Economic evaluation of a randomized controlled trial of ultrasound therapy for hard-to-heal venous leg ulcers.

BACKGROUND: A pragmatic, multicentre randomized controlled trial (VenUS III) was conducted to determine whether low-dose ultrasound therapy increased the healing rate of hard-to-heal leg ulcers. This study was a cost-effectiveness analysis of the trial data. METHODS: Cost-effectiveness and cost-utility analyses were conducted alongside the VenUS III trial, in which patients were randomly allocated to either ultrasound treatment administered weekly for 12 weeks along with standard care, or standard care alone. The time horizon was 12 months and based on the UK National Health Service (NHS) perspective. RESULTS: The base-case analysis showed that ultrasound therapy added to standard care was likely to be more costly and provide no extra benefit over standard care alone. Individuals who received ultrasound treatment plus standard care took a mean of 14.7 (95 per cent confidence interval - 32.7 to 56.8) days longer to heal, had 0.009 (-0.042 to 0.024) fewer quality-adjusted life years and had higher treatment costs by £ 197.88 (-35.19 to 420.32). Based on these point estimates, ultrasound therapy plus standard care for leg ulcers was dominated by standard care alone. The analysis of uncertainty showed that this treatment strategy is unlikely to be cost-effective. CONCLUSION: Ultrasound treatment was not cost-effective for hard-to-heal leg ulcers and should not be recommended for adoption in the NHS.

Cough hypersensitivity syndrome: a distinct clinical entity.

We postulate that most patients with chronic cough have a single discrete clinical entity: cough hypersensitivity syndrome. We constructed a questionnaire that elicits the major components of the syndrome. Here we describe the validation of this questionnaire. Following iterative development, the Hull Airway Reflux Questionnaire (HARQ) was administered to patients and normal volunteers. It is self-administered and comprises 14 items with a maximum score of 70. Unselected patients were recruited sequentially from the Hull Cough Clinic. Preclinic questionnaires were compared with those obtained at the clinic. Responsiveness was assessed 2 months after the clinic visit. One hundred eighty-five patients and 70 normal volunteers were included in this study. There was a marked difference in HARQ scores between patients with chronic cough and normal volunteers. The sensitivity (94%) and specificity (95%) of the HARQ was high, with an area under the ROC curve of 0.99. All items of the scale significantly correlated positively with others in the scale and with the total score. On repeatability testing using Cohen's kappa with quadratic weights, significant agreement was noted for all items. Good correlation was observed between the total scores (r = 0.78). The questionnaire was also responsive to treatment; the minimum clinically significant change was estimated to be 16 points. We have demonstrated the HARQ to have good construct and criterion validity. It is both reproducible and responsive to change. It can be used as a diagnostic instrument and demonstrates that chronic cough represents a single coherent entity: cough hypersensitivity syndrome.

Value of a modified clinical signs and symptoms of infection checklist for leg ulcer management.

BACKGROUND: The aim of this study was to analyse the validity of a modified Clinical Signs and Symptoms Checklist used to measure infection in a sample of patients with a leg ulcer. METHODS: Data from patients recruited to a randomized controlled trial evaluating larval therapy (VenUS II) were analysed using factor analysis to identify the underlying checklist structure. Linear regression analysis identified whether checklist items, patient characteristics and subjective judgement of infection could predict bacterial load. RESULTS: There were several redundant checklist items when implemented in this sample and items forming the scale had low internal consistency (alpha = 0.27). No clear structure to the checklist was detected, with only one underlying theme revealed which had low internal consistency (alpha = 0.45). Predictions of bacterial count were possible using the emerged theme, some checklist items and ankle circumference, but not using clinicians' subjective judgement alone (P = 0.315). CONCLUSION: The modified Clinical Signs and Symptoms Checklist does not currently represent a valid tool to measure infection in leg ulcers. Some checklist items may predict bacterial load and may be better than subjective judgement alone.

Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease.

BACKGROUND: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. HYPOTHESIS: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). ANIMALS: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). METHODS: Double-blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac-related death, euthanasia, or severe worsening of MR. RESULTS: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22-0.90; log rank test, P = .017). Risk of cardiac-related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13-0.76; P = .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). CONCLUSION AND CLINICAL IMPORTANCE: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac-related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD.

A new, minimally invasive technique for measuring cardiac index: clinical comparison of continuous cardiac dynamic monitoring and pulmonary artery catheter methods.

To assess the utility of a relatively simple bedside method of estimating cardiac index during major surgery or in the intensive care unit, we conducted a prospective study in patients undergoing elective cardiac bypass surgery where a pulmonary artery catheter was inserted as part of routine monitoring. The cardiac index was estimated using standard techniques and compared with estimates from continuous cardiac dynamic monitoring using HEARTSMART software. Two hundred and seventy sets of measurements were suitable for comparison. The mean bias (95% limits of agreement), for the pre-bypass cardiac index was -0.09 (-1.26 to 1.08) l x min(-1) x m(-2), and post-bypass was 0.12 l x min(-1) x m(-2) (-1.32 to 1.56). These results suggest that continuous cardiac dynamic monitoring using HEARTSMART is sufficiently accurate for assessment of haemodynamic variables in critically ill patients, facilitating goal-directed therapies.

The impact of assertive outreach teams on hospital admissions for psychosis: a time series analysis.

Although the assertive outreach model was developed in the United States and imported to the United Kingdom to date, there is only limited evidence to support its wide-scale implementation within the United Kingdom. This is the first study to have combined a large dataset with this type of research method to explore the impact of assertive outreach teams on hospital admissions. The introduction and expansion of assertive outreach teams was associated with reducing hospital admissions for people with psychosis. This study found a consistent summer peak in hospital admissions which community and in-patient mental health nurses should take account of and plan for. Ever since the Mental Health Policy Implementation Policy Guide paved the way for the introduction of the Assertive Outreach Treatment (AOT) model in England, the impact of this approach has been the subject of considerable debate but limited evaluation. To date, most of the evidence supporting this model has originated from outside the United Kingdom. A central aim of the AOT was to reduce the need for in-patient treatment. We aimed to assess the impact of the AOT model on hospital admissions for people with psychosis in England. Interrupted time series analysis was used in this study to evaluate the impact of the policy change. Following the introduction of the AOT model, a statistically significant reduction in hospital admissions for psychosis was found. In addition, we observed a repeated, annual summer peak in admissions. This study adds to the international evidence which supports the effectiveness of the AOT model in reducing hospital admissions for people with severe mental health problems. We offer five suggested implications for mental health nurses and clients based on our findings.

Nutrient intakes during pregnancy: observations on the influence of smoking and social class.

The influence of smoking and social class on dietary intake in pregnancy was investigated in a random sample of smokers (greater than or equal to 15 cigarettes/d) and nonsmokers. A total of 206 subjects (94 smokers and 112 nonsmokers) completed a 7-d weighed dietary intake at 28 wk gestation and 178 completed a second assessment at 36 wk. Nonsmokers had higher intakes of almost all nutrients than did smokers and the nutrient density of their diet was greater. Energy intake was nonsignificantly higher in nonsmokers. Women in higher social classes had the highest nutrient intakes. Smokers were shorter than nonsmokers and tended to be of lower social class. After maternal height and social class were controlled for, smoking had a significant effect on intake of many micronutrients. Dietary intake was reduced in late pregnancy, particularly in smokers. These data suggest that smokers in all social classes have a poorer quality of diet.

Peptide sweeteners. 8. Synthesis and structure-taste relationship studies of L-aspartyl-D-alanyl tripeptides.

Several L-aspartyl-D-alanyl tripeptides have been synthesized to investigate the structural requirements of the C-terminal amino acid needed to elicit a taste response. Following our suggestion that a rigid, hydrophobic residue is required, both alpha, alpha-dialkane and cycloalkane alpha-amino acid methyl esters were incorporated into the tripeptide. The L-aspartyl-D-alanine-based tripeptide derivatives of alpha-aminoisobutyric acid methyl ester, alpha, alpha-diethylglycine methyl ester, and alpha-aminocycloalkanecarboxylic acid methyl esters from three- to six-membered rings are sweet. The higher analogues of the cycloalkane series containing alpha-aminocycloheptanecarboxylic acid methyl ester and alpha-aminocyclooctanecarboxylic acid methyl ester are bitter. It is important to note that this series of tripeptides (analogous to the previously reported dipeptides) goes from sweet to bitter to tasteless as the ring size of the C-terminal amino acid increases. The relationships between effective volume of the C-terminal residue, size requirements of the sweet receptor, and taste are discussed.

Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy.

Morphometric and statistical techniques were used to assess the relation of myometrial interstitial trophoblast to the uteroplacental vasculature in 27 intact hysterectomy specimens ranging from 8 to 18 weeks' gestation. It was found that the volume density of cytotrophoblast in the myometrium and in particular the proximity of such trophoblast to the placental bed spiral arteries correlated significantly with morphological alterations in these vessels. The changes included swelling of endothelium, hypertrophy of individual medial smooth muscle cells, and oedema and disruption of the architecture of the vessel wall as a time-related continuum. Some of the changes, such as swollen endothelium and basophilia of medial smooth muscle cells were noted also in spiral arteries in the non-placental bed endometrium but to a considerably less extent than in the placental bed. Intimal vacuolation was common to placental bed and non-placental bed arteries, increased with gestational age and can be considered as a non-specific feature. The migration of endovascular trophoblast into the myometrial spiral arteries in the second trimester occurred only when these arteries had been considerably altered in their morphology. These findings indicate that migratory interstitial cytotrophoblast probably has a role to play in the preparation of the myometrial segments of the uteroplacental arteries for the second wave of endovascular trophoblast migration that occurs in the second trimester of human pregnancy.

The pattern of interstitial trophoblastic invasion of the myometrium in early human pregnancy.

The human placental bed myometrium, studied in 42 intact hysterectomy specimens ranging from 8 to 18 weeks' gestation, is characterized by the presence of large numbers of non-villous invasive cytotrophoblastic cells. Quantitative morphometric analysis reveals a tendency for maximal invasive activity to occur at the centre and, subsequently, to extend centrifugally to produce an annular pattern. Morphological observations suggest that the intimate mixture of cytotrophoblast with myometrial tissue must affect the mechanical properties of the myometrium. Local hormone production by trophoblast may induce or enhance these and other changes in uterine tissues that are essential for the establishment of human placentation. Cytotrophoblastic invasion into the myometrium appears to be restricted to the earlier stages of gestation and morphological evidence indicates that, subsequently, clumps of cytotrophoblast fuse to form multinuclear syncytiotrophoblast, the characteristic placental bed giant cells.

Risk factors for asthma up to 16 years of age. Evidence from a national cohort study.

From a national cohort of 8,806 children examined at ages seven, 11 and 16 years (National Child Development Study), data on asthma or wheezing illness (AW) were analyzed to describe its natural history in childhood and its risk factors. Factors found to predict the subsequent onset of asthma included male sex of child, mother's age at the child's birth, pneumonia, whooping cough, tonsillectomy/adenoidectomy, allergic rhinitis, eczema and periodic abdominal pain/vomiting attacks. A wide range of perinatal factors, including feeding practices, and social and family factors were shown to have no effect on natural history.

Comparing two methods of clinical measurement: a personal history.

Despite the fundamental importance of measurement in medicine, studies which compare methods of clinical measurement are often analysed inappropriately and may thus come to incorrect conclusions. We explain the problems with the main methods used, notably correlation and regression, and describe the limits of agreement approach which we have proposed. We consider why incorrect methods are so widely used and describe our own experience in bringing this issue to the attention of medical researchers.

The effect of birth month on asthma, eczema, hayfever, respiratory symptoms, lung function, and hospital admissions for asthma.

The relationship between month of birth and asthma, respiratory symptoms and peak expiratory flow rate has been investigated in population surveys of children and in hospital admission data. Several relationships with month of birth and various respiratory problems is likely. The mechanism remains obscure.

Prospective study of mortality associated with chronic lung disease and smoking in Papua New Guinea.

In Papua New Guinea a 15-year mortality follow-up was carried out among 2026 highlanders and 1734 coastal dwellers on whom data on respiratory symptoms and signs, and lung function had been obtained by prevalence surveys in 1970/71. Survival status was established in 99%, of whom 9.8% had died, the rate being higher in the highland (12.2%) than in the coastal population (7.0%). All abnormalities indicative of chronic lung disease were associated with increased mortality though this was statistically significant only for chronic shortness of breath (SMR 195) and wheezing (SMR 183) in coastal females. In those aged 25 years or more there was a strong association between reduced lung function (FEV1, FVC, FEV1/FVC%) and mortality, after controlling for age and height. The associations observed were as strong as those reported from prospective studies in developed countries. The most striking difference was that in Papua New Guinea mortality showed no association whatever with tobacco smoking; this may be because the traditional type of tobacco and method of smoking it resembles pipe/cigar smoking in developed countries.

Cigarette smoking and birthweight: type of cigarette smoked and a possible threshold effect.

The effects on birthweight of the number of cigarettes smoked and their tar, nicotine and carbon monoxide yields were investigated prospectively in 1309 pregnant women of whom 414 were smokers. Several approaches to modelling the effect of smoking were tried. These suggested that while both yield and quantity smoked were important, yield had the greatest effect. This led to an empirical approach whereby consistent smokers were divided into four categories according to whether they smoked a low or high quantity of cigarettes per day and whether they smoked low or high yield cigarettes. Using these four groups it emerged that women smoking a low quantity of low yield cigarettes had babies of a similar mean birthweight to those of non-smokers whereas those smoking a low quantity of high yield cigarettes had babies whose birthweight was reduced to the same degree (6% or more) as those of mothers who smoked higher quantities. This apparent threshold was estimated as 13 cigarettes/day and 15 mg/cigarette carbon monoxide. We conclude that brand smoked is at least as important as quantity and that in this population there is evidence for a threshold for tobacco smoke intake below which no discernible effect on birthweight is seen.

Maternal cotinine level during pregnancy and birthweight for gestational age.

BACKGROUND: Recent studies have found that cotinine is a better predictor of birthweight than the number of cigarettes smoked in pregnancy. In this paper we test this hypothesis and use cotinine to explore the effect of environmental tobacco smoke (ETS) on birthweight. METHODS: In all, 1254 white women were interviewed at booking, 28 and 36 weeks about the number and brand of cigarette smoked. Cotinine was assayed from blood samples taken on the day of interview. The outcome was birthweight for gestational age. RESULTS: There was good agreement between self-reported smoker/non-smoker status and maternal cotinine with 1.3% women mis-reported as non-smokers at booking, 0.6% and 1.8% mis-reported at 28 and 36 weeks respectively. Among smokers, cotinine was more closely related to birthweight than the number of cigarettes smoked at all three time points (r = -0.25 versus r = -0.16 at booking). A reduction in cotinine between booking and 28 weeks was associated with increased birthweight but the effect was not statistically significant. Among non-smokers the association between birthweight and cotinine was not statistically significant after adjusting for maternal height, parity, sex and gestational age. Difference in mean birthweight between non-smokers in the lower and upper quintiles of cotinine was 0.2% (95% CI: -2.4, 2.8). Pooling the results of 10 studies plus our own gave an estimated difference in mean birthweight between women unexposed and exposed to passive smoke of 31 g (95% CI: 19, 44). CONCLUSIONS: Cotinine is a better predictor of birthweight than the reported number of cigarettes smoked. If biochemical analysis is impossible, then self-reported smoking habit should be obtained prospectively using a structured approach. Any effect on birthweight of maternal passive smoking during pregnancy is small compared with the effects of maternal active smoking.

Regional variations in deaths from volatile solvent abuse in Great Britain.

AIMS: To assess geographical variations in mortality and the relationship of socio-economic correlates to deaths from volatile substance abuse (VSA) in Great Britain. DESIGN: Analysis of the National Register of deaths from VSA by linking the addresses (postcode) of the deceased to census enumeration districts and hence wards and counties. SETTING AND PARTICIPANTS: All 775 deaths in Great Britain listed in the national register between 1985-91. Population counts from the 1991 census were used as denominators. MEASUREMENT: The Poisson heterogeneity test was used to test the null hypothesis that all standardized mortality ratios were from the same population. The t-test was used to compare differences in Townsend Deprivation scores between wards with and without VSA deaths. Multiple regression was used to assess the relationship between indices of deprivation and deaths from VSA. FINDINGS: One-third of all VSA deaths occurred in six regions of Great Britain which accounted for 17% of the at risk population. There was considerable variation in age standardized mortality ratios (ASMR) across regions. A ward level analysis indicated that wards with a VSA death had significantly higher levels of deprivation. The Townsend deprivation index showed mean deprivation scores of 2.8 and 0.2, respectively, for wards with and without a registered death (p < 0.0001). Multiple regression at county/region level found that 45% of the variation in ASMR was explained by the components of the Townsend deprivation index. CONCLUSIONS: Factors associated with deprivation are important in VSA deaths and this should be taken into account in planning public health measures to prevent mortality.