Managing Injuries of the Neck Trial (MINT): a randomised controlled trial of treatments for whiplash injuries.

OBJECTIVES: To examine the clinical effectiveness of a stepped care approach over a 12-month period after an acute whiplash injury; to estimate the costs and cost-effectiveness of each strategy including treatments and subsequent health-care costs; and to gain participants' perspective on experiencing whiplash injury, NHS treatment, and recovery within the context of the Managing Injuries of the Neck Trial (MINT). DESIGN: Two linked, pragmatic, randomised controlled trials. In Step 1, emergency departments (EDs) were cluster randomised to usual care advice (UCA) or The Whiplash Book advice (WBA)/active management advice. In Step 2, participants were individually randomised to either a single session of advice from a physiotherapist or a physiotherapy package of up to six sessions. An economic evaluation and qualitative study were run in parallel with the trial. SETTING: Twelve NHS trusts in England comprising 15 EDs. PARTICIPANTS: People who attended EDs with an acute whiplash injury of whiplash-associated disorder grades I-III were eligible for Step 1. People who had attended EDs with whiplash injuries and had persistent symptoms 3 weeks after ED attendance were eligible for Step 2. INTERVENTIONS: In Step 1, the control intervention was UCA and the experimental intervention was a psycho-educational intervention (WBA/active management advice). In Step 2 the control treatment was reinforcement of the advice provided in Step 1 and the experimental intervention was a package of up to six physiotherapy treatments. MAIN OUTCOME: The primary outcome was the Neck Disability Index (NDI), which measures severity and frequency of pain and symptoms, and a range of activities including self-care, driving, reading, sleeping and recreation. Secondary outcomes included the mental and physical health-related quality-of-life (HRQoL) subscales of the Short Form questionnaire-12 items (SF-12) and the number of work days lost. RESULTS: A total of 3851 patients were recruited to Step 1 of the trial. 1598 patients attending EDs were randomised to UCA, and 2253 were randomised to WBA/active management. Outcome data were obtained at 12 months for 70% and 80% of participants at Step 1 and Step 2, respectively. The majority of people recovered from the injury. Eighteen per cent of the Step 1 cohort had late whiplash syndrome. There was no statistically or clinically significant difference observed in any of the outcomes for participants attending EDs randomised to UCA or active management advice [difference in NDI 0.5, 95% confidence interval (CI) -1.8 to 2.8]. In Step 2 the physiotherapy package resulted in improvements in neck disability at 4 months compared with a single advice session, but these effects were small at the population level (difference in NDI -3.2, 95% CI -5.8 to -0.7). The physiotherapy package was accompanied by a significant reduction in the number of work days lost at 4-month follow-up (difference -40.2, 95% CI -44.3 to -35.8). CONCLUSIONS: MINT suggests that enhanced psycho-educational interventions in EDs are no more effective than UCA in reducing the burden of acute whiplash injuries. A physiotherapy package provided to people who have persisting symptoms within the first 6 weeks of injury produced additional short-term benefits in neck disability compared with a single physiotherapy advice session. However, from a health-care perspective, the physiotherapy package was not cost-effective at current levels of willingness to pay. Both experimental treatments were associated with increased cost with no discernible gain in health-related quality of life. However, an important benefit of the physiotherapy package was a reduction in work days lost; consequently, the intervention may prove cost-effective at the societal level. TRIAL REGISTRATION: Current Controlled Trials ISRCTN33302125. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 49. See the HTA programme website for further project information.

A multicentred randomised controlled trial of a primary care-based cognitive behavioural programme for low back pain. The Back Skills Training (BeST) trial.

OBJECTIVES: To estimate the clinical effectiveness of active management (AM) in general practice versus AM plus a group-based, professionally led cognitive behavioural approach (CBA) for subacute and chronic low back pain (LBP) and to measure the cost of each strategy over a period of 12 months and estimate cost-effectiveness. DESIGN: Pragmatic multicentred randomised controlled trial with investigator-blinded assessment of outcomes. SETTING: Fifty-six general practices from seven English regions. PARTICIPANTS: People with subacute and chronic LBP who were experiencing symptoms that were at least moderately troublesome. INTERVENTIONS: Participants were randomised (in a ratio of 2:1) to receive either AM+CBA or AM alone. MAIN OUTCOME MEASURES: Primary outcomes were the Roland Morris Disability Questionnaire (RMQ) and the Modified Von Korff Scale (MVK), which measure LBP and disability. Secondary outcomes included mental and physical health-related quality of life (Short Form 12-item health survey), health status, fear avoidance beliefs and pain self-efficacy. Cost-utility of CBA was considered from both the UK NHS perspective and a broader health-care perspective, including both NHS costs and costs of privately purchased goods and services related to LBP. Quality-adjusted life-years (QALYs) were calculated from the five-item EuroQoL. RESULTS: Between April 2005 and April 2007, 701 participants were randomised: 233 to AM and 468 to AM+CBA. Of these, 420 were female. The mean age of participants was 54 years and mean baseline RMQ was 8.7. Outcome data were obtained for 85% of participants at 12 months. Benefits were seen across a range of outcome measures in favour of CBA with no evidence of group or therapist effects. CBA resulted in at least twice as much improvement as AM. Mean additional improvement in the CBA arm was 1.1 [95% confidence interval (CI) 0.4 to 1.7], 1.4 (95% CI 0.7 to 2.1) and 1.3 (95% CI 0.6 to 2.1) change points in the RMQ at 3, 6 and 12 months respectively. Additional improvement in MVK pain was 6.8 (95% CI 3.5 to 10.2), 8.0 (95% CI 4.3 to 11.7) and 7.0 (95% CI 3.2 to 10.7) points, and in MVK disability was 4.3 (95% CI 0.4 to 8.2), 8.1 (95% CI 4.1 to 12.0) and 8.4 (95% CI 4.4 to 12.4) points at 3, 6 and 12 months respectively. At 12 months, 60% of the AM+CBA arm and 31% of the AM arm reported some or complete recovery. Mean cost of attending a CBA course was 187 pounds per participant with an additional benefit in QALYs of 0.099 and an additional cost of 178.06 pounds. Incremental cost-effectiveness ratio was 1786.00 pounds. Probability of CBA being cost-effective reached 90% at about 3000 pounds and remained at that level or above; at a cost-effectiveness threshold of 20,000 pounds the CBA group had an almost 100% probability of being considered cost-effective. User perspectives on the acceptability of group treatments were sought through semi-structured interviews. Most were familiar with key messages of AM; most who had attended any group sessions had retained key messages from the sessions and two-thirds talked about a reduction in fear avoidance and changes in their behaviour. Group sessions appeared to provide reassurance, lessen isolation and enable participants to learn strategies from each other. CONCLUSIONS: Long-term effectiveness and cost-effectiveness of CBA in treating subacute and chronic LBP was shown, making this intervention attractive to patients, clinicians and purchasers. Short-term (3-month) clinical effects were similar to those found in high-quality studies of other therapies and benefits were maintained and increased over the long term (12 months). Cost per QALY was about half that of competing interventions for LBP and because the intervention can be delivered by existing NHS staff following brief training, the back skills training programme could be implemented within the NHS with relative ease. TRIAL REGISTRATION: Current Controlled Trials ISRCTN37807450. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A national survey of clinical practice for the management of whiplash-associated disorders in UK emergency departments.

OBJECTIVE: To undertake a national survey to determine current practice for the management of whiplash injuries in UK emergency departments (ED). METHODS: Postal questionnaire survey. 316 lead consultants from all UK ED with annual new attendances of over 50 000 people were asked to indicate the use of a range of treatments and the frequency with which these treatments were used. Samples of written advice were requested and content analysis was conducted and compared with survey responses. RESULTS: The response rate was 79% (251/316). The intervention most frequently used was verbal advice to exercise, reported by 84% of respondents for most or all cases, and advice against the use of a collar (83%). Other treatments reported as being used frequently were written advice and anti-inflammatory medication. 106 consultants (42%) provided a sample of written materials. Reference to expected recovery and encouragement for early return to activities were included in less than 6%. Nearly 50% of written materials contained information on how to use a soft collar and 61% contained information on solicitors and pursuing a personal injury claim. There were important differences between reported verbal behaviours and written advice. CONCLUSION: Verbal advice is the primary method for managing whiplash injuries in ED and is usually supplemented by written advice. Within individual hospitals there is a lack of consistency between verbal and written advice. The promotion of personal injury claims is a common feature of written advice. Research is required to develop effective and consistent models of advice.

Clinical and cost effectiveness of mechanical support for severe ankle sprains: design of a randomised controlled trial in the emergency department [ISRCTN 37807450].

BACKGROUND: The optimal management for severe sprains (Grades II and III) of the lateral ligament complex of the ankle is unclear. The aims of this randomised controlled trial are to estimate (1) the clinical effectiveness of three methods of providing mechanical support to the ankle (below knee cast, Aircast brace and Bledsoe boot) in comparison to Tubigrip, and (2) to compare the cost of each strategy, including subsequent health care costs. METHODS/DESIGN: Six hundred and fifty people with a diagnosis of severe sprain are being identified through emergency departments. The study has been designed to complement routine practice in the emergency setting. Outcomes are recovery of mobility (primary outcome) and usual activity, residual symptoms and need for further medical, rehabilitation or surgical treatment. Parallel economic and qualitative studies are being conducted to aid interpretation of the results and to evaluate the cost-effectiveness of the interventions. DISCUSSION: This paper highlights the design, methods and operational aspects of a clinical trial of acute injury management in the emergency department.

Cloning of rabies virus matrix protein mRNA and determination of its amino acid sequence.

A cDNA clone of mRNA for rabies virus matrix (M) protein has been identified. The clone hybridizes to an mRNA species from rabies virus-infected cells, whose size correlates to the size of the M protein in rabies virions, and selects an mRNA that translates into a polypeptide corresponding in size to M protein. The nucleotide sequence of the cloned cDNA was determined and from this a complete amino acid sequence for M protein was deduced. The deduced sequence of 202 amino acids bears no detectable sequence homology with vesicular stomatitis virus M protein although these proteins may share functional homology.

The nucleotide sequence and derived amino acid sequence of cDNA coding for mouse carbonic anhydrase II.

The nucleotide sequence of a clone containing mouse carbonic anhydrase (CA) cDNA in pBR322 has been determined. The cloned cDNA contains all of the coding region except for nucleotides specifying the first eight amino acids, and all of the 3' noncoding region, which consists of 700 nucleotides. A cDNA clone was identified which contains an additional 54 bp at the 5' end, so that the complete amino acid sequence of mouse CA could be deduced. This sequence showed a 73-81% homology with other mammalian CA form II isozymes, 56-63% with form I isozymes, and 52-56% with form III isozymes. By examination of the amino acids which are unique and invariant for each isozyme, the mouse amino acid sequence was found to contain 16 of the 23 residues that are unique and invariant to mammalian CA form II isozymes, but only one or no residue for forms I and III, respectively.

Immediate reconstruction of the pharynx and cervical esophagus with the pectoralis major myocutaneous flap following laryngopharyngectomy.

The "island" pectoralis major myocutaneous flap has been used in nine patients for immediate hypopharyngeal and cervicoesophageal reconstruction following laryngopharyngectomy. Two patients underwent total hypopharyngeal and cervicoesophageal reconstruction. Postoperative evaluation revealed adequate lumens with no evidence of stricture. There was retained innervation of the flaps through the lateral pectoral nerve, but no additional innervation from the cricopharyngeal musculature could be demonstrated. Normal esophageal motility was maintained, but cervicoesophageal pressures were diminished. Donor site morbidity was minimal, and the complication rate was low. We present the pectoralis major myocutaneous flap as an alternate method for hypopharyngeal and cervicoesophageal reconstruction.

Management of the brown recluse spider bite.

A model to study the dermonecrotic effects of a crude fraction of venom from the brown recluse spider (Loxosceles reclusa) was developed using female New Zealand white rabbits. In the rabbit model, surgical excision of the sites of intradermally injected crude venom did not always prevent subsequent necrosis or wound dehiscence despite the use of fluorescein to determine the surgical margin. Heparin and steroids did not prevent the venom-induced necrosis and were much less effective than surgical excision or injecting a specific antivenom. When given within 24 hours, the specific antivenom raised against the brown recluse spider venom blocked or markedly attenuated the toxic effects of the venom in the rabbit model system.

Anterior mediastinal tracheostomy with a pectoralis major musculocutaneous flap.

We suggest the pectoralis major musculocutaneous flap is a simple and reliable technique in constructing a mediastinal tracheostomy. It has the advantage of excellent vascularity and reliability even in those patients who have undergone preoperative radiation therapy. In addition, a well-vascularized lobe of thyroid tissue placed over the pharyngogastric anastomosis may decrease anastomotic leaks.

Reconstruction of the upper and lower lip using a modified Bernard-Burow technique.

Our experience with a modified Bernard-Burow technique for upper and lower lip reconstruction is described with preservation of the muscular lip sphincter. The use of local skin and buccal mucosal flaps sliding over the preserved muscular sphincter enables reconstruction with an acceptable cosmetic result even when almost total lip resection is required.

Further experience with the tensor fascia lata musculocutaneous flap.

We have found the tensor fascia lata myocutaneous flap to be exceedingly reliable with a consistent vascular pedicle; it can be elevated easily and rapidly in its subfascial plane. It is a useful flap in the paraplegic patient for colsure of ischial, trochanteric, and sacral pressure sores, and may also be used as a free flap with little donor morbidity. At present, we recommend this as the flap of choice for closure of trochanteric pressure sores. Additionally, it appears to have further applications in defects of the groin, perineum, abdominal wall, and lower chest wall. Eleven tensor fascia lata musculocutaneous flaps, utilized for soft tissue coverage for varying defects in 9 patients, are discussed.

Pectoralis major musculocutaneous flap: a new flap in head and neck reconstruction.

The pectoralis major musculocutaneous flap described by Ariyan has great potential in single stage reconstructions of the head and neck. The advantages of the flap are greater length, improved vascularity, bulk, and one-stage reconstruction of oropharyngeal defects. The flap was used successfully in eight patients to reconstruct large defects in the head and neck area. Experience to date indicates that this flap has greater versatility than the deltopectoral flap in one-stage head and neck reconstructions.

Long-term experience with childhood thyroid carcinoma.

Twenty patients with well-differentiated thyroid carcinoma, 20 yr of age or younger have been treated at Vanderbilt University Hospital. The young patient with thyroid carcinoma frequently presents with far-advanced disease but enjoys an improved survival. Preoperative scintiscanning is useful in the evaluation of patients with childhood thyroid carcinoma. A new noninvasive scan is described and appears to be promising in the preoperative differentiation between benign and malignant thyroid lesions in children and young adults. There is a high instance of nodal metastases, but long-term follow-up would indicate that lobectomy and modified neck dissection are sufficient for most patients. However, total thyroidectomy can be performed safely in those patients with disease in both lobes. Additionalally, frozen section diagnoses were found to be helpful in diagnosing and staging thyroid carcinoma.

Resection of a massive arteriovenous malformation of the head and neck.

We report a patient with a massive arteriovenous malformation of the head and neck treated by surgical extirpation of the lesion. Arteriography, hypotensive hypothermic anesthesia, and the intraoperative use of the Doppler flowmeter were most helpful in this case.

Use of the free dorsalis pedis flap in head and neck repairs.

Many defects of the head and neck can be readily repaired with a free dorsalis pedis flap, and we report success with these flaps in 9 of 12 cases. A precise knowledge of the anatomy of the arterial supply of the flap is necessary. Preoperative arteriography is recommended if the dorsalis pedis artery is not easily palpable, or if an anomalous distribution of the artery along the dorsum of the foot is sus pected. However, the transfer of the flap should be delayed for two weeks after preoperative arteriography is performed. The one-stage soft tissue reconstruction with a free dorsalis pedis flap has been associated with minimal morbidity and good acceptance by patients. A delay procedure for the flap seems to enhance the chances of complete survival which is so necessary in the repair of intraoral and pharyngeal defects. Careful attention to details and close monitoring of the flap will minimize morbidity. In case of an early failure of a flap, a secondary reconstruction by a different flap can be done in the first 48 to 72 hours. Early postoperative radiotherapy has been well tolerated over these free flaps.

Vascular access for chronic hemodialysis: use of bovine xenografts to create arteriovenous fistulas.

Adequate vascular access is the hallmark of successful chronic hemodialysis for end-stage renal disease. Between May 1975 and August 1975, it was necessary to use a bovine xenograft in 91 instances to create an arteriovenous fistula for vascular access in patients receiving chronic hemodialysis at the Vanderbilt University Affiliated Hospitals. Forty-two patients had one xenograft, 14 patients had two, and seven had three xenografts. Of all fistulas created with the xenografts, 53% were patent six months after the operation, 36% were patent at 12 months, and 15% have remained patent for 24 months. Thirty-seven percent of the xenografts failed during the first three months after operation. The most common reason for failure was thrombosis of the xenograft. Other complications encountered were false aneurysms, infection of the graft, ischemia of the extremity, and bleeding. Amputation of the lower extremity due to ischemia from septic emboli was necessary in one case. There was no deaths directly related to the use of these xenografts. It is out current opinion that the bovine xenograft should be reserved for use in patients who have had failure of the more conventional type of internal fistula (Cimino type). In selected patients in whom it is not possible to create a Cimino shunt, the xenograft offers adequate primary vascular access.