Clinical Ethics Case Study 8: Should we carry out a predictive genetic test in our young patient?

case studyReferral to the Clinical Ethics Committee: A request for genetic testing in childhood. S, a five-year old boy, has recently been seen with his mother C in the paediatric outpatient clinic. Sadly his father N died from metastatic cancer a few months ago, aged 30 years. Other members of N’s family have died in childhood or early adulthood from various forms of cancer. While N was unwell, it was discovered that he carried a mutation in the TP53 gene associated with Li-Fraumeni Syndrome (LFS). LFS is a cancer predisposition syndrome leading to a high risk of various aggressive cancers, including leukaemia, melanoma, soft-issue sarcoma and pancreatic, colon, brain or breast cancer. LFS runs in families and is inherited as an autosomal dominant trait, such that any child of a person with the TP53 gene change will have a 50% risk of inheriting the same mutation and a resultant high chance of developing one of these cancers. The type or age of onset of these cancers cannot be predicted. When N was unwell, his oncologists suggested that S be referred to a clinical genetics service for genetic testing for LFS. At that time the clinical team thought it was appropriate that testing should go ahead, however the laboratory that received the sample for testing let it be known that they thought it was not appropriate to test because S was a minor and that guidelines on genetic testing in children suggested such a test should not be done routinely. Testing therefore did not go ahead. The genetics team then referred S to a consultant paediatrician, recommending annual surveillance in accordance with professional guidelines written by a paediatric oncology society. This surveillance includes a thorough physical examination, routine blood tests (which may reveal leukaemia, for example), abdominal ultrasound to detect intra-abdominal malignancy and other indicated organ-specific surveillance tests. However, none of these measures have been shown to be effective in reducing morbidity or mortality for LFS. When we (the paediatricians) met S and his mother C in the outpatient clinic, we explained the surveillance programme, but indicated that a cancer, if it were to occur, might reveal itself between the annual checks, and might not be detected even if present. We discussed that there is little evidence that surveillance would improve the prognosis even if her son did carry the TP53 gene change. C was also warned that some screening methods, such as CT scanning, produce radiation in high doses and so could actually increase his risk of cancer if he was affected over and above detecting any abnormality. However, MRI scanning would be used when possible. During this recent appointment, C expressed her disappointment that S was not able to receive a genetic test for LFS. She was finding it difficult to manage his at-risk status and was particularly worried that whenever he developed an illness, or abdominal pain (both relatively common in childhood), he would require potentially complex and unpleasant tests. C said that if she knew his gene status, not only would she have greater certainty about what the future held, but unnecessary investigations might be avoided. We established that S was thriving and was not displaying any signs of ill health. We discussed the various issues with C, and although we felt that gene testing was a reasonable option we were concerned that to test now would deny S any say in the matter and that he might (when old enough) decide he would rather not know his risk status. On the other hand, we were also sympathetic to the idea of C’s parental autonomy to make decisions that were best for her family. If S’s status could be established now then he may be able to avoid further screening, although the uncertainty over the benefit of screening is also a difficult issue to resolve. We are approaching the ethics committee with the following questions in mind: 1. Should S be tested now for Li-Fraumeni syndrome? 2. In cases like this, how should we balance the interests of S with those of C or their wider family? 3. If we decide not to test S, how should this be managed in the clinic and with S over time? Or, If we do test him, how should this result be disclosed to S and when? 4. How should intra-disciplinary conflicts, such as a disagreement between the laboratory and the clinical team, be handled in practice?This article was written by Dr Ainsley Newson during the time of her employment with the University of Bristol, UK (2006-2012). Self-archived in the Sydney eScholarship Repository with permission of Bristol University, Sept 2014

Reproductive competition between polygynous parasite queens in ant colonies

BACKGROUND: Evaluation of percutaneous tracheostomy (PT) with the guide wire dilating forceps (GWDF) technique. METHODS: Prospective study of perioperative complications, retrospective analysis of early and late complications in an ICU in a teaching university hospital. RESULTS: The success rate of the procedure was 96.5%. The average procedure time in 171 consecutive patients was 5.0 min. Perioperative complications requiring surgical or medical intervention occurred in 6.4% of 171 patients. This included conversion to surgical tracheostomy, which was necessary in six patients (3.5%). Major complications while being cannulated occurred in 2.4% of 164 patients but seemed mostly unrelated with the GWDF technique itself. Late complications (after decannulation) were mostly minor and occurred in 22.6% of 106 patients. Only one patient (0.9%) had a symptomatic tracheal stenosis developed. CONCLUSION: Percutaneous tracheostomy with the guide wire dilating forceps technique is easy to perform at the bedside with few late complications. However, in our study, perioperative and immediate postoperative bleeding complications (minor and major) occur quite often

Pre-operative Evaluation of Eustachian Tube Function Using a Modified Pressure Equilibration Test is Predictive of Good Postoperative Hearing and Middle Ear Aeration in Type 1 Tympanoplasty Patients

ObjectivesThe Eustachian tube (ET) plays an important role in maintaining a normally aerated middle ear. Inflammation in middle ear disease is related to ET dysfunction, and postoperative restoration of middle ear integrity and hearing are closely related to ET function in chronic ear disease patients. After successful tympanoplasty, restoration of a well-aerated middle ear with good ET function can permit better compliance of the tympanic membrane. In this study, we evaluated the predictive validity of preoperative ET function measurements.MethodsWe reviewed 137 patients who underwent type 1 tympanoplasty. All patients had non-cholesteatomatous chronic otitis media and received canal wall-up-type tympanomastoidectomies. Patients were categorized into four groups according to preoperative ET function measurements using a modified pressure inflation-deflation equilibration test. Group I patients had residual pressures less than 10 daPa, and Group IV patients showed no pressure change (poor results). Groups II and III were intermediate. Hearing levels were determined using pure tone averages at four frequencies. Postoperative tympanography was performed to determine middle ear aeration.ResultsThe preoperative air bone (AB) gap was 29.6±7.0 dB, and the postoperative gap was 16.5±5.7 dB; thus, there was significant overall improvement. In all groups, hearing was significantly better after surgery, but the worst postoperative hearing level was seen in Group IV patients. Type B tympanograms were more frequently recorded in Group IV patients than they were in Group I or II patients. Postoperative AB gaps were 9.2±3.8 dB in patients with type A tympanograms, 13.4±2.1 dB in those with type As, 24.1±2.5 dB in those with type C, and 18.5±2.8 dB in those with type B.ConclusionET function measured with a modified pressure equilibration test using an inflation-deflation manometric method is a good indicator of an aerated middle ear and is predictive of improved postoperative hearing

Effectiveness of septoplasty versus non-surgical management for nasal obstruction due to a deviated nasal septum in adults: study protocol for a randomized controlled trial

Contains fulltext : 152163.pdf (publisher's version ) (Open Access)BACKGROUND: Septoplasty, i.e., surgical correction of the deviated nasal septum, is the most common ear, nose and throat (ENT) operation in adults. Currently the main indication to perform septoplasty is nasal obstruction. However, the effectiveness of septoplasty for nasal obstruction in adults with a deviated nasal septum remains uncertain. Scientific evidence is scarce and inconclusive, and internationally accepted guidelines are lacking. Moreover, there is no consensus on whether or not septoplasty should be combined with concurrent turbinate surgery. The objective of the current ongoing trial is to study the effectiveness of septoplasty (with or without concurrent turbinate surgery) as compared to non-surgical management for nasal obstruction in adults with a deviated nasal septum, both in terms of subjective (health-related quality of life) as well as objective (nasal patency) outcome measures. METHODS/DESIGN: The study is designed as a pragmatic, multicenter, parallel-group, randomized controlled trial. A total of 200 adults will be enrolled with nasal obstruction based on a deviated nasal septum and an indication for septoplasty according to current medical practice in the Netherlands. Participants will be randomized to either septoplasty (with or without concurrent turbinate surgery as originally indicated by the otorhinolaryngologist) or a non-surgical watchful waiting strategy. Follow-up visits will be scheduled at 0, 3, 6, 12, and 24 months. During each follow-up visit, health-related quality of life questionnaires will be administered and measurements of four-phase rhinomanometry and peak nasal inspiratory flow will be performed. Costs will be studied using a patient-based diary. Effects of septoplasty on health-related quality of life (primary outcome) and nasal patency will be calculated as mean differences with 95 % confidence intervals. Subgroup analyses according to gender, age, and severity of the septal deviation will be performed. All analyses will be performed on an intention-to-treat basis. DISCUSSION: With the results of this study we aim to contribute to the development of evidence-based guidelines regarding indications for septoplasty. TRIAL REGISTRATION: Nederlands Trial Register/Dutch Trial Registry ( www.trialregister.nl ), trial identifying number: NTR3868 . Registered on 21 February 2013

Three dimensional measurement of rhinoplasty results.

Contains fulltext : 81151.pdf (publisher's version ) (Open Access)BACKGROUND: Pre- and postoperative imaging is important and essential for evaluation of the results of rhinoplasty surgery. Two-dimensional photographs are used routinely for this purpose, but have several disadvantages as opposed to three-dimensional imaging techniques, such as stereophotogrammetry. This study is the first to describe the measurement of rhinoplasty results using stereophotogrammetry. The aim of this study was to evaluate the ability of 3D imaging to measure and objectify rhinoplasty results. METHODS: During a 6-month period all consecutive hump reduction patients were included in this prospective study. Pre- and postoperative 3D photographs were taken and compared. RESULTS: Twelve patients were studied. In ten of these twelve patients a significant volume reduction in the area of the nasal dorsum was found with stereophotogrammetry. The maximum decrease (i.e. lowering) of the nasal dorsum ranged from 0.8 to 4.4 mm. In two patients no reduction of the nasal dorsum was found. In both patients this was due to additional changes made to the nose during surgery. These changes, increased tip rotation and dorsal augmentation respectively, were also documented with stereophotogrammetry. CONCLUSIONS: Both pronounced as well as subtle postoperative changes of rhinoplasty surgery can be objectified and measured with stereophotogrammetry. This tool can be used to study whether surgical techniques have the desired effect on the nose, and to compare different techniques with each other

Validation of sonotubometry in healthy adults.

Contains fulltext : 51141.pdf (publisher's version ) (Open Access)BACKGROUND: Frequent active opening of the eustachian tube (ET) allows ventilation of the middle ear and equilibration of pressure changes. Active opening is accomplished by the contraction of the paratubal muscles during swallowing. Because a disturbance of the ventilatory function of the ET may contribute to the development of otitis media with effusion, it is important to investigate ET function. Sonotubometry can be used to detect whether the ET can open or not during swallowing acts. METHODS: We developed a sonotubometer to test ET ventilatory function in 36 healthy adults. The width of the test signal frequency was between 5500 and 8500 Hz (centre frequency of 7000 Hz) and the loudness was 95 dB. To test reproducibility, testing took place in two sessions of 10 swallowing acts each. RESULTS: Opening of the ET could be registered in 91.6 per cent of the subjects in at least one of the two measurements. The first and the second measurements were highly correlated, with a Spearman's coefficient of 0.907. CONCLUSION: We confirmed that there is generally a good ventilatory ET function in otologically healthy adults, although, in a few cases, ET opening was not registered. Furthermore, we confirmed that our sonometric test equipment had acceptable reproducibility. Sonotubometry is a promising method for assessing ventilatory ET function. Research is ongoing to test the discriminative power of sonotubometry in children with various otological conditions