Statistics notes. Interaction 2: Compare effect sizes not P values.
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Analysis of Variance↗
Biomedical subjects
J N Matthews
Publications and source records attributed to J N Matthews.
Statistics notes. Interaction 1: Heterogeneity of effects.
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Clinical Trials as Topic↗
Is delayed surgery really better for congenital diaphragmatic hernia?: a prospective randomized clinical trial.
Delayed surgery has become widely accepted in the management of congenital diaphragmatic hernia after comparing outcomes only with historical retrospective controls. It was the aim of this study to compare early and delayed hernia repair in a randomized prospective clinical trial. Fifty-four infants were randomized to receive either early repair (within 4 hours of admission) or delayed repair (more than 24 hours after birth). The survival rate was higher for the delayed group (57% v 46%), but the difference was not significant (difference: -11; 95% confidence limits: -37.5, 15.5). There were no significant differences between the two groups with respect to length of hospital stay, ventilator dependency, or survival time. Recorded preoperative risk factors were similar for the two groups. Eight infants in the delayed repair group died without having undergone surgery. The optimum time for surgery still needs clarification.
Blood Gas Analysis↗
Measuring blood glucose in neonatal units: how does hemocue compare?
Rapid and reliable determination of blood glucose concentration is essential during the neonatal period to prevent adverse neurodevelopmental outcome from hypoglycaemia. Despite their unreliability, reagent strip methods continue to be used extensively in neonatal nurseries due to their rapidity and convenience. Recently, a new portable laboratory standard technique has been introduced (HemoCue B-Glucose system) for whole blood glucose determination. It is particularly suitable for near-patient testing in neonatal units. This new method, as well as other established methods of whole blood (Yellow Springs Instrument (YSI) and a hexokinase method on Cobas Bio), and plasma (Kodak Ektachem) glucose measurement, were therefore evaluated for their accuracy and concordance of measurements taken in the neonatal period. There were substantial discrepancies among the four methods of glucose measurement with wide limits of agreement between these methods. The glucose concentrations measured by HemoCue and YSI (n = 206), HemoCue and hexokinase (n = 113), HemoCue and plasma glucose on Ektachem (n = 69) and hexokinase and Ektachem (n = 66) were likely to differ by -29 to +61%, -23 to +56%, -36 to +65%, and -19 to +30%, respectively. Even the laboratory methods of blood glucose determination, therefore, can not be used interchangeably. Using a model based approach, the probabilities of "discordant" classification as hypo- or normo-glycaemia were estimated to be 6.8%, 6.5%, and 7.1% between HemoCue and YSI, HemoCue and hexokinase on Cobas Bio, and HemoCue and Ektachem analysers, respectively. In view of these low probabilities of discordant classification with other glucose analysers, the HemoCue system may offer a reasonable compromise between bedside and laboratory blood glucose estimations in neonates.
Blood Glucose↗
A comparison of three brands of polysulfone membranes.
A prospective clinical crossover study comparing the functional performance and biocompatibility of three brands of polysulfone membranes (Fresenius Polysultone (Fresenius Ag, Bad Homburg, Germany), Polyphen (Minntech Corp., Minneapolis, MN), and Biosulfane (WR Grace Inc., Danvers, MA)) incorporated in ethylene oxide-sterilized dialyzers of comparable surface area (1.3 to 1.35 m2) was undertaken. The clearance of small molecules by each membrane was comparable. Plasma levels of beta 2 microglobulin fell to 49.9% of pretreatment values by 210 min when using the Fresenius Polysulfone membrane, 60.2% with the Polyphen membrane, and 63.1% with the Biosulfane membrane. The reduction achieved by the Fresenius Polysulfone membrane was superior (P = 0.003). The plasma reductions were associated with the recovery of 195 mg beta 2 microglobulin from the dialysate for the Fresenius Polysulfone membrane and 158 mg for the Polyphen membrane, but no beta 2 microglobulin was recovered from the dialysate with the Biosulfane membrane. The dialysate collected with the Fresenius Polysulfone membrane also contained a mean of 6853 mg of total protein, compared with 5490 mg with the Polyphen membrane and 8422 mg with the Biosulfane (P = 0.04) membrane. The neutropenia was slight and independent of membrane brand, as were the changes in C3a des arg and SC5b-9 complement components. The reduction in platelet counts was higher for the Biosulfane membrane than for the other brands (P = 0.003). This study indicates that whereas the polymer base of the membrane is the same, its production and subsequent handling during dialyzer production induce changes that attain statistical significance, most notably in the way that the membrane removes beta 2 microglobulin and interacts with proteins. The differences observed are a consequence of the different alloying polymers used during manufacture and, consequently, the membranes cannot be considered equivalent.
Adult↗
Reduced experimental contact sensitivity in squamous cell but not basal cell carcinomas of skin.
Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) show clinical and epidemiological differences not accounted for by different ultraviolet radiation exposure. We have studied experimentally induced contact sensitivity to dinitrochlorobenzene by measuring increases in skin-fold thickness. Patients (n = 37) with squamous tumours had impaired responses compared with controls (33) and patients with BCCs (31) (mean increase 4.5 vs 7.8 and 8.6 mm, respectively; p = 0.002). This diminished immunological response may be causally related to the development of SCC. Because glutathione S-transferase (GST) metabolises dinitrochlorobenzene and polymorphisms of GST are associated with multiple skin tumours, variations in GST may underlie these differences.
Basal Cell Carcinoma↗
Small clinical trials: are they all bad?
Statisticians have long argued that randomized controlled trials should be sufficiently large to achieve their purpose, and for common diseases with major public health implications this has brought many benefits. However, there are many instances where it is unrealistic to expect clinicians to provide the information on which sample sizes are calculated and undue emphasis on trial size can be counterproductive. Examples of such trials are given and some general issues discussed, including the unhelpful contribution of hypothesis testing, the need for replication and the role of the statistician.
Humans↗
Relation between size of skin excision, wound, and specimen.
BACKGROUND: Skin wounds differ in shape and size compared with the planned excision, and skin shrinks after excision and fixation. OBJECTIVE: This study was designed to quantify and to analyze the differences between the size and shape of the planned excision, wound, and specimen. METHODS: Eighty-six patients with 93 benign or malignant skin tumors were prospectively studied. Length and width measurements were made of the lesion, planned surgical excision, postexcision wound, and prefixation and postfixation specimens. The results were analyzed to identify the effects of patient age and sex, and lesion type and site. RESULTS: Wound size was larger than planned excision size in 90% of wounds, and this effect was greatest in young patients and at trunk and limb sites. Excision and fixation caused the specimens to shrink so that the postfixation area was on average 48% of the planned excision area; benign tumors shrank more than malignant tumors. CONCLUSION: Significant differences among planned excision, wound, and specimen sizes are influenced by patient age and by lesion site and type. These results demonstrate that wound size is not equivalent to tumor size, a conclusion often made in Mohs surgery. Furthermore, assessment of tumor clearance margins from fixed tissue does not reflect in vivo clearance margins.
Adolescent↗
Intrathecal fentanyl for post-thoracotomy pain.
This double-blind, placebo-controlled study investigated the efficacy of intermittent doses of intrathecal fentanyl in 30 patients undergoing thoracotomy. They were allocated randomly to three groups, two of which had microspinal catheters inserted into the lumbar subarachnoid space at the end of surgery; the third group acted as a control. Intrathecal fentanyl or 0.9% saline was administered through the catheters and all patients received morphine using a patient-controlled analgesia (PCA) system. Pain scores, morphine consumption and peak expiratory flow rates (PEFR) were recorded on an hourly basis. Intrathecal fentanyl resulted in a faster onset of analgesia (mean visual analogue scale (VAS) score at 1 h = 0.9 compared with 6.3 (95% confidence intervals for the difference -6.8, -4.0) for the other groups; P < 0.001) and significantly lower pain scores at rest, on cough and on movement. PEFR values were consistently higher in the intrathecal fentanyl group. There were no cases of early or delayed respiratory depression.
Adolescent↗
The effect of ketanserin on healing of fresh surgical wounds.
This study was designed to investigate the effect of topical ketanserin, a selective S2-serotonin antagonist, on wound healing and contraction in surgical wounds allowed to heal by second intention. Thirty-five patients applied placebo or 2% ketanserin gel, double-blind, to head and neck wounds resulting from skin tumour excision, and allowed to heal by second intention. Healing rate was assessed from the change in the square root of wound area, and in 11 patients wound contraction was assessed by the change in the area delineated by wound margin tattoo marks. There were no significant differences in any of the measurements made between the ketanserin- and placebo gel-treated patients. Wound healing was significantly faster in large wounds. Wound contraction was greatest in the early stages of healing, and accounted for 53% of healing. We conclude that, on normally vascularized skin, ketanserin gel has no significant effect on wound healing rate.
Adult↗
Measuring the fetal kidney with ultrasonography.
OBJECTIVES: To establish a normal range of measurements for the external and internal dimensions of the fetal kidney and, if possible, to correlate these measurements with gestational age. SUBJECTS AND METHODS: The external and internal dimensions of the fetal kidney were measured in 810 women selected on the grounds of obstetric, fetal or technical risk factors from a consecutive series of 1136 women attending the ante-natal ultrasonography clinic of a district general hospital. Post-natal data were obtained from medical records on 1122 newborns. The maximum of pairs of renal measurements was used for analysis. Measurements were cross-sectional in 347 cases and longitudinal in 463. The total number of measurement episodes was 2294. RESULTS: External renal dimension and gestational age were closely related, enabling accurate growth centile charts to be constructed. The correlation between renal pelvic dimension and gestational age was weak. The maximum dimension of the renal pelvis at any gestational age in 92.7% of fetuses was < 5 mm. Using longitudinal measurements, 6.5% of cases with a renal pelvic dimension of < 5 mm at the first scan measured > or = 5 mm at a subsequent scan, but 53.3% with a dimension of > or = 5 mm at the first scan also measured > or = 5 mm at the subsequent scan. CONCLUSION: It is possible to assess the growth and size of the fetal kidney according to gestational age but this does not apply to the renal pelvis. A renal pelvic dimension of > 5 mm at any gestational age is unusual and dilatation beyond this level should prompt a detailed post-natal urological investigation.
Female↗
Temperature response to severe head injury and the effect on body energy expenditure and cerebral oxygen consumption.
This study examines the relationship between core temperature and whole body energy expenditure, cerebral oxygen consumption (CMRO2), cerebral blood flow (CBF), and intracranial pressure (ICP) in severely head injured children. A total of 107 serial measurements of temperature, energy expenditure, CMRO2, CBF, and ICP were made in 18 head injured children receiving neurointensive care. Energy expenditure was measured using indirect calorimetry, and CMRO2 and CBF using the Kety-Schmidt technique. The mean rectal temperature was 37.8 degrees C (34-39.1 degrees C) despite modification with paracetamol. Within each child there was a positive relationship between rectal temperature and energy expenditure, energy expenditure increasing by a mean of 7.4% per degree C. There was no evidence of significant relationships between rectal temperature and CMRO2, CBF, or ICP. Mild induced hypothermia in two children did not result in decreased CMRO2 or CBF measurements. The efficacy of interventions aiming to modify cerebral energy metabolism by changing core temperature cannot be readily assessed by the response of the whole body.
Adolescent↗
Changes in cerebral oxygen consumption are independent of changes in body oxygen consumption after severe head injury in childhood.
This study examines the relation between cerebral O2 consumption (CMRO2) and the O2 consumption of the rest of the body (BVO2) after severe head injury. Seventy nine serial measurements of whole body O2 consumption, CMRO2, plasma adrenaline, T3, and glucagon concentrations were made in 15 children with severe head injuries receiving neurointensive care. Body O2 consumption was measured with indirect calorimetry and CMRO2 with the Kety-Schmidt technique. There was no evidence of a significant relation between CMRO2 and BVO2. Within each child there were statistically significant positive relations between BVO2 and adrenaline, T3, and glucagon. By contrast, there was only a weak significant positive relation between CMRO2 and T3. In conclusion, CMRO2 and BVO2 seem to be determined independently after severe head injury. Thus therapeutic measures aiming to reduce CMRO2 need to be specific to the brain and it should not be assumed that measures which decrease whole body energy expenditure will necessarily have the same effect on CMRO2.
Adolescent↗
The effect of severe head injury on whole body energy expenditure and its possible hormonal mediators in children.
This study examines the effects of severe head injury in children on whole body energy expenditure and the mediators that influence this. One hundred five serial measurements of whole body energy expenditure and plasma adrenaline, triiodothyronine, glucagon, cortisol, insulin, and growth hormone concentrations were made in 18 children aged 2-15 y receiving neurointensive care for severe head injury. Energy expenditure was measured using indirect calorimetry by a modified Douglas bag technique, and hormones were measured by RIA or radioenzymatic assay. Energy expenditure varied markedly between and within children (mean 97% of predicted, range 60-137%) and was significantly lower in the four children with a poor outcome (p = 0.03). Within each child there were statistically significant positive relationships between energy expenditure and adrenaline (p < 0.0001), triiodothyronine (p < 0.0001), and glucagon (p < 0.0001). However, there was evidence that the effect of adrenaline on energy expenditure was attenuated. This may be due to the effects of the cerebral trauma itself on central nervous influences on energy expenditure, to interactions between hormones, or to a global impairment of O2 utilization by the body's tissues.
Adolescent↗
N-methyl-D-aspartate (NMDA) receptors in the spinal cord and motor cortex in motor neuron disease: a quantitative autoradiographic study using [3H]MK-801.
The distribution and density of NMDA receptors in spinal cord and motor cortex was compared in motor neuron disease (MND; 10 cases) and controls (8 cases) using [3H]MK-801 autoradiography. In the spinal ventral horn of MND cases, [3H]MK-801 binding was reduced and there were fewer focal hot spots of binding. These changes are likely to reflect loss of motor neurons (MN) bearing NMDA receptors. [3H]MK-801 binding was increased in intermediate spinal grey matter and deeper layers of the motor cortex in MND cases compared to controls. This may represent either an adaptive response to MN loss or a pathophysiological phenomenon contributing to MN degeneration.
Aged↗
Improved prediction of the minimal phototoxic dose in PUVA therapy.
In an attempt to improve the prediction of PUVA erythemal sensitivity, we have examined, in 251 patients, the relationship between the minimal phototoxic dose (MPD) and a number of variables, including skin type, ingested dose of 8-methoxypsoralen (8-MOP) and history of previous PUVA treatment. The MPD was determined by phototesting 2 h after ingestion of crystalline 8-MOP, given at a standard dose of 0.6 mg/kg (calculated to the nearest 10 mg). No reaction to the highest dose of UVA used for phototesting occurred in 16% of cases; the dose of 8-MOP was significantly associated with non-response. In the patients in whom an erythemal response was obtained, a significant association was found between the MPD and the variables of skin type, ingested dose of 8-MOP, and history of previous PUVA treatment. Thus, by taking these factors into account, a more accurate prediction can be made of an individual patient's erythemal sensitivity to PUVA than relying on skin type alone. That erythemal sensitivity is affected by the ingested dose of 8-MOP (even when all patients received 0.6 mg/kg) suggests that conventional psoralen dosing according to body weight is not ideal.
Adolescent↗
What is a normal rate of weight gain in infancy?
We have retrieved weights from the Child Health records of an annual cohort of 3418 full-term children, aged 18-30 months in order to define a lower limit of normality for weight gain for both clinical and research purposes. There was a strong tendency for children at the extremes of the distribution to move inwards towards the average: only 26% of those below the 3rd centile for weight at six weeks were still below it at one year. We describe a method based on conditional standards to correct for this "regression to the mean" and produce a measure of the discrepancy between a child's predicted and actual growth: the "thrive index". The value of the thrive index below which only a minority of children fell provided a lower threshold for normality. While most children below the 3rd centile for weight at 9-24 months of age also had subnormal weight gain, 41% of those with subnormal weight gain had not fallen below the 3rd centile.
Child, Preschool↗
Multi-period crossover trials.
This paper presents a review of crossover designs for use in medical applications which have three or more treatment periods. Only outcomes which can be analysed as continuous variables are considered. Designs which purport to allow for carryover effects are reviewed in detail, as are methods for analysing data collected in such trials. In practice, it is often possible to eliminate carryover by interposing sufficiently long 'washout' periods between successive treatments, and suitable designs for this case are also mentioned. Much current practice revolves around a model which has been widely criticized: the shortcomings of this model and the implications of possible remedies, for design as well as analysis, are discussed.
Cross-Over Studies↗