (3 days vs. 24 days) and a fast VF rate greater than or equal to 120 beats per minute (4 days vs. 23 days).
Although infrequent, similar low numbers of events involving low battery and VF detection/therapy turned off were noted in both groups. More alerts, however, were noted for out-of-range lead impedance in the RM group (18 vs. 6 patients), and the time to detect these critical events was significantly shorter in the RM group (same day vs. 17 days).
Total in-office clinic visits were reduced by 38% from 6.27 visits per patient-year in the in-office follow-up group to 3.29 visits per patient-year in the remote follow-up group.
Health care utilization visits (N = 6,227) that included cardiovascular-related hospitalization, emergency department visits, and unscheduled clinic visits were not significantly higher in the remote follow-up group.
The overall mean length of hospitalization was significantly shorter (P = 0.002) for those in the remote follow-up group (3.3 days vs. 4.0 days) and was shorter both for patients with ICD (3.0 days vs. 3.6 days) and CRT (3.8 days vs. 4.7 days) implants.
The mortality rate between the study arms was not significantly different between the follow-up groups for the ICDs (P = 0.31) or the CRT devices with defribillator (P = 0.46).
There is limited clinical trial information on the effectiveness of RMSs for PMs. However, for RMSs for ICD devices, multiple cohort studies and 2 large multicenter RCTs demonstrated feasibility and significant reductions in in-office clinic follow-ups with RMSs in the first year post implantation. The detection rates of clinically significant events (and asymptomatic events) were higher, and the time to a clinical decision for these events was significantly shorter, in the remote follow-up groups than in the in-office follow-up groups. The earlier detection of clinical events in the remote follow-up groups, however, was not associated with lower morbidity or mortality rates in the 1-year follow-up. The substitution of almost all the first year in-office clinic follow-ups with RM was also not associated with an increased health care utilization such as emergency department visits or hospitalizations.
The follow-up in the trials was generally short-term, up to 1 year, and was a more limited assessment of potential longer term device/lead integrity complications or issues. None of the studies compared the different RMSs, particularly the different RMSs involving patient-scheduled transmissions or automatic transmissions. Patients’ acceptance of and satisfaction with RM were reported to be high, but the impact of RM on patients’ health-related quality of life, particularly the psychological aspects, was not evaluated thoroughly. Patients who are not technologically competent, having hearing or other physical/mental impairments, were identified as potentially disadvantaged with remote surveillance. Cohort studies consistently identified subgroups of patients who preferred in-office follow-up. The evaluation of costs and workflow impact to the health care system were evaluated in European or American clinical settings, and only in a limited way.
Internet-based device-assisted RMSs involve a new approach to monitoring patients, their disease progression, and their CIEDs. Remote monitoring also has the potential to improve the current postmarket surveillance systems of evolving CIEDs and their ongoing hardware and software modifications. At this point, however, there is insufficient information to evaluate the overall impact to the health care system, although the time saving and convenience to patients and physicians associated with a substitution of in-office follow-up by RM is more certain. The broader issues surrounding infrastructure, impacts on existing clinical care systems, and regulatory concerns need to be considered for the implementation of Internet-based RMSs in jurisdictions involving different clinical practices.
PMCID: PMC3377571  PMID: 23074419
20.  Total hip and knee replacement surgery results in changes in leukocyte and endothelial markers 
It is estimated that over 8 million people in the United Kingdom suffer from osteoarthritis. These patients may require orthopaedic surgical intervention to help alleviate their clinical condition. Investigations presented here was to test the hypothesis that total hip replacement (THR) and total knee replacement (TKR) orthopaedic surgery result in changes to leukocyte and endothelial markers thus increasing inflammatory reactions postoperatively.
During this 'pilot study', ten test subjects were all scheduled for THR or TKR elective surgery due to osteoarthritis. Leukocyte concentrations were measured using an automated full blood count analyser. Leukocyte CD11b (Mac-1) and CD62L cell surface expression, intracellular production of H2O2 and elastase were measured as markers of leukocyte function. Von Willebrand factor (vWF) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured as markers of endothelial activation.
The results obtained during this study demonstrate that THR and TKR orthopaedic surgery result in similar changes of leukocyte and endothelial markers, suggestive of increased inflammatory reactions postoperatively. Specifically, THR and TKR surgery resulted in a leukocytosis, this being demonstrated by an increase in the total leukocyte concentration following surgery. Evidence of leukocyte activation was demonstrated by a decrease in CD62L expression and an increase in CD11b expression by neutrophils and monocytes respectively. An increase in the intracellular H2O2 production by neutrophils and monocytes and in the leukocyte elastase concentrations was also evident of leukocyte activation following orthopaedic surgery. With respect to endothelial activation, increases in vWF and sICAM-1 concentrations were demonstrated following surgery.
In general it appeared that most of the leukocyte and endothelial markers measured during these studies peaked between days 1-3 postoperatively. It is proposed that by allowing orthopaedic surgeons access to alternative laboratory markers such as CD11b, H2O2 and elastase, CD62L, vWF and sICAM-1, an accurate assessment of the extent of inflammation due to surgery per se could be made. Ultimately, the leukocyte and endothelial markers assessed during this investigation may have a role in monitoring potential infectious complications that can occur during the postoperative period.
PMCID: PMC2820000  PMID: 20148137
21.  Nitrogen dioxide concentrations in neighborhoods adjacent to a commercial airport: a land use regression modeling study 
Environmental Health  2010;9:73.
There is growing concern in communities surrounding airports regarding the contribution of various emission sources (such as aircraft and ground support equipment) to nearby ambient concentrations. We used extensive monitoring of nitrogen dioxide (NO2) in neighborhoods surrounding T.F. Green Airport in Warwick, RI, and land-use regression (LUR) modeling techniques to determine the impact of proximity to the airport and local traffic on these concentrations.
Palmes diffusion tube samplers were deployed along the airport's fence line and within surrounding neighborhoods for one to two weeks. In total, 644 measurements were collected over three sampling campaigns (October 2007, March 2008 and June 2008) and each sampling location was geocoded. GIS-based variables were created as proxies for local traffic and airport activity. A forward stepwise regression methodology was employed to create general linear models (GLMs) of NO2 variability near the airport. The effect of local meteorology on associations with GIS-based variables was also explored.
Higher concentrations of NO2 were seen near the airport terminal, entrance roads to the terminal, and near major roads, with qualitatively consistent spatial patterns between seasons. In our final multivariate model (R2 = 0.32), the local influences of highways and arterial/collector roads were statistically significant, as were local traffic density and distance to the airport terminal (all p < 0.001). Local meteorology did not significantly affect associations with principal GIS variables, and the regression model structure was robust to various model-building approaches.
Our study has shown that there are clear local variations in NO2 in the neighborhoods that surround an urban airport, which are spatially consistent across seasons. LUR modeling demonstrated a strong influence of local traffic, except the smallest roads that predominate in residential areas, as well as proximity to the airport terminal.
PMCID: PMC2996366  PMID: 21083910
22.  Prosthesis alignment affects axial rotation motion after total knee replacement: a prospective in vivo study combining computed tomography and fluoroscopic evaluations 
Clinical consequences of alignment errors in total knee replacement (TKR) have led to the rigorous evaluation of surgical alignment techniques. Rotational alignment in the transverse plane has proven particularly problematic, with errors due to component malalignment relative to bone anatomic landmarks and an overall mismatch between the femoral and tibial components’ relative positions. Ranges of nominal rotational alignment are not well defined, especially for the tibial component and for relative rotational mismatch, and some studies advocate the use of mobile-bearing TKR to accommodate the resulting small rotation errors. However, the relationships between prosthesis rotational alignment and mobile-bearing polyethylene insert motion are poorly understood. This prospective, in vivo study evaluates whether component malalignment and mismatch affect axial rotation motions during passive knee flexion after TKR.
Eighty patients were implanted with mobile-bearing TKR. Rotational alignment of the femoral and tibial components was measured from postoperative CT scans. All TKR were categorized into nominal or outlier groups based on defined norms for surgical rotational alignment relative to bone anatomic landmarks and relative rotational mismatch between the femoral and tibial components. Axial rotation motion of the femoral, tibial and polyethylene bearing components was measured from fluoroscopic images acquired during passive knee flexion.
Axial rotation motion was generally accomplished in two phases, dominated by polyethylene bearing rotation on the tibial component in early to mid-flexion and then femoral component rotation on the polyethylene articular surface in later flexion. Opposite rotations of the femur-bearing and bearing-baseplate articulations were evident at flexion greater than 80°. Knees with outlier alignment had lower magnitudes of axial rotation and distinct transitions from external to internal rotation during mid-flexion. Knees with femoral-tibial rotational mismatch had significantly lower total axial rotation compared to knees with nominal alignment.
Maintaining relative rotational mismatch within ±5° during TKR provided for controlled knee axial rotation during flexion. TKR with rotational alignment outside of defined surgical norms, with either positive or negative mismatch, experienced measurable kinematic differences and presented different patterns of axial rotation motions during passive knee flexion compared to TKR with nominal mismatch. These findings support previous studies linking prosthesis rotational alignment with inferior clinical and functional outcomes.
Trial Registration
Clinical Trials NCT01022099
PMCID: PMC3575259  PMID: 23088451
Total knee replacement; Mobile-bearing prosthesis; Implant alignment; Surgical alignment; Knee kinematics; Axial rotation; Knee biomechanics; Knee arthroplasty
23.  Case Mix and Outcomes of Total Knee Replacement in Orthopaedic Specialty Hospitals 
Medical care  2008;46(5):476-480.
To examine patient characteristics and outcomes of total knee replacement (TKR) in orthopaedic specialty hospitals.
We performed a retrospective cohort study in the US Medicare population. We defined specialty hospitals for TKR as centers: (1) that performed >75 TKRs in Medicare recipients in 2000; (2) in which TKR accounted for >7% of all Medicare discharges; and (3) that had <300 beds. We divided specialty hospitals into those with ≤100 beds and those with 101–299 beds. We compared preoperative characteristics and complications among patients undergoing TKR in specialty and nonspecialty centers. We stratified patients according to risk of complications and performed stratum-specific analyses.
A total of 2417 patients received TKA in 19 specialty hospitals, accounting for 3% of all TKRs in 2000. The specialty hospitals had fewer patients with poverty level income. The smaller “boutique” specialty hospitals had lower complication rates than the larger specialty hospitals and the nonspecialty centers (P value for trend = 0.001). In analyses that adjusted for patient age and sex, low-risk patients had similar outcomes across all hospital categories. However, high-risk patients had statistically significantly greater benefit from treatment in smaller specialty hospitals, with the risk of any adverse event ranging from 1.4% (95% CI, 0%–3.5%) in smaller specialty hospitals to 4.9% (95% CI, 4.4%–5.5%) in low-volume centers.
Smaller specialty hospitals have low complication rates and are especially beneficial for high-risk patients. Further work should address functional outcomes, costs, and satisfaction in these specialty centers, and evaluate strategies to manage more high-risk patients in specialty centers.
PMCID: PMC2846305  PMID: 18438195
specialty hospitals; total knee replacement; complications
24.  Implantable Cardioverter Defibrillators. Prophylactic Use 
Executive Summary
The use of implantable cardiac defibrillators (ICDs) to prevent sudden cardiac death (SCD) in patients resuscitated from cardiac arrest or documented dangerous ventricular arrhythmias (secondary prevention of SCD) is an insured service. In 2003 (before the establishment of the Ontario Health Technology Advisory Committee), the Medical Advisory Secretariat conducted a health technology policy assessment on the prophylactic use (primary prevention of SCD) of ICDs for patients at high risk of SCD. The Medical Advisory Secretariat concluded that ICDs are effective for the primary prevention of SCD. Moreover, it found that a more clearly defined target population at risk for SCD that would be likely to benefit from ICDs is needed, given that the number needed to treat (NNT) from recent studies is 13 to 18, and given that the per-unit cost of ICDs is $32,000, which means that the projected cost to Ontario is $770 million (Cdn).
Accordingly, as part of an annual review and publication of more recent articles, the Medical Advisory Secretariat updated its health technology policy assessment of ICDs.
Clinical Need
Sudden cardiac death is caused by the sudden onset of fatal arrhythmias, or abnormal heart rhythms: ventricular tachycardia (VT), a rhythm abnormality in which the ventricles cause the heart to beat too fast, and ventricular fibrillation (VF), an abnormal, rapid and erratic heart rhythm. About 80% of fatal arrhythmias are associated with ischemic heart disease, which is caused by insufficient blood flow to the heart.
Management of VT and VF with antiarrhythmic drugs is not very effective; for this reason, nonpharmacological treatments have been explored. One such treatment is the ICD.
The Technology
An ICD is a battery-powered device that, once implanted, monitors heart rhythm and can deliver an electric shock to restore normal rhythm when potentially fatal arrhythmias are detected. The use of ICDs to prevent SCD in patients resuscitated from cardiac arrest or documented dangerous ventricular arrhythmias (secondary prevention) is an insured service in Ontario.
Primary prevention of SCD involves identification of and preventive therapy for patients who are at high risk for SCD. Most of the studies in the literature that have examined the prevention of fatal ventricular arrhythmias have focused on patients with ischemic heart disease, in particular, those with heart failure (HF), which has been shown to increase the risk of SCD. The risk of HF is determined by left ventricular ejection fraction (LVEF); most studies have focused on patients with an LVEF under 0.35 or 0.30. While most studies have found ICDs to reduce significantly the risk for SCD in patients with an LVEF less than 0.35, a more recent study (Sudden Cardiac Death in Heart Failure Trial [SCD-HeFT]) reported that patients with HF with nonischemic heart disease could also benefit from this technology. Based on the generalization of the SCD-HeFT study, the Centers for Medicare and Medicaid in the United States recently announced that it would allocate $10 billion (US) annually toward the primary prevention of SCD for patients with ischemic and nonischemic heart disease and an LVEF under 0.35.
Review Strategy
The aim of this literature review was to assess the effectiveness, safety, and cost effectiveness of ICDs for the primary prevention of SCD.
The standard search strategy used by the Medical Advisory Secretariat was used. This included a search of all international health technology assessments as well as a search of the medical literature from January 2003–May 2005.
A modification of the GRADE approach (1) was used to make judgments about the quality of evidence and strength of recommendations systematically and explicitly. GRADE provides a framework for structured reflection and can help to ensure that appropriate judgments are made. GRADE takes into account a study’s design, quality, consistency, and directness in judging the quality of evidence for each outcome. The balance between benefits and harms, quality of evidence, applicability, and the certainty of the baseline risks are considered in judgments about the strength of recommendations.
Summary of Findings
Overall, ICDs are effective for the primary prevention of SCD. Three studies – the Multicentre Automatic Defibrillator Implantation Trial I (MADIT I), the Multicentre Automatic Defibrillator Implantation Trial II (MADIT II), and SCD-HeFT – showed there was a statistically significant decrease in total mortality for patients who prophylactically received an ICD compared with those who received conventional therapy (Table 1).
Results of Key Studies on the Use of Implantable Cardioverter Defibrillators for the Primary Prevention of Sudden Cardiac Death – All-Cause Mortality
MADIT I: Multicentre Automatic Defibrillator Implantation Trial I; MADIT II: Multicentre Automatic Defibrillator Implantation Trial II; SCD-HeFT: Sudden Cardiac Death in Heart Failure Trial.
EP indicates electrophysiology; ICD, implantable cardioverter defibrillator; NNT, number needed to treat; NSVT, nonsustained ventricular tachycardia. The NNT will appear higher if follow-up is short. For ICDs, the absolute benefit increases over time for at least a 5-year period; the NNT declines, often substantially, in studies with a longer follow-up. When the NNT are equalized for a similar period as the SCD-HeFT duration (5 years), the NNT for MADIT-I is 2.2; for MADIT-II, it is 6.3.
GRADE Quality of the Evidence
Using the GRADE Working Group criteria, the quality of these 3 trials was examined (Table 2).
Quality refers to the criteria such as the adequacy of allocation concealment, blinding and follow-up.
Consistency refers to the similarity of estimates of effect across studies. If there is important unexplained inconsistency in the results, our confidence in the estimate of effect for that outcome decreases. Differences in the direction of effect, the size of the differences in effect, and the significance of the differences guide the decision about whether important inconsistency exists.
Directness refers to the extent to which the people interventions and outcome measures are similar to those of interest. For example, there may be uncertainty about the directness of the evidence if the people of interest are older, sicker or have more comorbidity than those in the studies.
As stated by the GRADE Working Group, the following definitions were used to grade the quality of the evidence:
High: Further research is very unlikely to change our confidence n the estimate of effect.
Moderate: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low: Any estimate of effect is very uncertain.
Quality of Evidence – MADIT I, MADIT II, and SCD-HeFT*
MADIT I: Multicentre Automatic Defibrillator Implantation Trial I; MADIT II: Multicentre Automatic Defibrillator Implantation Trial II; SCD-HeFT: Sudden Cardiac Death in Heart Failure Trial.
The 3 trials had 3 different sets of eligibility criteria for implantation of an ICD for primary prevention of SCD. Conclusions
Overall, there is evidence that ICDs are effective for the primary prevention of SCD. Three trials have found a statistically significant decrease in total mortality for patients who prophylactically received an ICD compared with those who received conventional therapy in their respective study populations.
As per the GRADE Working Group, recommendations consider 4 main factors:
The tradeoffs, taking into account the estimated size of the effect for the main outcome, the confidence limits around those estimates, and the relative value placed on the outcome;
The quality of the evidence (Table 2);
Translation of the evidence into practice in a specific setting, taking into consideration important factors that could be expected to modify the size of the expected effects, such as proximity to a hospital or availability of necessary expertise; and
Uncertainty about the baseline risk for the population of interest
The GRADE Working Group also recommends that incremental costs of health care alternatives should be considered explicitly with the expected health benefits and harms. Recommendations rely on judgments about the value of the incremental health benefits in relation to the incremental costs. The last column in Table 3 is the overall trade-off between benefits and harms and incorporates any risk or uncertainty.
For MADIT I, the overall GRADE and strength of the recommendation is “moderate” – the quality of the evidence is “moderate” (uncertainty due to methodological limitations in the study design), and risk/uncertainty in cost and budget impact was mitigated by the use of filters to help target the prevalent population at risk (Table 3).
For MADIT II, the overall GRADE and strength of the recommendation is “very weak” – the quality of the evidence is “weak” (uncertainty due to methodological limitations in the study design), but there is risk or uncertainty regarding the high prevalence, cost, and budget impact. It is not clear why screening for high-risk patients was dropped, given that in MADIT II the absolute reduction in mortality was small (5.6%) compared to MADIT I, which used electrophysiological screening (23%) (Table 3).
For SCD-HeFT, the overall GRADE and strength of the recommendation is “weak” – the study quality is “moderate,” but there is also risk/uncertainty due to a high NNT at 5 years (13 compared to the MADIT II NNT of 6 and MADIT I NNT of 2 at 5 years), high prevalent population (N = 23,700), and a high budget impact ($770 million). A filter (as demonstrated in MADIT 1) is required to help target the prevalent population at risk and mitigate the risk or uncertainty relating to the high NNT, prevalence, and budget impact (Table 3).
The results of the most recent ICD trial (SCD-HeFT) are not generalizable to the prevalent population in Ontario (Table 3). Given that the current funding rate of an ICD is $32,500 (Cdn), the estimated budget impact for Ontario would be as high as $770 million (Cdn). The uncertainty around the cost estimate of treating the prevalent population with LVEF < 0.30 in Ontario, the lack of human resources to implement such a strategy and the high number of patients required to prevent one SCD (NNT = 13) calls for an alternative strategy that allows the appropriate uptake and diffusion of ICDs for primary prevention for patients at maximum risk for SCD within the SCD-HeFT population.
The uptake and diffusion of ICDs for primary prevention of SCD should therefore be based on risk stratification through the use of appropriate screen(s) that would identify patients at highest risk who could derive the most benefit from this technology.
Overall GRADE and Strength of Recommendation for the Use of Implantable Cardioverter Defibrillators for the Primary Prevention of Sudden Cardiac Death
MADIT I: Multicentre Automatic Defibrillator Implantation Trial I; MADIT II: Multicentre Automatic Defibrillator Implantation Trial II; SCD-HeFT: Sudden Cardiac Death in Heart Failure Trial.
NNT indicates number needed to treat. The NNT will appear higher if follow-up is short. For ICDs, the absolute benefit increases over time for at least a 5-year period; the NNT declines, often substantially, in studies with a longer follow-up. When the NNT are equalized for a similar period as the SCD-HeFT duration (5 years), the NNT for MADIT-I is 2.2; for MADIT-II, it is 6.3.
NSVT indicates nonsustained ventricular tachycardia; VT, ventricular tachycardia.
PMCID: PMC3382404  PMID: 23074465
25.  Unicompartmental versus computer-assisted total knee replacement for medial compartment knee arthritis: a matched paired study 
International Orthopaedics  2006;31(3):315-319.
Patients older than 60 with unicompartmental knee arthritis can be treated with total or unicompartmental knee replacement. The aim of this study was to compare the results of matched paired groups of patients with isolated medial compartment knee arthritis replaced with either UKR (group A) or computer-assisted TKR (group B). The results included 68 knees at a minimum follow-up of 3 years. All patients had a varus deformity no greater than 8º and a BMI lower than 30. Patients were matched in terms of preoperative arthritis severity, age, gender and preoperative range of motion. In the computer-assisted TKR group, all the implants were positioned within 4º of the correct hip-knee-ankle angle and frontal tibial component angle. The surgical time and hospital stay were statistically longer in the CA TKR group. During the study no implant required revision. The results showed higher scores for a UKR in the treatment of isolated primary unicompartmental knee arthritis in patients older than 60 compared to a computer-assisted TKR. In this study a computer-assisted alignment system for TKR with optimal implant positioning did not produce equivalent clinical results compared to a UKR, but did increase the financial costs.
PMCID: PMC2267582  PMID: 16896871

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