Colin Sanderson

Global and regional risk of disabling sequelae from bacterial meningitis: a systematic review and meta-analysis.

Few data sources are available to assess the global and regional risk of sequelae from bacterial meningitis. We aimed to estimate the risks of major and minor sequelae caused by bacterial meningitis, estimate the distribution of the different types of sequelae, and compare risk by region and income. We systematically reviewed published papers from 1980 to 2008. Standard global burden of disease categories (cognitive deficit, bilateral hearing loss, motor deficit, seizures, visual impairment, hydrocephalus) were labelled as major sequelae. Less severe, minor sequelae (behavioural problems, learning difficulties, unilateral hearing loss, hypotonia, diplopia), and multiple impairments were also included. 132 papers were selected for inclusion. The median (IQR) risk of at least one major or minor sequela after hospital discharge was 19.9% (12.3-35.3%). The risk of at least one major sequela was 12.8% (7.2-21.1%) and of at least one minor sequela was 8.6% (4.4-15.3%). The median (IQR) risk of at least one major sequela was 24.7% (16.2-35.3%) in pneumococcal meningitis; 9.5% (7.1-15.3%) in Haemophilus influenzae type b (Hib), and 7.2% (4.3-11.2%) in meningococcal meningitis. The most common major sequela was hearing loss (33.9%), and 19.7% had multiple impairments. In the random-effects meta-analysis, all-cause risk of a major sequela was twice as high in the African (pooled risk estimate 25.1% [95% CI 18.9-32.0%]) and southeast Asian regions (21.6% [95% CI 13.1-31.5%]) as in the European region (9.4% [95% CI 7.0-12.3%]; overall I(2)=89.5%, p<0.0001). Risks of long-term disabling sequelae were highest in low-income countries, where the burden of bacterial meningitis is greatest. Most reported sequelae could have been averted by vaccination with Hib, pneumococcal, and meningococcal vaccines.

Threats to Applicability of Randomised Trials: Exclusions and Selective Participation

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.

Consensus Development Methods: A Review of Best Practice in Creating Clinical Guidelines

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 users 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.

Timing of children's vaccinations in 45 low-income and middle-income countries: an analysis of survey data

BACKGROUND Vaccinations are often delayed until well after the recommended ages, leaving many children exposed for longer than they should be. We estimated vaccination coverage at different ages, and delays in administration, in 45 low-income and middle-income countries. METHODS We used data for 217 706 children from Demographic and Health Surveys between 1996 and 2005 (median 2002), which provided data for vaccination of children on the basis of events recorded on vaccination cards and interviews with mothers, with imputation of missing values and survival analysis. We devised an index combining coverage and delay. FINDINGS For vaccinated children, the median of the median delays in the 45 countries was 2.3 weeks (IQR 1.4-4.6) for bacille Calmette-Guérin (BCG); 2.4 weeks (1.2-3.3) for diphtheria, tetanus, and pertussis (DTP1); 2.7 weeks (1.7-3.1) for measles-containing vaccine (MCV1); and 6.2 weeks (3.5-8.5) for DTP3. However, in the 12 countries with the longest delays for each vaccination, at least 25% of the children vaccinated were more than 10 weeks late for BCG, 8 weeks for DTP1, 11 weeks for MCV1, and 19 weeks for DTP3. Variation within countries was substantial: the median of the IQRs in the 45 countries for delay in DTP3 was 10.9 weeks, 7.9 weeks for MCV1, 5.4 weeks for BCG, and 5.3 weeks for DTP1. The median of the national coverage rates for DTP1 increased from 57% in children aged 12 weeks to 88% at 12 months, and for DTP3 from 65% at 12 months to 76% at 3 years. INTERPRETATION The timeliness of childrens vaccination varies widely between and particularly within countries, and published yearly estimates of national coverage do not capture these variations. Delayed vaccination could have important implications for the effect of new and established vaccines on the burden of disease. FUNDING WHOs Initiative for Vaccine Research.

Developing clinical guidelines: a challenge to current methods

Current methods for producing clinical guidelines are cumbersome and not always reliable. Could a more streamlined approach improve coverage and make decisions more transparent?

Health status and quality of life of British men with lower urinary tract symptoms: results from the SF-36.

OBJECTIVES To determine the extent to which urinary symptoms, and resulting bothersomeness interfere with daily activities and affect health status, as measured using the Medical Outcomes Study 36-item short form health survey (SF-36). METHODS Postal population survey in a British health region of 217 men aged 55 years and over known to have reported mild, moderate, or severe lower urinary tract symptoms. Outcome measures are self-reported urinary symptoms, their bothersomeness, general health status, and quality of life (measured using the SF-36). RESULTS Response rate among eligible subjects was 84%. Depending on the activity, between 9% and 49% of men with moderate or severe urinary symptoms reported interference with some of their daily activities. Increasing symptom severity was associated with worsening physical role, social functioning, vitality, mental health, and perception of general health, and increasing bothersomeness was associated with worsening of all dimensions of general health status and quality of life. The association between these measures and bothersomeness was stronger than with symptom score. Compared with the general population, men bothered by their symptoms to the extent that they were a medium or a large problem have worse health status for all dimensions except physical functioning. CONCLUSIONS The SF-36 demonstrates a deterioration in general health status and quality of life with increasing lower urinary tract symptoms and the extent to which those symptoms are bothersome. As such, it provides a generic measure of the burden of ill health arising from these symptoms at a population level. There is, however, considerable individual variation in the way that men respond to their symptoms.

Conditions for Which Onset or Hospital Admission is Potentially Preventable by Timely and Effective Ambulatory Care

Objectives: To identify, using a consensus development process, a list of common conditions likely to be ambulatory care sensitive (ACS); i.e. conditions for which practicable improvements in access to timely and effective ambulatory care in the English National Health Service would either reduce the incidence of the condition or avoid substantial proportions of current hospital admissions. Methods: Three panels of clinicians each reviewed about a third of an initial list of 174 conditions commonly recorded as hospital discharge diagnoses for residents of the North West Thames Region. For each condition, panellists estimated the proportion of cases currently admitted to hospital for which, given timely and effective ambulatory care: onset of disease could have been prevented; admission for existing disease could have been prevented; admission, once indicated, should take place within 48 hours. After an introductory meeting to discuss and clarify the task, panel members completed three rounds of a questionnaire, with postal feedback between each round, and a second meeting to discuss interim results before the final round. Seventeen general practitioners (GPs) and 17 hospital specialists working in the region comprised the panels. Results: The panels considered that for 30 of the 174 conditions at least 70% of admissions to hospital could be avoided, either by prevention of disease onset or timely and effective ambulatory care, though predominantly through the latter. For each of a further 66 conditions, 50–69% of admissions could be prevented. Within-panel agreement between hospital specialists and GPs was generally good, although the GPs tended to give slightly higher scores for avoidability of admissions than the specialists. There was marked convergence of scores in succeeding rounds. Conclusions: Although a consensus-based list of ACS conditions cannot be definitive, the clear view of the panels was that the scope for avoiding admission through better ambulatory care is very substantial.

A comparison of formal consensus methods used for developing clinical guidelines.

Objectives: To compare two consensus development methods commonly used for developing clinical guidelines in terms of the judgments produced, closeness of consensus, amount of change between rounds, concordance with research evidence and reliability. Methods: In all, 213 general practitioners and mental health professionals from England participated in four Delphi and four nominal groups. They rated the appropriateness of four treatments (cognitive behavioural therapy [CBT], behavioural therapy [BT], brief psychodynamic interpersonal therapy [BPIT] and antidepressants) for three conditions. First, participants rated the appropriateness of interventions independently, using a postal questionnaire. For nominal groups, the ratings were fed back and discussed at a meeting, and then group members privately completed the questionnaire again. For Delphi groups, there was feedback but no discussion, and the entire process was conducted by postal questionnaire. Results: The effect of consensus method on final ratings varied with therapeutic intervention, with nominal groups rating CBT and antidepressants more favourably than Delphi groups. Consensus was closer in the nominal than in the Delphi groups in both rounds. There was no overall difference between groups in their concordance with research evidence (odds ratio 1.13, 95% confidence interval 0.79–1.61). In this study, the Delphi method was more reliable (κ coefficients 0.88 and 0.89 compared with 0.41 and 0.65 for nominal groups). Conclusions: The advantages of nominal groups (more consensus; greater understanding of reasons for disagreement) could be combined with the greater reliability of the Delphi approach by developing a hybrid method.

A person based formula for allocating commissioning funds to general practices in England: development of a statistical model.

Objectives To develop a formula for allocating resources for commissioning hospital care to all general practices in England based on the health needs of the people registered in each practice Design Multivariate prospective statistical models were developed in which routinely collected electronic information from 2005-6 and 2006-7 on individuals and the areas in which they lived was used to predict their costs of hospital care in the next year, 2007-8. Data on individuals included all diagnoses recorded at any inpatient admission. Models were developed on a random sample of 5 million people and validated on a second random sample of 5 million people and a third sample of 5 million people drawn from a random sample of practices. Setting All general practices in England as of 1 April 2007. All NHS inpatient admissions and outpatient attendances for individuals registered with a general practice on that date. Subjects All individuals registered with a general practice in England at 1 April 2007. Main outcome measures Power of the statistical models to predict the costs of the individual patient or each practice’s registered population for 2007-8 tested with a range of metrics (R2 reported here). Comparisons of predicted costs in 2007-8 with actual costs incurred in the same year were calculated by individual and by practice. Results Models including person level information (age, sex, and ICD-10 codes diagnostic recorded) and a range of area level information (such as socioeconomic deprivation and supply of health facilities) were most predictive of costs. After accounting for person level variables, area level variables added little explanatory power. The best models for resource allocation could predict upwards of 77% of the variation in costs at practice level, and about 12% at the person level. With these models, the predicted costs of about a third of practices would exceed or undershoot the actual costs by 10% or more. Smaller practices were more likely to be in these groups. Conclusions A model was developed that performed well by international standards, and could be used for allocations to practices for commissioning. The best formulas, however, could predict only about 12% of the variation in next year’s costs of most inpatient and outpatient NHS care for each individual. Person-based diagnostic data significantly added to the predictive power of the models.

Nurse staffing, medical staffing and mortality in intensive care: an observational study

OBJECTIVES To investigate whether the size of the workforce (nurses, doctors and support staff) has an impact on the survival chances of critically ill patients both in the intensive care unit (ICU) and in the hospital. BACKGROUND Investigations of intensive care outcomes suggest that some of the variation in patient survival rates might be related to staffing levels and workload, but the evidence is still equivocal. DATA Information about patients, including the outcome of care (whether the patient lived or died) came from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme. An Audit Commission survey of ICUs conducted in 1998 gave information about staffing levels. The merged dataset had information on 65 ICUs and 38,168 patients. This is currently the best available dataset for testing the relationship between staffing and outcomes in UK ICUs. DESIGN A cross-sectional, retrospective, risk adjusted observational study. METHODS Multivariable, multilevel logistic regression. OUTCOME MEASURES ICU and in-hospital mortality. RESULTS After controlling for patient characteristics and workload we found that higher numbers of nurses per bed (odds ratio: 0.90, 95% confidence interval: [0.83, 0.97]) and higher numbers of consultants (0.85, [0.76, 0.95]) were associated with higher survival rates. Further exploration revealed that the number of nurses had the greatest impact on patients at high risk of death (0.98, [0.96, 0.99]) whereas the effect of medical staffing was unchanged across the range of patient acuity (1.00, [0.97, 1.03]). No relationship between patient outcomes and the number of support staff (administrative, clerical, technical and scientific staff) was found. Distinguishing between direct care and supernumerary nurses and restricting the analysis to patients who had been in the unit for more than 8h made little difference to the results. Separate analysis of in-unit and in-hospital survival showed that the clinical workforce in intensive care had a greater impact on ICU mortality than on hospital mortality which gives the study additional credibility. CONCLUSION This study supports claims that the availability of medical and nursing staff is associated with the survival of critically ill patients and suggests that future studies should focus on the resources of the health care team. The results emphasise the urgent need for a prospective study of staffing levels and the organisation of care in ICUs.