Methods in health services research. Interpreting the evidence: choosing between randomised and non-randomised studies.
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Biomedical subjects
Publications and source records attributed to C Sanderson.
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BACKGROUND: The evaluation of community services for preschool children is hampered by the lack of valid and routinely available outcome measures. This study examines the use of data collected by teachers in response to educational legislation to determine whether a routine measure of attainments in primary school is sensitive to factors known to affect mental development. METHOD: A community child health dataset for the cohort of children born in Sheffield in 1990-1991 was matched with a dataset provided by schools in 1995-1996. The educational data consisted of the Infant Index scores which measure education attainments in reception class pupils. RESULTS: We matched 4487 children from both datasets, which represented 75 per cent of all children born in the 1990-1991 cohort. Factors which predicted a poor Infant Index included male gender (odds ratio (OR) = 2.1, 95 per cent confidence interval (CI)= 1.8-2.6), low birthweight (OR = 1.4, 95 per cent CI = 1.1-1.9) and lack of breast feeding either by intention to feed (OR = 1.3, 95 per cent CI = 1.1-1.7) or actual feeding practice at one month (OR = 1.5, 95 per cent CI = 1.1-2.0). Other factors associated with a poor outcome for the child were postnatal depression, number of pregnancies, ethnicity, pre-school educational experiences and poor housing. CONCLUSIONS: Although the results are interesting in themselves, the main significance of our project is in establishing a link between routinely collected health data and routine education data. This could facilitate research in the future thus leading to a considerable saving in the cost of long-term intervention studies.
BACKGROUND: Although the randomised controlled trial (RCT) is regarded as the 'gold standard' in terms of evaluating the effectiveness of interventions, it is susceptible to challenges to its external validity if those participating are unrepresentative of the reference population for whom the intervention in question is intended. In the past, reporting on numbers and types of potential subjects that have been excluded by design, and centres, clinicians or patients that have elected not to participate, has generally been poor, and the threat to inference posed by possible selection bias is unclear. METHODS: A systematic review was undertaken, based largely on MEDLINE and EMBASE with follow-up of cited references, to assess the extent, nature and importance of excluding potential subjects or the unwillingness of particular centres, clinicians or patients to participate. RESULTS: RCTs vary widely in the extent to which potential future recipients of treatment are included. The reasons cited for excluding certain categories of patient may be medical or scientific. Medical reasons include a high risk of adverse effects and the belief that benefit will be relatively small or absent (or has already been established) in the groups in question. Scientific reasons include more precise estimates of treatment effect because of a relatively homogeneous sample and the reduction of potential bias by excluding those individuals most likely to be lost to follow-up. Many RCTs have blanket exclusions, such as the elderly, women and ethnic minorities, but reasons for these exclusions are seldom given. Evaluative research is undertaken predominantly in university or teaching centres. Non-randomised studies are more likely than RCTs to include non-teaching centres. The effect of patient non-participation appears to depend on whether the RCT is concerned with treatment of an existing condition or with disease prevention. Participants in treatment trials tend to be more severely ill than those who do not participate. In contrast, those who participate in prevention trials are more likely to have adopted a healthy lifestyle than those who decline. Most evaluative studies fail to document adequately the characteristics of those who, while eligible, do not participate. However, subjects included in RCTs (i.e. eligible and participating) tend to have a different prognosis than patients identified from clinical databases. CONCLUSIONS: Narrow inclusion criteria may offer benefits such as increased precision and reduced loss to follow-up, but there are important disadvantages, such as uncertainty about extrapolation of results, which may result in denial of effective treatment to groups who might benefit, and delay in obtaining definitive results because of reduced recruitment rate. Selective participation by teaching centres and sicker patients in treatment RCTs may exaggerate the measured treatment effect. Prevention trials, on the other hand, may underestimate effects as participants have less capacity to benefit.
BACKGROUND: Although there is debate about the appropriate place of guidelines in clinical practice, guidelines can be seen as one way of assisting clinicians in decision-making. Given the likely diversity of opinion that any group of people may display when considering a topic, methods are needed for organising subjective judgements. Three principal methods (Delphi, nominal group technique, consensus development conference) exist which share the common objective of synthesising judgements when a state of uncertainty exists. OBJECTIVES: To identify the factors that shape and influence the clinical guidelines that emerge from consensus development methods and to make recommendations about best practice in the use of such methods. METHODS: Five electronic databases were searched: Medline (1966-1996), PsychLIT (1974-1996), Social Science Citation Index (1990-1996), ABI Inform and Sociofile. From the searches and reference lists of articles a total of 177 empirical and review articles were selected for review. RESULTS: The output from consensus development methods may be affected by: the way the task is set (choice of cues, recognition of contextual cues, the focus of the task, the comprehensiveness of the scenarios); the selection of participants (choice of individuals, degree of homogeneity of the group, their background, their number); the selection and presentation of scientific information (format, extent to which its quality and content is assessed); the way any interaction is structured (number of rating rounds, ensuring equitable participation, physical environment for meetings); and the method of synthesising individual judgements (definition of agreement, rules governing outliers, method of mathematical aggregation). CONCLUSIONS: Although a considerable amount of research has been carried out, many aspects have not been investigated sufficiently. For the time being at least, advice on those aspects has, therefore, to be based on the user's own commonsense and the experience of those who have used or participated in these methods. Even in the long term, some aspects will not be amenable to scientific study. Meanwhile, adherence to best practice will enhance the validity, reliability and impact of the clinical guidelines produced.
Heparanases are mammalian endoglycosidases that cleave heparan sulphate glycosaminoglycans from proteoglycan core proteins and degrade them into shorter chains. The enzymes have been proposed to act in a variety of cellular processes, including proteoglycan catabolism, remodelling of basement membranes and release of heparan sulphate-binding ligands from their extracellular storage sites. Additional functions for heparanases may be to generate short heparan sulphate chains that stabilize or activate other proteins. While heparanase activities have been described in a number of tissues and cell lines, it is not known how many different enzymes are responsible for these activities. Our recent studies characterizing the short glycosaminoglycans produced in Chinese hamster ovary (CHO) cells suggested that multiple heparanases are necessary for the formation of the short heparan sulphate chains [Bame and Robson (1997) J. Biol. Chem. 272, 2245-2251]. We examined whether this is the case by purifying heparanase activity from CHO cell homogenates. Based on their ability to bind ion-exchange resins and their elution from gel-filtration columns, four separate heparanase activities were partially purified. All four activities cleave free glycosaminoglycans over a broad pH range of 3.5-6.0 or 6. 5, suggesting that they act in the endosomal/lysosomal pathway. The sizes of the short heparan sulphate chains generated by the partially purified heparanases ranged from 6 to 9 kDa, and for two of the activities the product size is pH-dependent. Three of the four activities degrade proteoglycans as well as the free glycosaminoglycan chain. Interestingly, all four enzymes generate short glycosaminoglycans with a sulphate-rich, modified domain at the non-reducing end of the newly formed chain. Since our previous studies showed that in CHO cells there is also a population of short heparan sulphates with a modified domain at the reducing end of the chain, this suggests that there may be another heparanase in CHO cells that was not purified. Alternatively, our findings suggest that the formation of short heparan sulphate glycosaminoglycans inside CHO cells may be a result of the concerted action of multiple heparanases, and may depend on the proportions of the different enzymes and the environment in which the chains are degraded.
Metal implants are being used with increasing frequency for the treatment of many diseases in the field of orthopedics, cardiology, cardiovascular surgery, and otolaryngology. Unfortunately, metals can be a source of submicron particles, which may have adverse effects on tissues. This article describes a technique that uses backscattered electron imaging and energy dispersive X-ray microanalysis, which have the capacity to perform both quantitative and qualitative analysis. The particles can be characterized by size, shape, amount, and composition. Although this technique can be used near the implant interface, it is particularly helpful in tissues a great distance from the implant site with a low concentration of metal debris. In addition, the sensitivity and specificity of this technique can be adjusted to the investigator's needs.
Interleukin-5 (IL-5) is a potential candidate gene in the pathogenesis of asthma, as it is the main cytokine controlling eosinophil activity and eosinophils are pivotal in the development of airway inflammation. Mutation detection studies were performed on the IL-5 gene and the alpha-chain of its receptor in 30 asthmatic and 30 nonasthmatic subjects. Single-strand conformational polymorphism (SSCP) and heteroduplex analysis (HA) did not reveal any change from the reported normal sequence in all 4 exons of IL-5 as well as the promoter and 3'-untranslated regions of the gene. No SSCP variations were seen within the complete coding sequence of the IL-5 receptor alpha-chain. Mutations of the IL-5 gene coding region, its promoter and receptor are unlikely to be common causes of an inherited predisposition to asthma.
BACKGROUND: The aim of the study was to assess the reproducibility of clinical coding in two National Health Service hospitals within North West Thames region. METHODS: A retrospective audit was carried out, of clinical coding in hospital episode statistics, involving comparison of the codes assigned by local staff with those assigned by members of an external team unaware of the locally assigned codes. Where local and external coders disagreed, the records were reviewed for a third time by a further independent coder. The subjects were a random sample of 1607 non-maternity, non-psychiatric admissions occurring between 1991 and 1993, stratified for year and type of disease (asthma, diabetes, appendicitis, fractured femur and 'general'--a random selection of any diagnoses). The main outcome measures were the levels of exact agreement between local and external teams over codes for main diagnosis and procedure, and the level of approximate agreement (over the first three characters of the ICD-9 code for diagnosis and the letter and first two digits of the OPCS-4 code for procedure). For disagreements, the outcome measure was the level of agreement between the 'third' coder and the local and external coders. RESULTS: For the main diagnosis in the 'general' group at hospital A, internal and external coders agreed exactly in 43 per cent of the admissions examined and agreed 'approximately' in 55 per cent (kappa = 0.54). For hospital B the corresponding figures were 60 per cent and 72 per cent (kappa = 0.72). Approximate agreement was higher for the specific diseases considered, particularly for asthma (A: 86 per cent; B: 91 per cent) and fractured femur (A: 84 per cent; B: 89 per cent). For the main procedure at hospital A, there was exact agreement for 58 per cent and approximate agreement for 70 per cent (kappa = 0.66). For hospital B, the corresponding figures were 76 per cent and 83 per cent (kappa = 0.80). In cases of disagreement over the first three digits of the ICD-9 code for main diagnosis, the third coder disagreed with both local and external coders in 53 per cent at hospital A and 38 per cent at hospital B. Agreement was slightly better for discharges in 1992-1993 than in 1991-1992. CONCLUSIONS: The full clinical codes in NHS hospital episode statistics (HES) data should be treated with caution. The first three characters of ICD-9 codes for diagnoses and the OPCS-4 codes for procedures were more reliable. For some specific conditions such as asthma and fractured femur, reliability of the first three characters is much higher (for example, 86 per cent and 91 per cent for asthma in the two hospitals), but for the full codes can be worse. Secondary diagnoses or comorbidities may be significantly undercoded. A higher level of agreement in 1992-1993 than in 1991-1992 suggests that coding may be improving.
BACKGROUND: Seasonal variation in mortality has been investigated in many countries but not, until recently, in Russia. There are some grounds for suspecting that it may differ in Russia from what is seen in western countries. This paper explores patterns of seasonal variation in mortality in Moscow between 1993 and 1995. METHODS: Analysis was based on individual data on deaths occurring in Moscow between January 1993 and December 1995, grouped by four-week period and by calendar month and on mean monthly temperature in Moscow for the same period. Crude, smoothed and deseasonalized trends were inspected. Auto-correlation functions were estimated and deaths were regressed against temperature. RESULTS: As in other northern hemisphere countries, there is a winter excess of deaths but this is much smaller than in many western countries. It is restricted to some causes of death, such as ischaemic heart disease and cerebrovascular disease, and is associated with low temperature. In contrast, there is a marked summer increase in deaths among young people, especially from accidents and other deaths associated with alcohol consumption. Over the three-year period studied, there was an initial underlying increase in alcohol-related deaths that subsequently fell, coinciding with a previously observed increase in life expectancy. CONCLUSIONS: It is possible that the low level of excess winter mortality reflects warmer indoor environments than in the west. The seasonal variation of deaths among young people reinforces evidence of the important role of alcohol in the Russian mortality crisis.
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Ethylenediaminetetraacetic acid (EDTA) solution is used to decalcify bone specimens for histological examination. Sodium hydroxide (NaOH) has been used to dissolve EDTA and to bring EDTA solutions to neutral pH. This solution, however, requires several weeks to decalcify bone specimens. We investigated a new decalcification fluid using concentrated ammonium hydroxide (NH4OH) to dissolve EDTA and to adjust the pH to neutral. Decalcification was performed using a magnetic stirrer with and without vacuum, or with a sonic cleaner. Decalcification end point was confirmed using both the weight loss and X-ray methods. After decalcification, specimens were processed through paraffin and sections were stained with hematoxylin and eosin. Decalcification employing NH4OH required an average of six days. Light microscopy indicated good retention of cellular detail.
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OBJECTIVE: To develop a single, short, acceptable, and validated postal questionnaire for assessing patients' experiences of the process and outcome of day surgery. DESIGN: Interviews and review of existing questionnaires; piloting and field testing of draft questionnaires; consistency and validity checks. SETTING: Four hospitals, in Coventry (two), Swindon, and Milton Keynes. PATIENTS: 373 patients undergoing day surgery in 1990. MAIN MEASURES: Postoperative symptoms, complications, health and functional status, general satisfaction, and satisfaction with specific aspects of care. RESULTS: Response rates of 50% were obtained on field testing draft questionnaires preoperatively and one week and one month after surgery. 28% of initial non-responders replied on receiving a postal reminder, regardless of whether or not a duplicate questionnaire was sent; a second reminder had little impact. Many patients who expressed overall satisfaction with their care were nevertheless dissatisfied with some specific aspects. Outcome and satisfaction were related to three aspects of case mix; patient's age, sex, and type of operative procedure. The final questionnaire produced as a result of this work included 28 questions with precoded answers plus opportunities to provide qualitative comments. Several factors (only one, shorter questionnaire to complete, fewer categories of nonresponders, and administration locally) suggested that a response rate of at least 65% (with one postal reminder) could be expected. CONCLUSION: A validated questionnaire for day surgery was developed, which will be used to establish a national comparative database.
OBJECTIVES: To develop software for hospitals to analyse their own survey data on patients' experiences of day surgery and to create and test the feasibility of a national comparative audit service. DESIGN: Software development and testing; database analysis. SETTING: Eleven general hospitals in England. PATIENTS: 1741 day surgery patients undergoing procedures during 1991-2. MAIN MEASURES: Postoperative symptoms, complications, health and functional status, general satisfaction, and satisfaction with specific aspects of care. RESULTS: Software for data entry and analysis by hospitals was successfully used at the pilot sites. The overall response rate for the 11 hospitals using the questionnaire was 60%, ranging from 33% to 90% depending on the way the survey was managed. Data from all 11 hospitals were included in the national comparative audit database. Hospitals showed little variation in measures of patients' overall satisfaction (around 85%), but significant differences were apparent for specific aspects such as receiving adequate written information before admission (range 50%-89%), provision of adequate parking facilities (14%-92%) and experiencing a significant amount of postoperative pain (8%-42%). The proportion of day case patients undergoing procedures that could have been performed in outpatient departments varied from 0 to 27% between hospitals. Further comparisons of outcome, in particular measures of effectiveness, must await the development of validated case mix adjustment methods. CONCLUSION: Establishing a comparative audit database is feasible but several methodological problems remain to be resolved.
The study described here used routine data sources to consider three aspects of hospital workload-volume and case-mix of inpatients; volume of outpatients; and volume of procedures.