A graphical sensitivity analysis for clinical trials with non-ignorable missing binary outcome

Many clinical trials are analysed using an intention-to-treat (ITT) approach. A full application of the ITT approach is only possible when complete outcome data are available for all randomized subjects. In a recent survey of clinical trial reports including an ITT analysis, complete case analysis (excluding all patients with a missing response) was common. This does not comply with the basic principles of ITT since not all randomized subjects are included in the analysis. Analyses of data with missing values are based on untestable assumptions, and so sensitivity analysis presenting a range of estimates under alternative assumptions about the missing-data mechanism is recommended. For binary outcome, extreme case analysis has been suggested as a simple form of sensitivity analysis, but this is rarely conclusive. A graphical sensitivity analysis is proposed which displays the results of all possible allocations of cases with missing binary outcome. Extension to allow binomial variation in outcome is also considered. The display is based on easily interpretable parameters and allows informal examination of the effects of varying prior beliefs.     

Caloric restricted male rats demonstrate fewer synapses in layer 2 of sensorimotor cortex

Previous studies have demonstrated an age-related decline in the density of presumptive inhibitory synapses in layer 2 of rat sensorimotor cortex [J. Comp. Neurol. 439(1) (2001) 65]. Caloric restriction has been shown to ameliorate age-related deterioration in a variety of systems and to extend life span. The present study tested the hypothesis that caloric restriction would prevent the previously reported age-related synaptic decline. Accordingly, synaptic density in layer 2 of sensorimotor cortex was compared between 29-month-old male rats fed ad libitum and 29-month-old male rats that were caloric restricted (60% of ad libitum calories) from 4 months of age. In serial electron micrographs, the physical disector was used to determine the numerical density of presumptive excitatory and inhibitory synapses (those containing round or nonround vesicles, respectively) as well as that of neurons. Not only was the previously reported age-related decline in numerical density of presumptive inhibitory synapses not ameliorated by caloric restriction, the numerical density was significantly lower in caloric restricted than in ad libitum fed rats for total as well as for presumptive excitatory and inhibitory synapses. Analysis further revealed no difference in the numerical density of neurons in this region. Relating synapse density to neuron density as the ratio of synapses to neuron also demonstrated significantly fewer synapses per neuron in caloric restricted than in ad libitum fed old rats. Finally, synapse length was significantly less in caloric restricted rats. These results suggest that not only does caloric restriction fail to prevent the age-related decline in presumptive inhibitory synapses, it results in fewer presumptive excitatory synapses as well.     

Contrast-enhanced MR angiography of the hand.

Contrast material-enhanced magnetic resonance (MR) angiography of the hand noninvasively provides information comparable to that provided by conventional angiography. It is a quick and easy examination that takes less than 5 minutes to perform and produces high-quality images with use of a dedicated surface coil that provides a high signal-to-noise ratio, allowing small pixel size and high spatial resolution. Contrast-enhanced MR angiography requires intravenous injection of gadopentetate dimeglumine and acquisition of a volumetric slab of image data from the hand. This information is then projected with a maximum-intensity-projection algorithm. The technique is generally robust with reproducible findings. Image interpretation requires an understanding of (a) the normal vascular anatomy and anatomic variants of the hand and (b) common vascular diseases. MR angiography of the hand is commonly used to create an arterial "road map" prior to surgery, manage traumatic transection, and identify emboli. Vascular malformations are readily identified and connective tissue disorders including vasculitis are well demonstrated with this technique, which can also be used to assess bone viability following trauma to the carpus or to evaluate the viability of vascularized bone. Common artifacts may be secondary to contracture deformities or "wraparound" effect. However, most potential pitfalls can be avoided by being vigilant.     

Parents' perceptions towards their child's use of inhaled medications for asthma therapy

Objective : Understanding patients' and their parents' perceptions towards asthma medication is important in developing strategies to ensure patient compliance. In this study, parents' perceptions towards their children's use of inhaled medication for asthma treatment were evaluated.
Methodology : A questionnaire was administered by interviewing parents of 210 asthmatic children attending the Department of Paediatrics, National University Hospital.
Results : Our results showed that 76/210 (36%) of parents either felt opposed to inhaler therapy and/or preferred oral medications. The main reasons for their reluctance to use inhalers were related to fear of dependence, side effects and overdosage, and the child's dislike for inhalers. A third of these parents felt that inhalers were only indicated for very severe asthma.
Conclusions : We conclude that a significant proportion of parents have reservations regarding the use of inhalers for the treatment of asthma. These factors should be taken into consideration when planning an effective asthma education programme.     

Abnormal anatomy of the lumbosacral region imaged by magnetic resonance in children with anorectal malformations

OBJECTIVE: To investigate the frequency of lumbosacral anomalies, the association with urogenital abnormalities, and the correlation with defaecation pattern by magnetic resonance imaging (MRI). METHODS: A prospective analysis was performed of routine MRI in patients with anorectal malformations. Between 1990 and 1994, MRI was performed in 43 such patients: 31 boys and 12 girls. Twenty four had a high anorectal malformation, 16 had a low anorectal malformation, and three had Currarino's triad. MRI was performed before reconstruction in 26, and postoperatively in 17. Urogenital anomalies were found in 21. RESULTS: Abnormalities of the spinal cord and spine were found with MRI in 20 patients (46.5%); caudal regression syndrome in 10, tethered cord in two, a combination of both in three, and other spinal anomalies in five. These anomalies were found in 30% of the patients with low anorectal malformations, and in 50% with high anorectal malformations. In patients with urogenital malformations, MRI more often showed spinal anomalies (13/21, 62%) than in patients without (7/22, 32%). In high anorectal malformations, defaecation was more often a problem in patients with spinal anomalies (12/15, 80%) than in patients without (2/8, 25%). CONCLUSIONS: Spinal anomalies in the lumbosacral region were found with MRI in 46.5% of patients with anorectal malformations. Since presence of these anomalies seems to be related to clinical outcome, MRI should be performed routinely in all such patients.     

The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study

BACKGROUND: Microfracture is a frequently used technique for the repair of articular cartilage lesions of the knee. Despite the popularity of the technique, prospective information about the clinical results after microfracture is still limited. The purpose of our study was to identify the factors that affect the clinical outcome from this cartilage repair technique. METHODS: Forty-eight symptomatic patients with isolated full-thickness articular cartilage defects of the femur in a stable knee were treated with the microfracture technique. Prospective evaluation of patient outcome was performed for a minimum follow-up of twenty-four months with a combination of validated outcome scores, subjective clinical rating, and cartilage-sensitive magnetic resonance imaging. RESULTS: At the time of the latest follow-up, knee function was rated good to excellent for thirty-two patients (67%), fair for twelve patients (25%), and poor for four (8%). Significant increases in the activities of daily living scores, International Knee Documentation Committee scores, and the physical component score of the Short Form-36 were demonstrated after microfracture (p < 0.05). A lower body-mass index correlated with higher scores for the activities of daily living and SF-36 physical component, with the worst results for patients with a body-mass index of >30 kg/m(2). Significant improvement in the activities of daily living score was more frequent with a preoperative duration of symptoms of less than twelve months (p < 0.05). Magnetic resonance imaging in twenty-four knees demonstrated good repair-tissue fill in the defect in thirteen patients (54%), moderate fill in seven (29%), and poor fill in four patients (17%). The fill grade correlated with the knee function scores. All knees with good fill demonstrated improved knee function, whereas poor fill grade was associated with limited improvement and decreasing functional scores after twenty-four months. CONCLUSIONS: Microfracture repair of articular cartilage lesions in the knee results in significant functional improvement at a minimum follow-up of two years. The best short-term results are observed with good fill grade, low body-mass index, and a short duration of preoperative symptoms. A high body-mass index adversely affects short-term outcome, and a poor fill grade is associated with limited short-term durability.