Randomised controlled trial of a short course of traditional acupuncture compared with usual care for persistent non-specific low back pain.

OBJECTIVE: To determine whether a short course of traditional acupuncture improves longer term outcomes for patients with persistent non-specific low back pain in primary care. DESIGN: Pragmatic, open, randomised controlled trial. SETTING: Three private acupuncture clinics and 18 general practices in York, England. PARTICIPANTS: 241 adults aged 18-65 with non-specific low back pain of 4-52 weeks' duration. INTERVENTIONS: 10 individualised acupuncture treatments from one of six qualified acupuncturists (160 patients) or usual care only (81 patients). MAIN OUTCOME MEASURES: The primary outcome was SF-36 bodily pain, measured at 12 and 24 months. Other outcomes included reported use of analgesics, scores on the Oswestry pain disability index, safety, and patient satisfaction. RESULTS: 39 general practitioners referred 289 patients of whom 241 were randomised. At 12 months average SF-36 pain scores increased by 33.2 to 64.0 in the acupuncture group and by 27.9 to 58.3 in the control group. Adjusting for baseline score and for any clustering by acupuncturist, the estimated intervention effect was 5.6 points (95% confidence interval -0.2 to 11.4) at 12 months (n = 213) and 8.0 points (2.8 to 13.2) at 24 months (n = 182). The magnitude of the difference between the groups was about 10%-15% of the final pain score in the control group. Functional disability was not improved. No serious or life threatening events were reported. CONCLUSIONS: Weak evidence was found of an effect of acupuncture on persistent non-specific low back pain at 12 months, but stronger evidence of a small benefit at 24 months. Referral to a qualified traditional acupuncturist for a short course of treatment seems safe and acceptable to patients with low back pain. TRIAL REGISTRATION: ISRCTN80764175 [controlled-trials.com].

Longer term clinical and economic benefits of offering acupuncture care to patients with chronic low back pain.

OBJECTIVES: To test whether patients with persistent non-specific low back pain, when offered access to traditional acupuncture care alongside conventional primary care, gained more long-term relief from pain than those offered conventional care only, for equal or less cost. Safety and acceptability of acupuncture care to patients, and the heterogeneity of outcomes were also tested. DESIGN: A pragmatic, two parallel group, randomised controlled trial. Patients in the experimental arm were offered the option of referral to the acupuncture service comprising six acupuncturists. The control group received usual care from their general practitioner (GP). Eligible patients were randomised in a ratio of 2:1 to the offer of acupuncture to allow between-acupuncturist effects to be tested. SETTING: Three non-NHS acupuncture clinics, with referrals from 39 GPs working in 16 practices in York, UK. PARTICIPANTS: Patients aged 18-65 years with non-specific low back pain of 4-52 weeks' duration, assessed as suitable for primary care management by their general practitioner. INTERVENTIONS: The trial protocol allowed up to ten individualised acupuncture treatments per patient. The acupuncturist determined the content and the number of treatments according to patient need. MAIN OUTCOME MEASURES: The Short Form 36 (SF-36) Bodily Pain dimension (range 0-100 points), assessed at baseline, and 3, 12 and 24 months. The study was powered to detect a 10-point difference between groups at 12 months post-randomisation. Cost--utility analysis was conducted at 24 months using the EuroQoL 5 Dimensions (EQ-5D) and a preference-based single index measure derived from the SF-36 (SF-6D). Secondary outcomes included the McGill Present Pain Index (PPI), Oswestry Pain Disability Index (ODI), all other SF-36 dimensions, medication use, pain-free months in the past year, worry about back pain, satisfaction with care received, and safety and acceptability of acupuncture care. RESULTS: A total of 159 patients were in the 'acupuncture offer' arm and 80 in the 'usual care' arm. All 159 patients randomised to the offer of acupuncture care chose to receive acupuncture treatment, and received an average of eight acupuncture treatments within the trial. Analysis of covariance, adjusting for baseline score, found an intervention effect of 5.6 points on the SF-36 Pain dimension [95% confidence interval (CI) -1.3 to 12.5] in favour of the acupuncture group at 12 months, and 8 points (95% CI 0.7 to 15.3) at 24 months. No evidence of heterogeneity of effect was found for the different acupuncturists. Patients receiving acupuncture care did not report any serious or life-threatening events. No significant treatment effect was found for any of the SF-36 dimensions other than Pain, or for the PPI or the ODI. Patients receiving acupuncture care reported a significantly greater reduction in worry about their back pain at 12 and 24 months compared with the usual care group. At 24 months, the acupuncture care group was significantly more likely to report 12 months pain free and less likely to report the use of medication for pain relief. The acupuncture service was found to be cost-effective at 24 months; the estimated cost per quality-adjusted (QALY) was 4241 pounds sterling (95% CI 191 pounds sterling to 28,026 pounds sterling) using the SF-6D scoring algorithm based on responses to the SF-36, and 3598 pounds sterling (95% CI 189 pounds sterling to 22,035 pounds sterling) using the EQ-5D health status instrument. The NHS costs were greater in the acupuncture care group than in the usual care group. However, the additional resource use was less than the costs of the acupuncture treatment itself, suggesting that some usual care resource use was offset. CONCLUSIONS: Traditional acupuncture care delivered in a primary care setting was safe and acceptable to patients with non-specific low back pain. Acupuncture care and usual care were both associated with clinically significant improvement at 12- and 24-month follow-up. Acupuncture care was significantly more effective in reducing bodily pain than usual care at 24-month follow-up. No benefits relating to function or disability were identified. GP referral to a service providing traditional acupuncture care offers a cost-effective intervention for reducing low back pain over a 2-year period. Further research is needed to examine many aspects of this treatment including its impact compared with other possible short-term packages of care (such as massage, chiropractic or physiotherapy), various aspects of cost-effectiveness, value to patients and implementation protocols.

A prospective survey of adverse events and treatment reactions following 34,000 consultations with professional acupuncturists.

The paper describes the type and frequency of adverse events and transicnt reactions following consultations with professional acupuncturists. In a postal survey, involving 1,848 professional acupuncturists, all of whom were members of the British Acupuncture Council and practising in the UK, details of adverse events and transient reactions following treatment were recorded on standardised self-report forms. A sample size of 30,000 treatments was sought, and piloting indicated that a four-week period was required. Practitioners also provided information on themselves, including age, sex, length of training and years of practice. A total of 574 practitioners responded. 31% of the total population. These practitioners reported on adverse events and transient reactions associated with 34,407 treatments. No serious adverse events were reported, where these were defined as requiring hospital admission, prolonging hospital stays, permanently disabling, or resulting in death (95% CI: 0 to 1.1 per 10,000 treatments). A total of 43 significant minor adverse events were reported, a rate of 1.3 per 1,000 treatments (95% CI: 0.9 to 1.7). These included severe nausea and actual fainting (12), unexpected, severe and prolonged aggravation of symptoms (7), prolonged and unacceptable pain and bruising (5) and psychological and emotional reactions (4). There were three avoidable events: two patients had needles left in by mistake, and one patient had moxa burns to the skin, also caused by practitioner error. The acupuncturists also recorded 10,920 mild transient reactions occurring in 5136 treatments. 15% (95% CI: 14.6 to 15.3) of the 34,407 total. In terms of local reactions, there were reports of mild bruising (1.7%), pain (1.2%) and bleeding (0.4%). Practitioners reported that patients experienced an aggravation of existing symptoms after 2.8% of treatments. The most common mild transient reactions to treatment were feeling relaxed (11.9%) and feeling energised (6.6%). In this prospective survey of 34,407 treatments, practitioners reported no serious adverse events. This conclusion was based on data collected from one in three members of the British Acupuncture Council. Given that the whole membership delivers between one and a half and two million treatments a year, this is important evidence on public health and safety. When compared with medication routinely prescribed in primary care, the results suggest that acupuncture is a relatively safe treatment modality.

Longer-term clinical and economic benefits of offering acupuncture to patients with chronic low back pain assessed as suitable for primary care management.

This paper presents the research protocol for a pragmatic study of the benefits of providing an acupuncture service to patients in primary care with chronic low back pain. The proposal was written in response to a call for bids from the NHS Executive's centrally funded research programme for Health Technology Assessment (HTA). The research question posed was 'Does acupuncture have long-term effectiveness in the management of pain in primary care?' The present study was designed as a collaboration between an interdisciplinary team drawn from health services researchers at the University of Sheffield, acupuncture researchers from the Foundation for Traditional Chinese Medicine in York, and practitioners from general practice and acupuncture in York. The proposal presented here was submitted in response to an invitation from the Commissioning Board following a successful outline bid. It is reproduced here, largely as submitted in January 1998, using the headings under which information was requested. We also present an appendix describing methodological alterations made to the design in response the Commissioning Board's comments on the proposal. We present it in this format to give an idea of the evolution of the design and the process by which the research proposal was shaped. The final working protocol comprises a combination of these two elements.

Acupuncture for low back pain: results of a pilot study for a randomized controlled trial.

OBJECTIVES: To pilot procedures to be used in a randomized controlled trial of acupuncture for low back pain. DESIGN: Uncontrolled clinical trial. SETTING: Primary care and acupuncture clinics in York, England. SUBJECTS: 20 patients with low back pain lasting 1 month or more. INTERVENTIONS: 10 sessions of individualized acupuncture from a traditional acupuncturist. MAIN OUTCOME MEASURES: Change in Oswestry low back pain disability questionnaire; present pain intensity scale; effect on daily living scale, and SF-36 general health questionnaire at post-treatment and 6 months after the end of treatment. RESULTS: 14 patients completed follow-up. Patients had similar severity scores at baseline to those referred to an NHS outpatient clinic. Post-treatment, there were statistically significant improvements in Oswestry, present pain intensity, effect on daily living and the physical functioning, social functioning, bodily pain, vitality and mental health sub-scales of the SF36. Similar results were found at the six month follow-up. Oswestry scores showed reduced levels of pain at 6 months compared to than at post-treatment, falling approximately 40% from baseline. CONCLUSIONS: Though the improvements in pain and quality in life may be due to the natural course of back pain, the promising responses justify further research. The procedures used in the study are appropriate for a randomized controlled trial. Drop-out could be reduced by more careful patient monitoring.

Patients' views on health screening in general practice.

This paper describes the reactions of 159 patients to the way in which they were invited to participate in a health screening programme and their views on the screening appointment itself. It was found that those invited by letter, rather than opportunistically during a routine consultation, thought their appointment time harder to keep. A group of patients identified as relatively infrequent consulters were less likely to believe that the invite showed the practice to be interested in their health. However, overall the patients' perceptions of both the way in which they were invited and the screening appointment itself were found to be very positive and their satisfaction ratings high.

The potential and limitations of opportunistic screening: data from a computer simulation of a general practice screening programme.

Given the continuing emphasis on preventive medicine in general practice, there is considerable interest in the relative effectiveness of different ways of inviting patients to attend for screening. Recently, opportunistic methods have been advocated as being particularly useful but these methods often fail to reach a high proportion of the target population. Many patients do not consult and when they do they are not always invited to attend for screening. In this study a computer simulation model has been used to examine the effects of these variables in more detail. The notes of a random sample of 190 patients (97 women, 93 men) aged 30-50 years, registered with one general practitioner, were used to provide data for the model. The simulation model showed that increasing the number of screening appointments available each week has only a small effect on screening rates and that a ceiling is reached when 25 appointments per 1000 patients are available. In contrast, increasing the proportion of eligible consulting patients who are invited has a substantial effect such that it could take nearly 12 years to screen 90% of a target population if only one out of every four patients were invited compared with under four years if three out of every four patients were invited. The results suggest therefore that opportunistic screening methods are unlikely to achieve desired screening rates within acceptable time limits. It is argued that to achieve target levels of screening, practices will need to combine opportunistic methods with more formal methods of invitation.

General practitioners' subjective experience of surgery workload.

General practitioners (GPs) in the U.K. frequently cite heavy workload as a major source of work-related stress. However, there is little direct evidence either to support this claim or to suggest whether the source of this stress lies in the amount, or rather the type, of work undertaken. The present paper uses a within-subjects design to address these issues in the surgery context. Over a two-week period three GPs gave ratings of subjective workload following each of their surgeries (N = 20-23). Correlational analysis showed a wide range of surgery characteristics to predict the GPs' reactions, including the length of surgeries, the number of consultations, the number of re-presentations, and the number of follow-ups and investigations requested. The GPs' perceptions of their patients (e.g. in terms of their health status and the appropriateness of the consultation), in contrast, did not emerge as significant predictors. The results of multiple regression analyses, however, revealed that most of the first-order effects could be accounted for by surgery length. Thus while the study supported the hypothesised link between the overall level of surgery work demands and the subjective experience of workload, it failed to confirm any consistent additional effects of the type of work involved. It was also found that as the length of surgeries increased, the GPs were more likely to arrange follow-up appointments. The implications of the present findings are therefore two-fold.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of monoclonal antibodies to protoplast membranes of Nicotiana tabacum identified by an enzyme-linked immunosorbent assay.

Murine monoclonal antibodies to protoplast membrne antigens were generated using mouse myelomas and spleen cells from mice immunized with Nicotiana tabacum L. leaf protoplasts. For selecting antibody-secreting clones, a sensitive and rapid enzyme-linked immunosorbent assay (ELISA) for monoclonal antibody binding to immobilized cellular membrane preparations or immobilized protoplasts was developed. With intact protoplasts as immobilized antigen, the ELISA is selective for antibodies that bind to plasma-membrane epitopes present on the external surface of protoplasts. Using the membrane ELISA, a total of 24 hybridoma lines were identified that secreted antibodies to plant membrane epitopes. The protoplast ELISA and subsequent immunofluorescence studies identified four hybridoma lines as secreting antibodies which bound to the external surface of protoplasts and cells. The corresponding antigens were not species- or tissue-specific, were periodatesensitive, and were located in membranes which equilibrated broadly throughout a linear sucrose gradient. When protein blots of electrophoretically separated membrane proteins were probed with these antibodies, a band of Mr 14 kilodaltons (kDa) and a smear of bands of Mr 45-120 kDa were labeled. An additional set of three antibodies appeared by immunofluorescence to bind to the plasma membrane of broken but not intact protoplasts and labeled membranes equilibrating at a density of approx. 1.12 kg·l(-1) in a linear sucrose density gradient. These classes of monoclonal antibodies enlarge the library of monoclonal antibodies (Norman et al. 1986, Planta 167, 452-459) available for the study of plant plasma-membrane structure and function.

Identification of somatic hybrids in plant protoplast fusions with monoclonal antibodies to plasma-membrane antigens.

Monoclonal antibodies generated by immunization with a plasma-membrane preparation from suspension-cultured cells of Nicotiana glutinosa L. were used in combination with fluoresceinor rhodamine-labeled goat anti-mouse immunoglobulins to identify heterokaryons in protoplast fusion procedures. Antibody labeling did not inhibit callus formation nor plantlet regeneration. The antibodies are non-invasive and surface labeling provides clear optical discrimination of true heterokaryons from unfused aggregates as well as from parental protoplasts and homokaryons. Labeling is stable throughout fusion and hence by pre-labeling parental protoplast populations the strategy is both versatile and of general applicability.

An interactive computerized protocol for the management of hypertension: effects on the general practitioner's clinical behaviour.

This paper reports an experimental study of general practitioners' use of an interactive computerized protocol for the management of hypertension, focussing particularly on the protocol's effects on doctors' clinical behaviour. Prior to its computerization a paper-based version of the protocol was used enabling a comparison of the alternative forms. Doctors' delivery of care was assessed from video recordings of 89 consultations and from the records made during these consultations. Comparisons were made of consultations conducted under control and experimental conditions. Use of paper and computer protocols resulted in significant improvements in the doctors' delivery of care, in terms of the range of verbal and physical examinations conducted and recorded. The protocol's effects were most marked when the computerized version was used. However, use of the computer protocol resulted in the recording of information on the non-occurrence of certain events which had not been explicitly elicited during the verbal examination; features of the design which were intended to encourage adherence to the protocol may have been inappropriate to the realities of a general practice consultation. The findings provide some useful insights for the design of future computerized protocols for the management of chronic conditions.

Monoclonal antibodies to plant plasma-membrane antigens.

Murine monoclonal antibodies to membrane antigens were generated by immunization with a crude cellular membrane preparation from suspension-cultured cells of Nicotiana glutinosa L. From a panel of thirteen monoclonal antibodies, seven were found to be directed against antigens present on the plasma-membrane by immunofluorescence visualization of antibody binding to the surface of isolated protoplasts. The corresponding set of plasma-membrane antigen(s) were present in root, shoot and leaf tissue and some but not all of these antigens were of wide species distribution, being found in Nicotiana tabacum L., N. plumbaginifolia L., Glycine max L., Phaseolus vulgaris L. and Triticum aestivum L. Topologically specific labeling of intact protoplasts with a monoclonal antibody reactive with an epitope present on the plasma-membrane specifically labeled a membrane fraction which equilibrated at a density of 1.14 kg/l following centrifugation in a sucrose gradient. In addition to use as biochemical markers for fractionation and molecular characterization of plasma-membranes, these monoclonal antibodies provide the basis for new selection tools in plant cell and gene manipulations.

Computers and audit.

A computerized information system was installed in a large group practice. This paper describes how the computer system was used for the systematic auditing of clinical activities, and also demonstrates how it acted as a catalyst for the review and changes of administrative and management procedures. An analysis of the issues that arose in an audit group is used to identify how the objectives and activities of the group evolved with experience. It is demonstrated that a computer system and audit can complement and enhance each other to the benefit of clinical and managerial decision making.

Mature phenotype in Hemerocallis plantlets fortuitously generated in vitro.

Daylily plantlets generated on semi-solid media from morphogenetically competent cells or morphogenetically competent cells regenerated from protoplasts can give rise in aseptic culture to plantlets with a mature phenotype. The individual leaves of these plantlets open to the extreme base so that no encircling leaf sheath is present. This permits the overlapping bases and leaves to assume an open fan-like arrangement. The occurrence of fans correlates with exceptionally tightly sealed culture vessels and experiments to date suggest a gaseous component is associated with this change of growth form. It has not been possible to fix the mature growth mode, however, and new leaf growth assumes the more normal juvenile phenotype when the gaseous environment is altered by admitting or exposure to room air.

Consultation use of a computer by general practitioners.

Reporting on an experimental field study of computer use by general practitioners during consultations, this paper focuses particularly on the experiences of the doctors in their efforts to communicate concurrently with a patient and a computer. Through the analysis of logs of computer use, video recordings of consultations and interviews with doctors, the authors report on the uptake of the computer facilities, the impact of such use on information handling during the consultation, the doctors' views about using the system, and finally the relationship between doctors' ;natural' consulting styles and their uptake and views of the system.

Susceptibility of zoopathogenic fungi to phytoalexins.

Phytoalexins are a group of low-molecular-weight antibiotics produced by higher plants in response to infection by relatively avirulent microorganisms. They are of relatively low toxicity for mammalian cells and have been reported to possess a broad spectrum of antimicrobial activity against bacteria and phytopathogenic fungi. Employing a broth dilution technique, we have found the zoopathogens Petriellidium boydii, Aspergillus flavus, A. fumigatus, Candida albicans, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, Rhizopus oryzae, Sporothrix schenckii, and Trichophyton rubrum to be inhibited by one or more of the phytoalexins maackiain, medicarpin, phaseollin, phaseollin isoflavan, pisatin, sativan, and vestitol in concentrations of from 12.5 to 50 microgram/ml. Phaseollin isofalvan was the most effective of these. In agar cup diffusion tests growth of the yeast form of Blastomyces dermatitidis was inhibited by phaseollin at 50 microgram/ml and by phaseollin isoflavan at 25 microgram/ml. Susceptibility of the mycelial form of B. dermatitidis to these two compounds was demonstrated by inhibition of radial extension on agar plates.