Rationale, design and critical end points for the Riluzole in Acute Spinal Cord Injury Study (RISCIS): a randomized, double-blinded, placebo-controlled parallel multi-center trial.

BACKGROUND: Riluzole is a sodium channel-blocking agent used in treating amyotrophic lateral sclerosis. It has been approved by the U.S. Food and Drug Administration, Canadian and Australian authorities, and in many other countries. A phase I trial of riluzole for acute spinal cord injury (SCI) provided safety and pharmacokinetic data and suggested neuroprotective benefits. A phase IIB/III double-blinded randomized controlled trial (RCT) started in January 2014 (https://clinicaltrials.gov, NCT01597518). This article describes the pathophysiological rationale, preclinical experience and design of the phase IIB/III RCT of Riluzole in Acute Spinal Cord Injury Study (RISCIS). OBJECTIVES: The primary objective of the trial is to evaluate the superiority of riluzole, at a dose of 100 mg BID in the first 24 h followed by 50 mg BID for the following 13 days post injury, compared with placebo in improving neurological motor outcomes in patients with C4-C8 level, International Standards for Neurological Classification of Spinal Cord Injury Examination (ISNCSCI) grade A, B or C acute (within 12 h post injury) SCI. SETTING: Acute trauma centers worldwideMethods:A double-blind, multi-center, placebo-controlled RCT will enroll 351 participants randomized 1:1 to riluzole and placebo. The primary end point is the change between 180 days and baseline in ISNCSCI Motor Score. This study has 90% power to detect a change of nine points in ISNCSCI Motor Score at one-sided α=0.025. RESULTS: Currently enrolling in 11 centers. CONCLUSION: This study will provide class I evidence regarding the safety and neuroprotective efficacy of riluzole in patients with acute cervical SCI.

[Outcome parameters for clinical studies: change of paradigm?]. / Klinische Studien, Outcome-Parameter. Ein Paradigma-Wechsel?

In the context of comparative clinical studies in surgery and in orthopedic surgery different therapies, techniques, or implants have been compared. Recent scientific publications mainly mention clinical outcome measurements such as fracture union, ROM, infection rate, as well as patient-related criteria such as pain or return to work (RTW) in order to evaluate the success of the treatment. It becomes obvious that more often than not the term "return to work" is not clearly defined. It is not mentioned who measures which criteria at which point in time, nor are part-time occupation, job change, or training on a new job part of the considerations.

[Norwegian breast cancer mortality rates and validity of Swedish mammographic studies]. / Norske tall for brystkreftdødelighet og validitet i svenske mammografistudier.

BACKGROUND: The claim that screening for breast cancer with mammography reduces breast cancer mortality is mainly based on the results from the Swedish two-county trial (WE study), where the effect was reported to be 30% for the age group 50-69 years. The two-county trial has recently been criticised for inadequate randomisation and for not following the study protocol. METHODS: We do some simple calculations to study whether the WE study is robust for an alternative statistical analysis. We use stage-specific breast cancer mortality in the Norwegian population as the baseline mortality rate in Sweden. Then we study the expected reduction in overall breast cancer mortality in the WE study while we vary the mortality rate in stage 1 and the stage distribution. RESULTS: We show that a 30% reduction in overall mortality rate is in conflict with observed decline in mortality in stage 1 and the expected stage migration. One either has to decrease mortality in stage 1, or increase the reduction of tumours with distant metastases, or both, to much higher levels than those reported in Sweden to get a 30% reduction in overall mortality of breast cancer. CONCLUSIONS: Our study adds further evidence to the proposal that the WE study is biased and not valid.

[A potential for prevention of bicycling-related head injuries]. / Potensial for forebygging av sykkelrelaterte hodeskader.

BACKGROUND: Bicycle helmets prevent head injury in bicycle riders. Still, only a portion of bicycle riders in Norway use bicycle helmets. The aim of this study was to estimate the number of head injuries among bicycle riders that might be prevented by increased helmet use in Norway. MATERIAL AND METHODS: We used data from the Norwegian National Injury Register for the years 1995 and 1996 to estimate the number of bicycle injuries in Norway. In order to estimate the number of bicycle users and helmet users in different age groups, we used data from earlier surveys of bicycle use. Data on the effectiveness of helmet promotion interventions have been obtained from a systematic review of the literature. RESULTS: The overall annual incidence rate was 92 injuries per 100,000 bicycle users. The incidence varied with age and was highest among children. If every rider used a helmet, about 1,600 head injuries would be avoided every year, of these, 800 among children aged 0-14. Currently available helmet promotion interventions may improve the use among children by about 40%, thus preventing about 1,500 head injuries over a period of three years. Successful helmet promotion interventions use a combination of health education and helmet distribution strategies. INTERPRETATIONS: There is a significant health improvement potential in promoting bicycle helmets in Norway by implementation of evaluated modes of intervention.

Population preventable fraction of bicycle related head injuries.

OBJECTIVE: This study analyzes the population attributable fraction (PAF) of bicycle head injuries due to non-helmet use. METHODS: The concept of the PAF and Levin's formula for its calculation were used to develop mathematical models for estimation of: (i) attributable fraction of bicycle related head injuries in the population due to non-helmet use, (ii) expected proportion of helmeted cases among all head injuries, and (iii) estimate of the helmet use rate in the population based on patient case information. The PAF was calculated for a sample of injuries from Stavanger, Norway. RESULTS: Levin's formula was used to calculate the PAF. Two additional mathematical models were developed for calculating the expected proportion of helmeted cases and the estimation of the helmet use rate in the population. The P calculation examples for all models were is shown. It was estimated that 133 out of 210 injuries could have been avoided in Stavanger between 1990 and 1996 if all children aged 0-14 had used helmets. CONCLUSIONS: If applied correctly, the PAF is a valid and useful indicator for the population effects of bicycle helmets. The models developed in this study may help to better interpret and predict the population effects of helmet promotion interventions.

Age gradient in the cost-effectiveness of bicycle helmets.

OBJECTIVES: This study analyzed the reduction in risk of head injuries associated with use of bicycle helmets among persons ages 3 to 70 and the cost-effectiveness of helmet use based on this estimated risk reduction. METHODS: To derive our cost-effectiveness estimates, we combined injury incidence data gathered through a detailed and comprehensive injury registration system in Norway, acute medical treatment cost information for the Norwegian health service, and information reported in the scientific literature regarding the health protective effects of helmet use. The analysis included all cases of head injuries reported through the registration system from 1990 through 1996. We performed an age-stratified analysis to determine the incidence of bicycle-related head injuries, the 5-year reduction in absolute risk of injury, the number needed to treat, and the cost-effectiveness of helmet use. To test the robustness of the findings to parameter assumptions, we performed sensitivity analysis. RESULTS: The risk of head injury was highest among children aged 5 to 16. The greatest reduction in absolute risk of head injury, 1.0 to 1.4% over 5 years estimated helmet lifetime, occurred among children who started using a helmet between the ages of 3 and 13. Estimates indicate that it would cost approximately U.S. $2,200 in bicycle helmet expenses to prevent any one upper head injury in children ages 3-13. In contrast, it would cost U.S. $10,000-25,000 to avoid a single injury among adults. CONCLUSIONS: Bicycle safety helmets appear to be several times more cost-effective for children than adults, primarily because of the higher risk of head injury among children. Programs aiming to increase helmet use should consider the differences in injury risk and cost-effectiveness among different age groups and target their efforts accordingly.

[Injuries connected to violence--an analysis of data from the injury registry]. / Voldsskader i Norge--en analyse av data fra personskaderegisteret.

BACKGROUND: Injury purposely inflicted by other persons is a potentially significant public health problem in Norway, and the size of the problem has received little attention. MATERIAL AND METHODS: We used data from the Norwegian National Injury Sample Registry from 1990-1997 and investigated occurrence of such injuries. RESULTS: A total of 9,649 injuries were included in this study, or 3.8 injuries per 1,000 person-years. Of these, 16% (0.6 per 1,000 person-years) required inpatient treatment. Injuries due to violence represented 2.4% of all injuries among women and 5.5% of all injuries among men. The incidence rate for men and women was highest in the age group 15-24 years. The incidence rate among men in this age group was 4-5 times the rate among women. Domestic violence caused at least 39% of injuries among women. Weekend injuries were overrepresented; about 64% of the injuries occurred from Friday to Sunday. INTERPRETATION: Figures represented in this study reveal only a portion of the problem of violent injuries. Spouse abuse, mental abuse, maltreatment, and sexual abuse without a physical injury are not represented in our data.

[School injuries among 7 to 15 years old children]. / Skader oppstått på skolen hos barn mellom sju og 15 år.

This study had two purposes: first, to describe the incidence and characteristics of school injuries among 7 to 15 year old pupils in Norway; second, to identify effective preventive measures. Data on school injuries were taken from the Norwegian National Injury Register (National Institute of Public Health) for the 1995-97 period, n = 2,975. The incidence of school injuries was 29 per 1,000 children-years. Over the nine-year age span, boys had a higher cumulative incidence (292 injuries per 1,000 boys) than girls (239 injuries per 1,000 girls); 1% of the injuries was categorized as severe. Among pupils aged 7-12, 34% of injuries occurred during sports activities; among the 13-15 age group, 60% were related to sports. A literature review was conducted in order to identify preventive measures shown to be effective in reducing school injuries. The databases used were Cochrane Library (issue 4, 1998), Medline (1966-98) and Embase (1980-98). However, no studies found in the literature had evaluated preventive measures. On the basis of our findings, we suggest that preventive measures should emphasise non-sport injuries among the younger pupils and sport injuries among the older pupils. Preventive measures should be evaluated.

Survival after hip fracture: short- and long-term excess mortality according to age and gender.

The purpose of this study was to analyze the excess mortality after hip fracture and to reveal whether, and eventually when, the excess mortality vanished in different groups of age and gender. A population-based, prospective, matched-pair, cohort study among persons 50 years of age and older was conducted involving 1338 female and 487 male hip fracture patients with 11 086 and 8141 controls respectively. Occurrence of hip fracture and mortality were recorded from 1986 until 1995. We studied the excess mortality of the hip fracture patients versus controls by using Kaplan-Meier curves and extended Cox regression with hip fracture (yes/no) as time-dependent covariate. The male hip fracture patients had higher mortality than the women the first year after the injury, irrespective of age, both in absolute terms (31% and 17% respectively) and relative to their age-matched controls. The relative risk (RR) of dying within 1 year for hip fracture patients versus controls was 3.3 (95% confidence interval (CI) 2.1-5.2) for women and 4.2 (95% CI 2.8-6.4) for men below 75 years of age. The corresponding figures for persons 85 years and older were 1.6 (95% CI 1.2-2.0) for women and 3.1 (95% CI 2.2-4.2) for men. All groups of age and gender, except women 85 years and older, had a large and significant excess mortality lasting for many years after the hip fracture - at least 5-6 years for women below 75 years of age (RR = 3.2, 95% CI 1.9-5.6). The excess mortality after hip fracture for women 85 years and older had vanished after 3 months (RR = 1.0, 95% CI 0.8-1.1). When referring to the excess mortality after hip fracture it is therefore necessary to specify sex, age and time since injury.

Moped injuries among adolescents: a significant forgotten problem?

OBJECTIVES: The study's objective is to investigate the size of the problem of moped injuries among children and young adults. DESIGN: A comprehensive prospective injury registration has been carried out at the Central Hospital and Emergency Clinic in Rogaland county in Norway. Out of this system we selected cases of traffic injuries occurring from 1990 to 1996 among a defined population aged 0-24 years and analyzed incidence of traffic injury by the type of transport of the victim. RESULTS: Moped injuries represented 9% (85 per 100,000 person-years) of all (hospitalized and non-hospitalized) traffic related injuries among people under 25 years and 44% of all cases among persons aged 16 and 17 years. Moped injuries represented 13% of hospitalized cases altogether and 50% of hospitalized traffic injuries among persons aged 16 and 17 years. The overall male:female moped injury incidence rate ratio was 2.7 (95% CI 2.0-3.7). Police records captured only 40% of the moped injuries overall. 43% of moped injuries were lone accidents and 40% occurred in a moped-car collision. CONCLUSION: Moped injuries represent a major source of serious traffic injury among older children. This risk seems to be partially overlooked. Significantly higher attention seems to be warranted to reduce the risk of moped injury in populations where the moped is a popular means of transport among older children.

[Injuries among children treated at emergency medical centers and in hospitals 1990-97]. / Skader blant barn behandlet ved legevakt og i sykehus 1990-97.

The Norwegian National Injury Sample Registry is a prospective case register of injuries occurring in the defined population of four cities. All injuries treated in hospitals and emergency wards are recorded in the registry. We used data from this registry to provide an epidemiologic overview of the incidence of injuries among children aged 0-14 in Norway. The study population consisted of approximately 61,500 children annually or approximately 492,000 children-years over the 1990-97 period. A total of 57,000 injuries were registered, or 116 injuries per 1,000 children-years. Approximately 2% of the injuries were classified as severe. 36% of all injuries occurred at home, 13% during sport activities and 13% were caused by accidents at school. Incidence was higher among boys than girls in all age groups. During their first 15 years of life, boys sustained on average 2.0 injuries and girls 1.5 injuries. Data from the Norwegian National Sample Injury Registry may provide useful information for prevention of and research on injuries among children.

Occurrence and trends in ski injuries in Norway.

OBJECTIVES: To provide an overview of ski injuries in Norway and to describe the changes between 1990 and 1996. METHODS: All ski injuries (7966) treated at four hospitals providing health care to a defined population of about 11% of the Norwegian population were registered prospectively from 1990 to 1996. For this study, 6462 injuries sustained in cross country skiing, downhill skiing, telemark skiing, and snowboarding were selected for further analysis. RESULTS: The relative distribution of ski injuries by type of skiing changed significantly from 1990 to 1996 (p<0.001). Injuries from snowboarding showed the highest relative increase, and those sustained during downhill skiing showed a decline. The proportion of fractures in all types of skiing increased during the study period (p=0.001). The proportion of injuries to knee/lower leg decreased and the proportion to the forearm/wrist/hand increased during the study period (p=0.03). The mean age of the injured skiers differed significantly among the different types of skiing activity (p<0.001): cross country skiers were the oldest followed by telemark skiers, downhill skiers, and snowboarders. CONCLUSIONS: Ski injury surveillance results in early detection of changes in temporal injury trends, allowing timely adjustment of injury prevention strategies. Injuries from snowboarding are on the increase in Norway, warranting more effective injury prevention measures.

Fractures among children: incidence and impact on daily activities.

OBJECTIVES: The study's objective was to examine incidence of fractures and associated activity restriction among children aged 0-12 years. DESIGN: Injuries were prospectively recorded over the four year period from 1992-95 in a cohort of children aged 0-12 years, representing 193,540 children years. Information about length and extent of activity restriction was collected from parents by a mailed questionnaire for a subsample of 192 children with a fracture. RESULTS: A total of 2477 fractures occurred in the study population (128 per 10,000 children annually). The incidence increased linearly with age, by 14 cases per 10,000 children year for each year of age. Boys and girls showed similar patterns of fracture occurrence. There was a significant difference in length of activity restrictions for different types of fractures. The mean and 95% confidence interval (CI) of activity restricted days for leg fractures were 26 (95% CI 7 to 45) days, for arm fractures, 14 (95% CI 8 to 20) days, and for other fractures, 5 (95% CI 1 to 8) days. Arm fractures represented 66% of the cases and 62% of the activity restricted days; leg fractures 19% of cases and 33% of all activity restricted days; and other fractures 16% of the cases but only 5% of the activity restricted days in this population. CONCLUSION: The incidence of fractures increases in childhood. Different types of fractures among children cause different amounts of activity restriction.

Population-based study of unintentional injuries in the home.

There is little current understanding of the risk for occurrence of unintentional injury in the home. The authors estimated the incidence of unintentional home injuries for an entire community, adjusting for actual time spent awake in the home and, in addition, analyzed the costs of these injuries. Cases of unintentional home injuries occurring from 1990 to 1993 among the residents of Stavanger, Norway (approximately 100,000 population) were identified through a prospective, ongoing injury registration system. Age- and sex-specific per-population incidence and incidence per time spent awake at home were estimated. Time exposure data for adults were obtained from the Norwegian Time Budget Survey and were estimated directly for children. The cost of injuries was estimated based on a random sample of 289 patients. A total of 8,580 persons received medical treatment for unintentional injuries in the home (22.0 per 1,000 population annually, 71.9 per 10 million hours awake at home). The per-population incidence was highest among children age 6 years or younger and among people aged 65 or older (51.0 and 32.7 respectively, per 1,000 population annually). The high population incidence for children was not accounted for by time spent awake at home. For people aged 65-74 years, however, increased incidence was primarily a function of greater time spent awake at home. For persons aged 75 years or older, the high population incidence was due to both high exposure-adjusted incidence and greater time spent awake at home. The male-female ratio of age-standardized per-population incidence was 1.07 (95% confidence interval 1.04-1.10), and the ratio of age-standardized exposure-adjusted incidence was 1.22 (95% confidence interval 1.17-1.28). The estimated cost (direct and indirect) per injury was $1,300 during the first year after injury. Persons aged 75 years or older accounted for 12% of the injuries but 50% of the total medical costs.

The SF-36 health survey: a valid measure of changes in health status after injury.

OBJECTIVES: The aim of this study is to evaluate the criterion validity and responsiveness to changes over time of the Medical Outcome Study Short Form 36 (MOS SF-36) measure. METHODS: A consecutive sample of 775 patients 16 to 78 years treated for an unintentional injury at the hospital or emergency clinic in Drammen, Norway was selected for the study. Data about activity restrictions and health status measured by SF-36 were obtained by a postal questionnaire 6-10 weeks after the injury. A follow up survey was sent 24-28 weeks later to all who reported activity restriction at the time of the first survey. Fifty two of these replied (63%). RESULTS: 469 patients responded to the survey questionnaire and of these, 82 experienced some restriction of activity. These scored lower (p < 0.01) on all eight SF-36 health dimensions (physical functioning, social functioning, role limitation (physical), role limitation (emotional), bodily pain, mental health, vitality, and general health) than the 387 patients without activity restriction. Scores on physical functioning, social functioning, role limitation (physical), bodily pain, and vitality significant improved (p < 0.01) among the 52 patients who were followed up. Scores on the other dimensions, however, showed no significant changes over time. CONCLUSION: The MOS SF-36 appears to be a valid instrument, responsive to changes in health status over time among unintentionally injured adult people. Thus it may be possible to use the SF-36 to describe changes in health due to injury. The applicability of this or similar measures for injured children remains to be established.

Access to war weapons and injury prevention activities among children in Croatia.

To investigate the exposure of children in Croatia to war weapons, we surveyed random samples of children (n=986) aged 11 to 16 years and of parents (1469) of children aged 7 to 16 years in April 1994 in four war-affected districts in Croatia. The children's survey indicated that 57% of the boys and 36% of the girls had access to weapons at home, at some other place, or at both. Eighteen percent of the boys and 5% of the girls reported playing with weapons. The parents' survey showed that 68% of the households possessed weapons, with 19% of the children having access to weapons at home. Influenced by preliminary findings of these surveys, the Croatian government modified its national campaign (one partially supported by international aid) to prevent war-related injuries among children. This study demonstrates the feasibility of scientific evaluation of humanitarian aid programs.

Home injuries among adults in Stavanger, Norway.

Norwegian injury register data were analyzed to examine unintentional home injuries among persons ages 25 to 64 years residing in Stavanger, Norway, during 1992. A total of 782 persons received medical treatment for injury during 1992 (15.4 per 1000 population). The incidence was similar for males and females (15.8 and 14.9 per 1000 population); however, the exposure-specific injury rate was significantly higher for males (6.0 vs 4.1 per 1 million person-hours). This difference was entirely due to the much higher injury rate among males aged 25 to 44 years. The estimated first year cost (direct and indirect) per injury was $2700. Home injuries among adults appear to be an overlooked public health problem that warrants increased attention.