Sheila M. Gore

Quality of life measures in health care. I: Applications and issues in assessment

Many clinicians remain unsure of the relevance of measuring quality of life to their clinical practice. In health economics quality of life measures have become the standard means of assessing the results of health care interventions and, more controversially, the means of prioritising funding; but they have many other applications. This article--the first of three on measuring quality of life--reviews the instruments available and their application in screening programmes, audit, health care research, and clinical trials. Using the appropriate instrument is essential if outcome measures are to be valid and clinically meaningful.

Statistical guidelines for contributors to medical journals.

Most papers published in medical journals contain analyses that have been carried out without any help from a statistician. Although nearly all medical researchers have some acquaintance with basic statistics, there is no easy way for them to acquire insight into important statistical concepts and principles. There is also little help available about how to design, analyse, and write up a whole project. Partly for these reasons much that is published in medical journals is statistically poor or even wrong.1 A high level of statistical errors has been noted in several reviews of journal articles and has caused much concern. Few journals offer even rudimentary statistical advice to contributors. It has been suggested1 2 that comprehensive statistical guidelines could help by making medical researchers more aware of important statistical principles, and by indicating what information ought to be supplied in a paper. We present below an attempt to do this. Deciding what to include in the guidelines, how much detail to give, and how to deal with topics where there is no consensus has been problematic. These guidelines should thus be seen as one view of what is important, rather than as a definitive docu? ment. We have not set out to provide a set of rules but rather to give general information and advice about important aspects of statistical design, analysis, and presentation. Those specific recommendations that we have made are mostly strong advice against certain practices. Some familiarity with statistical methods and ideas is assumed, since some knowledge of statistics is necessary before carrying out statistical analyses. For those with only a limited acquaintance with statistics, the guidelines should show that the subject is very much wider than mere significance testing and illustrate how important correct interpretation is. The lack of precise recommendations indicates that good statistical analysis re? quires common sense and judgment, as well as a repertoire of formal techniques, so that there is an art in statistics as well as in medicine. We hope that the guidelines present an uncontro versial view of the most frequently used and accepted statistical procedures. We have deliberately limited the scope of the guidelines to cover the more common statistical procedures. Readers may find that a relevant section presents information or advice that is unfamiliar or is not understood. In such circumstances, although almost all of the topics covered may be found in the more comprehensive medical statistics text? books,3 4 we strongly recommend that they should seek the advice of a statistician. The absence from the guidelines of specific references is intentional : it is better to get expert personal advice if further insight is needed. Moreover, because mistakes in design cannot later be rectified, professional advice should first be obtained when planning a research project rather than when analysing the data.

Quality of life measures in health care. II: Design, analysis, and interpretation.

The choice of dimensions is influenced by the severity and nature of the disease, the expected benefits and adverse effects of treatment, and considerations such as the length of the study, the availability of suitable instruments, and the environment in which the measurements will take place. For example, most patients with severe heart failure are elderly, retired, and physically inactive, and benefits of treatment are likely to be improvements in physical and social functioning at an already restricted level. But in trials in hypertensive patients dimensions need to be chosen that reflect potential adverse effects of treatment such as poorer work performance, problems with sexual function, and deleterious effects on mood.

Misuse of statistical methods: critical assessment of articles in BMJ from January to March 1976.

Sixty-two reports that appeared as Papers and Originals (excluding short reports) in 13 consecutive issues of the British Medical journal included statistical analysis. Thirty-two had statistical errors of one kind or another; in 18 fairly serious faults were discovered. The summaries of five reports made some claim that was unsupportable on re-examination of the data. Medical investigators should consult with people who have a real understanding of statistical methods throughout their projects.

Impact of rice based oral rehydration solution on stool output and duration of diarrhoea: meta-analysis of 13 clinical trials.

OBJECTIVE--To define the benefit of rice oral rehydration salts solution in relation to the glucose based World Health Organisation oral rehydration salts solution for treating and preventing dehydration in patients with severe dehydrating diarrhoea. DESIGN--Meta-analysis using data from 13 available randomised trials that compared these two formulations. SUBJECTS--The studies compared 1367 patients with cholera, severe cholera-like diarrhoea, or acute non-cholera diarrhoea. 668 received the standard WHO solution and 699 the rice based solution. INTERVENTION--Each trial report was reviewed to determine patient eligibility, the number of patients who were randomised and the number of these excluded from analysis, details of the randomisation procedure, and the precise timing of the outcome measurements. MAIN OUTCOME MEASURES--Stool output during the first 24 hours; weighted estimates of the difference in mean stool output between treatments. RESULTS--The rice solution significantly reduced the rate of stool output during the first 24 hours by 36% (95% confidence interval 28 to 44%) in adults with cholera and by 32% (19 to 45%) in children with cholera. The rate of stool loss in infants and children with acute non-cholera diarrhoea was reduced by only 18% (6 to 30%). CONCLUSIONS--The benefit of rice oral rehydration salts solution for patients with cholera is sufficiently great to warrant its use in such patients. The benefit is considerably smaller for children with acute, noncholera diarrhoea and should be more precisely defined before its practical value can be judged.

Long-term survival of patients with breast cancer: a study of the curability of the disease.

A retrospective analysis was made of 3878 cases of breast carcinoma first seen in Edinburgh from 1954 to 1964. During this time there was a policy to treat breast cancer by simple mastectomy and x-ray therapy, and over 90% of cases classified as international stages I and II were so treated. The mortality in these women was compared with that in an equivalent normal population using Scottish national age-specific death rates. For every year of follow-up within 20 years of initial treatment there was an excess mortality from all causes. There was an overall excess mortality of 58% among patients with breast cancer 15-20 years after initial treatment, and 20 times more deaths occurred in this period from breast cancer than in a normal population. For patients disease-free after 15 years there was still a 28% excess mortality from all causes. Factors known to be of major prognostic significance for five-year survivorship had less influence than might have been expected when the ratio of observed to expected deaths was considered for longer periods of follow-up. The effect of clinical staging (I, II, or III), though initially marked, largely disappeared by the 10th year of follow-up, and after allowing for age there was no evidence beyond 10 years of an effect on survival of the original stage of the disease. Similarly, the effect of tumour size on survival disappeared after 10 years. Women who were premenopausal at presentation still had a significant excess of deaths in the fourth quinquennium of follow-up. In the menopausal and postmenopausal groups combined there was still a small non-significant excess of deaths from all causes after 15 years but this almost disappeared when patients who had already relapsed were excluded. In terms of overall mortality only patients who have undergone the menopause before presentation and who are disease-free 15 years after primary treatment may prove to be cured by conventional techniques such as simple mastectomy and postoperative radiotherapy.

Conclusions of the corneal transplant follow-up study

AIM On the basis of finalised data from the Corneal Transplant Follow up Study to identify and quantify factors influencing corneal graft outcome in terms of graft survival, rejection, visual acuity, and astigmatism. METHODS Multifactorial analysis of 2777 grafts registered by the UK Transplant Support Service from July 1987 to June 1991. RESULTS Several recipient factors influencing graft survival, rejection, and visual acuity were identified, but no donor factors. Of the operative factors amenable to change, mixed suturing was associated with reduced graft survival, and larger grafts with increased risk of rejection but better visual acuity when surviving. There was increased risk of rejection with poor matching at HLA class I antigens, but mismatched HLA-DR grafts suffered less rejection than those with zero HLA-DR mismatches. Recipient age below 10 years was associated with increased risk of both rejection and graft failure. However, whereas increasing age above 10 years was not associated with differential graft survival, it was significantly associated with decreasing risk of rejection. CONCLUSIONS While confirming possible benefits of HLA-A and B matching, the expense and delay involved in awaiting matched HLA-DR tissue is unlikely to be justified. Other donor factors are unrelated to graft outcome following screening of tissue by eye banks. The highest rates of graft failure and rejection happen in the early postoperative period, and factors influencing visual outcome are also apparent at this stage.

Drug injection and HIV prevalence in inmates of Glenochil prison

Abstract Objective: To determine prevalence of HIV infection and drug injecting behaviour among inmates of Glenochil Prison on a specified date a year after an outbreak of hepatitis B and HIV infection. Design: Cross sectional: voluntary, anonymous HIV salivary antibody surveillance and linked self completion questionnaire on risk factors. Setting: Glenochil prison, Scotland, a year after an outbreak of hepatitis B and HIV transmission related to drug injection. Subjects: 352 prisoners, of whom 295 (84%) took part; 284 questionnaires (96%) passed logical checks. Main outcome measures: HIV prevalence; proportion of all inmates who had ever injected drugs, had ever injected inside prison, had started injecting drugs while inside prison. Results: More than half (150/284) the current inmates were also in Glenochil Prison during the critical period of January to June 1993, when hepatitis B and HIV were transmitted. Similar proportions of current inmates and men who were also in Glenochil during the critical period were drug users (27% (75/278) v 30% (44/149)). A quarter of injecting drug users (18/72) had first injected inside prison, irrespective of whether they were in Glenochil in January to June 1993 and regardless of the calendar period when they first injected. Significantly more inmates from Glasgow (41%; 56/138) than from Edinburgh (21%; 7/34) or elsewhere (11%; 12/106) were injecting drug users. On testing for HIV, seven saliva samples out of 293 gave positive results—four were presumed to be from inmates known to be infected with HIV, and the others from injecting drug users from Glasgow, all of whom had been in Glenochil during January to June 1993, when two of the three had injected drugs and had been tested for HIV, with negative results. The ratio of overall (2.4%) to disclosed (1.4%) HIV prevalence was 1.7. For men who had injected drugs in Glenochil during January to June 1993, HIV prevalence was estimated at 29%. Conclusion: Between a quarter and a third of prisoners who injected drugs in Glenochil in January to June 1993 were infected with HIV. There is widespread ongoing risk of bloodborne virus infection within prisons, which is probably long standing but demands urgent attention. Key messages Key messages The proportion of injecting drug users differed according to residence before prison: 41% of Glasgow residents, 21% of Edinburgh residents, and 11% of those resident elsewhere A quarter of injecting drug users in Glenochil prison had started injecting while in some prison Between a quarter and a third of men who injected drugs in Glenochil prison in January to June 1993 became infected with HIV while in prison Widespread risk of bloodborne virus infections in British prisons demands urgent attention

Influence of donor and histocompatibility factors on corneal graft outcome.

The Corneal Transplant Follow-up Study has followed 2311 penetrating keratoplasties for up to 450 days after transplant. A total of 207 failures were observed, including 65 classical rejections and 35 endothelial decompensations. At 12 months, graft survival was 89%, and survival free from rejection was 87%. For surviving grafts, risk of failure reduced from 4.8% in the first 75 days and stabilized after 5 months at 1.2% in each 75-day interval. Risk of rejection initially followed a similar pattern, but then increased after 12 months. Multifactorial analyses accounted for differences in recipient characteristics and interrelationships of donor factors. Donor age, sex, cause of death, and method of corneal storage were not found to influence significantly either time to graft failure or time to first rejection. Grafts in prospectively tissue-typed donor-recipient pairs were generally considered before surgery to be at increased risk of either graft failure or rejection. With due allowance, increasing risk of rejection was associated with increasing numbers of mismatches at HLA-A and HLA-B broad antigens. The opposite was true at HLA-DR broad antigens, where increased risk of rejection was observed with no mismatches.

Corneal Graft Survival and Visual Outcome: A Multicenter Study

PURPOSE The Corneal Transplant Follow-up Study has followed 2385 corneal transplants performed in the United Kingdom and the Republic of Ireland for up to 450 days to quantify factors influencing corneal graft survival and visual outcome 3 and 12 months postoperatively. METHODS Multifactorial analyses of grafts registered by United Kingdom Transplant Support Service from July 1987 to June 1990 were used. Corrected visual acuity of functioning grafts was assessed at 3 and 12 months. RESULTS Of 2385 corneal transplants followed, 214 failures were observed: graft survival was 95% at 3 months and 89% at 1 year. Similar factors affected outcome at each time. Decreased risk of failure was associated with surgeons reporting most grafts, and increased risk was associated with regrafts, patients younger than 10 years of age, nonvisual reasons for grafting, endothelial failure, and deep vascularization. Visual outcome was worse in older patients and was associated with cosmetic reasons for grafting, superficial vascularization preoperatively, and secondary endothelial failure. Visual acuity was better when the other eye had been grafted previously, or when the diagnosis was keratoconus or stromal dystrophy. CONCLUSIONS Primary endothelial failure was associated with high failure rates but good visual results when functioning. Most other factors had similar effects on both outcome measures. Improved outcome under highest-reporting surgeons was slight, and indicated possible differences in postoperative care.