The relationship between patients' perception of the effects of neurofibromatosis type 2 and the domains of the Short Form-36.

OBJECTIVES: To investigate the relationship between those issues concerning quality of life in patients with neurofibromatosis type 2 (NF2) as identified by the closed set NF2 questionnaire and the eight norm-based measures and the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form-36 (SF-36) Questionnaire. DESIGN: Postal questionnaire study. SETTING: Questionnaires sent to subjects' home addresses. PARTICIPANTS: Eighty-seven adult subjects under the care of the Manchester Multidisciplinary NF2 Clinic were invited to participate. MAIN OUTCOME MEASURES: Sixty-two (71%) completed sets of closed set NF2 questionnaires and SF-36 questionnaires were returned. RESULTS: Subjects with NF2 scored less than the norm of 50 on both the physical component summary and mental component summary scores and the eight individual norm-based measures of the Short Form-36 questionnaire. Correlations (using Kendall's tau) were examined between patients' perceptions of their severity of difficulty with the following activities and the eight norm-based measures and the physical component summary and mental component summary scores of the Short Form-36 questionnaire: Communicating with spouse/significant other (N = 61). The correlation coefficients were significant at the 0.01 level for the mental component summary score, together with three of the norm-based scores [vitality (VT), social functioning and role emotional]. Social communication (N = 62). All 10 correlations were significant at the 0.01 or 0.001 level. Balance (N = 59). All 10 correlations were highly significant at the P < 0.001 level. Hearing difficulties (N = 61). All correlations were significant at either the 0.01 level or less apart from the mental component summary score and three of the norm-based scores (role physical, VT and mental health). Mood change (N = 61). All correlations were significant at the 0.01 level or less, apart from one norm-based score (role physical). CONCLUSIONS: The Short Form-36 questionnaire has allowed us to relate patients' perceptions of their difficulties, as identified by the closed set NF2 questionnaire, to the physical and mental domains measured by this validated and widely used scale, and has provided further insight into areas of functioning affected by NF2.

Use of a closed set questionnaire to measure primary and secondary effects of neurofibromatosis type 2.

OBJECTIVES: To identify the greatest difficulties reported by people affected by neurofibromatosis type 2, and to determine the relationship between the primary and secondary effects of the disease. DESIGN: Postal questionnaire study. SETTING: Questionnaire sent to subjects' home addresses. PARTICIPANTS: Eighty-seven adult patients under the care of the Manchester multidisciplinary neurofibromatosis type 2 team were invited to take part. MAIN OUTCOME MEASURE: The response rate was 62 out of 87 (71 per cent). RESULTS: Respondents' answers emphasised that their greatest problem was deafness, which resulted in communication difficulties with social contacts, close partners, family and friends. Correlation coefficients indicated a relationship between general mood changes and hearing difficulties, social communication problems, balance difficulties and mobility problems. Self-confidence was significantly related only to social communication problems. CONCLUSIONS: The use of a closed set neurofibromatosis type 2 questionnaire identified hearing problems and subsequent communication difficulties as the main problems faced by people with this condition.

Comparison of different methods of risk stratification in urgent and emergency surgery.

BACKGROUND: The aim was to compare a number of risk scoring systems prospectively in a cohort of patients who underwent non-elective surgery. METHODS: This was a cohort study of 2349 consecutive patients who had urgent or emergency surgery in a district general hospital in the UK. All patients were scored prospectively using the Revised Goldman Cardiac Risk Index (RGCRI), Portsmouth modification of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM), Surgical Risk Score (SRS) and Biochemistry and Haematology Outcome Models (BHOM). Actual 30-day and 1-year survival rates were compared with the predicted outcomes using receiver-operator characteristic (ROC) curves and Hosmer-Lemeshow analysis. RESULTS: Some 141 patients (6.0 per cent) died within 30 days of operation. This increased to 254 (10.8 per cent) by 1 year. The area under the ROC curve for death within 30 days was 0.90 for P-POSSUM, 0.85 for SRS, 0.84 for BHOM and 0.73 for RGCRI. Only the first three risk scores were able to discriminate accurately within the groups (area under ROC curve over 0.8), with no significant variation between expected and observed mortality rates confirmed by Hosmer-Lemeshow analysis. Similar results were found for the ability of each score to predict outcome at 1 year. CONCLUSION: P-POSSUM, SRS and BHOM scoring systems were all able to predict outcome after emergency and urgent surgery, but the SRS had the advantage of ease of calculation. BHOM requires only the most commonly available blood test data and the computer holding these data can easily perform the calculation.

Lessons learned from a randomised controlled study of perioperative beta blockade in high risk patients undergoing emergency surgery.

BACKGROUND: Perioperative beta blockade has been shown to reduce mortality after major elective surgery. The aim of this study was to determine whether it could reduce the rate of death and morbidity from cardiac complications in high risk patients undergoing emergency surgery. METHODS: Over a one-year interval all patients undergoing major non-elective orthopaedic or general surgery were screened to identify those at high risk of cardiac complications. Consenting, high risk patients were randomly allocated atenolol or placebo for seven days, commencing at anaesthetic induction. Deaths and cardiac complications within 30 days were recorded. RESULTS: Some 2351 patients had an emergency operation; 145 were at high risk and eligible for the study. Of 89 patients approached, 57 initially consented. Only 38 patients, however, completed the study protocol, 19 were withdrawn. Of those who completed the study, 5/20 patients in the placebo group and 3/18 in the treatment group died before hospital discharge (p=0.520). Four others in the placebo group and two in the atenolol group had post-operative non-fatal cardiac events (positive troponin T), p=0.311. CONCLUSIONS: This study of emergency surgery proved more difficult than similar trials in elective surgery. The final study groups were small and there were no significant differences in outcomes. A much larger study is required for a definitive answer.

Identifying high-risk patients undergoing urgent and emergency surgery.

INTRODUCTION: The aim was to identify high-risk patients undergoing non-elective orthopaedic and general surgery. PATIENTS AND METHODS: This was a retrospective cohort study of all non-elective general and orthopaedic surgical procedures performed in a 1-year interval in a district general hospital. A total of 1869 patients underwent urgent or emergency surgery in the calendar year 2000. Outcomes were identified from various related hospital databases. Case notes of those who died were reviewed. Risk factors for mortality were examined using univariate and multivariate analysis. RESULTS: The mortality rates were 89/1869 (5%) at 30 days and 216 (12%) after 1 year. The high initial death rate continued for about 100 days after surgery. Increasing age (P < 0.0001), size of operation (P = 0.004) and American Society of Anesthesiologists (ASA) fitness grade (P < 0.0001) were associated with significantly higher risk of death at 1 year on multivariate analysis. A high risk group was identified of 273 patients aged over 50 years, of ASA Grade III or above who needed major surgery; they had a 30-day mortality rate of 18%. CONCLUSIONS: A simple scoring system could be used to identify high-risk patients who require non-elective surgery that could be a target for interventions to try and reduce their risk of death.

School hearing screening programme in the UK: practice and performance.

BACKGROUND: Paediatric audiology services and screening programmes are currently under review. AIMS AND METHODS: To investigate current practice and performance of the school hearing screening programme (SHSP) by means of a questionnaire. RESULTS: SHSP was found to detect previously unrecognised hearing loss at low cost. Wide variation in practice was shown, and the majority of services had no computerised system for data collection. CONCLUSION: There is a need for nationally agreed protocols and quality assurance procedures.

Comparison of POSSUM scoring and the Hardman Index in selection of patients for repair of ruptured abdominal aortic aneurysm.

BACKGROUND: The aim was to assess to what extent the POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity) and Hardman scoring systems were predictive of outcome after surgery for ruptured abdominal aortic aneurysm (RAAA). METHODS: From January 1990 to December 2001, 232 patients presented with RAAA. Forty-one were treated conservatively and all died; the remainder had emergency surgery. The case notes of all but three of these patients were reviewed retrospectively. POSSUM and Hardman scores were calculated and related to mortality. RESULTS: The mortality rate after emergency repair was 54 per cent (104 of 191). The physiology-only POSSUM score specific for RAAA and the Hardman Index score were both significantly associated with increased mortality after operation (P < 0.001). Most non-operated patients were in the highest risk bands. CONCLUSION: Both POSSUM and Hardman scoring systems predicted outcome after emergency surgery for RAAA. The Hardman Index was simpler to calculate, but POSSUM identified a higher number of patients at risk. Risk scoring may help identify patients with RAAA for whom surgery is futile.

The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM).

BACKGROUND AND METHODS: The development of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is described and its methods of analysis and value in a modern surgical practice are reviewed. A computerized search of all published data in Medline, the Cochrane Library and Embase was made for the last 12 years. Relevant articles were then searched manually for further papers on risk analysis, case-mix comparison and POSSUM methodology. RESULTS AND CONCLUSION: POSSUM has been evaluated extensively in both general and specialist surgery. While there are problems with both data collection and analysis, when used correctly POSSUM can usefully compare outcomes between surgeons and between hospitals. In specialist surgery, individual regression equations may be needed for each index procedure.

Molecular genetic analysis of the NF2 gene in young patients with unilateral vestibular schwannomas.

Neurofibromatosis type 2 (NF2) must be suspected in patients presenting with a unilateral vestibular schwannoma at a young age who are therefore at theoretical risk of developing bilateral disease. We identified 45 patients aged 30 years or less at the onset of symptoms of a unilateral vestibular schwannoma. Molecular genetic analysis of the NF2 gene was completed on peripheral blood samples in all 45 and on 28 tumour samples. No pathogenic NF2 mutations were identified in any of the blood samples. NF2 point mutations were identified in 21/28 (75%) tumour samples and loss of heterozygosity (LOH) in 21/28 (75%) tumour samples. Both mutational hits were identified in 18/28 (65%) tumour samples. In one multilobular tumour, one (presumably first hit) mutation was confirmed which was common to different foci of the tumour, while the second mutational event differed between foci. The molecular findings in this patient were consistent with somatic mosaicism for NF2 and the clinical diagnosis was confirmed with the presence of two meningiomas on a follow up MRI scan. A further patient developed a contralateral vestibular schwannoma on a follow up MRI scan in whom neither of the truncating mutations in the vestibular schwannoma were present in blood. It is important when counselling patients with unilateral vestibular schwannomas to identify (1) those at risk of bilateral disease, (2) those at risk of developing other tumours, and (3) other family members at risk of developing NF2. Comparing tumour and blood DNA cannot exclude mosaicism in the index case and cannot, therefore, be used to predict those at risk of developing further tumours. However, identification of both mutations or one mutation plus LOH in the tumour and exclusion of those mutations in the blood samples of the sibs or offspring of the affected case may be sufficient to render further screening unnecessary in these relatives.

Short-term results of femoropopliteal subintimal angioplasty.

BACKGROUND: Subintimal angioplasty may be more successful than conventional (intraluminal) angioplasty for treatment of long femoropopliteal occlusions. This study assessed the clinical and haemodynamic outcome of subintimal angioplasty. METHODS: All patients with femoropopliteal occlusions treated by subintimal angioplasty over a 3-year period at two centres were reviewed. Clinical assessment and colour duplex imaging were carried out. RESULTS: Sixty-nine procedures were performed in 33 men and 33 women of median age 74 (range 47-92) years. Indications for treatment were intermittent claudication in 26 (38 per cent) and critical limb ischaemia in 43 (62 per cent). Median occlusion length was 10 (range 2-50) cm. Primary technical success was achieved in 51 occlusions (74 per cent). There were 11 complications (16 per cent); the majority were minor but surgical intervention was required in two patients (3 per cent). At 6 months the cumulative symptomatic and haemodynamic primary patency rates were 60 and 51 per cent respectively, analysed on an intention-to-treat basis. The symptomatic and haemodynamic patency rates for technically successful procedures were 80 and 77 per cent respectively. CONCLUSION: In this series the short-term clinical success of subintimal angioplasty was poor because of a high incidence of reocclusion and restenosis, despite a relatively high initial technical success rate.

Probability of bilateral disease in people presenting with a unilateral vestibular schwannoma.

BACKGROUND: Some 4%-5% of those who develop vestibular schwannomas have neurofibromatosis type 2 (NF2). Although about 10% of these patients present initially with a unilateral vestibular schwannoma, the risk for a patient with a truly sporadic vestibular schwannoma developing contralateral disease is unknown. METHODS: A United Kingdom survey of 296 patients with NF2 was reviewed for laterality of vestibular schwannoma at presentation and the presence of other NF2 related features. The time to presentation of bilateral disease was calculated for patients presenting with a unilateral tumour. Mutation analysis of the NF2 gene was carried out on all available cases presenting initially with unilateral disease. RESULTS: Of 240 patients with NF2 with vestibular schwannomas, 45 (18%; 32 sporadic, 13 familial) had either a unilateral tumour or delay in detection between the first and contralateral tumours. Among those tested for NF2 mutations, eight of 27 and nine of 13 were identified among sporadic and familial cases respectively. Sporadic cases showed a high female to male ratio and 19 of 32 have not as yet developed a contralateral tumour (mean 4.1 years after diagnosis of the first). Thirteen of 32 sporadic patients developed a contralateral tumour (mean 6.5 years after the first tumour diagnosis, range 0-22 years) compared with 11 of 13 familial patients (mean delay 5 years, range 0-16 years). Seven of the 45 patients had neither a family history of NF2 nor evidence of related tumours at initial presentation (six before the age of 35 years). CONCLUSION: The risk of patients with sporadic unilateral vestibular schwannomata developing a contralateral tumour in the absence of family history or other features of NF2 is low, but those presenting with other neurogenic tumours in addition to vestibular schwannoma are at high risk of harbouring an NF2 mutation in at least a proportion of their somatic cells.

Differential diagnosis of type 2 neurofibromatosis: molecular discrimination of NF2 and sporadic vestibular schwannomas.

Patients who present with unilateral vestibular schwannomas either at a young age or with additional features of type 2 neurofibromatosis (NF2) are at risk of developing bilateral disease and transmitting a risk of neurogenic tumours to their offspring. We have identified 15 patients from a series of 537 with unilateral vestibular schwannomas who also had one or more of the following: other tumours (10/15), features of NF2 (3/15), or a family history of neurogenic tumours (5/15). No germline NF2 mutations were detected and in 7/9 cases where tumour material was available for analysis a germline mutation in the NF2 gene has been excluded. Although a possibility of gonosomal mosaicism still exists, exclusion tests for the offspring are now possible. We suggest a general strategy, based on analysis of tumour DNA, for distinguishing sporadic and familial cases of tumours caused by two hit mechanisms. Application of this strategy suggests that most instances of unilateral vestibular schwannoma which do not fulfil criteria for NF2 represent chance occurrences.

A clinical, genetic and audiological study of patients and families with unilateral vestibular schwannomas. II. Audiological findings in 93 patients with unilateral vestibular schwannomas.

Nine-three patients with histologically or radiologically confirmed unilateral vestibular schwannomas were recruited. Audiological testing for retrocochlear pathology was undertaken. Patients' hospital records were examined for previous audiological and radiological results. The audiometric configuration was designated as one of the following: normal, sloping, low frequency, peak, trough or flat. A sloping sensorineural audiometric configuration was present in 68 per cent of cases. No significant correlation was found between tumour size and average pure tone threshold 500 Hz to 4000 Hz, optimum discrimination score or interaural differences for wave V. Ninety-one per cent of cases had abnormalities on auditory evoked potential; 92 per cent of cases showed abnormalities on stapedial reflex testing. The limitations of audiological testing in the investigation of patients with suspected unilateral vestibular schwannomas are discussed. A protocol for the investigation of such patients is presented.

A clinical, genetic and audiological study of patients and families with unilateral vestibular schwannomas. I. Clinical features of neurofibromatosis in patients with unilateral vestibular schwannomas.

Ninety-three patients with unilateral vestibular schwannomas were examined in a clinical, genetic and audiological study, to determine whether they had features associated with neurofibromatosis Type 1 or neurofibromatosis Type 2. In 91 families, one patient only was found to be affected with a unilateral vestibular schwannoma. Patients did have a few café-au-lait macules, but fewer than six in number. None of the patients satisfied the cutaneous diagnostic criteria for neurofibromatosis Type 1. Neither Lisch nodules nor presenile posterior subcapsular lenticular opacities or cortical opacities were a feature. Five patients with unilateral vestibular schwannomas are described where the clinical findings raised the possibility of neurofibromatosis Type 2. It is suggested that certain individuals with unilateral vestibular schwannomas are at risk of developing neurofibromatosis Type 2. Furthermore, the possibility of neurofibromatosis Type 2 should be considered if more than one individual in a family is found to be affected with a unilateral vestibular schwannoma.

A clinical, genetic and audiological study of patients and families with bilateral acoustic neurofibromatosis.

The neurofibromatoses consist of at least two distinct autosomal dominant hereditary disorders. Neurofibromatosis type 1 (NF1) is due to a lesion on chromosome 17q. Neurofibromatosis type 2 (NF2) is caused by a defect on chromosome 22q. The hallmark of NF2 is the development, in the second and third decades, of bilateral acoustic neuromas. NF1 is characterized by the appearance of café-au-lait spots and neurofibromas in addition to iris hamartomas, or Lisch nodules, of the eye, during the first and second decades. Ten families were personally studied. A total of 16 members were found to be affected with NF2. A protocol for evaluation and review of subjects and relatives of NF2 families is proposed. A team approach, coordinating the expertise of multiple specialties is recommended.

A genetic study of type 2 neurofibromatosis in the United Kingdom. I. Prevalence, mutation rate, fitness, and confirmation of maternal transmission effect on severity.

A clinical and genetic study of type 2 neurofibromatosis (NF2) has been carried out in the United Kingdom. Virtually complete ascertainment of cases in the north-west of England was achieved and suggests a population incidence of 1 in 33,000 to 40,000. In the UK as a whole, 150 cases have been identified and been used to study the clinical and genetic features of NF2. The autosomal dominant inheritance of NF2 was confirmed, 49% of cases were assessed as representing new mutations, and the mutation rate was estimated to be 6.5 x 10(-6). Evidence to support a maternal gene effect was found in that age at onset was 18.17 years in 36 maternally inherited cases and 24.5 in 20 paternally inherited cases (p = 0.027). The preponderance of maternally inherited cases was also significant (p = 0.03). Data are presented which suggest that there are two types of NF2, one with later onset and bilateral vestibular schwannomas as the only usual feature, and the other with earlier onset and multiple other tumours. A considerable number of cases did not fall easily into one or other group and other factors such as maternal effect on severity and anticipation need to be considered.

A genetic study of type 2 neurofibromatosis in the United Kingdom. II. Guidelines for genetic counselling.

The major defining features, age at onset of symptoms, and survival in 150 patients with type 2 neurofibromatosis (NF2) have been studied. The mean age at onset was 21.57 years (n = 110) and no cases presented after 55 years of age. Patients presented with symptoms attributable to vestibular schwannomas (acoustic neuroma), cranial meningiomas, and spinal tumours. In 97 cases studied personally by the authors, skin and eye examination were found to be useful to detect early signs of the condition. Examination of the skin is likely to assist in early diagnosis in at least 10% of cases and examination of the eye for a lens opacity or cataract in at least as many again. There are marked interfamilial differences in disease severity and tumour susceptibility. Vestibular schwannomas are not fully penetrant, but the condition is usually expressed in another way. Alteration to the current diagnostic criteria is advocated to cover the lack of provision for new mutations. A screening protocol is proposed and the effect of disease heterogeneity on management is discussed.

A clinical study of type 2 neurofibromatosis.

The clinical features, age at onset of symptoms and survival of 150 patients with type 2 neurofibromatosis were studied. The mean age at onset was 21.57 years (n = 110) and no patients presented after 55 years of age. Patients presented with symptoms attributable to vestibular schwannomas (acoustic neuroma), cranial meningiomas and spinal tumours. In 100 patients studied personally by the authors 44 per cent presented with deafness and this was unilateral in the majority (35/44). Deafness was accompanied by tinnitus in a further 10 per cent and muscle weakness or wasting was the first symptom in 12 per cent. Less common presenting symptoms were seizures (8 per cent), vertigo (8 per cent) numbness and tingling (2 per cent) and blindness (1 per cent). Eleven patients were diagnosed asymptomatically through screening. Café au lait spots occurred in 43 per cent (n = 43) but only one case had six. Skin tumours were detected in 68 per cent (68/100) and 38 per cent (34/90) had an identifiable lens opacity or cataract. The mean age at death in 40 cases was 36.25 years and all but one death was a result of a complication of neurofibromatosis. There are marked inter-family differences in disease severity and tumour susceptibility.