Justifying CT prior to MRI in cases of suspected occult hip fracture. A proposed diagnostic protocol.

INTRODUCTION: Patients with clinical suspicion of hip fracture, but negative radiographs are suspected of having an occult hip fracture (OHF). Different diagnostic modalities are available for investigating OHF and various protocols have been suggested. MRI has the highest sensitivity and specificity, however availability is limited in many institutes. CT is readily accessible in the large majority of hospitals throughout the world but has lower sensitivity and may miss some fractures. In this article we investigate a protocol that balances these issues providing a practical and cost-effective solution. METHODS: During a four-year period between 2012 and 2016 a strict diagnostic protocol was followed at our Medical Center for patients suspected of OHF. This MRI selective protocol consisted of CT initially being performed and only when negative for fracture, followed by an MRI. Retrospective analysis of all patients who followed the protocol was performed. The patients were divided into two groups: those diagnosed by CT alone and those diagnosed by MRI after having a negative CT scan. Diagnostic performance, time to diagnosis and the cost of this protocol were evaluated. RESULTS: 103 patients were treated under the protocol. In 50 patients (49%) hip fracture was diagnosed by CT alone. In the remaining 53 patients (51%) no definitive diagnosis was reached by CT and MRI was subsequently performed. 12 of these 53 patients (23%) were diagnosed with hip fracture necessitating surgery. In the CT only group mean time from admission to diagnosis was 3 hours, in the CT + MRI group this rose to 40 hours. Cost analysis showed that this protocol was more cost-effective than performing MRI in all patients, saving an estimated 66,805 Euro during the study period. CONCLUSION: The clinical challenge of diagnosing OHF can be minimised by implementing a diagnostic protocol. The protocol should take into consideration the diagnostic sensitivity, availability and cost of different imaging modalities. An MRI selective strategy with initial CT scanning is recommended, as it reduces time to diagnosis and lowers overall costs.

Detection of hydrothermal precursors to large northern california earthquakes.

During the period 1973 to 1991 the interval between eruptions from a periodic geyser in Northern California exhibited precursory variations 1 to 3 days before the three largest earthquakes within a 250-kilometer radius of the geyser. These include the magnitude 7.1 Loma Prieta earthquake of 18 October 1989 for which a similar preseismic signal was recorded by a strainmeter located halfway between the geyser and the earthquake. These data show that at least some earthquakes possess observable precursors, one of the prerequisites for successful earthquake prediction. All three earthquakes were further than 130 kilometers from the geyser, suggesting that precursors might be more easily found around rather than within the ultimate rupture zone of large California earthquakes.

Development and initial psychometric evaluation of the sport interference checklist.

The Sport Interference Checklist (SIC) was developed in 141 athletes to assist in the concurrent assessment of cognitive and behavioral problems experienced by athletes in both training (Problems in Sports Training Scale, PSTS) and competition (Problems in Sports Competition Scale, PSCS). An additional scale (Desire for Sport Psychology Scale, DSPS) was developed to assess the degree to which athletes desire sport psychology assistance in areas that are determined to be problematic. Factor analysis of PSCS items reveals six factors (Dysfunctional Thoughts and Stress, Academic and Adjustment Problems, Injury Concerns, Lack of Motivation, Overly Confident/Critical, Pain Intolerance), accounting for 64% of the total variance. PSTS and DSPS items yield four factors (Dysfunctional Thoughts and Stress, Academic Problems, Injury Concerns, Poor Team Relationships), accounting for 59% and 63% of total variance, respectively. Scores from these scales demonstrate acceptable internal consistency and convergent and discriminative validity. Response patterns of SIC scales are not influenced by gender or athlete type.

Guillain Barré syndrome precipitated by the use of antilymphocyte globulin in the treatment of severe aplastic anaemia.

This report describes the case of a 54 year old woman with very severe aplastic anaemia who was treated with antilymphocyte globulin (ALG) and developed Guillain Barré syndrome (GBS). No antecedent infective aetiology was identified. Although there are numerous reports of autoimmune disease after treatment with ALG in aplastic anaemia, and GBS after immunosuppressive treatment, there are none reporting GBS after the use of ALG for severe aplastic anaemia. The occurrence of autoimmune disease after immunosuppressive treatment, in particular ALG, is discussed, together with the possible mechanisms that result from T cell depression.

Standardization of magnetization transfer imaging for multicenter studies.

Magnetization transfer (MT) techniques may be applied to magnetic resonance imaging (MRI) to evaluate the inherent relaxation properties of heterogeneous tissues. In addition to providing a unique contrast mechanism for the purpose of qualitative imaging, the MT effect may be quantified by various means to provide useful data that relate either to the pathological or associated clinical features of multiple sclerosis (MS) and other neurological disorders. The variable and relatively unpredictable course of neurological disorders such as MS often necessitates the study of large patient cohorts in multiple MRI centers to define either the natural history of the disease or its modification by potential therapies. For multicenter studies, precision (reproducibility, or lack of random error) and accuracy (closeness to the truth, or lack of systematic error) are important requirements for the acquisition of standardized and comparable data. For serial studies, quality assurance is important to determine pathological change from fluctuation in scanner performance. This review addresses how MT imaging techniques may be utilized to provide standardized and clinically relevant measures.

Serial magnetization transfer imaging to characterize the early evolution of new MS lesions.

OBJECTIVE: To explore the temporal relation of demyelination and blood-brain barrier breakdown during new lesion formation. BACKGROUND: Conventional MRI appears sensitive for detecting changes due to MS, but may be limited by poor pathologic specificity. By indirectly assessing protons bound to rigid macromolecules, magnetization transfer (MT) imaging may provide information relating to tissue structure and, by inference, myelin integrity. METHODS: Gadolinium contrast-enhanced MRI and MT imaging were performed at weekly intervals for 3 months in three patients with MS. For each enhancing lesion, the largest corresponding area of proton density hyperintensity seen during the study was outlined and magnetization transfer ratio (MTR) calculated at each time point from coregistered calculated MTR images. Lesions greater than 20 mm2, not affected by partial volume effects, and first enhancing after the baseline study were analyzed. Two-dimensional registration software allowed accurate evaluation of MTR in regions both before and after the initial appearance of MS lesions. RESULTS: Mean lesion MTR decreased significantly during the first week of enhancement (29.6 percent units [pu] immediately pre-enhancement versus 28.2 pu at first documented stage of enhancement). No significant MTR reduction was noted before this. CONCLUSION: The lack of observable change in MTR before the first detectable gadolinium enhancement within MS lesions suggests that blood-brain barrier disruption is closely related to, but not preceded by, demyelination.

The normal appearing grey matter in primary progressive multiple sclerosis: a magnetisation transfer imaging study.

BACKGROUND: In 10-15 % of patients with multiple sclerosis (MS), the clinical course is characterized by slow progression in disability without relapses (primary progressive (PP) MS). The mechanism of disability in this form of MS is poorly understood. Using magnetization transfer ratio (MTR) imaging, we investigated normal appearing white matter (NAWM) and normal appearing grey matter (NAGM) in PPMS and explored the relationship of MTR measures with disability. METHODS: Thirty patients with PPMS and 30 age matched controls had spin echo based MTR imaging to study lesions and normal appearing tissues. The brain was segmented into NAWM and NAGM using SPM99 with lesions segmented using a semiautomated local thresholding technique. A 75% probability threshold for classification of NAWM and NAGM was used to diminish partial volume effects. From normalized histograms of MTR intensity values, six MTR parameters were measured. Mean lesion MTR and T2 lesion volume were also measured. Disability was assessed using Kurtzke's expanded disability status scale (EDSS). RESULTS: Compared with controls, patients exhibited a significant reduction in mean NAWM (p = 0.001) and NAGM (p = 0.004) MTR. Spearman's rank correlation of EDSS with the six MTR parameters in NAWM and NAGM, mean lesion MTR, and T2 lesion volume, was only significant with mean NAGM MTR (r = -0.41, p = 0.02), the 25th percentile of NAGM MTR intensity (r = -0.37, p = 0.05), and T2 lesion volume (r = 0.39, p = 0.04). Multiple regression analysis of the relationship between EDSS and 4 MR parameters representing each tissue type (mean NAWM MTR, mean NAGM MTR, mean lesion MTR, T2 lesion volume) showed that the association of EDSS with mean NAGM MTR remained significant. CONCLUSIONS: There appear to be significant abnormalities in the NAGM in PP MS. Further investigation of the pathological basis and functional significance of grey matter abnormality in PPMS is warranted.

A modified protocol to improve the detection of enhancing brain and spinal cord lesions in multiple sclerosis.

By detecting focal blood-brain barrier (BBB) breakdown, gadolinium (Gd-DTPA) contrast-enhanced T1-weighted magnetic resonance imaging (MRI) allows assessment of inflammatory activity in multiple sclerosis (MS) and provides a sensitive means of monitoring immunomodulatory therapies in exploratory trials. Serial monthly studies were performed in eight relapsing-remitting and eight secondary progressive patients to assess new and more sensitive techniques for enhanced MRI. Brain and spine imaging was carried out at 1.5-T on two occasions 24-72 h apart using a conventional imaging protocol with T1-weighted MRI at single-dose (0.1 mmol/kg) Gd-DTPA and a potentially more sensitive "modified" protocol with T1-weighted MRI at triple-dose (0.3 mmol/kg) Gd-DTPA (with addition of delay and magnetisation transfer presaturation for brain imaging). For each MRI protocol the total numbers of enhancing lesions (97 paired studies) and new enhancing lesions (81 paired studies) were assessed. The total number of enhancing lesions seen was 347/75 on conventional brain/cord MRI respectively, and 754/123 on modified brain/cord MRI. The respective numbers of new enhancing lesions were 168/40 on conventional and 276/71 on modified scans. Smaller increases were seen in the proportion of active scans using the modified protocol. Sample size calculations showed no reduction in sample sizes required for a parallel group study but a reduced sample size for crossover studies using the modified protocol; the addition of cord to brain imaging did not improve power for either trial design. A combined modified brain and cord imaging protocol markedly improves the detection of areas of focal BBB leakage in MS and may be useful in selected natural history studies. The modified brain protocol reduces sample size requirements for crossover studies but not necessarily for parallel design trials.

Single-dose gadolinium with magnetization transfer versus triple-dose gadolinium in the MR detection of multiple sclerosis lesions.

PURPOSE: To compare the efficacy of single-dose gadolinium with magnetization transfer contrast (MTC) with that of triple-dose gadolinium in detecting enhancing multiple sclerosis lesions. METHODS: Twenty-one patients with multiple sclerosis were examined with MR imaging first with 0.1 mmol/kg gadolinium (single dose) and then, after 24 to 72 hours, with 0.3 mmol/kg gadolinium (triple dose). T2-weighted fast spin-echo and T1-weighted spin-echo MR images with and without MTC were obtained before contrast administration followed by either T1-weighted spin-echo images with MTC (single dose) or conventional T1-weighted spin-echo images (triple dose), starting 5, 17, and 29 minutes after contrast administration. All images were evaluated in a blinded fashion and scored in random order by two readers. Outcome parameters included number of enhancing lesions, number of active MR examinations (those containing at least one enhancing lesion), contrast ratio (signal intensity of enhancing lesion divided by signal intensity of normal-appearing white matter), and size of enhancing lesions. RESULTS: Eighty-one percent more enhancing lesions and 49% more active MR examinations were detected when a triple dose of gadolinium was used as compared with a single dose. The level of agreement between readers as to the number of enhancing lesions was significantly higher for triple-dose than for single-dose gadolinium. With triple-dose gadolinium, contrast ratios and areas of enhancement increased by 10% and 33%, respectively. Delayed imaging increased the size of the lesion by 11% on single-dose MTC images and by 18% on triple-dose images. CONCLUSION: Triple-dose gadolinium is more effective (higher sensitivity and interobserver agreement) than single-dose gadolinium in combination with MTC in detecting enhancing multiple sclerosis lesions.

Magnetisation transfer ratio histogram analysis of primary progressive and other multiple sclerosis subgroups.

INTRODUCTION: Global magnetisation transfer ration (MTR) histogram analysis in the brain offers a method for evaluating pathological change both as a result of lesions and microscopic changes in normal appearing tissues. METHODS: 39 controls and 83 MS patients (46 primary progressive, 11 benign, 10 relapsing-remitting, 16 secondary progressive) were studied to explore the relationship of six conventional MTR histogram parameters with MS clinical subgroups and disability. Principal component (PC) analysis, which makes use of all the histogram data, was also used to examine the relationship between the MTR histogram and disability. RESULTS: When primary progressive patients were compared to controls, there were abnormalities of average MTR, and MTR at the 25th, 50th and 75th percentile. Disabled relapsing onset patients exhibited abnormalities in the same four parameters. Benign and nondisabled relapsing onset patients exhibited no significant abnormalities. Modest correlations were observed between disability and individual MTR parameters in relapse onset but not primary progressive patients--PC analysis revealed stronger and significant associations with disability in both subgroups. (r=0.40 for primary progressive and r=0.51 for relapsing onset). CONCLUSION: A number of MTR parameters are abnormal in primary progressive MS. MTR abnormalities are seen in disabled patients, whether of relapsing or primary progressive onset. The improved correlation with disability obtained by PC analysis suggests a useful role of this method for following clinically relevant pathological changes depicted in the MTR histogram.

Raised serum nitrate and nitrite levels in patients with multiple sclerosis.

Nitric oxide and its highly reactive derivative peroxynitrite have been implicated as non-specific inflammatory mediators of neuronal and oligodendrocyte damage and death in multiple sclerosis. In a cross-sectional study we found levels of the nitric oxide metabolites nitrate and nitrite to be raised in the serum of patients with demyelinating disease (65.6 microM (SD 32.9)), acquired immune deficiency syndrome (57.9 microM (SD 34.9)) and inflammatory neurological disease (57.5 microM (SD 31.3)), compared with normal control subjects (32.8 microM (SD 12.2)) and patients with non-inflammatory neurological disease (41.1 microM (SD 12.3), p < 0.001). Nitric oxide metabolites were raised in all clinical subtypes of multiple sclerosis, as well as in clinically isolated syndromes compatible with demyelination, and were not related to progressive disease or disability. This study provides further evidence for a role of nitric oxide in the immunopathogenesis of inflammatory diseases of the central nervous system, including multiple sclerosis.

Infratentorial hypointense lesion volume on T1-weighted magnetic resonance imaging correlates with disability in patients with chronic cerebellar ataxia due to multiple sclerosis.

In multiple sclerosis (MS), hypointense lesions on T1-weighted magnetic resonance imaging are thought to represent areas of tissue disruption and axonal loss. In previous studies of MS patients, infratentorial T1 hypointense lesions were found to be rare. In MS patients selected to have chronic cerebellar ataxia, we have determined the extent of infratentorial T1 hypointense lesions and their relationship with disability. We recruited nine patients with chronic cerebellar ataxia due to MS. An expanded disability status scale (EDSS) assessment was performed on each. The patients' brains were then imaged with axial-oblique dual-echo fast spin-echo and contrast-enhanced T1-weighted conventional spin-echo sequences. The number and total volume of infratentorial high-signal lesions on T2-weighted images and infratentorial hypointense lesions on T1-weighted images were calculated by a blinded observer using a computer-assisted contouring technique. A total of 96 infratentorial high-signal lesions were present, of which 62 (64.6%) appeared isointense and 34 (35.4%) hypointense with respect to the surrounding brain substance on the T1-weighted images. There was a median of 3 (range 0-10) and median volume of 0.43 ml (range 0-0.85 ml) infratentorial T1 hypointense lesions per patient. The EDSS score correlated with both the number (r=0.68, p=0.043) and the volume per patient (r=0.89, p=0.001) of infratentorial T1 hypointense but not T2 high-signal lesions. Infratentorial T1 hypointense lesions are often seen in patients with MS and chronic cerebellar ataxia. They may play a significant role in the disability suffered by these patients.

Psychometric evaluation of self- and collateral timeline follow-back reports of drug and alcohol use in a sample of drug-abusing and conduct-disordered adolescents and their parents.

One hundred eighty-eight drug-abusing and conduct-disordered adolescents and their parents provided retrospective reports of the youths' frequency of alcohol and illicit drug use for each of the 6 months preceding their initial session in an outpatient treatment program. Youths' and parent reports of youths' drug and alcohol use for each month were similar. For marijuana and alcohol, frequency reports were related for each month, whereas hard drug reports were related only for the 4 months preceding intake. Relationships among alcohol and hard drug reports were strong during Months 1, 2, and 4 preceding intake, whereas strength of relationship among marijuana reports was similar throughout the 6 months.

A Monte Carlo evaluation of tests for comparing dependent correlations.

The authors conducted a Monte Carlo simulation of 8 statistical tests for comparing dependent zero-order correlations. In particular, they evaluated the Type I error rates and power of a number of test statistics for sample sizes (Ns) of 20, 50, 100, and 300 under 3 different population distributions (normal, uniform, and exponential). For the Type I error rate analyses, the authors evaluated 3 different magnitudes of the predictor-criterion correlations (rho(y,x1) = rho(y,x2) = .1, .4, and .7). For the power analyses, they examined 3 different effect sizes or magnitudes of discrepancy between rho(y,x1) and rho(y,x2) (values of .1, .3, and .6). They conducted all of the simulations at 3 different levels of predictor intercorrelation (rho(x1,x2) = .1, .3, and .6). The results indicated that both Type I error rate and power depend not only on sample size and population distribution, but also on (a) the predictor intercorrelation and (b) the effect size (for power) or the magnitude of the predictor-criterion correlations (for Type I error rate). When the authors considered Type I error rate and power simultaneously, the findings suggested that O. J. Dunn and V. A. Clark's (1969) z and E. J. Williams's (1959) t have the best overall statistical properties. The findings extend and refine previous simulation research and as such, should have greater utility for applied researchers.

Sexual esteem, sexual depression, and sexual preoccupation in the exchange approach to sexuality.

A sample of 124 undergraduate students completed the Sexuality Scale and the Sexual Approach Questionnaire developed by Snell. The analysis indicated that those who scored high on the Exchange approach to sexuality (n = 43) scored lower on Sexual Esteem and higher on Sexual Depression and Sexual Preoccupation than those who scored low on Exchange (n = 43). Furthermore, men (n = 49) scored higher on preoccupation with sex than did women (n = 75).

Sex differences in color preferences among an elderly sample.

The purpose of the study was to assess differences in color preferences between the sexes. A sample of 193 retirees were asked to report their favorite colors. The pattern of frequencies for preferred color differed as a function of sex. Blue was chosen as the most preferred color by both sexes. Women preferred black and purple more than men did. Moreover, the men preferred red over pink, whereas the women preferred red and pink equally. The rank order of color preferences for this elderly group were very similar to the findings of Silver, et al. who sampled young adults in 1988.

Response variations to Stroop color-word stimuli.

Reaction times (RTs) and net interference measures were obtained for 64 Stroop color-word stimuli from 8 common colors. Subjects were 64 college students, 32 of each sex. The incongruous stimulus was designated as either the ink interpretation different from the word or the word interpretation different from the ink. Consistently large variations within Stroop stimuli and Word x Ink interactions were found. Complex qualitative and quantitative differences were revealed between sexes. Females had faster RTs, but showed no significant superiority in measured net interference. The derived rank orders of net interference between sexes were correlated when using the ink, but not when using the word. Neither word nor ink were related in ranking RTs. For net interference, however, derived RTs were highly related for women using the ink interpretation, but not when using the word; they were unrelated for men using either interpretation. Two interrference types were highly correlated for women, but not for men. An additional experiment with a color-blind group cast an interesting light on the issue. Our Stroop data, rank ordered by sex for each measure, may assist viable theory constructions, including the context-dependent interaction hypothesis.

Randomised clinical trial: the safety and tolerability of Trichuris suis ova in patients with Crohn's disease.

BACKGROUND: Recent evidence suggests that embryonated eggs of the porcine whipworm Trichuris suis ova (TSO) may be an effective treatment for inflammatory bowel disease (IBD). AIM: To assess the safety and tolerability of TSO following a single dose in patients with Crohn's disease. METHODS: This was a sequential dose-escalation (500, 2500 and 7500 viable embryonated TSO), randomised, double-blind, placebo-controlled study to evaluate the safety of a single dose of oral suspension TSO in patients with Crohn's disease. Twelve patients were randomised into each of three cohorts. Patients were assessed 1, 3, 5, 7, 9, 11 and 14 days following dosing (via a telephone call and diary symptom collection through 14 days postdose) for adverse events, changes to concomitant medications and gastrointestinal (GI) signs and symptoms. Patients were again assessed at Months 1, 2 and 6. RESULTS: Eighteen males and 18 females were enrolled, ages 20 to 54 years. All patients were dosed and completed the initial 2-month follow-up period (five patients did not attend their 6-month study visit). GI disorders were reported with the highest frequency; 7 (25.9%) TSO-treated patients and 3 (33.3%) placebo-treated patients. No dose-dependent relationship was observed, with 3 (33.3%) placebo, 4 (44.4%) TSO 500, 0 (0.0%) TSO 2500 and 3 (33.3%) TSO 7500 patients experiencing at least one GI event, and no clinically meaningful changes in GI signs and symptoms. CONCLUSIONS: A single dose of Trichuris suis ova up to 7500 ova was well tolerated and did not result in short- or long-term treatment-related side effects. Clinicaltrials.gov NCT01576461.

Sample size determination for health psychology interventions with binomially distributed outcomes.

Health intervention outcomes are often assessed as binomially distributed variables. In designing such interventions it is important to model the pre-intervention rate of the target behavior when performing sample size calculations. Unfortunately, the majority of sample size programs model post-intervention outcomes only, which results in exaggerated sample size estimates. An exception is Yoo and Spoth's (1993) conditional binomial method of sample size determination. This approach explicitly models pre-intervention behavior by focusing on baserate-adjusted post-intervention outcomes, and always results in smaller sample size estimates than conventional approaches. Advantages of the conditional binomial method are discussed and user-friendly software is presented.