Improved Screening Test for Idiopathic Infantile Hypercalcemia Confirms Residual Levels of Serum 24,25‐(OH)2D3 in Affected Patients

CYP24A1 mutations are now accepted as a cause of idiopathic infantile hypercalcemia (IIH). A rapid liquid‐chromatography tandem mass spectrometry (LC‐MS/MS)‐based blood test enabling measurement of the 25‐OH‐D₃:24,25‐(OH)₂D₃ ratio (R) can identify IIH patients on the basis of reduced C24‐hydroxylation of 25‐OH‐D₃ by CYP24A1 in vivo. Although values of this ratio are significantly elevated in IIH, somewhat surprisingly, serum 24,25‐(OH)₂D₃ remains detectable. The current study explores possible explanations for this including: residual CYP24A1 enzyme activity in individuals with certain CYP24A1 genotypes, expression of alternative C24‐hydroxylases, and the possibility of isobaric contamination of the 24,25‐(OH)₂D₃ peak on LC‐MS/MS. We employed an extended 20‐min run time on LC‐MS/MS to study serum vitamin D metabolites in patients with IIH due to mutations of CYP24A1 or SLC34A1; in unaffected heterozygotes and dialysis patients; in patients with vitamin D deficiency; as well as in normal subjects exhibiting a broad range of 25‐OH‐D levels. We identified 25,26‐(OH)₂D₃ as a contaminant of the 24,25‐(OH)₂D₃ peak. In normals, the concentration of 24,25‐(OH)₂D₃ greatly exceeds 25,26‐(OH)₂D₃; however, 25,26‐(OH)₂D₃ becomes more significant in IIH with CYP24A1 mutations and in dialysis patients, where 24,25‐(OH)₂D₃ levels are low when CYP24A1 function is compromised. Mean R in 30 IIH‐CYP24A1 patients was 700 (range, 166 to 2168; cutoff = 140) as compared with 31 in 163 controls. Furthermore, patients possessing CYP24A1 L409S alleles exhibited higher 24,25‐(OH)₂D₃ levels and lower R (mean R = 268; n = 8) than patients with other mutations. We conclude that a chromatographic approach which resolves 24,25‐(OH)₂D₃ from 25,26‐(OH)₂D₃ produces a more accurate R that can be used to differentiate pathological states where CYP24A1 activity is altered. The origin of the residual serum 24,25‐(OH)₂D₃ in IIH patients appears to be multifactorial. © 2017 American Society for Bone and Mineral Research.     

Epidemiology of injuries and illnesses in America's Cup yacht racing

Objectives

To determine the incidence and severity of injuries and illnesses incurred by a professional America''s Cup yacht racing crew during the preparation for and participation in the challenge for the 2003 America''s Cup.

Methods

A prospective study design was used over 74 weeks of sailing and training. All injuries and illnesses sustained by the 35 professional male crew members requiring medical treatment were recorded, including the diagnosis, nature, location, and mechanism of injury. The volume of sailing and training were recorded, and the severity of incidents were determined by the number of days absent from both sailing and training.

Results

In total, 220 injuries and 119 illnesses were recorded, with an overall incidence of 8.8 incidents/1000 sailing and training hours (injuries, 5.7; illnesses, 3.1). The upper limb was the most commonly injured body segment (40%), followed by the spine and neck (30%). The most common injuries were joint/ligament sprains (27%) and tendinopathies (20%). The incidence of injury was significantly higher in training (8.6) than sailing (2.2). The most common activity or mechanism of injury was non‐specific overuse (24%), followed by impact with boat hardware (15%) and weight training (13%). “Grinders” had the highest overall injury incidence (7.7), and “bowmen” had the highest incidence of sailing injuries (3.2). Most of the illnesses were upper respiratory tract infections (40%).

Conclusions

The data from this study suggest that America''s Cup crew members are at a similar risk of injury to athletes in other non‐collision team sports. Prudent allocation of preventive and therapeutic resources, such as comprehensive health and medical care, well designed conditioning and nutritional programmes, and appropriate management of recovery should be adopted by America''s Cup teams in order to reduce the risk of injury and illness.     

White matter disease in AIDS: findings at MR imaging

A review of the magnetic resonance (MR) images of 365 patients with acquired immunodeficiency syndrome (AIDS) revealed that 112 (31%) had signal abnormalities confined to the white matter. Four patterns were observed: (a) diffuse: widespread involvement of a large area; (b) patchy: localized involvement with ill-defined margins; (c) focal: well-defined areas of involvement; and (d) punctate: small foci less than 1 cm in diameter. Clinical or pathologic findings were available in 60 of the 112 patients and were correlated with the white matter patterns seen on MR images. The diffuse pattern correlated with AIDS dementia complex (ADC), which was the most common clinical diagnosis. Patchy or punctate lesions may be seen with ADC but are less common. Focal white matter lesions were not seen in patients with ADC but were seen in all six patients with progressive multifocal leukoencephalopathy, in both patients with lymphoma, and in one patient with toxoplasmosis. The authors conclude that white matter lesions are are common in AIDS and are often secondary to direct infection of the brain with human immunodeficiency virus, which causes the ADC and usually produces a diffuse white matter pattern. Biopsy is probably not indicated in these patients. Focal white matter lesions suggest a focal infection or tumor, and biopsy may be warranted.     

The yield of colorectal cancer among fast track patients with normocytic and microcytic anaemia

Introduction

We receive fast track referrals on the basis of iron deficiency anaemia (IDA) for patients with normocytic anaemia or for patients with no iron studies. This study examined the yield of colorectal cancer (CRC) among fast track patients to ascertain whether awaiting confirmation of IDA is necessary prior to performing bowel investigations.

Methods

A review was undertaken of 321 and 930 consecutive fast track referrals from Centre A and Centre B respectively. Contingency tables were analysed using Fisher’s exact test. Logistic regression analyses were performed to investigate significant predictors of CRC.

Results

Overall, 229 patients were included from Centre A and 689 from Centre B. The odds ratio for microcytic anaemia versus normocytic anaemia in the outcome of CRC was 1.3 (95% confidence interval [CI]: 0.5–3.9) for Centre A and 1.6 (95% CI: 0.8–3.3) for Centre B. In a logistic regression analysis (Centre B only), no significant difference in CRC rates was seen between microcytic and normocytic anaemia (adjusted odds ratio: 1.9, 95% CI: 0.9–3.9). There was no statistically significant difference in the yield of CRC between microcytic and normocytic anaemia (p=0.515, Fisher’s exact test) in patients with anaemia only and no colorectal symptoms. Finally, CRC cases were seen in both microcytic and normocytic groups with or without low ferritin.

Conclusions

There is no significant difference in the yield of CRC between fast track patients with microcytic and normocytic anaemia. This study provides insufficient evidence to support awaiting confirmation of IDA in fast track patients with normocytic anaemia prior to requesting bowel investigations.     

Perineum compression during EAUS enhances visualization of anterior anal sphincter defects

Objective  Endo-anal ultrasound (EAUS) can detect anal sphincter injuries. However, anterior external anal sphincter (EAS) defects can be difficult to define. We assessed different EAUS techniques to determine if any particular method improved defect identification.
Method  Ninety females with faecal incontinence were prospectively studied. Wexner faecal incontinence scores were obtained. All patients underwent anorectal manometry and EAUS using three different techniques: standard, digit-assisted (gloved finger pressing on posterior vaginal wall) and balloon-assisted (standard balloon inflated into the vagina). The three techniques were assessed by comparing defect characteristics (detection, angle, edges and scar tissue), and perineal body thickness. All measurements were performed at the mid anal canal level. Results are expressed as medians (IQR).
Results  Standard EAUS (S-EAUS) identified a sphincter defect in 54 patients. Digit assisted EAUS (D-EAUS) and balloon-assisted EAUS (B-EAUS) ultrasound revealed a sphincter defect in additional 11 and 9 patients respectively compared to S-EAUS. Correlation of maximum squeeze pressure with EAUS findings improved on D-EAUS and B-EAUS. The defect angle was significantly wider with D-EAUS and B-EAUS [S-EAUS 90°(63–97), D-EAUS 100°(81–101.5), B-EAUS 100°(80–105), P  = 0.0005]. The perineal body was significantly thicker when measured with B-EAUS [D-EAUS 9 mm (7–10) vs B-EAUS 10 mm (8–11), P  = 0.0005]. Inter-observer agreement was comparable [S-EAUS (K) = 0.677, D-EAUS (K) = 0.658, B-EAUS (K) = 0.601].
Conclusion  EAS anterior defect detection and definition on EAUS may be improved by the demarcation and gentle pressure on the posterior vaginal wall.     

Health outcome measures in the evaluation of total hip arthroplasties--a comparison between the Harris hip score and the Oxford hip score

There has been an increasing need for the sensitive and reproducible measurement of the outcome after hip surgery. Numerous hip scoring systems, varying in their complexity and disease specificity, have been designed to achieve a measure of outcome-some rely ultimately on the judgement of the surgeon, whereas others rely on the patients' perceptions. The Oxford hip score (OHS) has been found to be easier to administer and achieves a much higher follow-up rate than that of the Harris hip score (HHS). Unfortunately, with the availability of numerous scoring systems and the publication of data in these systems, it has been difficult to compare results. Our aim was to compare the more widely used HHS to the shorter OHS. We followed 200 consecutive primary total hip arthroplasties (196 patients between January 1994 and May 1995) for an average of 5 years. All patients had a preoperative HHS recorded. At the 5-year review, assessment was made using OHS and the HHS. There were 115 hips that had full OHS and HHS available. The mean OHS was 19.1 (range 12-52, SD 9.5), and HHS was 89.4 (range 47-100, SD 13.3) at follow-up. The Spearman correlation showed good negative correlation between the 2 results (Spearman rank -0.712, P < .0001). The HHS vs OHS shows good correlation at 5 years. This is the first study to confirm that correlation persists for the OHS in the medium term. We include a classification of OHS of excellent (<19), good (19-26), fair (27-33), and poor (>33) outcomes which correlate well with the HHS. This study enables the case for the Oxford data with its easier analysis and higher compliance rate to be used more directly to compare studies that use the HHS.     

Fifth metatarsal tuberosity fracture fixation: a biomechanical study

This study tested the hypothesis that fixation of a fifth metatarsal tuberosity fracture with a lag screw that engages the intact medial cortex is biomechanically stronger than fixation with a long intramedullary screw (control). The right and left feet from 10 male cadavers were alternately assigned to the two fixation groups. After fracture reduction and fixation, each specimen was potted in acrylic cement and tested on a servohydraulic testing machine. The repairs were then distracted until failure by placing the peroneus brevis tendon under tension at a rate of 1 mm/s. The lag screw technique resulted in a significantly greater mean (+/- SD) load to failure (150 +/- 90 N) than did intramedullary screw fixation (70 +/- 60 N) (p < .05) and may offer a useful method of internal fixation of fifth metatarsal tuberosity fractures when surgical stabilization is indicated.     

Evaluation of the technical performance of novel holotranscobalamin (holoTC) assays in a multicenter European demonstration project.

A commercially available holotranscobalamin (holo-TC) radioimmunoassay (RIA) (Axis-Shield, Dundee, Scotland) was evaluated in four laboratories and compared with a holoTC ELISA run in one laboratory. The performance of the holoTC RIA assay was comparable in three of the four participating laboratories. The results from these three laboratories, involving at least 20 initial runs of "low", "medium" and "high" serum-based controls (mean holoTC concentrations 34, 60 and 110 pmol/L, respectively) yielded an intra-laboratory imprecision of 6-10%. No systematic inter-laboratory deviations were observed on runs involving 72 patient samples (holoTC concentration range 10-160 pmol/L). A fourth laboratory demonstrated higher assay imprecision for control samples and systematic deviation of results for the patient samples. Measurement of holoTC by ELISA showed an imprecision of 4-5%, and slightly higher mean values for the controls (mean holoTC concentrations 40, 70 and 114 pmol/L, respectively). Comparable results were obtained for the patient samples. The long-term intra-laboratory imprecision was 12% for the holoTC RIA and 6% for the ELISA. In conclusion, it would be prudent to check the calibration and precision prior to starting to use these holoTC assays in research or clinical practice. The results obtained using the holoTC RIA were similar to those obtained using the holoTC ELISA assay.     

Identifying Opportunities for Peer Learning: An Observational Study of Medical Students on Clinical Placements

Phenomenon: Peer assisted learning (PAL) is frequently employed and researched in preclinical medical education. Fewer studies have examined PAL in the clinical context: These have focused mainly on the accuracy of peer assessment and potential benefits to learner communication and teamwork skills. Research has also examined the positive and negative effects of formal, structured PAL activities in the clinical setting. Given the prevalence of PAL activities during preclinical years, and the unstructured nature of clinical placements, it is likely that nonformal PAL activities are also undertaken. How PAL happens formally and informally and why students find PAL useful in this clinical setting remain poorly understood. Approach: This study aimed to describe PAL activities within the context of clinical placement learning and to explore students' perceptions of these activities. An ethnographic study was conducted to gather empirical data on engagement in clinical placement learning activities, including observations and interviews with students in their 1st clinical year, along with their supervising clinicians. Thematic analysis was used to interrogate the data. Findings: On average, students used PAL for 5.19 hours per week in a range of activities, of a total of 29.29 hours undertaking placements. PAL was recognized as a means of vicarious learning and had greater perceived value when an educator was present to guide or moderate the learning. Trust between students was seen as a requirement for PAL to be effective. Students found passive observation a barrier to PAL and were able to identify ways to adopt an active stance when observing peers interacting with patients. For example, learners reported that the expectation that they had to provide feedback to peers after task observation, resulted in them taking on a more critical gaze where they were encouraged to consider notions of good practice. Insights: Students use PAL in formal (i.e., tutorial) and nonformal (e.g., peer observation and feedback on the ward; discussion during lunch) situations in clinical education and find it useful. The educator is crucial in fostering PAL through providing opportunities for learners to practice together and in helping to moderate discussions about quality of performance. Student engagement in PAL may reduce passivity commonly reported in clinical rotations. Further directions for research into PAL in clinical education are identified along with potential strategies that may maximize the benefits of peer to peer learning.