Patient actions and reactions after receiving negative results from expanded carrier screening.

With the expansion of carrier screening to general preconception and prenatal patient populations, most patients will receive negative results, which we define as indicating <25% risk of having a child with a genetic condition. Because there is limited experience with expanded carrier screening, it is important to understand how receiving negative results affects patients, especially as providers, payers, and policymakers consider whether to offer it. In this mixed-methods study, we asked preconception patients enrolled in the NextGen study about their expectations and experiences receiving negative expanded carrier screening results. Participants completed surveys at study enrollment (n = 110 women, 51 male partners), after receiving carrier results (n = 100 women, 38 male partners), after receiving secondary findings (n = 98 women, 36 male partners), and 6 months after receiving results (n = 95 women, 28 male partners). We also interviewed a subset of participants 12 to 24 months after receiving results (n = 24 women, 12 male partners). We found minimal negative emotional impact and privacy concerns, increased confidence in reproductive plans, and few changes to health behaviors, although some patients made health decisions based on misunderstandings of their results. These findings suggest that expanded carrier screening causes minimal psychosocial harms, but systems are needed to reduce the risk of misinterpreting results.

Loss of NPC1 function in a patient with a co-inherited novel insulin receptor mutation does not grossly modify the severity of the associated insulin resistance.

In Npc1 null mice, a model for Niemann Pick Disease Type C1, it has been reported that hepatocyte insulin receptor function is significantly impaired, consistent with growing evidence that membrane fluidity and microdomain structure have an important role in insulin signal transduction. However, whether insulin receptor function is also compromised in human Niemann Pick disease Type C1 is unclear. We now report a girl who developed progressive dementia, ataxia and opthalmoplegia from 9 years old, followed by severe acanthosis nigricans, hirsutism and acne at 11 years old. She was diagnosed with Niemann Pick Disease type C1 (OMIM#257220) based on positive filipin staining and reduced cholesterol-esterifying activity in dermal fibroblasts, and homozygosity for the p.Ile1061Thr NPC1 mutation. Further analysis revealed her also to be heterozygous for a novel trinucleotide deletion (c.3659 + 1_3659 + 3delGTG) at the end of exon 20 of INSR, encoding the insulin receptor, leading to deletion of Trp1193 in the intracellular tyrosine kinase domain. INSR mRNA and protein levels were normal in dermal fibroblasts, consistent with a primary signal transduction defect in the mutant receptor. Although the proband was significantly more insulin resistant than her father, who carried the INSR mutation but was only heterozygous for the NPC1 variant, their respective degrees of IR were very similar to those previously reported in a father-daughter pair with the closely related p.Trp1193Leu INSR mutation. This suggests that loss of NPC1 function, with attendant changes in membrane cholesterol composition, does not significantly modify the IR phenotype, even in the context of severely impaired INSR function.

Personal protective equipment provision in prehospital care: a national survey.

BACKGROUND: Safety in prehospital practice is a paramount principle. Personal protective equipment (PPE) use is intrinsic to safe practice. There is varied guidance as to what constitutes effective PPE. No evidence is available of what current provision encompasses. METHODS: A questionnaire-based study directed to all ambulance trusts, British Association for Immediate Care (BASICS) schemes and air ambulance operations in England, Scotland and Wales. RESULTS: Total response rate was in excess of 66%. A specific protocol for PPE use was issued by 81%, 89% and 38% of ambulance trusts, air ambulance and BASICS schemes, respectively. There was a wide variation in provision of PPE both within and between different groups of providers. Fewer than 55% of providers had an evaluation system in place for reviewing PPE use. CONCLUSIONS: Many reasons account for the differences in provision. There is a clear need for a standard to be set nationally in conjunction with locally implemented evaluation and re-accreditation processes.

Ultra-high resolution array painting facilitates breakpoint sequencing.

OBJECTIVE: To describe a considerably advanced method of array painting, which allows the rapid, ultra-high resolution mapping of translocation breakpoints such that rearrangement junction fragments can be amplified directly and sequenced. METHOD: Ultra-high resolution array painting involves the hybridisation of probes generated by the amplification of small numbers of flow-sorted derivative chromosomes to oligonucleotide arrays designed to tile breakpoint regions at extremely high resolution. RESULTS AND DISCUSSION: How ultra-high resolution array painting of four balanced translocation cases rapidly and efficiently maps breakpoints to a point where junction fragments can be amplified easily and sequenced is demonstrated. With this new development, breakpoints can be mapped using just two array experiments: the first using whole-genome array painting to tiling resolution large insert clone arrays, the second using ultra-high-resolution oligonucleotide arrays targeted to the breakpoint regions. In this way, breakpoints can be mapped and then sequenced in a few weeks.

Driving behaviors associated with emergency service vehicle crashes in the U.S. fire service.

OBJECTIVE: Emergency service vehicle incidents are a leading cause of firefighter fatalities and are also hazardous to civilian road users. Modifiable driving behaviors may be associated with emergency service vehicle incidents. The goal of this study was to use telematics to identify driving behaviors associated with crashes in the fire service. METHODS: Forty-three emergency service vehicles in 2 fire departments were equipped with telematics devices (12 in Department A and 31 in Department B). The devices collected vehicle coordinates, speed, and g forces, which were monitored for exceptions to driving rules established by the fire departments regarding speeding, harsh braking, and hard cornering. Fire department administrative reports were used to identify vehicles involved in crashes and merged with daily telematics data. Penalized logistic regression was used to identify driving rules associated with crashes. Least absolute shrinkage and selection operator (LASSO) regression was used to generate a telematics-based risk index for emergency service vehicle incidents. RESULTS: Nearly 1.1 million km of driving data and 44 crashes were recorded among the 2 departments during the study. Harsh braking was associated with increased odds of crash in Department A (odds ratio [OR] = 2.22; 95% confidence interval [CI], 1.09-4.51) and Department B (OR = 1.55; 95% CI, 1.12-2.15). For every kilometer of nonemergency speeding, the odds of crash increased by 35% in Department A (OR = 1.35; 95% CI, 1.03-1.77) and by over 2-fold in Department B (OR = 2.09; 95% CI, 1.19-3.66). In Department B, hard cornering (OR = 1.14; 95% CI, 1.03-1.26) and emergency speeding (OR = 1.65; 95% CI, 1.06-2.57) were also associated with increased odds of crash. The final LASSO risk index model had a sensitivity of 73% and specificity of 57%. CONCLUSIONS: Harsh braking and excessive speeding were driving behaviors most associated with crash in the fire service. Telematics may be a useful tool for monitoring driver safety in the fire service.

Anatomical measurements of porcine lumbar vertebrae.

BACKGROUND: Porcine spines are frequently used as an alternative to human specimens for spinal implant testing. Morphometric data of the normal porcine lumbar vertebrae are lacking at this time, yet these data are crucial for application to such studies. This study provides such a database and highlights the differences between porcine and human specimens. METHODS: All the lumbar vertebrae (L1-L6) from six adult (18-24 month old, 60-80 kg) male porcine spines were used in our study (n=36). A total of 15 anatomical parameters from each vertebra were measured by two observers. Linear parameters were measured using digital calipers. The mean, standard deviation and standard error of mean were calculated using Microsoft Excel. Results from our study were compared with available data on human vertebra. FINDINGS: Compared to the human vertebrae, there were several anatomical differences in the porcine thoracolumbar vertebrae including smaller end plate area, larger pedicles, taller and narrower vertebral bodies, narrower spinal canals and smaller spinous process lengths. INTERPRETATION: Our results provide a database of anatomical measurements for porcine lumbar vertebrae and highlight their differences with human vertebrae. Porcine vertebrae may be used as an alternative to human specimen if these differences are taken into account. Studies which involve testing implants such as interbody cages, disc replacements and pedicle screw-rod systems in porcine spines should match implant size appropriately.

Tourniquet use in the civilian prehospital setting.

Tourniquets are an effective means of arresting life-threatening external haemorrhage from limb injury. Their use has not previously been accepted practice for pre-hospital civilian trauma care because of significant concerns regarding the potential complications. However, in a few rare situations tourniquet application will be necessary and life-saving. This review explores the potential problems and mistrust of tourniquet use; explains the reasons why civilian pre-hospital tourniquet use may be necessary; defines the clear indications for tourniquet use in external haemorrhage control; and provides practical information on tourniquet application and removal. Practitioners need to familiarise themselves with commercial pre-hospital tourniquets and be prepared to use one without irrational fear of complications in the appropriate cases.

The complex nature of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes.

OBJECTIVE: To describe the systematic analysis of constitutional de novo apparently balanced translocations in patients presenting with abnormal phenotypes, characterise the structural chromosome rearrangements, map the translocation breakpoints, and report detectable genomic imbalances. METHODS: DNA microarrays were used with a resolution of 1 Mb for the detailed genome-wide analysis of the patients. Array CGH was used to screen for genomic imbalance and array painting to map chromosome breakpoints rapidly. These two methods facilitate rapid analysis of translocation breakpoints and screening for cryptic chromosome imbalance. Breakpoints of rearrangements were further refined (to the level of spanning clones) using fluorescence in situ hybridisation where appropriate. RESULTS: Unexpected additional complexity or genome imbalance was found in six of 10 patients studied. The patients could be grouped according to the general nature of the karyotype rearrangement as follows: (A) three cases with complex multiple rearrangements including deletions, inversions, and insertions at or near one or both breakpoints; (B) three cases in which, while the translocations appeared to be balanced, microarray analysis identified previously unrecognised imbalance on chromosomes unrelated to the translocation; (C) four cases in which the translocation breakpoints appeared simple and balanced at the resolution used. CONCLUSIONS: This high level of unexpected rearrangement complexity, if generally confirmed in the study of further patients, will have an impact on current diagnostic investigations of this type and provides an argument for the more widespread adoption of microarray analysis or other high resolution genome-wide screens for chromosome imbalance and rearrangement.

Array painting: a method for the rapid analysis of aberrant chromosomes using DNA microarrays.

OBJECTIVE: The authors describe a method, termed array painting, which allows the rapid, high resolution analysis of the content and breakpoints of aberrant chromosomes. METHODS: Array painting is similar in concept to reverse chromosome painting and involves the hybridisation of probes generated by PCR of small numbers of flow sorted chromosomes on large insert genomic clone DNA microarrays. RESULTS: and CONCLUSIONS: By analysing patients with cytogenetically balanced chromosome rearrangements, the authors show the effectiveness of array painting as a method to map breakpoints prior to cloning and sequencing chromosome rearrangements.

Bacterial meningitis in the absence of CSF pleocytosis.

Two cases of acute bacterial meningitis occurred with an absent CSF WBC response. To determine the incidence and clinical characteristics of such patients, 50 consecutive cases of meningitis were reviewed retrospectively. In addition to the two initially noted cases, five additional cases were found. In the seven cases, there were six or fewer cells, but bacteria were detected in the CSF. A distinctive clinical and laboratory syndrome emerged. All seven patients were either old or had Hodgkin's disease or severe alcoholism. All patients had evidence of an overwhelming infection with confusion or nuchal rigidity. As compared with the remaining 45 patients with meningitis and CSF pleocytosis, no fever (less than 38 degrees C), a lower peripheral WBC count, and near-normal CSF glucose and protein concentrations were common. Organisms involved were EScherichia coli in three patients, Pneumococcus in three patients, and mixed anaerobes in patient. A fatal outcome ensued in six of seven patients. Despite the correct choice of an antibacterial agent, doses were late and suboptimal for meningitis. This syndrome is surprisingly common in host-defective cases, has an ominous prognosis, and must be treated expectantly with antimicrobial agents that enter the CSF.

Passing the Diploma in Immediate Medical Care of the Royal College of Surgeons of Edinburgh.

The Diploma in Immediate Care of the Royal College of Surgeons of Edinburgh is increasingly recognised as a gold standard for immediate care practitioners, including doctors with a significant involvement in prehospital care, paramedics who wish to enhance their knowledge base or obtain the Diploma as an entry requirement for a post registration degree, and for nurses who have a recognised and developing role in the evolving emergency medical services. This paper provides information about the Diploma examination including eligibility, the syllabus and the components of the examination, and comments on the reason for failure and provides suggestions for training and education to enhance the candidate's opportunity of passing the examination.

Emergencies in the air.

Medical emergencies in the air are topical. This study, undertaken by the Faculty of Prehospital Care at the Royal College of Surgeons of Edinburgh, analyses retrospectively consecutive medical emergencies occurring over a 6 month period on a single major international airline. Clinical problems are related to pre-existing problems (65%), new medical problems (28%), and traumatic injury (7%). The paper highlights the need for better pre-flight health advice and screening, a reminder to carry personal medication-especially for asthma-and the need to include ankle and leg exercises prior to getting out of the seat to reduce the incidence of syncope, which was responsible for 91% of new medical problems.

Prehospital management of lower limb fractures.

Lower limb fractures are common injuries in prehospital care. Untreated fractures can lead to hypovolaemic shock especially if open, and should be treated with effective haemorrhage control and splintage. A brief assessment for open fractures, deformity, and neurovascular compromise should be followed by effective analgesia, wound management, reduction (if needed), splintage, and packaging of the patient. Early appropriate management reduces the morbidity and mortality of lower limb fractures.

Are we able to comply with the NICE head injury guidelines?

BACKGROUND: An estimated 120,000 patients are admitted to hospital in England and Wales each year for neurological observations following a head injury. The National Institute for Clinical Excellence (NICE) has issued guidelines on the quality and frequency of neurological observations that should be made. OBJECTIVE: Review of frequency and quality of observations in one trauma unit. STUDY DESIGN: Prospective audit of current practice. METHOD: Data on 100 consecutive patients admitted to a trauma unit for neurological observations were audited to monitor the consistency and frequency of neurological observations requested by the admitting doctor. Medical staff had previously been briefed on the recommendations of the NICE head injury guidelines. RESULTS: A detailed evaluation revealed inconsistency and inexplicable gaps in observations. No single set of observations was complete. Sequential regular monitoring was difficult for many reasons, bringing into question the safety and reliability of current practice. CONCLUSIONS: The introduction of the new guidelines which recommend more frequent neurological observations has major staffing implications, where underperformance raises significant clinical governance issues. All hospitals admitting patients with head injuries should have an established protocol based on the NICE guidelines with observations recorded on an appropriately designed data collection form. Trained nursing staff have enormous work and time pressures including direct patient care, ward rounds, drug rounds, administration, management, and responding to emergencies. The development of a competency based training programme for auxiliary nursing staff to undertake neurological observations, including when to report concerns, is one solution to reduce the pressure on trained nursing staff.

Reduction of the posterior pelvic ring by non-invasive stabilisation: a report of two cases.

We demonstrate radiological evidence that an external pelvic splint is effective at reducing open book pelvic fractures. Its use in the pre-hospital and emergency department settings should be encouraged in the initial management and resuscitation of patients with pelvic fractures.

The UK emergency department practice for spinal board unloading. Is there conformity?

INTRODUCTION: Guidelines for the management of suspected spinal injury patients from the scene of their accident to the emergency department were published in September 1998. This study was commissioned on behalf of the Faculty of Pre-hospital Care at the Royal College of Surgeons of Edinburgh, to examine the handling of patients on spinal boards on arrival in the emergency department. METHOD: In July 2000, 132 postal questionnaires were sent to the consultants of the emergency departments in the United Kingdom (UK) that receive more than 50000 patients per annum. Four simple questions related to spinal board handling were asked. RESULTS: A response rate of 63.6% was achieved and analysis showed that log roll was the technique most commonly used to remove the patient from the board in 90% of cases. In 76.3% of departments this occurred as part of secondary survey although in which part of the secondary survey that this took place was less clear. CONCLUSIONS: It is suggested that as the spine board is such a widely used piece of equipment, there should be some guidelines to standardise its use at the emergency department interface with pre-hospital care. We recommend that spinal board removal should be part of the completion of the primary survey.

A review of emergency equipment carried and procedures performed by UK front line paramedics.

OBJECTIVES: To assess which items of resuscitation equipment are carried on United Kingdom (UK) front line ambulances and what procedures paramedics are able to perform. To compare these findings with those of a previous survey in 1997. METHOD: Postal survey to the chief executives of all the UK ambulance services and direct comparison with the data from 1997. RESULTS: Nasopharyngeal airway usage (NPA) has increased (21-55%) and the laryngeal mask airway (LMA) (from 10 to 26%). No services employ the Combitube. 94% of services use a Hudson type trauma mask (increase of 17%). One service no longer allows its paramedics to deliver 12-15 l of oxygen. 68% of trust paramedics can perform needle thoracocentesis (increase of 35%). No paramedics perform chest drain insertion. All services have 14G intravenous cannulae available and 45% carry the intraosseous needle (increase of 30%). No services employ the MAST suit. There is an increase by 29% in the use of crystalloids and a decrease in the use of colloids of 22%. 23% of fluid resuscitation protocols are based upon the principles of hypotensive resuscitation. Spinal boards and extrication devices are used by 97% of services. The use of inflatable splints has decreased (38-23%). There has been a minor increase in the use of traction splints to 74% of services. The use of Entonox is universal. Nalbuphine (Nubain) is the most widely used opioid. The use of morphine/diamorphine has doubled to 10% with a further 26% to introduce their use. 29% of services have equipped some vehicles with automatic external defibrillators. CONCLUSIONS: The equipment available to UK paramedics and procedures that they may perform continues to expand. There are still variations in the basic management of airway, breathing and circulation care and only some services are keeping up to date with current medical thinking, for example the increasing use of crystalloids and hypotensive resuscitation. It remains to be seen whether the widespread use of Nalbuphine as a first line analgesic may decrease as the use of natural strong opiates becomes more widespread.

Pre-hospital care--the evolution of a course for undergraduates.

Newly qualified doctors are ill equipped to deal with pre-hospital trauma emergencies. There is a public perception that medical education provides both experience and knowledge in this field. In Birmingham, United Kingdom (UK), committed doctors and nurses trained in pre-hospital care have evolved a specific course designed to equip the medical undergraduate to deal with pre-hospital trauma scenario. The pre-hospital trauma course for medical students has run annually from 1993 to 2000. The course caters for 200 students with a faculty of 30 instructors. Successful completion of the course which is rigorously assessed grants a certificate awarded by the Faculty of Pre-hospital Care at the Royal College of Surgeons of Edinburgh. Most importantly it equips the undergraduate with essential theoretical knowledge and practical skills to handle a pre-hospital trauma emergency.

Hindfoot disability after a tibial shaft fracture treated by internal fixation.

One hundred patients who had sustained a fracture of the tibial shaft and had been treated by internal fixation were reviewed to obtain information on residual ankle and subtalar disability. This study reinforces the belief that early mobilisation of patients with tibial shaft fractures does help to preserve subtalar movement.

The resolution of protrusio acetabuli treated with Ring's hip prosthesis.

Seven hips with protrusio acetabuli which showed complete or partial resolution of the protrusion after replacement with Ring's prosthesis are reported. It is suggested that this prosthesis offers a simple and effective method of treating painful protrusion into the pelvis; it allows healing of the medial wall of the acetabulum while avoiding many of the hazards of other methods of treatment.