A decision analysis of long-term lithium treatment and the risk of renal failure.

OBJECTIVE: To establish whether lithium or anticonvulsant should be used for maintenance treatment for bipolar affective disorder (BPAD) if the risks of suicide and relapse were traded off against the risk of end-stage renal disease (ESRD). METHOD: Decision analysis based on a systematic literature review with two main decisions: (1) use of lithium or at treatment initiation and (2) the potential discontinuation of lithium in patients with chronic kidney disease (CKD) after 20 years of lithium treatment. The final endpoint was 30 years of treatment with five outcomes to consider: death from suicide, alive with stable or unstable BPAD, alive with or without ESRD. RESULTS: At the start of treatment, the model identified lithium as the treatment of choice. The risks of developing CKD or ESRD were not relevant at the starting point. Twenty years into treatment, lithium still remained treatment of choice. If CKD had occurred at this point, stopping lithium would only be an option if the likelihood of progression to ESRD exceeded 41.3% or if anticonvulsants always outperformed lithium regarding relapse prevention. CONCLUSION: At the current state of knowledge, lithium initiation and continuation even in the presence of long-term adverse renal effects should be recommended in most cases.

An evidence-based guideline for children presenting with acute breathing difficulty.

OBJECTIVE: The aim of this study was to develop an evidence-based guideline for use primarily by junior clinicians to assist with the management of children presenting to the hospital with an acute breathing difficulty. METHODS: An overview of the literature provided a framework of clinical questions for the management of a child with an acute breathing difficulty on which to base a systematic literature review. Relevant articles were appraised by the research fellow and graded according to their quality. A national panel of 50 clinicians was provided, by post, with the clinical questions, research papers, appraisals and the grades of recommendations generated. They were asked to check the grades allocated to the recommendations and the accuracy of the language used. They were also provided with all the clinical questions for which there was insufficient evidence to reach a conclusion but for which a consensus recommendation was required. A Delphi method was used to formalise the consensus process. For all recommendations, panel members were asked to rate their level of agreement on a 1-9-point Likert scale. The results of the first round were fed back, and appropriate alterations to the recommendations made or additional recommendations included. The process of rating was repeated, and the final guideline was developed based on the consensus reached. RESULTS: Following two iterative rounds, the guideline was completed as a full technical document, with a series of key recommendations and an algorithm. It was based on 10 grade A (evidence from systematic review or meta-analyses), 5 grade B, 17 grade C and 31 grade D (consensus or expert opinion) recommendations. CONCLUSION: We have developed an evidence-based guideline that has subsequently been successfully implemented in the paediatric emergency departments and disseminated nationally. Results showing the effect of the guideline upon practice will be published separately.

Potential health risks of complementary alternative medicines in HIV patients.

OBJECTIVES: To determine the prevalence and purpose of complementary alternative medicines (CAMs) use in people receiving treatment for HIV infection. To identify and quantify potential health risks of CAM use in this population and to explore options for improved pharmacovigilance. METHODS: Cross-sectional questionnaire survey of 293 patients receiving antiretroviral (ARV) therapy at three specialist HIV out-patient clinics in central London, UK. The use of herbal medicines and supplements was explored, and potentially adverse side effects or significant drug interactions with conventional therapies were identified. RESULTS: Of the 293 patients included, 61% (n=179) were taking herbal remedies or supplements and 35% (n=103) were using physical treatments. Twenty-seven per cent (n=80) used a combination of both. Twenty per cent (n=59) potentially compromised their HIV management through using CAM therapy. Ten per cent (n=29) were advised to stop their CAMs and 15% (n=43) were made aware of potential drug interactions and adverse effects and were advised to monitor their care. CONCLUSIONS: There are potentially significant health risks posed by the concomitant use of CAMs in patients taking ARV therapy. Medical practitioners need to be able to identify CAM use in HIV-positive patients and recognize potential health risks. Patients should be encouraged to disclose CAM use to their clinicians and other healthcare professionals.

Antidepressants and sexual dysfunction.

OBJECTIVE: Many patients with depression suffer from sexual dysfunction and sexual dysfunction is a recognized side-effect of antidepressants. The aim of this review was to examine the prevalence of psychosexual dysfunction associated with antidepressants, and to review treatment options which are specific to the affected component of sexual functioning and antidepressants. METHOD: Comprehensive literature review using Medline and Cochrane databases. RESULTS: Up to 70% of patients with depression may have sexual dysfunction. Tricyclic antidepressants, selective-serotonin reuptake inhibitors and venlafaxine are most and the non-serotonergic antidepressants and duloxetine least likely to produce sexual dysfunction. Pharmacological treatment options include antidepressants less likely associated or 'antidotes' to reverse sexual dysfunction. CONCLUSION: Sexual dysfunction may be a preventable or treatable side-effect of antidepressants. Patients need routinely to be asked about sexual function to identify problems early. If sexual dysfunction is ignored it may maintain the depression, compromise treatment outcome and lead to non-compliance.

The impact of presenting problem based guidelines for children with medical problems in an accident and emergency department.

AIMS: To evaluate the impact of presenting problem based guidelines in managing children with either diarrhoea (with or without vomiting) or seizure (with or without fever). METHODS: This prospective observational study with an intervention was based on a paediatric accident and emergency (A&E) department in Nottingham. All patients (either GP or self referred) were acute attenders aged 0-15 years, with a medical presenting problem during 4 months in the spring of 1997 and 1999. Five hundred and thirty-one diarrhoea attendances (292 before guideline implementation and 239 after) and 411 seizure attendances (212 before guideline implementation and 199 after) were recorded. Evidence based and consensus ratified guidelines developed for the study were implemented using care pathway documentation. Process (documentation, time in the department, investigations, treatment) and outcome (admission to hospital, returns to A&E) data were collected from case notes. RESULTS: The percentage of children investigated with blood tests fell significantly (haematology requests in diarrhoea presentations from 11% to 4%, biochemistry in seizure presentations from 29% to 17%). Intravenous infusions in diarrhoea presenters fell (9% to 1%), and more appropriate oral fluids were used. Management time in A&E was reduced (diarrhoea presenters: median of 55-40 minutes, seizure presenters: 80-55 minutes, but remained static for other presenting problems). Marked improvements in documentation were seen. Admission rates for diarrhoea attenders increased (27% to 34%) but remained the same for seizure (69% v 73%). CONCLUSIONS: The implementation of a presenting problem based guideline as a care pathway was associated with improvements in the quality of care by: improved documentation; reduced invasive investigations; more appropriate treatment, and reduced time spent in A&E.

Potential health risks of complementary alternative medicines in cancer patients.

Many cancer patients use complementary alternative medicines (CAMs) but may not be aware of the potential risks. There are no studies quantifying such risks, but there is some evidence of patient risk from case reports in the literature. A cross-sectional survey of patients attending the outpatient department at a specialist cancer centre was carried out to establish a pattern of herbal remedy or supplement use and to identify potential adverse side effects or drug interactions with conventional medicines. If potential risks were identified, a health warning was issued by a pharmacist. A total of 318 patients participated in the study. Of these, 164 (51.6%) took CAMs, and 133 different combinations were recorded. Of these, 10.4% only took herbal remedies, 42.1% only supplements and 47.6% a combination of both. In all, 18 (11.0%) reported supplements in higher than recommended doses. Health warnings were issued to 20 (12.2%) patients. Most warnings concerned echinacea in patients with lymphoma. Further warnings were issued for cod liver/fish oil, evening primrose oil, gingko, garlic, ginseng, kava kava and beta-carotene. In conclusion, medical practitioners need to be able to identify the potential risks of CAMs. Equally, patients should be encouraged to disclose their use. Also, more research is needed to quantify the actual health risks.

Behavioural management of antipsychotic-induced weight gain: a review.

OBJECTIVE: Although psychiatrists are aware of weight gain induced by atypical antipsychotics, only few studies on behavioural interventions in this patient group are published. This review aims to summarize the evidence on effectiveness of behavioural interventions for weight gain in the general population and in-patients treated with atypical antipsychotics. METHOD: Medline and Cochrane databases search for evidence on effectiveness of behavioural interventions. RESULTS: In general, behavioural approaches including, diet, exercise and drug treatments may be effective. There were only 13 studies of behavioural interventions for patients taking antipsychotic medication. No study met the criteria for a RCT. Calorie restriction in a controlled ward environment, structured counselling combined with cognitive behavioural therapy and counselling on life style and provision of rewards may potentially lead to weight loss. CONCLUSION: Currently only limited, methodologically flawed, evidence is available that behavioural interventions in overweight patients treated with antipsychotics, although intuitively appealing, actually work.

An evidence and consensus based guideline for the management of a child after a seizure.

OBJECTIVE: An evidence and consensus based guideline for the management of the child who presents to hospital having had a seizure. It does not deal with the child who is still seizing. The guideline is intended for use by junior doctors, and was developed for this common problem (5% of all paediatric medical attenders) where variation in practice occurs. OPTIONS: Assessment, investigations (biochemistry, lumbar puncture, serum anticonvulsant levels, EEG in particular), and/or admission are examined. OUTCOMES: The guideline aims to direct junior doctors in recognising those children who are at higher risk of serious intracranial pathology including infection, and conversely to recognise those children at low risk who are safe to go home. EVIDENCE: A systematic review of the literature was performed. Articles were identified using the electronic data bases Medline (from 1966 to June 1998), Embase (from 1980 to June 1998) and Cochrane (to June 1998), and selected if they investigated the specified clinical question. Personal reviews were excluded. Selected articles were appraised, graded, and synthesised qualitatively. Statements of recommendation were made. CONSENSUS: An anonymous, postal Delphi consensus development was used. A national panel of 30 medical and nursing staff regularly caring for these children were asked to grade their agreement with the statements generated. They were sent the relevant original publications, the appraisals, and literature review. On the second and third rounds they were asked whether they wished to re-grade their agreement in the light of other panellists' responses. Consensus was defined as 83% of panellists agreeing with the statement. Recommendations in brief: For afebrile seizures all children should have their blood pressure recorded, but no other investigations are routine although a seizing or somnolent child should have blood glucose measured; all children under 1 year should be admitted. For seizures with fever, clinical signs indicating the need to treat as meningitis are given. Children should be admitted if they are under 18 months old, have had a complex seizure, or after pretreatment with antibiotics. VALIDATION: The guideline has undergone implementation and evaluation in a paediatric accident and emergency department, the results of which will be published separately. Only one alteration was made to the guideline as a result of this validation process, which is included here.

Options for pharmacological management of obesity in patients treated with atypical antipsychotics.

Obesity is associated with considerable morbidity and decreased life expectancy. Weight gain is a commonly encountered problem associated with antipsychotic treatment. We reviewed the literature regarding the mechanisms of weight gain in response to these agents and eight substances implicated as potential obesity prevention or treatment: orlistat, sibutramine, fluoxetine, topiramate, amantadine, nizatidine and cimetidine, and metformin. Weight gain in response to antipsychotic treatment may be mediated through serotonergic, dopaminergic, adrenergic, cholinergic, histaminergic and glutaminergic receptors. Sex hormone dysregulation and altered insulin sensitivity have also been implicated. Two compounds, orlistat and sibutramine, have been shown to help prevent weight gain following a hypocaloric diet, but orlistat requires compliance with a fat-reduced diet, and sibutramine is unsuitable for patients taking serotonergic agents. The weight reducing effect of fluoxetine, even in conjunction with a hypocaloric diet, is only transient. Topiramate, amantadine and metformin may have adverse side-effects potentially outweighing the weight reducing potential. The effectiveness of cimetidine and nizatedine remains unclear. The hazards of these agents in a psychiatric population are discussed. It is concluded that the current evidence does not support the general use of pharmacological interventions for overweight patients treated with antipsychotic medication, although individually selected patients may benefit.

A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review.

The herbal remedy St John's wort is widely used as an antidepressant but its efficacy has not been systematically investigated. Meta-analyses and systematic reviews of published trials strongly suggest St John's wort is more effective than placebo although comparative efficacy to standard antidepressants is less clearly established. We updated and expanded previous meta-analyses of St John's wort, scrutinised the validity of published reports and examined possible mechanisms of action. Twenty-two randomised controlled trials were identified. Meta-analysis showed St John's wort to be significantly more effective than placebo (relative risk (RR) 1.98 (95% CI 1.49-2.62)) but not significantly different in efficacy from active antidepressants (RR 1.0 (0.90-1.11)). A sub-analysis of six placebo-controlled trials and four active comparator trials satisfying stricter methodological criteria also suggested that St John's wort was more effective than placebo (RR 1.77 (1.16-2.70)) and of similar effectiveness to standard antidepressants (RR 1.04 (0.94-1.15)). There was no evidence of publication bias. Adverse effects occurred more frequently with standard antidepressants than with St John's wort. The mechanism of action of St John's wort remains unknown. Future research should include large scale, appropriately powered comparisons of St John's wort and standard antidepressants.

Recent trends in hospital use by children in England.

BACKGROUND: Routine hospital statistics for England appear to overestimate use of children's wards and include numbers of well newborn babies staying with their mothers after delivery ("well babies"). AIM: To review trends in use of children's wards excluding data on newborn babies. METHODS: We reviewed routine, published, and age stratified data requested from the Department of Health to identify separately "well babies" and babies receiving neonatal specialist care from admissions (surgical and paediatric) to children's wards. RESULTS: Routine reports for paediatric activity contain large numbers of "well babies", (almost half the total) as well as babies receiving specialist neonatal care. After excluding these, paediatric admissions represent 9.9% of the child population aged under 5 years each year (an additional 2.5% are admitted for surgical care). Between 1989 and 1997 paediatric admissions rose by 19% and surgical admissions fell by 25% with a plateau reached in overall child admissions. There are now fewer beds in which children stay for a shorter time and there is more day case surgery. Neonatal specialist care work has risen despite a fall in births. CONCLUSION: Categories should be established for reporting paediatric episodes on children's wards separately from those on neonatal units, with better identification of "well babies". When monitoring use of children's inpatient facilities or planning new units, care must be taken to separate paediatric data on neonatal units from work on children's wards. Children's surgical episodes should also be taken into account.

An evidence and consensus based guideline for acute diarrhoea management.

OBJECTIVE: To develop an evidence and consensus based guideline for the management of the child who presents to hospital with diarrhoea (with or without vomiting), a common problem representing 16% of all paediatric medical attenders at an accident and emergency department. Clinical assessment, investigations (biochemistry and stool culture in particular), admission, and treatment are addressed. The guideline aims to aid junior doctors in recognising children who need admission for observation and treatment and those who may safely go home. EVIDENCE: A systematic review of the literature was performed. Selected articles were appraised, graded, and synthesised qualitatively. Statements on recommendation were generated. CONSENSUS: An anonymous, postal Delphi consensus process was used. A panel of 39 selected medical and nursing staff were asked to grade their agreement with the generated statements. They were sent the papers, appraisals, and literature review. On the second and third rounds they were asked to re-grade their agreement in the light of other panelists' responses. Consensus was predefined as 83% of panelists agreeing with the statement. RECOMMENDATIONS: Clinical signs useful in assessment of level of dehydration were agreed. Admission to a paediatric facility is advised for children who show signs of dehydration. For those with mild to moderate dehydration, estimated deficit is replaced over four hours with oral rehydration solution (glucose based, 200-250 mOsm/l) given "little and often". A nasogastric tube should be used if fluid is refused and normal feeds started following rehydration. Children at high risk of dehydration should be observed to ensure at least maintenance fluid is tolerated. Management of more severe dehydration is detailed. Antidiarrhoeal medication is not indicated. VALIDATION: The guideline has been successfully implemented and evaluated in a paediatric accident and emergency department.

Determining the common medical presenting problems to an accident and emergency department.

All accident and emergency (A&E) attendances over a one year period were prospectively studied in order to determine common medical presenting problems. Data were collected on children (0-15 years) attending a paediatric A&E department in Nottingham between February 1997 and February 1998. A total of 38 982 children were seen. The diagnoses of 26 756 (69%) were classified as trauma or surgical, and 10 369 (27%) as medical; 1857 (4%) could not be classified. The commonest presenting problems reported for "medical" children were breathing difficulty (31%), febrile illness (20%), diarrhoea with or without vomiting (16%), abdominal pain (6%), seizure (5%), and rash (5%). The most senior doctor seeing these patients in A&E was a senior house officer (intern or junior resident) in 78% of cases, paediatric registrar (senior resident) in 19%, consultant (attending physician) in 1.4%, and "other" in 2.6%. Guidelines developed for A&E should target the commonest presenting problem categories, six of which account for 83% of all medical attendances, and be directed towards senior house officers.

Accounting for overlap? An application of Mezzich's kappa statistic to test interrater reliability of interview data on parental accident and emergency attendance.

STUDY RATIONALE: The number of interview studies with service users is rising because of growth in health services research. The level of agreement between multiple interview data coders requires statistical calculation to support results. Basic kappa statistics are often used but this depends on having mutually exclusive data. Researchers should be aware that this is not valid when an interview word or paragraph can be coded into more than one category. The 'proportional overlap' kappa extension by Mezzich et al. (1981, Journal of Psychiatric Research 16, 29-39) has been investigated as an original solution. OBJECTIVES: To assess the level of agreement beyond chance between several raters of interview data by applying the 'proportional overlap' kappa statistic by Mezzich et al. to verbal interview data. The clinical area investigated was child attendance at an Accident and Emergency Department, where parental attendance experiences have been under-explored. METHODS: Two researchers using a coding schedule coded a random sample of interview transcripts. These data were applied to Mezzich's procedure; coder 1 notes that a paragraph refers to category A and B but coder 2 notes A, B and C. The total agreement overlap in this case was 0.66 because two actual agreements out of three possible agreements were made. This was repeated for each paragraph and divided by the number of coding pairs. All agreement values were summed then subsequently divided by the total number of paragraphs to get Po (total number of observed agreements) and by the total number of coding pairs to get Pe (total number of agreements by chance alone). Po and Pe were used in the basic kappa formula to assess interview coding reliability. RESULTS: The overall mean Po was 0.61, the mean Pe was 0.32, with a kappa score of 0.43; a moderate level of agreement which was statistically significant (t=4.8, P < 0.001, d.f.=23). CONCLUSION: Mezzich's procedure may be applied to interview data to calculate agreement levels between several coders.

The stability of the factor structure of the General Health Questionnaire.

BACKGROUND: Different versions of the General Health Questionnaire (GHQ), including the GHQ-12 and GHQ-28 have been subjected to factor analysis in a variety of countries. The World Health Organization study of psychological disorders in general health care offered the opportunity to investigate the factor structure of both GHQ versions in 15 different centres. METHODS: The factor structures of the GHQ-12 and GHQ-28 extracted by principal component analysis were compared in participating centres. The GHQ-12 was completed by 26,120 patients and 5,273 patients completed the GHQ-28. The factor structure of the GHQ-28 found in Manchester in this study was compared with that found in the earlier study in 1979. RESULTS: For the GHQ-12, substantial factor variation between centres was found. After rotation, two factors expressing depression and social dysfunction could be identified. For the GHQ-28, factor variance was less. In general, the original C (social dysfunction) and D (depression) scales of the GHQ-28 were more stable than the A (somatic symptoms) and B (anxiety) scales. Multiple cross-loadings occurred in both versions of the GHQ suggesting correlation of the extracted factors. In Manchester, the factor structure of the GHQ had changed since its development. Validity as a case detector was not affected by factor variance. CONCLUSIONS: These findings confirm that despite factor variation for the GHQ-12, two domains, depression and social dysfunction, appear across the 15 centres. In the scaled GHQ-28, two of the scales were remarkably robust between the centres. The cross-correlation between the other two subscales, probably reflects the strength of the relationship between anxiety and somatic symptoms existing in different locations.

Clinical training experience in district general hospitals.

AIMS: To estimate the nature and quantity of clinical experience available for trainees in paediatrics or general practice in acute general hospitals of differing sizes in the UK. To discuss implications for training and service configuration taking account of current Royal College recommendations (a minimum of 1,800 acute contacts each year and ideally covering a population of 450,000 to 500,000 people). METHODS: Observed frequencies of diagnoses in Pinderfields Hospital, Wakefield were compared with those in five other hospitals in Yorkshire and four in the South of England, and with expected frequencies from a review of selected marker conditions using national routine and epidemiological data. Based on the Pinderfields data, we modelled expected frequencies of a wider range of diagnoses for different sized hospitals. RESULTS: Small units (1,800 or less acute referrals a year) provide adequate exposure to common conditions such as gastroenteritis (157 per annum) and asthma (171 per annum) but encounter serious or unusual disease rarely. When modelled for units serving larger populations, numbers of such disorders remain small. For example, about 0.5% of admissions require intensive care to the level of ventilatory support. Medium size units offer a wide range of experience but differ little from those serving the population of 500,000 proposed as being optimal for training. This standard is not justified by the evidence in this review. Closing or amalgamating units on the scale necessary to achieve this ideal would be impractical as only five hospitals in England have a paediatric workload equivalent to this population; it would also raise issues of access and equity.

Parental and professional perception of need for emergency admission to hospital: prospective questionnaire based study.

AIM: To compare views of parents, consultants, and general practitioners on severity of acute illness and need for admission, and to explore views on alternative services. METHOD: Prospective questionnaire based study of 887 consecutive emergency paediatric admissions over two separate three week periods in summer and winter of five Yorkshire hospitals, combined with a further questionnaire on a subsample. OUTCOME MEASURES: Parental scores of need for admission and parent and consultant illness severity scores out of 10. Consultant judgment of need for admission. Alternatives to admission considered by consultants and, for a subsample, by parents and family GP. RESULTS: Ninety nine per cent of parents thought admission was needed. Parents scored need for admission more highly than severity of illness with no association observed between severity and presenting problem or diagnosis. High parental need score was associated with a fit, past illness, and length of stay. Consultant illness severity scores were skewed to the lower range. Consultants considered admission necessary in 71%, especially for children aged over 1 year, presentation with breathing difficulty or fit, and after a longer stay. More admissions in the evening were considered unnecessary as were admissions after longer preadmission illness, gastroenteritis, or upper respiratory tract infection. Of a subsample of parents, 81% preferred admission during the acute stage of illness even if home nursing had been available. Similar responses were obtained from GPs. Alternative services could have avoided admission for 19% of children, saving 15.6% of bed days used. CONCLUSIONS: Medical professionals and parents differ in their views about admission for acute illnesses. More information is needed on children not admitted. Alternative services should take account of patterns of illness and should be acceptable to parents and professionals; cost savings may be marginal.

Medical and social factors associated with the admission and discharge of acutely ill children.

AIM: To examine medical and sociodemographic factors involved in acute paediatric admission. To compare outcome of admission with factors present at time of admission. METHODS: Prospective questionnaire based study of 887 consecutive emergency general paediatric admissions to five Yorkshire hospitals during two separate three week periods in summer and winter. MAIN OUTCOME MEASURES: Discharge diagnosis, length of stay. RESULTS: Most admissions (53%) occurred "out of hours" with a peak during the evening. Two thirds (64%) of patients were under 3 years of age and clinical problems varied with age. Self referral via an accident and emergency department occurred in one third and was more likely after a fit in older children and in more socioeconomically deprived children. The most frequent presenting problems were breathing difficulty (24%), fit (16%), and feverish illness (15%). One quarter (24%) were discharged within 24 hours and 61% spent, at most, one night in hospital. Length of stay was shorter for night admissions and longer for children with a discharge diagnosis of asthma. Although most children had mild, self limiting illnesses, serious illness was subsequently found in 13% and could not be predicted from the presenting problems. CONCLUSIONS: Current demand on emergency paediatric admission is mainly from young children with mild self limiting illnesses who spend one night or less in hospital. Changes in delivery of care to acutely ill children must take account of the pattern and nature of presenting problems and be rigorously audited to ensure that improvements in the health of children continue.