Ladders: accidents waiting to happen.

OBJECTIVES: To examine the nature, severity and outcomes of injuries sustained from ladder falls. DESIGN: Retrospective survey of medical records. PATIENTS AND SETTING: Patients who presented after a fall from a ladder to the emergency department of a tertiary hospital in Melbourne, Victoria, between January 1994 and December 1997. MAIN OUTCOME MEASURES: Demographic characteristics; height and mechanism of fall; injury site and Injury Severity Score (ISS); rate of hospital admissions. RESULTS: 163 patients presented after ladder falls. They were aged 2.5 to 86 years (mean age, 48 years); 83% were male, and 78% were injured in non-occupational settings. Almost half the accidents (43%) were caused by ladder instability (ladder sliding from position or tilting sideways). Most patients had mild or moderate injuries (usually of the extremities), but 13% had an ISS > or = 16 (indicating severe trauma), usually with head, chest or spinal injuries; 42% were admitted to hospital. Multiple regression analyses showed that ISS increased signficantly with height of fall and age (P< 0.05 for both), although a substantial amount of variation was not attributable to these variables. Likelihood of hospital admission increased linearly with increasing ISS to an ISS of 8 and remained high thereafter. CONCLUSIONS: Ladder falls resulted in significant morbidity, with men undertaking non-occupational activities comprising most of those injured. New strategies to encourage safe ladder use are needed.

Tests against qualitative interaction: exact critical values and robust tests.

Consider a study to evaluate treatment A with a placebo in two or more groups of patients. If treatment A is beneficial to one group of patients and harmful to another, then we say that there is qualitative interaction or crossover interaction between patient groups and the treatments. Gail and Simon (1985, Biometrics 41, 361-372) developed a large-sample procedure for this testing problem. Their test has received favorable coverage in the literature. In this article, we obtain corresponding exact finite sample results for normal error distribution and provide a table of critical values. The test statistic is similar to the familiar F-ratio, and its p-value is equal to a weighted sum of tail areas of F-distributions. The computations to implement this are simple. A simulation study shows that the exact critical values provided here for normal error distribution are preferable to the asymptotic critical values for a wide range of error distributions. We also develop tests that are power robust against long-tailed error distributions. Our robust test uses M-estimators instead of the least squares estimators. We show that the efficiency robustness of the M-estimator translates to power robustness of the corresponding test. Therefore, our robust tests are better if outliers are expected. A simulation study illustrates the substantial power advantages of our robust tests.

Epileptology of the first-seizure presentation: a clinical, electroencephalographic, and magnetic resonance imaging study of 300 consecutive patients.

BACKGROUND: Prognosis and treatment of the first seizure depends on identification of a specific epilepsy syndrome, yet patients with first seizures are generally regarded as a homogeneous group. We studied whether it is possible to diagnose specific epilepsy syndromes promptly by use of standard clinical methods, electroencephalography (EEG) and magnetic resonance imaging (MRI). METHODS: 300 consecutive adults and children presented with unexplained seizures. We systematically collected clinical data from patients and witnesses, and attempted to obtain an EEG within 24 h of the seizure. Where the EEG was negative, a sleep-deprived EEG was done. MRI was done electively. FINDINGS: A generalised or partial epilepsy syndrome was clinically diagnosed in 141 (47%) patients. Subsequent analysis showed that only three of these clinical diagnoses were incorrect. Addition of the EEG data enabled us to diagnose an epilepsy syndrome in 232 (77%) patients. EEG within 24 h was more useful in diagnosis of epileptiform abnormalities than later EEG (51 vs 34%). Neuroimaging showed 38 epileptogenic lesions, including 17 tumours. There were no lesions in patients for whom generalised epilepsy was confirmed by EEG. Our final diagnoses were: generalised epilepsy (23% of patients); partial epilepsy (58%); and unclassified (19%). INTERPRETATION: An epilepsy syndrome can be diagnosed in most first-seizure patients. Ideally, an EEG should be obtained within 24 h of the seizure followed by a sleep deprived EEG if necessary. MRI aids diagnosis and should be done for all patients except for those with idiopathic generalised epilepsies and for children with benign rolandic epilepsy.

On tests against one-sided hypotheses in some generalized linear models.

One-sided hypotheses arise naturally in many situations. When testing against such hypotheses, it is desirable to take the available one-sided information into account, rather than simply applying a two-sided test. What we expect to gain by applying a one-sided test instead of a two-sided test is an increase in the power of the test. We consider various tests of one-sided hypotheses in a class of models that includes generalized linear and Cox regression models. The tests are likelihood ratio, Wald, score, generalized distance, and a Pearson chi-square. It is shown that these test statistics are asymptomatically equivalent in terms of local power; this is a generalization of the well-known corresponding result for two-sided alternatives. Two examples are also discussed. They are on (1) testing for interaction in binomial response models, and (2) comparison of treatments with ordinal categorical responses.

Epidermal growth factor alters the electrolyte profile of lactating ewes (Ovis aries).

1. Lactating ewes were treated with mouse epidermal growth factor (EGF) at a dose rate of 0.5 mg/day for 4 days and its effects on the electrolyte profile were observed. 2. There was no effect of EGF on plasma concentrations of sodium or potassium, although urinary and total (in urine and milk) losses of both were reduced. 3. EGF-induced hypocalcaemia was associated with reduced milk calcium secretion and increased urinary calcium excretion whereas EGF-induced hypermagnesaemia was associated with reduced urinary and total magnesium losses. 4. Glomerular filtration rate was reduced during EGF infusion. 5. Chronic intravenous EGF infusion affects the electrolyte profile by altering electrolyte secretion by the mammary gland and renal electrolyte excretion.

Fluid balance, electrolyte profiles and plasma parathyroid hormone concentrations in ewes treated with epidermal growth factor.

The infusion of low doses of epidermal growth factor (EGF) into lactating ewes stimulates water intake and urine volume. The plasma concentrations and daily output of various electrolytes in milk and urine are also affected. We have investigated this further by recording the effects of EGF infusion on fluid balance, electrolyte profiles and plasma concentrations of glucose and parathyroid hormone (PTH) in non-pregnant, non-lactating ewes. Twenty-four animals (n = 8 per group) received infusions of 100 ml saline/day into the jugular vein for 10 days (days 1-10) followed by EGF at a dose rate of either 1 (low dose), 5 (medium dose) or 10 (high dose) micrograms/kg liveweight per day in 100 ml saline for 5 days (days 11-15). All ewes then received an infusion of 100 ml saline/day for 10 days (days 16-25). Most plasma and urine samples had undetectable concentrations of EGF-immunoreactive material during the periods of saline infusion. During EGF infusion, the highest amounts of EGF infusate excreted in urine were 1.6, 5.9 and 5.6% for ewes in low, medium and high dose groups respectively. Water intake increased by 17% (0.5 kg), 88% (2.5 kg) and 89% (2.3 kg) and urine volume increased by 29% (0.5 kg), 108% (2.2 kg) and 134% (2.1 kg) for the three groups respectively. Fluid balance and feed intake were not affected by EGF infusion, but the output of faecal dry matter was reduced in ewes receiving the two higher doses of EGF. All levels of EGF resulted in hypocalcaemia, increased plasma PTH concentrations and hypermagnesaemia. There was no effect of EGF on plasma concentrations of K+ and glucose or on daily urinary excretion of K+ and Mg2+. The only response to the low dose was a reduced plasma concentration of Na+ and an increased daily urinary urate excretion. The two higher doses increased the daily urinary excretion of Na+, PO4(3-) and urate, but had no effect on the respective concentrations in plasma. Urinary Ca2+ excretion was reduced only during infusion of the medium dose of EGF. The responses of most variables were similar during infusion of the medium and high doses of EGF. All three doses of EGF induced polydipsic and diuretic responses in ewes, and infusions of 5-10 micrograms EGF/kg liveweight per day affected renal excretion of Ca2+, Na+ and PO4(3-). We interpret the responses of the kidney and plasma PTH concentrations as a means of maintaining the homeostasis of plasma profiles of electrolytes.

Lack of effect of epidermal growth factor treatment in late-pregnant ewes on subsequent lactation.

Twin-bearing ewes were treated with epidermal growth factor (EGF) to determine its effect on mammogenesis and resultant milk production and composition. The EGF was infused intravenously at a dose rate of 0.5 mg/d in 300 ml saline between days 117 and 139 of gestation; control animals received placebo infusions of saline. All animals then received continuous infusions of 300 ml/d saline on days 139-144. Following parturition 1-5 d later, ewes were milked by hand for 10 d and thereafter were machine-milked until day 16 of lactation. At this level of treatment, EGF was not detected in the circulation during infusion and feed intake was not affected. All ewes gave birth to healthy twin lambs. There were no effects of EGF on birth weights of lambs, live weights of ewes or lengths of gestation. An EGF-immunoreactive material was detected in the mammary secretions of control ewes at a mean concentration of 2 micrograms/l on day 1 of lactation. Two ewes had detectable levels on day 2, but none was found in the milk thereafter. In the EGF-infused group, concentrations of EGF in colostrum were approximately 10 times higher than in the control ewes on day 1 of lactation and EGF was detected in mammary secretions on day 2 but not in subsequent milk samples. A range of 0.3-0.5% of the EGF infused appeared in mammary secretions over the first 2 d of lactation. No other differences were observed for colostrum composition, subsequent milk yield or composition between the two groups of ewes indicating that mammary gland development and function were unaffected. The levels of EGF observed in the mammary secretions of treated and control ewes indicate that the mammary glands accumulate and store EGF in the pre partum period.

Blood pressure, salt appetite and mortality of genetically hypertensive and normotensive rats maintained on high and low salt diets from weaning.

1. Blood pressure, bodyweight, saline preference and mortality rate were examined in spontaneously hypertensive rats (SHR) of the Okamoto strain and normotensive control Wistar-Kyoto (WKY) rats maintained on low (0.1% NaCl w/w), control (0.8% w/w) and high (3% w/w) salt diets from weaning until 6 months of age. 2. The growth rate of SHR on high salt diet was not significantly different from that on control diet but SHR maintained on a low salt diet exhibited a markedly reduced growth rate. While the growth rate of WKY on low salt diet was not significantly different from that on control diet, the bodyweights of WKY on high salt diet were significantly greater than those of animals on control diet. 3. While low salt diet markedly attenuated the development of hypertension in the SHR, high salt diet significantly exacerbated the blood pressure of this strain. Neither high nor low salt diet altered the blood pressure of WKY. 4. SHR on high and low salt diets had an increased mortality rate compared with SHR on control salt diet but these differences were of slight statistical significance. Conversely, WKY on all three diets exhibited similar mortalities over the 6-month observation period. There were no significant differences in mortalities between SHR and WKY on any diet. 5. The preference for 0.9% saline, when offered as a choice with water, was not significantly different between SHR on the different diets. WKY on high salt diet, however, exhibited a significantly reduced preference for saline over the 10-day test period compared with animals on control or low salt diet. 6. Thus dietary salt modulates the hypertension of SHR but not the blood pressure of WKY. SHR would appear to require more dietary sodium for normal growth and perhaps full expression of its hypertension. The higher and lower blood pressures of the SHR on high and low salt diet, respectively, were associated with increased mortality, which was a trend not seen in the WKY.

High salt diet decreases longevity in the spontaneously hypertensive rat.

1. Blood pressure, body weight and mortality rate were examined in female spontaneously hypertensive rats (SHR) of the Okamoto strain maintained on a lifelong high (5% NaCl w/w) or low (0.1% NaCl w/w) salt diet. 2. A high salt diet increased mortality and decreased body weight in SHR, but failed to significantly alter blood pressure up to 24 months of age. 3. Hence, a low salt diet does not appear to be a long-term risk factor and may protect the SHR from cardiovascular accidents.