Predicting medical students who will have difficulty during their clinical training.

BACKGROUND: We aimed to classify the difficulties students had passing their clinical attachments, and explore factors which might predict these problems. METHODS: We analysed data from regular student progress meetings 2008-2012. Problem categories were: medical knowledge, professional behaviour and clinical skills. For each category we then undertook a predictive risk analysis. RESULTS: Out of 561 students, 203 were found to have one or more problem category and so were defined as having difficulties. Prevalences of the categories were: clinical skills (67%), knowledge (59%) and professional behaviour (29%). A higher risk for all categories was associated with: male gender, international entry and failure in the first half of the course, but not with any of the minority ethnic groups. Professional and clinical skills problems were associated with lower marks in the Undergraduate Medical Admissions Test paper 2. Clinical skills problems were less likely in graduate students. CONCLUSIONS: In our students, difficulty with clinical skills was just as prevalent as medical knowledge deficit. International entry students were at highest risk for clinical skills problems probably because they were not selected by our usual criteria and had shorter time to become acculturated.

Cardiac cephalgia: a diagnostic headache.

A 73-year-old man presented with a 6-month history of exertional headaches. Exercise tolerance test demonstrated progressive ischaemic changes concomitant with worsening headache. Cardiac cephalgia was diagnosed and his symptoms resolved after coronary artery bypass surgery. Cardiac cephalgia may occasionally present as exertional headache without chest symptoms.

Heparin-based treatment to prevent symptomatic deep venous thrombosis, pulmonary embolism or death in general medical inpatients is not supported by best evidence.

Prevention of venous thromboembolism (VTE) in medical patients is controversial. In contrast to surgical patients, the evidence supporting the use of heparin-based treatment for prevention of VTE (HVTEp) may not justify current guidelines. This study aims to determine whether current clinical guidelines for HVTEp are appropriate for medical patients. We searched medical databases for original randomised placebo-controlled studies of HVTEp in medical patients, excluding those with stroke and in intensive care. From 401 potentially relevant studies, we selected eight, which included over 16 000 patients. HVTEp decreased the incidence of all deep venous thromboses (DVT): 4.3% in the placebo group versus 2.3% in the treatment group, P = 0.002, number needed to treat, 50. However, this treatment effect was not seen for symptomatic DVT: 1.2% versus 0.9%, P = 0.18, odds ratio (OR) 0.72 (0.45-1.16). Similarly, HVTEp did not decrease the incidence of pulmonary embolism (PE): 0.54% versus 0.27%, P = 0.3, OR 0.57 (0.21-1.53), or fatal PE: 0.1% versus 0.0%, P = 0.3, OR 0.2 (0.01-4.11). Furthermore, HVTEp did not decrease total mortality: 5.63% versus 5.39%, P = 0.92, OR 0.96 (0.78-1.18). The use of HVTEp in hospitalised general medical patients does not result in a significant reduction in symptomatic DVT, PE, fatal PE or total mortality. The best evidence does not support the recommendations of the current clinical guidelines.

Adverse drug events are a major cause of acute medical admission.

BACKGROUND: Adverse drug events (ADE) contribute significantly to hospital admissions. Prospective New Zealand data are scant, and the ability of clinical coding to identify ADE associated admissions is uncertain. Outcomes after cessation of causative medications are unknown. AIMS: To assess the frequency, nature and causality of ADE associated with acute admissions to General Medicine at Christchurch Hospital. METHODS: Prospective observational study of patients admitted to our medical team over 20 weeks. RESULTS: Of 336 admissions, 96 (28.6%) were ADE related. Sixty-five (19.3%) were caused by an ADE, and 31 (9.2%) were contributed to by an ADE. The mean age of non-ADE patients was 64.3 years (range 16-91), which was similar to the mean age of ADE patients (65.9 years; 21-92). However, if intentional overdoses and recreational drug use were excluded, ADE patients were significantly older at 72.4 years (21-92) (P = 0.0007). ADE patients took more regular medications on admission (mean 6.6, range 0-22) than non-ADE patients (mean 5.0, 0-18), (P = 0.003). The average length of stay was similar. The commonest medications implicated were vasodilators, psychotropics and diuretics. The most common adverse effects were postural hypotension and/or vasovagal syncope (29% of ADE), intentional overdoses and recreational drug use (15%) and acute renal failure and/or clinical dehydration (10%). Seventy-six patients had culprit medications stopped or reduced, and this potentially contributed to six readmissions. Coding identified 61% of ADE associated admissions. CONCLUSION: ADE are a common cause of hospital admission. The most frequent problems are postural hypotension and vasovagal syncope, intentional drug misuse and dehydration.

A Coordinated Effort to Manage Soybean Rust in North America: A Success Story in Soybean Disease Monitoring.

Existing crop monitoring programs determine the incidence and distribution of plant diseases and pathogens and assess the damage caused within a crop production region. These programs have traditionally used observed or predicted disease and pathogen data and environmental information to prescribe management practices that minimize crop loss. Monitoring programs are especially important for crops with broad geographic distribution or for diseases that can cause rapid and great economic losses. Successful monitoring programs have been developed for several plant diseases, including downy mildew of cucurbits, Fusarium head blight of wheat, potato late blight, and rusts of cereal crops. A recent example of a successful disease-monitoring program for an economically important crop is the soybean rust (SBR) monitoring effort within North America. SBR, caused by the fungus Phakopsora pachyrhizi, was first identified in the continental United States in November 2004. SBR causes moderate to severe yield losses globally. The fungus produces foliar lesions on soybean (Glycine max) and other legume hosts. P. pachyrhizi diverts nutrients from the host to its own growth and reproduction. The lesions also reduce photosynthetic area. Uredinia rupture the host epidermis and diminish stomatal regulation of transpiration to cause tissue desiccation and premature defoliation. Severe soybean yield losses can occur if plants defoliate during the mid-reproductive growth stages. The rapid response to the threat of SBR in North America resulted in an unprecedented amount of information dissemination and the development of a real-time, publicly available monitoring and prediction system known as the Soybean Rust-Pest Information Platform for Extension and Education (SBR-PIPE). The objectives of this article are (i) to highlight the successful response effort to SBR in North America, and (ii) to introduce researchers to the quantity and type of data generated by SBR-PIPE. Data from this system may now be used to answer questions about the biology, ecology, and epidemiology of an important pathogen and disease of soybean.

At the heart of the arterial baroreflex: a physiological basis for a new classification of carotid sinus hypersensitivity.

The aim of this review is to provide an update of the current knowledge of the physiological mechanisms underlying reflex syncope. Carotid sinus syncope will be used as the classical example of an autonomic reflex with relatively well-established afferent, central and efferent pathways. These pathways, as well as the pathophysiology of carotid sinus hypersensitivity (CSH) and the haemodynamic effects of cardiac standstill and vasodilatation will be discussed. We will demonstrate that continuous recordings of arterial pressure provide a better understanding of the cardiovascular mechanisms mediating arterial hypotension and cerebral hypoperfusion in patients with reflex syncope. Finally we will demonstrate that the current criteria to diagnose CSH are too lenient and that the conventional classification of carotid sinus syncope as cardioinhibitory, mixed and vasodepressor subtypes should be revised because isolated cardioinhibitory CSH (asystole without a fall in arterial pressure) does not occur. Instead, we suggest that all patients with CSH should be thought of as being 'mixed', between cardioinhibition and vasodepression. The proposed stricter set of criteria for CSH should be evaluated in future studies.

MSNA during prolonged post-faint hypotension.

BACKGROUND: Following tilt-induced syncope, blood pressure usually recovers rapidly after tilt back to the horizontal position. However, in some patients, hemodynamic recovery is delayed, a condition recently termed "prolonged post-faint hypotension" (PPFH). The mechanism is thought to be mediated by increased vagal outflow rather than exaggerated peripheral vasodilatation and sympathetic withdrawal. To date, no muscle sympathetic nerve activity (MSNA) recordings have been reported in this condition, so we aimed to confirm that neither vasodilatation nor MSNA withdrawal was responsible. OBJECTIVES: To retrospectively select patients with satisfactory recordings of continuous BP and MSNA during tilt-induced syncope. To compare hemodynamic and MSNA profiles in patients with PPFH to patients with normal recovery (NR) after tilt-back. METHODS: All patients were studied in Christchurch, New Zealand, between 1998 and 2008 using continuous arterial BP monitoring, and microneurographic recordings of MSNA from the right leg. Only patients with satisfactory BP and MSNA data throughout baseline, head-up tilt and presyncope were selected. Stroke volume (SV), cardiac output (CO), and total peripheral resistance (TPR) were derived using Modelflow. After baseline measurements, patients were tilted to the head-up 60° position and given GTN spray if asymptomatic after 20 min. Following the onset of presyncope, patients were tilted slowly back to the horizontal. PPFH was defined as systolic BP <85 mmHg for at least 2 min after tilt-back. Measurements were averaged at baseline, early tilt, presyncope, early and late recovery. Within-group comparisons were made between baseline and all other time points. Between-group comparisons were made over all time points. RESULTS: Patients with PPFH (7 males, age 46 ± 5 years, n = 8) and with NR (8 males, age 47 ± 6 years, n = 8) were selected. Presyncope was provoked by GTN in 4/8 patients in each group. In both groups, MAP remained below baseline during early and late recovery: PPFH 84 ± 5 versus 51 ± 5 and 64 ± 5 mmHg (p = 0.001, p = 0.001); NR 104 ± 5 versus 83 ± 5 and 93 ± 5 mmHg (p = 0.001, p = 0.03). However, MAP and HR were lower in the PPFH group (p = 0.004, p = 0.023). During early recovery, CO remained below baseline only in the PPFH group (p = 0.001), whereas TPR remained constant in both groups. In both groups, all MSNA indices tended to remain above baseline levels during early and late recovery. PPFH 25 ± 2 increased to 31 ± 6 and 29 ± 4 bursts/min (p = 0.09, 0.02); NR 23 ± 3 increased to 33 ± 3 and 34 ± 3 bursts/min (p = 0.06, 0.01). CONCLUSIONS: PPFH does not appear to be mediated by exaggerated vasodilatation or sympathetic withdrawal. Delayed recovery of cardiac output by increased vagal outflow is a more likely mechanism.

Polypharmacy--we make it worse! A cross-sectional study from an acute admissions unit.

Although polypharmacy is a major problem in the elderly, very few data have been published from Australasia. We retrospectively audited 68% of elderly patients admitted acutely to our medical unit (n= 424, mean age 80.3 ± 8 years) during a 30-day period (September, 2008). We found that long-term medications increased during hospital stay from 6.6 ± 4 to 7.7 ± 4 (P < 0.001). Adverse drug reactions were responsible for 24 admissions (5.7%). Polypharmacy is made worse by acute admission to hospital.

Prolonged post-faint hypotension can be reversed by dynamic tension.

A severe variant of vasovagal syncope, observed during tilt tests and blood donation has recently been termed "prolonged post-faint hypotension" (PPFH). A 49-year-old male with a life-long history of severe fainting attacks underwent head-up tilt for 20 min, and developed syncope 2 min after nitroglycerine spray. He was unconscious for 40 s and asystolic for 22 s. For the first 2 min of recovery, BP and HR remained low (65/45 mmHg and 40 beats/min) despite passive leg-raising. Blood pressure (and symptoms) only improved following active bilateral leg flexion and extension ("dynamic tension"). During PPFH, when vagal activity is extreme, patients may require central stimulation as well as correction of venous return.

Forensic validation of a SNP and INDEL panel for individualisation of timber from bigleaf maple (Acer macrophyllum Pursch).

Illegal logging is one of the largest illicit trades in the world, with high profits and generally low risks of detection and prosecution. Timber identification presents problems for law enforcement as traditionally used forensic methods such as wood anatomy and dendrochronology are often unable to confidently match wood evidence to the remains of illegally felled trees. Here we have developed and validated a set of genetic markers for individualisation in bigleaf maple (Acer macrophyllum), a high value timber species often felled illegally in the USA. Using 128 single nucleotide polymorphisms and three insertion/deletion markers developed through massively parallel sequencing, 394 individuals were genotyped on the MassARRAY® iPLEX™ platform (Agena Bio-science™, San Diego, USA) to produce a population reference database for the species. We demonstrate that the resulting DNA assay is reliable, species specific, effective at low DNA concentrations (<1 ng/µL) and suitable for application to timber samples. The PID for the most common profile, calculated using an overall dataset level FST-correction factor, was 1.785 × 10-25 and PID-SIB across all individuals (treated as a single population) was 2.496 × 10-22. The further development of forensic identification assays for timber species has the potential to deliver robust tools for improved detection and prosecution of illegal logging crimes as well as for the verification of legality in reputable supply chains.

Vagolysis.

We describe the case of a 75-year-old man presenting with labile hypertension and symptomatic postural hypotension 13 months following radiotherapy for squamous cell carcinoma of his external auditory canal. Magnetic resonance image (MRI) scan demonstrated scarring and a probable recurrence of his tumour. He underwent autonomic testing, including muscle sympathetic nerve activity (MSNA), heart rate (HR) and blood pressure (BP) responses to a variety of stimuli. Results were consistent with baroreflex failure. Urinary catecholamine levels were within the high normal range. We postulate that baroreflex failure was caused by vagal and glossopharyngeal nerve damage secondary to radiotherapy and tumour recurrence. This diagnosis is rare, but should be considered with pure autonomic failure and phaeochromocytoma in the presence of labile hypertension, especially in patients with a history of radiotherapy to the neck and high-normal catecholamine levels.

Tilt-test diagnosis of hypotensive transient ischaemic attacks.

Eight elderly patients with postural hypotension who presented with transient ischaemic attacks are reported. Six patients underwent head-up tilt testing with continuous blood pressure monitoring. During tilt, postural hypotension was found in five patients and in three patients transient ischaemic attacks were reproduced. Postural hypotension is probably a rare cause of transient ischaemic attacks, but may be underrecognized.

The crystal structure of plasminogen activator inhibitor 2 at 2.0 A resolution: implications for serpin function.

BACKGROUND: Plasminogen activator inhibitor 2 (PAI-2) is a member of the serpin family of protease inhibitors that function via a dramatic structural change from a native, stressed state to a relaxed form. This transition is mediated by a segment of the serpin termed the reactive centre loop (RCL); the RCL is cleaved on interaction with the protease and becomes inserted into betasheet A of the serpin. Major questions remain as to what factors facilitate this transition and how they relate to protease inhibition. RESULTS: The crystal structure of a mutant form of human PAI-2 in the stressed state has been determined at 2.0 A resolution. The RCL is completely disordered in the structure. An examination of polar residues that are highly conserved across all serpins identifies functionally important regions. A buried polar cluster beneath betasheet A (the so-called 'shutter' region) is found to stabilise both the stressed and relaxed forms via a rearrangement of hydrogen bonds. CONCLUSIONS: A statistical analysis of interstrand interactions indicated that the shutter region can be used to discriminate between inhibitory and non-inhibitory serpins. This analysis implied that insertion of the RCL into betasheet A up to residue P8 is important for protease inhibition and hence the structure of the complex formed between the serpin and the target protease.

Assessing Heterodera glycines-Resistant and Susceptible Cultivar Yield Response.

The soybean cyst nematode Heterodera glycines (SCN) is of major economic importance and widely distributed throughout soybean production regions of the United States where different maturity groups with the same sources of SCN resistance are grown. The objective of this study was to assess SCN-resistant and -susceptible soybean yield responses in infested soils across the north-central region. In 1994 and 1995, eight SCN-resistant and eight SCN-susceptible public soybean cultivars representing maturity groups (MG) I to IV were planted in 63 fields, either infested or noninfested, in 10 states in the north-central United States. Soil samples were taken to determine initial SCN population density and race, and soil classification. Data were grouped for analysis by adaptation based on MG zones. Soybean yields were 658 to 3,840 kg/ha across the sites. Soybean cyst nematode-resistant cultivars yielded better at SCN-infested sites but lost this superiority to susceptible soybean cultivars at noninfested sites. Interactions were observed among initial SCN population density, cultivar, and location. This study showed that no region-wide predictive equations could be developed for yield loss based on initial nematode populations in the soil and that yield loss due to SCN in our region was greatly confounded by other stress factors, which included temperature and moisture extremes.

Adrenomedullin increases cardiac sympathetic nerve activity in normal conscious sheep.

The sympathetic nervous system and adrenomedullin (AM) both participate in the regulation of cardiac and circulatory function but their interaction remains uncertain. We have examined the effects of AM on cardiac sympathetic nerve activity (CSNA) and hemodynamics and contrasted these effects with pressure-matched nitro-prusside (NP) administration in normal conscious sheep. Compared with vehicle control, arterial pressure fell similarly with AM (P=0.04) and NP (P<0.001). Heart rate rose in response to both AM (P<0.001) and NP (P=0.002) but the rise with AM was significantly greater than that induced by NP (P<0.001). Cardiac output increased in response to AM compared with both control and NP (both P<0.001). CSNA burst frequency (bursts/min) were increased in response to both AM (P<0.001) and NP (P=0.005) with the rise in burst frequency being greater with AM compared with NP (P<0.001). CSNA burst area/min was also raised by both AM (P=0.03) and NP (P=0.002) with a trend for burst area being greater with AM than NP (P=0.07). CSNA burst incidence (bursts/100 beats) showed no significant differences between any treatment day. In conclusion, we have demonstrated that AM is associated with a greater increase in CSNA and heart rate for a given change in arterial pressure than seen with the classic balanced vasodilator NP.