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.

How safe are day care centers? Day care versus home injuries among children in Norway.

OBJECTIVES: The study's objective was to examine and compare injury rates of children ages 6 months to 6 years in day care centers and homes. More specifically, we tested the hypothesis that the injury rate is lower in day care centers than at homes, as suggested by previous studies. METHODS: A comprehensive prospective injury registration was carried out in Stavanger, Norway, during 1992. We obtained data from this system to identify injuries occurring in day care centers, homes, and other places during 1992. Exposure-adjusted incidence rates were calculated to compare the risk of injury at day care centers, homes, and other places. We also obtained data from medical records on use and costs of medical care. In addition, a parent questionnaire was developed and used to gather data on the amount of injury-related restricted activity. RESULTS: Among 9454 children ages 6 months to 6 years in Stavanger, 770 injuries occurred during 1992: 96 in day care centers, 472 at home, and 202 at other places. For children ages 6 months to 2 years, the rate of injuries was significantly lower in day care centers than at home (1.2 and 2.5, respectively, per 100,000 children-hours), but for children ages 3 to 6, the rates of injuries were similar in day care centers and at home (1.3 and 1.5, respectively, per 100,000 children-hours). The great majority of children attending day care centers were from 3 to 6 years of age. No significant differences were found in the severity of the injuries. CONCLUSIONS: For children ages 3 to 6 years, which included most of the children attending day care centers in Stavanger, Norway, day care centers were not found to be safer than homes. We think continuing attention should be paid to injury control in day care centers.

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.

Prostaglandin F2 alpha, progesterone and estradiol concentrations in human follicular fluid and their relation to success of in vitro fertilization.

Prostaglandin F2 alpha (PGF2 alpha), progesterone (P4) and estradiol-17 beta (E2) in follicular fluid were measured by radioimmunoassay in patients undergoing in vitro fertilization and embryo transfer. Follicular growth was induced using clomiphene citrate-hMG-hCG (15 patients) and FSH-hMG-hCG (4 patients). There was no significant difference in follicular fluid PGF2 alpha and P4 concentrations relative to oocyte maturity as assessed morphologically. The highest PGF2 alpha concentration was found in fluid from FSH-hMG-hCG cycles where fertilization occurred. The value is significantly higher (p less than 0.002) than in fluid from clomiphene-hMG-hCG cycles whether fertilization took place or not. There was no significant difference in P4 and E2 levels in relation to the type of ovarian induction or success in fertilization. Positive correlation between P4 and E2 in follicular fluid was found (r = 0.404). The positive correlation between total dose of hMG given to the patients and PGF2 alpha concentration in their preovulatory follicular fluid (r = 0.434) suggests that PGF2 alpha is secreted locally as the result of hMG and hCG stimulation. It is proposed that PGF2 alpha could be a biochemical marker for assessing the success of in vitro fertilization.

Protein concentration in pre-ovulatory follicular fluid related to ovarian stimulation.

Sixty follicular fluids obtained from 26 women with either clomiphene citrate and human menopausal gonadotropins (hMG) or hMG-induced ovulation were analyzed for the contents of total proteins, fibrinogen, plasminogen, antithrombin III, ceruloplasmin, alpha-2 macroglobulin, alpha-1 antitrypsin and immunoglobulins (IgG, IgA, IgM). Concentrations of these proteins was correlated to the type of ovarian follicle growth induction. Follicular fluids from patients stimulated with clomiphene citrate-hMG contained significantly higher concentrations of ceruloplasmin than those treated with hMG alone. No significant differences in the concentrations of other proteins were noted between the two types of ovarian induction. A multivariate data analysis resulted in three Varimax factors (VRX I) suggesting that proteins with antiprotease activity in the follicular fluid may play a role in human follicle maturation. Follicular fluid Ig may reflect the degree of follicular wall permeability under hMG treatment. Accordingly, it may be assumed that a combination of different proteins described by VRX factors could be used for evaluation of ovarian stimulation.

[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.

[Immunologic and respiratory findings in workers on a pig farm]. / Imunoloski i respiratorni nalazi radnika u svinjogojstvu.

The prevalence of respiratory symptoms and ventilatory capacity in relation to immunological status were studied in 32 swine workers and in 39 controls. A large number of swine workers reacted to antigen of swine hair (34%) and to swine confinement antigen (28%) but also to other antigens such as animal food (78%), and corn flour (37%). Control workers showed comparable prevalence in their reaction to these antigens (17%, 25%, 51%, 25%). Increased IgE serum level was determined in three swine workers (9.4%) and in one control worker (2.6%). Swine workers with positive skin tests demonstrated significantly larger acute reductions in FEF50 and FEF25 than those with negative skin tests (P less than 0.01). The ventilatory capacity data measured before shift in swine workers with positive skin tests were significantly lower than the predicted normal values. Swine confinement antigen caused a dose-related contraction of guinea pig smooth muscle in vitro. Our data indicate that non-immunological reactions may be partly responsible for the acute and/or chronic changes in respiratory function.

[Varicosities of the lower extremities in workers in positions requiring continuous standing or sitting positions]. / Varikoziteti donjih ekstremiteta u radnika na poslovima koji zahtijevaju kontinuirani stojeci ili sjedeci polozaj.

An epidemiological study of the prevalence of varicose veins of lower extremities was carried out in an industrial population of 434 men and 345 women. A statistically significant (p less than 0.05) association between the varicose disease and duration of work was found in all groups of workers, except for women sitting at work. Decrease in the prevalence of varicose veins after 20 years of employment may be explained at least partly, by the factor of self-selection in the industry. However, there was no difference in the prevalence of varicose veins between workers standing and those sitting at work.

[Ventilatory capacity and respiratory symptoms in hemp-processing workers]. / Ventilacijski kapacitet i respiratorni simptomi radnika na preradi konoplje.

The prevalence of respiratory symptoms and changes in ventilatory capacity were studied in 84 female (mills A and B) and 27 male hemp workers employed in textile mills. Forty-nine women and 30 men from a non-dusty industry served as controls. A significantly higher prevalence of almost all chronic respiratory symptoms was found in exposed female workers compared to controls. For men the differences were significant for nasal catarrh and sinusitis. A high prevalence of byssinosis was found among female workers in both mills (A = 47.8%); B = 57.9%) as well as in male workers (66.7%). Statistically significant acute across work shift reductions in ventilatory capacity were found for all measurements in female and male hemp workers (P greater than 0.01) varying from 7.1% for FEV1 to 15.1% for FEF50. Measured Monday baseline values before the work shift were significantly lower than expected for hemp workers being particularly reduced for FEF25 and FEF50. The data suggest that exposure to hemp dust is a major risk factor for the development of occupational lung disease.

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.

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.

[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.

Time variations in injury incidence.

STUDY OBJECTIVE: to present time variations in the incidence of injuries on a community level. POPULATION AND METHODS: all injuries which occurred in a defined population of the municipality of Harstad were registered prospectively from 1 January 1986 to 31 December 1991. Variations over time in monthly incidence of seven types of injuries (home, traffic, street, sports, work, other, unknown) were analysed by the Autoregressive Integrated Moving Average Analysis (ARIMA). RESULTS: a total of 9,685 injuries was registered during the six year follow-up period. No significant secular trend was observed for any of the analysed types of injuries. Series of monthly incidence of traffic, street, and sports injuries showed seasonal-dependent variations. Incidence of traffic injuries was highest during the summer months, while incidence of sports and street injuries was highest during the winter months. CONCLUSIONS: both the existence of seasonal dependency in injury incidence and the relatively high random variations in monthly injury incidence imply that evaluation of community based injury control programmes should include incidence during at least a one year period before the intervention has started.

[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.

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.

[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.

["The patient slipped on the ice...". Non-traffic related fractures among pedestrians, occurrence and seasonal variations]. / "Pasienten gled på hålken...". Ikke-trafikkrelaterte bruddskader blant fotgjengere, forekomst og årstidsvariasjoner.

The epidemiology of non-traffic-related fractures among pedestrians in three Norwegian towns (Drammen, Harstad and Stavanger, 515,602 person years) during the period 1 January 1988 to 31 December 1990 was studied on the basis of data form The Norwegian Injury Register. 1,104 such fractures occurred during the study period (21 per 10,000). The incidence increased with age from 12 per 10,000 in the age group < or = 14 years, to 47 per 10,000 in the group > or = 65 years. 57% of all patients with fractures were under the age of 65. Higher incidence during the winter months was observed in all three towns during the whole period. The increase occurred in the age groups 25-64 and > or = 65 years, both in males and females, but not in the age groups < or = 14 or 15-24 years. In 1990 we obtained more accurate information on the injury incident. 39% of all the fractures were caused by slipping on ice or snow. 45% of these were fractures of the elbow or lower arm. There seems to be a substantial potential for targeted preventive measures.

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.

Cycling to school--a significant health risk?

OBJECTIVES: The risk of injury to children riding bicycles has been previously documented. However, the specific risk arising from the use of bicycles as a mode of transportation to and from school is unknown. This study examines the incidence of bicycle related injuries among school age children. METHODS: A comprehensive prospective injury registration system was established in Stavanger, Norway. Data were obtained from this system to identify bicycle related injuries occurring from 1990-3 to children aged 10-15. The incidence of injuries was computed for two groups of children: (1) children cycling to school and (2) children cycling for other purposes. RESULTS: 352 children received medical treatment for bicycle related injuries, 12.6/1000 bicycle riders; 108 (30%) of the 352 children were injured while cycling to or from school. The incidence of bicycle related injuries was significantly higher for boys than girls. Seventy seven per cent of the injuries occurred in a non-collision accident, 9% in a collision with another bicycle, and 14% in a collision with a motor vehicle. Twenty per cent of the injured children sustained upper head injuries and 13% required inpatient treatment. Average maximum abbreviated injury severity (MAIS) score was similar for the injuries sustained during travel to/from school and other injuries. CONCLUSIONS: Bicycle related injuries occurring during travel to or from school are a significant contributor to the total incidence of bicycle related injuries. Increased attention among parents, school officials, public health officials, and medical professionals should be paid to this health risk.

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.