Showing papers in "Health Technology Assessment in 1997"

Systematic review of outpatient services for chronic pain control.

Abstract: AIM OF REPORT. This report reviews the evidence about the effectiveness of treatments for chronic pain. While treatment of chronic pain is usually seen as an integrated service, this report concentrates on the individual interventions that constitute the service. HOW THE RESEARCH WAS CONDUCTED. Searches of databases and journals identified over 15,000 randomised studies with pain as an outcome, and many more which were not randomised. Over 150 systematic reviews relevant to chronic pain treatment were identified and their quality assessed using a simple scoring system. Systematic reviews conducted for this report were based mainly on randomised trials. The number needed to treat (NNT) was chosen as the output for the report. NNTs of 2-4 indicate effective treatments. Because NNT is treatment-specific it overcomes problems associated with highly variable placebo or control event rates in pain trials. Such variability is predominantly due to the limited numbers of patients in the clinical trials. Dichotomous outcome measures are important in synthesising information from many studies, and in deriving NNTs. Methods have been developed which allow mean information on pain relief and intensity to be converted reliably into the simple dichotomous outcome of at least 50% pain relief. RESEARCH FINDINGS. PHYSICAL INTERVENTIONS. Transcutaneous electrical nerve stimulation (TENS) has been shown not to be effective in postoperative and labour pain. In chronic pain, there is evidence that TENS effectiveness increases slowly, and that large doses need to be used. There is lack of evidence for the effectiveness of TENS in chronic pain. There is a lack of evidence for the effectiveness of relaxation. Intravenous systemic regional blockade with guanethidine has been shown to be without effect. Epidural corticosteroids are effective in the short term for back pain and sciatica. Injections of corticosteroids in or around shoulder joints for shoulder pain have been shown not to be effective. There is a lack of evidence supporting spinal cord stimulators. Case series are of poor quality and do not provide evidence of effectiveness, although at least 50% pain relief at 5 years is reported in over 50% of patients. PHARMACOLOGICAL INTERVENTIONS. Minor analgesics are important in chronic pain. NNTs were calculated for analgesics given orally for moderate or severe acute postoperative pain. The NNTs found ranged from 17 (poor) for codeine, 60 mg, to 2.5 (good) for ibuprofen, 400 mg. Anticonvulsant and antidepressant drugs are prescribed for neuropathic pains like diabetic neuropathy. NNTs are of the order of 2.5, showing them to be effective treatments. However, there are too few studies with too few patients to determine which is the best drug. Minor adverse events are common, and major adverse events occur in about 1 in 20 patients. There are no studies comparing antidepressants and anticonvulsants directly. Systemic local anaesthetic-type drugs have been shown to be effective in nerve injury pain but there is little or no evidence to support their use in migraine or cancer-related pain. Topical NSAIDs (for example, gels, creams) are effective in rheumatological conditions with an overall NNT of 3. There are too few studies to determine which is the best agent. Topical NSAIDs have few adverse events; most importantly they are without the major gastrointestinal adverse events found with oral NSAIDs, which might make them an important choice for some patients with peripheral arthritis. (ABSTRACT TRUNCATED)

A critical review of the role of neonatal hearing screening in the detection of congenital hearing impairment

Abstract: Background This review was commissioned because of the increasing doubt about the ability of existing screening programmes (mainly the health visitor distraction test (HVDT) at 7-8 months) to identify children with congenital hearing impairment, and technological advances which have made neonatal hearing screening an alternative option. Objectives To review the available literature on the screening of permanent childhood hearing impairment. To provide commissioners and providers of health care with information about how to deliver a more uniform service, better outcomes, and more cost-effective screening. To identify areas for further research and service development. How the research was conducted The research involved a review of the available published and unpublished literature, and a comprehensive survey of current pre-school hearing screening provision in the UK coupled with a health economics study of hearing screening costs. The research also included a number of focus groups and visits to key centres in the UK and North America. Research findings EPIDEMIOLOGY OF PERMANENT CHILDHOOD HEARING IMPAIRMENT: There are approximately 840 children a year born in the UK with significant permanent hearing impairment likely to affect their own and their family's quality of life. Present services will miss about 400 of these children by 1 1/2 years of age, and about 200 of these children by 3 1/2 years of age. Such late identification of hearing impairment greatly reduces the responsiveness of the services for individual children. Evidence for improved outcomes with earlier identification Hearing-impaired children identified late are at risk of substantial delay in their acquisition of language and communication skills, with consequent longer-term risk to education achievement, mental health and quality of life. Theoretical arguments on neural development support the limited evidence here for the increased benefit for child and family associated with very early identification. In general, parents and professionals want very early identification, which, if implemented properly, does not cause undue anxiety. Current uk practice The survey of current practice indicated a major problem with poor information systems. This problem was further highlighted as a major concern by the multi-disciplinary focus groups. Practice varies. There are two District-wide programmes in which all newborn babies are neonatally screened, a large number of ad hoc programmes for neonatal screening of 'at-risk' babies, a variety of early surveillance programmes, and widespread use of the HVDT. Intervention and habilitation for the majority of those screened neonatally is routinely undertaken within 6 months of birth. For those screened only by the health visitor, identification was on average at about 26 months of age with intervention at about 32 months on average. (ABSTRACT TRUNCATED)

Routine preoperative testing: a systematic review of the evidence.

Abstract: OBJECTIVES. To review the available evidence on the value of routine preoperative testing in healthy or asymptomatic adults. To assess the completeness of existing reviews of preoperative testing and how applicable their conclusions are to the UK. To identify areas for further research. HOW THE RESEARCH WAS CONDUCTED. The databases Medline, Embase, Biological Abstracts, Science Citation Index and HealthSTAR were thoroughly searched for relevant articles which were then classified and appraised. The databases of the Centre for Reviews and Dissemination (DARE and NHS Economic Evaluations Database) and the Cochrane Collaboration (the Cochrane Library) were also used to verify the completeness of the search. In this review, 'routine' tests are defined as those ordered for an asymptomatic, apparently healthy individual in the absence of any specific clinical indication, to identify conditions undetected by clinical history and examination. RESEARCH FINDINGS. No controlled trials of the value of the following routine preoperative tests have been published. All available evidence reports the results of case-series. CHEST X-RAY. Few studies allow the outcome of routine chest X-rays to be distinguished from those of indicated chest X-rays, and fewer have gone beyond abnormality yields to examine the impact on clinical management. Findings from routine preoperative chest X-ray are reported as abnormal in 2.5-37.0% of cases, and lead to a change in clinical management in 0-2.1% of patients. The effect on patient outcomes is unknown. Both abnormality yield and impact on patient management rise with age and poorer American Society of Anesthesiologists (ASA) status. The limited evidence on the value of a chest X-ray as a baseline measure suggests that it will be of value in less than 9% of patients. ELECTROCARDIOGRAPHY. The findings from routine preoperative electrocardiograms (ECGs) are abnormal in 4.6-31.7% of cases, and lead to a change of management in 0-2.2% of patients. The effect on patient outcomes is unknown. The proportion of abnormal tests rises with age and worsening ASA status. The predictive power of preoperative ECGs for postoperative cardiac complications in non-cardiopulmonary surgery is weak. There is no evidence to support the value of recording a preoperative ECG as a 'baseline.' HAEMOGLOBIN MEASUREMENT AND BLOOD COUNTS. Routine preoperative measurement shows that the haemoglobin level may be lower than 10-10.5 g/dl in up to 5% of patients, but that it is rarely lower than 9 g/dl. The routine test leads to a change of management in 0.1% to 2.7% of patients. Routine preoperative measurement shows that the platelet count is abnormally low in less than 1.1% of patients, and that platelet count results rarely if ever lead to change in management of patients. Routine preoperative white blood cell count is abnormal in less than 1% of patients, and rarely if ever leads to change in management of patients. TESTS OF HAEMOSTASIS. Abnormalities of bleeding time, prothrombin time and partial thromboplastin time are found in up to 3.8%, 4.8% and 15.6% of routine preoperative tests, respectively. The results of these tests very rarely lead to change in the clinical management of patients. BIOCHEMISTRY. In routine preoperative tests of serum biochemistry, abnormal levels of sodium or potassium are found in up to 1.4% of patients, and abnormal levels of urea or creatinine are found in up to 2.5% of patients. Abnormal levels of glucose are found in up to 5.2% of patients. These abnormalities rarely lead to change in clinical management of patients. URINE TESTING. Routine preoperative urinalysis finds abnormal results in 1-34.1% of patients, and leads to a change of management in 0.1-2.8% of patients. The only abnormality that leads to a change in management of patients is the finding of white blood cells in the urine. There is no good evidence that preoperative abnormal urinalysis is associated with any postoperative complication in non-urinary tract surgery. (ABSTRACT TRUNCATED)

Newborn screening for inborn errors of metabolism: a systematic review.

Abstract: Objectives: to establish a database of literature and other evidence on neonatal screening programmes and technologies for inborn errors of metabolism. To undertake a systematic review of the data as a basis for evaluation of newborn screening for inborn errors of metabolism. To prepare an objective summary of the evidence on the appropriateness and need for various existing and possible neonatal screening programmes for inborn errors of metabolism in relation to the natural history of these diseases. To identify gaps in existing knowledge and make recommendations for required primary research. To make recommendations for the future development and organisation of neonatal screening for inborn errors of metabolism in the UK. How the research was conducted: there were three parts to the research. A systematic review of the literature on inborn errors of metabolism, neonatal screening programmes, new technologies for screening and economic factors. Inclusion and exclusion criteria were applied, and a working database of relevant papers was established. All selected papers were read by two or three experts and were critically appraised using a standard format. Seven criteria for a screening programme, based on the principles formulated by Wilson and Jungner (WHO, 1968), were used to summarise the evidence. These were as follows. Clinically and biochemically well-defined disorder. Known incidence in populations relevant to the UK. Disorder associated with significant morbidity or mortality. Effective treatment available. Period before onset during which intervention improves outcome. Ethical, safe, simple and robust screening test. Cost-effectiveness of screening. A questionnaire which was sent to all newborn screening laboratories in the UK. Site visits to assess new methodologies for newborn screening. The classical definition of an inborn error of metabolism was used (i.e., a monogenic disease resulting in deficient activity in a single enzyme in a pathway of intermediary metabolism). Research findings: inborn errors of metabolism. Phenylketonuria (PKU) (incidence 1:12,000) fulfilled all the screening criteria and could be used as the 'gold standard' against which to review other disorders despite significant variation in methodologies, sample collection and timing of screening and inadequacies in the infrastructure for notification and continued care of identified patients. Of the many disorders of organic acid and fatty acid metabolism, a case can only be made for the introduction of newborn screening for glutaric aciduria type 1 (GA1; estimated incidence 1:40,000) and medium-chain acyl CoA dehydrogenase (MCAD) deficiency (estimated incidence 1:8000-1:15,000). Therapeutic advances for GA1 offer prevention of neurological damage but further investigation is required into the costs and benefits of screening for this disorder. MCAD deficiency is simply and cheaply treatable, preventing possible early death and neurological handicap. Neonatal screening for these diseases is dependent upon the introduction of tandem mass spectrometry (tandem MS). This screening could however also simultaneously detect some other commonly-encountered disorders of organic acid metabolism with a collective incidence of 1:15,000

Neonatal screening for inborn errors of metabolism: cost, yield and outcome

Abstract: OBJECTIVES. To systematically review the literature on inborn errors of metabolism, neonatal screening technology and screening programmes in order to analyse the costs and benefits of introducing screening based on tandem mass-spectrometry (tandem MS) for a wide range of disorders of amino acid and organic acid metabolism in the UK. To evaluate screening for cystic fibrosis, Duchenne muscular dystrophy and other disorders which are tested on an individual basis. HOW THE RESEARCH WAS CONDUCTED. Systematic searches were carried out of the literature on inborn errors of metabolism, neonatal screening programmes, tandem MS-based neonatal screening technology, economic evaluations of neonatal screening programmes and psychological aspects of neonatal screening. Background material on the biology of inherited metabolic disease, the basic philosophy, and the history and current status of the UK screening programme was also collected. Relevant papers in the grey literature and recent publications were identified by hand-searching. Each paper was graded. For each disease an aggregate grade for the state of knowledge in six key areas was awarded. Additional data were prospectively collected on activity and costs in UK neonatal screening laboratories, and expert clinical opinion on current treatment modalities and outcomes. These data were used to construct a decision-analysis model of neonatal screening technologies, comparing tandem MS with the existing phenylketonuria screening methods. This model determined the cost per additional case identified and, for each disease, the additional treatment costs per case, and the cost per life-year saved. All costs and benefits were discounted at 6% per annum. One-way sensitivity analysis was performed showing the effect of varying the discount rate, the incidence rate of each disorder, the number of neonates screened and the cost of tandem MS, on the cost per life-year gained. RESEARCH FINDINGS. The UK screening programmes for phenylketonuria and congenital hypothyroidism have largely achieved the expected objectives and are cost-effective. Current concerns are the difficulty of maintaining adequate coverage, perceived organisational weaknesses, and a lack of overview. For many of the organic acid disorders it was necessary to rely on data obtained from clinically-diagnosed cases. Many of these diseases can be treated very effectively and a sensitive screening test was available for most of the diseases. Except for cystic fibrosis, there have been no randomised controlled trials of the overall effectiveness of neonatal screening. Despite the anxiety generated by the screening process, there is strong parental support for screening. The effects of diagnosis through screening on subsequent reproductive behaviour is less clear. Conflicts exist between current concepts and the traditional principles of screening. The availability of effective treatment is not an absolute prerequisite: early diagnosis is of value to the family concerned and, to the extent that is leads to increased use of prenatal diagnosis, may help to reduce the overall burden of disease. Neonatal screening is also of value in diseases which present early but with non-specific symptoms. Indeed, almost all of the diseases considered could merit neonatal screening. The majority of economic evaluations failed to incorporate the health benefits from screening, and therefore failed to address the value of the information which the screening programmes provided to parents. The marginal cost of changing from present technology to tandem MS would be approximately 0.60 pounds per baby at a workload of 100,000 samples a year, and 0.87 pounds at 50,000 samples per year. The ability to screen for a wider range of diseases would lead to the identification of some 20 additional cases per 100,000 infants screened, giving a laboratory cost per additional diagnosis of 3000 pounds at an annual workload of 100,000 babies per year.(ABSTRACT TRUNCATED)

Diagnosis, management and screening of early localised prostate cancer

Abstract: The incidence of prostate cancer is rising worldwide, caused mainly by demographic factors, particularly the increasingly elderly population and, more importantly, the increasing number of cases identified following prostate specific antigen (PSA) testing. It is commonly quoted that many more men die with prostate cancer than of it. Autopsy/post-mortem studies show that while a very high proportion of elderly men have histological evidence of the disease, a much smaller proportion develop clinically apparent cancer. The natural history of prostate cancer is poorly understood, but progression appears to be related to stage and grade of tumour. Prostate cancer can be diagnosed by digital rectal examination (DRE), serum PSA test, and/or transrectal ultrasound (TRUS), with confirmation by biopsy. Each test identifies a proportion of cancers, with higher rates of detection when they are used in combination. The tests are also used to determine which tumours are localised within the prostate and are, thus, potentially treatable. Unfortunately, clinical staging is unreliable, with approximately one half of all tumours upstaged following surgery. Three major treatment options are available for localised prostate cancer: radical prostatectomy, radical radiotherapy and conservative management (involving monitoring and treatment of symptoms). Although radical treatment rates are rising, good quality evidence concerning their comparative effectiveness and cost-effectiveness is lacking. Observational studies of highly selected patient groups suggests that there may be a slightly lower mortality rate following radical treatments compared with conservative management, but there has been very little research into treatment complications and quality of life of men after any of the treatments. In the past, investigations of prostate cancer were reserved largely for patients exhibiting symptoms, but the introduction of the PSA test has opened up the possibility of screening healthy men for the disease. Observational studies suggest that DRE and PSA, combined with TRUS and biopsy, can identify localised prostate cancer in 3-5% of men, although the tests do result in a number of false positives and negatives. Major questions remain concerning the natural history of the disease, potential costs (financial, social and psychological) of a screening programme, and the effectiveness and cost-effectiveness of treatments for localised disease. The lack of good quality data and the strength of these concerns means that population screening for prostate cancer cannot be recommended.

Preschool vision screening.

Abstract: Objectives To undertake a systematic review of the effectiveness of preschool vision screening. To provide evidence on which decisions about the future provision of this service can be made. To indicate areas for further research. Study selection The Centre for Reviews and Dissemination guidelines for systematic reviews were used. The research questions were formulated using the Wilson and Jungner criteria for evaluating screening programmes. They concerned prevalence, natural history, disability, treatment and screening in relation to three target conditions: amblyopia, refractive errors and squints which are not cosmetically obvious. Studies were considered for inclusion according to pre-determined criteria for the age group studied, the outcomes measured and the study design. The following types of study design were considered: cross-sectional studies of prevalence, cohort studies of natural history, any type of study (e.g., cross-sectional surveys, case-series, qualitative studies) of disability attributable to a target condition, controlled trials, observational studies and audits of screening programmes, and prospective controlled trials of treatment. Data sources The following electronic databases were searched: Biological Abstracts, CINAHL, Embase, ERIC, IAC Health Periodicals, IAPV, Medline, Psychlit, Science Citation Index, System for Information on Grey Literature in Europe, DHSS-Data, Faculty of Public Health Medicine Database of Dissertations, Index of Scientific and Technical Proceedings, Dissertation Abstracts, Index of Theses, NHS Research Register, Public Health Information Sharing Database. A limited amount of handsearching was undertaken. Reference lists were scanned to identify other relevant studies, and requests for unpublished data were made to people working in the field. Data extraction Data was extracted by the first author and then checked by the second. Data synthesis Quantitative analysis was undertaken where possible. Qualitative analysis was performed where studies were too heterogeneous for the data to be combined, or for research questions that were not suitable for quantitative synthesis. Research findings The electronic search yielded over 5000 references, and over 500 abstracts were downloaded from the databases for further scrutiny. A total of 85 studies were included in the main analysis. Prevalence No studies were found with the primary aim of establishing the prevalence of visual defects in preschool children. Data from studies of screening programmes report a range of yields for all the target conditions combined of 2.4-6.1%. NATURAL HISTORY: No studies designed with the intention of documenting the natural history of the target conditions in children aged 3 or 4 years were found. Other studies that provide some natural history data suggest that mild degrees of amblyopia may resolve spontaneously. In the absence of information about natural history it is impossible to estimate the effect of treatment from studies without a control group that was not treated. DISABILITY: A total of 21 studies exploring disability in relation to the target conditions were included. The literature provides a reasonable basis for generating plausible hypotheses about the ways in which the target conditions might disable people, but is insufficient to draw any firm conclusions about their impact on quality of life. The research to date is not sufficient to determine appropriate outcomes for controlled trials of treatment. Treatment Five randomised controlled trials of treatment and six prospective controlleld trials without randomisation were found. No studies compared treatment with no treatment. Most of the studies were methodologically flawed.(ABSTRACT TRUNCATED)

Systematic review of the effectiveness of laxatives in the elderly.

Abstract: Objectives To determine the effectiveness and cost of laxatives in the prevention and treatment of constipation in the elderly. How the research was conducted Randomised controlled trials (RCTs) of treatment or prevention of constipation were included in the review. Interventions The four classes of laxatives, bulk, osmotic, stimulant laxatives and faecal softeners, were covered by the review. The main laxatives included in the trials were bran, psyllium, prucara, cascara, dioctyl sodium, lactulose, and lactitol. Participants Elderly people suffering from chronic functional constipation. A trial was eligible for inclusion if all participants were aged 55 years or older and being treated for chronic constipation. The trials reviewed did not provide further subcategorisation by aetiology. Main outcomes Number of bowel movements per week; symptom improvement; stool consistency; abdominal pain. Data sources The recent systematic review by Tramonte and colleagues was used as a source of trials (J Gen Intern Med 1997;12:15-24). In addition, the following databases were searched: Embase, Psychlit, Medline, the Cochrane library, the nursing database CINAHL, International Pharmaceutical Abstracts, and the alternative therapies database, AMED. Authors and manufacturers were also asked for information. Studies in any language were eligible for inclusion. Decisions on the relevance of primary studies were made independently by two reviewers. Economic information was searched for in Current Contents/Clinical Medicine, Medline, and the NHS Economic Evaluation Database (NEED). VALIDITY ASSESSMENT: The quality of primary studies was summarised on a 6-item scale. This covered reporting of inclusion and exclusion criteria, randomisation method, standardised assessmment of adverse effects, double-blind design, description of withdrawals, and statistical analysis. The assessment of validity of included studies was carried out independently by two reviewers. Data were extracted from studies independently by two reviewers. Authors were contacted for more information where necessary to obtain unpublished information. Clinical trials included Ten trials comparing single agents with placebo were identified, with a total of 367 patients were identified, with a total of 367 patients who had a mean age of about 74 years. Two of these presented no information on the numbers of men and women (54%) in the remaining eight trials. The majority of patients were in an institutional setting, such as a nursing home or hospital. Ten trials compared one laxative agent with another. The mean age of participants in these trials was estimated at 77 years. Only one trial examined patients in an outpatient setting; the other trials were carried out in nursing homes or hospitals. (ABSTRACT TRUNCATED)

When and how to assess fast-changing technologies: a comparative study of medical applications of four generic technologies.

Abstract: OBJECTIVES. To try to identify the optimal time at which to start assessing new and fast-evolving health technologies. To provide insight into factors influencing the timing of assessments and the choice of methods for assessing new and fast-changing technologies. HOW THE RESEARCH WAS CONDUCTED. A series of literature reviews were undertaken covering the general principles involved in the timing of health technology assessments (HTAs). Additionally, the reported assessments of laparoscopic cholecystectomy, chorionic villus sampling (CVS), teleradiology, teledermatology, genetic screening for predisposition to breast cancer, and gene therapy for cystic fibrosis were reviewed to try to identify the factors that influenced the timing of these assessments. Key individuals in each field were also interviewed. The selected technologies allowed comparison between those that were new and evolving and those that were relatively well-established. A bibliometric study of publication trends was also undertaken to see whether these trends would suggest points in the development of a technology that could be used as indicators that assessment should be started. RESEARCH FINDINGS. TIMING. The precise point at which assessment should start was not identified but the bibliometric study suggested that extending this approach might give useful results. For all health technologies, more regular reporting of outcomes and side-effects should be encouraged during the period after initial assessment and, where the technology is fast-changing, reassessment should take place from time to time. The precise intervals were not identified and the problem remains of deciding when a technology has changed enough to warrant reassessment. FACTORS INFLUENCING TIMING. Published reports of assessments did not generally specify the reasons for their timing, but a number of factors appear to have influenced the timing of those assessments, directly or indirectly. Product champions and opinion leaders pioneer the introduction of new technologies into clinical practice, and their reports may lead to the rapid diffusion of such technologies before they have been adequately evaluated, as was the case with laparoscopic cholecystectomy; this diffusion may limit the methods of evaluation that can then be used. It is therefore important to assess new health technologies before diffusion takes place. The extent to which regulatory control is imposed on the introduction of new health technologies can also influence the timing of assessments. Such controls might have helped to restrict the diffusion of laparoscopic cholecystectomy, making a large and widely generalisable randomised controlled trial (RCT) feasible. The source and availability of funding for studies may influence the nature and timing of trials. Many telemedicine evaluations were funded by commercial telecommunications organisations and were thus restricted in their timing (and biased towards the technological aspects of the applications) by the availability of funds. Media coverage undoubtedly has an influence although this influence is not always predictable; it may generate 'favourable' publicity about new health technologies, which can lead to immediate demands for the new technique, as was the case with laparosocpic cholecystectomy with its apparent benefits. Thus assessments should be made before media coverage exerts popular pressure on purchasers to adopt the technology and dissuades patients from participating in RCTs (because of fear they may be randomised to the standard treatment as occurred in a US trial of CVS). Innovators should also be cautious in the claims that they make to the media.(ABSTRACT TRUNCATED)

Home parenteral nutrition: a systematic review.

Abstract: Objectives The objective of this Review was to locate, appraise and summarise evidence from scientific studies on home parenteral nutrition (HPN) in order to answer specific research questions on the effectiveness of this technology. The following questions were asked. What patients have received HPN? What has been the experience of patients on HPN programmes? How have HPN programmes been organised, and what techniques and equipment have been used, and to what effect? What comparative information is available on effectiveness? What evidence exists for the cost-effectiveness of HPN? What questions about the provision of HPN could be answered with additional research, and what studies would be most suitable? Data sources A comprehensive list of studies was provided by an extensive search of electronic databases (including MEDLINE, Embase, Science Citation Index, Uncover, Cinahl, Caredata, Food Science and Technology Abstracts, NTIS, Pascal, Psychlit, and Economic Literature Index), relevant journals (including Journal of Parenteral and Enteral Nutrition, Clinical Nutrition, American Journal of Clinical Nutrition, Nutrition, Clinical Gastroenterology, Nutrition Reviews, Annals of Nutrition and Metabolism, Nutrition and Cancer, Nutrition and Health, and Journal of Paediatric Nutrition and Metabolism), and scanning of reference lists, as well as other search strategies outlined in the protocol. Study selection Studies relevant to the questions were selected. The inclusion criteria were fairly broad because of the quality of the studies located. Data extraction Data extraction forms were used to collect data from studies included in the review. The data was checked by a second researcher to reduce error. Data synthesis Quantitative analysis was difficult owing to the type of studies located. The data is discussed in a qualitative manner. Where complication rates have been given, we have attempted to combine the results in a quantitative manner. Results The age and sex of patients on HPN varies according to the underlying disease but, on the whole, patients are young (see Tables 4a and 4b). There are trends showing an increased use of the technology at the extremes of the age range. There are marked differences between countries on the underlying diseases for which HPN is indicated. For example, many more patients with an underlying malignancy are treated in Italy and the USA than in the UK (40-67% versus 8%). Morbidity rates for the majority of patients are acceptable (see Table 8), the complications tend to be related to the central venous catheter. It is fairly clear that a minority of patients are susceptible to recurrent problems and that many patients have very few complications. The mortality rate for HPN patients (see Table 10) was good for those patients with benign underlying disease (for example, 5% of Crohn's HPN patients die per year), and there are very few reports of patients dying from complications of the technology. The survival of those with malignant disease and AIDS is poor, almost all having died from the underlying disease at one year; despite this, most programme growth worldwide is due to an increase in the numbers of patients with these diagnoses (see Table 5). Quality of life is reasonable for patients with benign disease (see Table 9); no studies were found that examined the quality of life of HPN patients with malignant disease. Economic analysis shows that the cost of HPN treatment is cheaper than the alternative of in-patient care (see Table 18). There is a paucity of comparative studies examining different aspects of the technology, and this accounted for the majority of gaps in the evidence. Conclusions The use of HPN for benign intestinal failure is supported by evidence from the scientific studies located. There are, however, large gaps in the evidence, particularly relating to the use of HPN in malignant disease and AIDS. A programme of research is suggested at the end of this review.

A review of near patient testing in primary care.

Abstract: Aims and objectives The aim was to identify publications relating to near patient testing (NPT), the use of alternative delivery systems between laboratory and general practice, including electronic data interchange (EDI), and computerised diagnostic decision support (CDDS), in the primary care setting to answer the following questions What is the availability of NPT for primary care? What evidence is available to support the clinical effectiveness of NPT? What evidence is available on the accuracy and reliability of NPT within primary care? What evidence is available on the cost-effectiveness of different NPTs? How may CDDS improve the effectiveness of NPT? What evidence is available that compares NPT and existing laboratory services? What evidence is available on the cost-effectiveness of EDI or alternative delivery systems? How the research was conducted Eight databases were searched, and the bibliographies from relevant publications checked for completeness Unpublished work and publications not included in the databases were obtained by personal contact with collaborators, and from a postal survey sent to heads of academic departments of general practice and clinical chemistry and to researchers active or interested in the field worldwide Questionnaires were also sent to 150 commercial organisations Publications that met agreed definitions and reported original data were included in the systematic review Of the 1057 publications identified, 102 (92 related to NPT, eight to CDDS, and two to EDI) were passed to the reviewers for appraisal of validity The limited amount of published research relating to any particular NPT prohibited meta-analysis Scoring systems to assess the validity of evaluations were also difficult to apply Research findings A wide variety of NPT systems have been developed In general, the quality of the methods reported in the literature was poor The issue of patient convenience and acceptability has not been adequately addressed No evaluations of alternative delivery systems met the review criteria No studies have evaluated the telephone or fax machine as a means of reporting results For EDI, the majority of papers were descriptive EDI and alternative delivery systems are not a replacement for NPT when the provision of an immediate result might have an impact on the quality of care EDI may have clinical and cost advantages over traditional means of communication, but this has not been evaluated The advisory role of the laboratory can be supported by CDDS The use of CDDS and NPT has not, however, been fully evaluated Few economic analyses have been conducted, and most were simple cost analyses There are insufficient data for conclusions to be drawn on the cost-effectiveness of NPT in primary care Recommendations FURTHER SYSTEMATIC REVIEWS: Subject-specific systematic reviews are required that include laboratory and secondary care studies, and consider the potential for altering current management and patient acceptability Priority topics include: biochemistry profiles on desktop analysers; cholesterol testing; urinalysis for the diagnosis of urinary tract infection; anticoagulation control; NPTs for the identification of acute infection (ABSTRACT TRUNCATED)

Screening for fragile X syndrome.

Abstract: BACKGROUND AND AIM OF REVIEW In 1991, the gene responsible for fragile X syndrome, a common cause of learning disability, was discovered As a result, diagnosis of the disorder has improved and its molecular genetics are now understood This report seems to provide the information needed to decide whether to use DNA testing to screen for the disorder HOW THE RESEARCH WAS CONDUCTED A literature search of electronic reference databases of published and 'grey' literature was undertaken together with hand searching of the most recent publications RESEARCH FINDINGS NATURAL HISTORY Physical characteristics of fragile X syndrome include facial atypia, joint laxity and, in boys, macro-orchidism Most affected males have moderate-to-severe learning disabilities with IQs under 50 whereas most females have borderline IQs of 70-85 Behavioural problems are similar to those seen with autism and attention-deficit disorders Although fragile X syndrome is not curable there are a number of medical, educational, psychological and social interventions that can improve the symptoms About 6% of those with learning disabilities tested in institutions have fragile X syndrome Population prevalence figures are 1 in 4000 in males and 1 in 8000 in females GENETICS The disorder is caused by a mutation in a gene on the X chromosome which includes a trinucleotide repeat sequence The mutation is characterized by hyper-expansion of the repeat sequence leading to down-regulation of the gene In males an allele with repeat size in excess of 200, termed a full mutation (FM), is always associated with the affected phenotype, whereas in females only half are affected Individuals with alleles having repeat size in the range 55-199 are unaffected but in females the sequence is heritably unstable so that it is at high risk of expansion to an FM in her offspring This allele is known as a pre-mutation (PM) to contrast it with the FM found in the affected individual No spontaneous expansions directly from a normal allele to an FM have been observed SCREENING STRATEGIES The principal aims of screenng for fragile X syndrome is to reduce the birth prevalence of the disorder, by prenatal diagnosis and selective termination of pregnancy, or by reducing the number of pregnancies in women who have the FM or PM alleles Possible screening strategies are: routine antenatal testing of apparently low risk pregnancies, preconceptual testing of young women, and systematic testing in affected families ('cascade' screening) A secondary aim is to bring forward the diagnosis of affected individuals so that they might benefit from early treatment Active paediatric screening and neonatal screening could achieve this but there is no direct evidence of any great benefit from early diagnosis SCREENING TESTS Cytogenetic methods are unsuitable for screening purposes Southern blotting of genomic DNA can be used but is inaccurate in measuring the size of small PMs, there is a long laboratory turnaround time, and it is relatively expensive The best protocol is to amplify the DNA using polymerase chain reaction on all samples, and when there is a possible failure to amplify, a Southern blot(ABSTRACT TRUNCATED)

Implications of Socio-Cultural Contexts for the Ethics of Clinical Trials

Abstract: BACKGROUND Health technology assesment (HTA) requires scientifically rigorous experimentation involving patients as subjects. HTA itself is required so that treatment given to patients will be both effective and efficient; this requirement is itself ethical in nature. At the same time it is essential that the methods used in HTA are ethically sound. Most healthcare researchers agree that the most effective and soundest method for assessing treatments is the randomised controlled trial (RCT). However, some researchers believe that the RCT is unethical, either in essence, or for use in some forms of medical research and HTA. Furthermore, many patients seem unable to understand the principles and purposes of the RCT, a factor which is highly detrimental for the validity of informed consent. Informed consent is the key to the ethics of medical research, both in most theories and in all codes of research conduct. Many RCTs therefore risk being unethical in practice, even if ethical in principle. AIM OF REPORT To survey the main objections to the RCT and its alternatives. To assess the philosophical and methodological basis of these objections, and of the methods recommended for addressing them. To identify areas where objections are founded in social or cultural factors normally overlooked in ethical argument about the RCT methodology. To identify alternative arguments or methods which might resolve ethical conflicts in this area. HOW THE RESEARCH WAS CONDUCTED The methods used were adapted from systematic reviews in medicine. Systematic searches of Medline, Psychlit and Sociofile CD-ROM databases; hand-searches of the major journals in general medicine and surgery, medical ethics and philosophy; and searches of books were carried out. The literature survey was restricted to articles published or abstracted in English. A database of the most relevant and useful materials was compiled, and is accessible on the Internet (http://www.liv.ac.uk/sdthomps/page1.html). RESEARCH FINDINGS UNDERSTANDING RCTS AND THEIR ALTERNATIVES: There is some evidence of difficulty in understanding the aims and methods of RCTs, and some disquiet about elements of the RCT methodologies. These objections are well known and much discussed, and concern the use of placebo, the continuation of trials after significant differentials in benefit or harm are apparent, and randomisation. CULTURAL OR RELIGIOUS OBJECTIONS There was an absence of evidence of cultural or religious objections to randomisation, placebo or other kinds of controlled prospective trials. This most likely reflects an absence of research rather than absence of objections. (ABSTRACT TRUNCATED)

Home parenteral nutrition: a systematic review.

Abstract: Objectives The objective of this Review was to locate, appraise and summarise evidence from scientific studies on home parenteral nutrition (HPN) in order to answer specific research questions on the effectiveness of this technology. The following questions were asked. What patients have received HPN? What has been the experience of patients on HPN programmes? How have HPN programmes been organised, and what techniques and equipment have been used, and to what effect? What comparative information is available on effectiveness? What evidence exists for the cost-effectiveness of HPN? What questions about the provision of HPN could be answered with additional research, and what studies would be most suitable? Data sources A comprehensive list of studies was provided by an extensive search of electronic databases (including MEDLINE, Embase, Science Citation Index, Uncover, Cinahl, Caredata, Food Science and Technology Abstracts, NTIS, Pascal, Psychlit, and Economic Literature Index), relevant journals (including Journal of Parenteral and Enteral Nutrition, Clinical Nutrition, American Journal of Clinical Nutrition, Nutrition, Clinical Gastroenterology, Nutrition Reviews, Annals of Nutrition and Metabolism, Nutrition and Cancer, Nutrition and Health, and Journal of Paediatric Nutrition and Metabolism), and scanning of reference lists, as well as other search strategies outlined in the protocol. Study selection Studies relevant to the questions were selected. The inclusion criteria were fairly broad because of the quality of the studies located. Data extraction Data extraction forms were used to collect data from studies included in the review. The data was checked by a second researcher to reduce error. Data synthesis Quantitative analysis was difficult owing to the type of studies located. The data is discussed in a qualitative manner. Where complication rates have been given, we have attempted to combine the results in a quantitative manner. Results The age and sex of patients on HPN varies according to the underlying disease but, on the whole, patients are young (see Tables 4a and 4b). There are trends showing an increased use of the technology at the extremes of the age range. There are marked differences between countries on the underlying diseases for which HPN is indicated. For example, many more patients with an underlying malignancy are treated in Italy and the USA than in the UK (40-67% versus 8%). Morbidity rates for the majority of patients are acceptable (see Table 8), the complications tend to be related to the central venous catheter. It is fairly clear that a minority of patients are susceptible to recurrent problems and that many patients have very few complications. The mortality rate for HPN patients (see Table 10) was good for those patients with benign underlying disease (for example, 5% of Crohn's HPN patients die per year), and there are very few reports of patients dying from complications of the technology. The survival of those with malignant disease and AIDS is poor, almost all having died from the underlying disease at one year; despite this, most programme growth worldwide is due to an increase in the numbers of patients with these diagnoses (see Table 5). Quality of life is reasonable for patients with benign disease (see Table 9); no studies were found that examined the quality of life of HPN patients with malignant disease. Economic analysis shows that the cost of HPN treatment is cheaper than the alternative of in-patient care (see Table 18). There is a paucity of comparative studies examining different aspects of the technology, and this accounted for the majority of gaps in the evidence. Conclusions The use of HPN for benign intestinal failure is supported by evidence from the scientific studies located. There are, however, large gaps in the evidence, particularly relating to the use of HPN in malignant disease and AIDS. A programme of research is suggested at the end of this review.