Survival ratio plots with permutation envelopes in survival data problems.

A new method is proposed, based on a simple ratio plot, which is useful for identifying time intervals or regions in which survival prospects differ between two distinct populations or treatments. In order to investigate whether any observed difference or trend is due to sampling variation or is due to a possible real effect, resampling techniques are used to generate permutation envelopes as reference bands. The method is applicable to the comparison of survival in two populations for both independent and paired survival problems and also to the assessment of the symmetry of a bivariate survival function.

Sickness scoring and response to treatment as predictors of outcome from critical illness.

A physiological sickness scoring system (SS), based on the APACHE II score, has been used to assess outcome from critical illness in 128 patients admitted to a general intensive care unit. Physiological data were collected on each patient from admission until death or discharge from the unit, and survival was recorded as survival to home. The admission SS correctly classified 80.6% of survivors, and 70.4% of non-survivors. Predictive power did not improve with time using the daily SS. However, when the proportional change in SS over time was included in the analysis, predictive power improved; and at day 4, 87.1% of survivors and 75% of non-survivors were correctly classified. At intermediate levels of sickness severity (admission score of 13-18), a reduction in SS of 30% by day 4 reduced the risk of death by 32%; at higher levels (greater than 18) a similar reduction in SS was associated with a 47% reduction in death-risk. Failure to obtain a reduction in score by day 4 was associated with increased risk of death. Survivors consistently showed a greater fall in SS by day 4 than non-survivors. The APACHE score and its modifications provide an accurate, unitary measure of physiological disturbance. Correction of abnormal physiology, and the measurement of responsiveness to therapy are important components in the prediction of outcome from critical illness.

Sedation in intensive care: morphine and renal function.

Intravenous morphine infusions have been administered to 12 critically-ill patients during controlled ventilation. Acute oliguric renal failure was present in 4 patients, who were treated with a combination of haemofiltration and haemodialysis. Severity of physiological disturbance was assessed using a modified APACHE Score, level of sedation by a linear-analogue scale, and blood morphine levels by high-pressure liquid chromatography. Morphine clearance was impaired in renal failure, and was dependent on haemofiltration volumes; accumulation of morphine did not occur during this form of treatment. Conscious level was clearly more closely related to the degree of physiological disturbance than blood morphine levels; and for a given blood morphine level, depression of consciousness was more pronounced the greater the degree of physiological disturbance. Use of a physiological sickness score may help to clarify some of the factors influencing cerebral function during critical illness. Careful clinical monitoring of level of sedation is important in patients with oliguric renal failure receiving morphine, and haemofiltration appears to reduce the risk of morphine accumulation in these patients.

The effect of nebulised pentamidine on the concentration of intra-oral Candida albicans in HIV-infected patients.

This prospective study investigated whether oral candidal carriage in HIV-infected patients was altered by pentamidine therapy. Repeated oral rinses were taken from 56 HIV-positive patients over a 2-year period. Oral candidal carriage was investigated in two groups of patients, one receiving prophylactic pentamidine therapy and the other not receiving regular prophylaxis. Patients receiving pentamidine had lower concentrations of Candida albicans intra-orally than patients who did not receive it. Furthermore, patients who received pentamidine at one stage of the study, but not another, also had lower concentrations of C. albicans intra-orally when receiving pentamidine. These findings indicate that pentamidine is useful as a local agent for prophylaxis against intra-oral candidosis in HIV-infected patients.

The effect of sucrose application and implantation of mutans streptococci on the microbial composition of three-week experimental plaque--an in situ study.

This study describes the predominant cultivable microflora of three-week-old plaque samples obtained from human enamel sites, on the basis of microbial identification of over 9000 fresh isolates. Lower removable appliances, on which were mounted enamel sections and slabs, were worn by five young adult subjects under three experimental protocols. These were (1) 'normal' plaque conditions, (2) extra-oral sucrose applications nine times daily, and (3) inoculation of each subject's own mutans streptococci onto the enamel test sites and sucrose applications, as described above. With the exception of slightly higher proportions of Gram-negative bacilli associated with slab plaque following sucrose application, no significant differences in percentage or absolute counts of organisms were found between normal and sucrose plaques. The inoculation of mutans streptococci, combined with extra-oral sucrose applications, was associated with significantly higher percentages and absolute mean counts of both mutans streptococci and lactobacilli, and lower proportions of S. sanguis and S. oralis. Although the isolation frequency of mutans streptococci increased in all subjects and the overall mean proportion rose following inoculation, considerable inter-subject variation was seen in mean percentage counts of these organisms isolated from the three-week plaque samples.

An inner city preschool visual screening programme: long-term visual results.

AIMS: The aim of this study was to investigate the long-term outcome of the treatment of amblyopia as a sequel to preschool screening, which has not hither-to been described. METHODS: All patients originally referred from a preschool screening programme were recalled for examination by letter. 255 patients were reviewed at least 4 years after discharge of which 88 were definitely amblyopic at presentation and 107 were not amblyopic at presentation and were used as controls. RESULTS: 79% of the amblyopes improved or maintained visual acuity after discharge but this was reduced to 42% after an age induced increase (estimated from the controls) was compensated for. The mean drop in visual acuity in the amblyopic eyes which deteriorated was 0.23 (SD 0.15) logMAR units. Stepwise multiple linear regression showed that the best single predictor of post-discharge deterioration in visual acuity was the improvement in visual acuity seen during treatment (R2 = 19%). Eccentric fixation at time of follow up (increasing R2 to 47%) and good presenting acuity (further raising R2 to 57%) contributed additional information, and were both associated with greater post-discharge deterioration in visual acuity. CONCLUSIONS: The majority of amblyopes who attended for follow up maintained or improved their visual acuities after discharge. Those patients who demonstrated deterioration of their amblyopia had usually improved well during the programme and were often fixating eccentrically at follow up.

Traumatic wound rupture after penetrating keratoplasty in Africa.

AIM: To investigate risk factors, visual outcome, and graft survival for traumatic wound rupture after penetrating keratoplasty. METHODS: A retrospective analysis of 336 patients who underwent penetrating keratoplasty from 1988 to 1995. RESULTS: 19 patients (5.7%) suffered traumatic postoperative wound rupture requiring surgical repair. They were younger (mean age 16.6 years, 95% CI 13.2-20.6) and more frequently keratoconic (p = 0.01) than other patients (mean age 28.9 years, 95% CI 26.-31.0). Mean postoperative follow up was 37.7 (SD 22.9) months and 24.5 (18.9) months for the rupture and non-rupture patients. Mean interval between keratoplasty and rupture was 18 (21) weeks. The lens was damaged and removed in 37% of ruptured eyes. For keratoconics, the probability of graft survival at 5 years was lower (p = 0.03) in the ruptured eyes (75%) than in the non-ruptured eyes (90%). Endothelial failure was a more common (p <0.05) cause of graft opacification in ruptured grafts than in intact grafts. Of the ruptured eyes, 53% achieved a final corrected acuity of at least 6/18 and 63% achieved at least 6/60 compared with 48% and 71% of the intact eyes respectively (both p >0.1). The proportion of keratoconic eyes which achieved at least 6/60 was lower (p = 0.02) in the ruptured eyes (67%) than the non-ruptured eyes (87%). Eyes with wound ruptures of 5 clock hours or greater were less likely (p <0.05) to achieve an acuity of 6/18 and were more likely (p <0.05) to have an associated lens injury. CONCLUSIONS: Graft rupture is relatively common in African practice, particularly in young keratoconics. Visual outcome and graft survival are not significantly worse than for other grafted eyes, but are significantly worse than for other grafted keratoconic eyes.

Survival analysis: the importance of censored observations.

We have considered the issue of predicting from diagnosis of a condition such as malignant melanoma survival past an often arbitrarily chosen fixed time-point, such as 5 years. Prediction of survival past any time-point becomes rather complicated due to the presence of 'censored observations', and these observations are often ignored in any analysis. Censored observations are subjects who either die of causes other than the disease of interest or are lost to follow-up. The aim of this paper is to show that the result of ignoring these 'censored observations' is an underestimation of the probability of survival beyond the fixed time-point. Ignoring these censored observations results in potentially valuable information on survival being thrown away. This underestimation will often prove to be of considerable magnitude and dependent on the proportion of censored observations present in the data. It is therefore essential to carry out a full actuarial survival analysis which will incorporate all the information contained in these censored observations.

Oral disease in terminally ill cancer patients with xerostomia.

Xerostomia is common among patients with advanced cancer and is likely to contribute to oral disease. This study determined the prevalence of oral signs and symptoms among a group of 70 terminally ill cancer patients [25 male, 45 female; age range 42-88 (mean 66) years] complaining of oral dryness, and examined the associated oral microflora. Imprint cultures for yeasts, coliforms and staphylococci were collected from the tongue and, in denture wearers, from the plate and denture fitting surface. A swab was collected for culture of herpes simplex virus. 68 patients (97%) complained of oral dryness during the day and 59 patients (84%) complained of oral dryness at night. Oral soreness was reported by 22 patients (31%). 46 patients (66%) had difficulty talking and 36 (51%) reported difficulty eating. Of the 56 denture wearers, 40% complained of denture problems. On examination, 63 (90%) of the patients had clinically dry mouths. Oral mucosal abnormalities were detected in 45 patients (65%), most commonly erythema (20%), coated tongue (20%), atrophic glossitis (17%), angular cheilitis (11%) and pseudomembraneous candidosis (9%). 47 (67%) of the patients carried yeasts, 18 (26%) were carriers of Staphylococcus aureus and 13 (19%) carried coliforms. Herpes simplex virus was isolated from 5 patients, of whom 2 had herpetic stomatitis. Oral complications and abnormalities of the oral microflora can be detected among significant numbers of terminally ill cancer patients with xerostomia.

Beta 2-agonists and running economy in prepubertal boys.

Asthmatic athletes (adults and junior) have competed successfully at the highest level for many years assisted by pre-event medication with beta 2-agonists. To examine the impact of beta 2-agonists upon submaximal running economy (oxygen consumption at a given submaximal work load), we studied 10 nonasthmatic boys (age, 10.4 +/- 0.48 years, mean +/- SD). They each completed submaximal (speeds, 7.2, 8.0 and 8.8 km/hr) and peak treadmill running protocols preceded by treatment with beta 2-agonist (terbutaline, 500 micrograms via nebuhaler) or placebo in a randomized, crossover single-blind study. No significant differences were found between running economy and heart rate during the submaximal exercise tests or between peak oxygen consumption (VO2), peak respiratory exchange ratio, peak heart rate (HR), or total running time during the peak VO2 test. Pretreatment with terbutaline did produce small but nonsignificant increases in aerobic fractional utilization (percent peak VO2 on drug: 65.9%, 72.6%, and 76.7% vs. placebo: 65.1%, 70%, and 75.5%), at the three submaximal work loads. Respiratory exchange ratio (RER) values were elevated throughout the submaximal tests (on drug: 0.94, 0.93, and 0.94 vs placebo: 0.91, 0.92, and 0.91, P < 0.05). No significant differences were found between drug and placebo for minute ventilation (VE) and ventilatory equivalent for oxygen (VE/VO2), at both submaximal and peak exercise intensities.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of an energy and micronutrient supplement on growth and activity, correcting for non-supplemental sources of energy input in undernourished children in Indonesia.

OBJECTIVES: This paper investigates simultaneously the growth and activity of children that received an early energy and micronutrient supplement, adjusting for all non-supplemental energy intakes. Any additional change in growth and activity after this adjustment was then compared across supplements at three points felt to be representative of the study. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care-centers. Twenty children that received S belonged to the 12- and 18-month-old cohorts. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Length was measured with a portable measuring board; a Detecto scale with an accuracy of 0.1 kg was used for the measurement of body weight. Arm and head circumferences were measured using similar fiberglass tapes. Motor activity was assessed through continuous 4 h observations at home and at day care centers. Anthropometry and activity were measured every two months over 12 months. RESULTS: After correcting for non-supplemental sources of energy intake, the effects of the supplement on weight and activity were observed at 2 months; effects on length and activity were observed at 6 months; and effects on weight alone were observed at 12 months.

Effects of an energy and micronutrient supplement on anthropometry in undernourished children in Indonesia.

OBJECTIVES: This paper reports the effects of early supplementary feeding on body weight, length, head circumference and arm circumference among the children in the Pangalengan study. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care centers. Twenty children that received S belonged to the 12- and 18-month cohorts. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: Length was measured with a portable measuring board; a Detecto scale with an accuracy of 0.1 kg was used for the measurement of body weight. Arm and head circumferences were measured using similar fiberglass tapes. RESULTS: Body weight showed effects on both cohorts at 2, 8 and 12 months; head circumference showed effects at 4 months in the 12-month-old cohort and at 10 months among the females of the 18-month-old cohort; and arm circumference showed effects across cohorts at 2, 8 and 12 months. In general the benefits are clearer for females and for the 12-month-old cohort.

Nutritional intake of an undernourished infant population receiving an energy and micronutrient supplement in Indonesia.

OBJECTIVES: This paper reports the dietary intake (home, day care centers, supplement and breast milk) of the children in the clinical trial in Pangalengan. DESIGN: Two cohorts of children were randomly assigned to three treatments: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. SETTING: The sites were six tea plantations in Pangalengan, West Java. SUBJECTS: A 12-month-old (n = 53) and an 18-month-old (n = 83) cohort were recruited from day-care-centers. Twenty children who received S belong to the 12- and 18-month-old cohorts. Inclusion criteria were: no chronic disease; length-for-age < or = -1 standard deviation (s.d.) and weight-for-length between -1 and -2 s.d. of the median of the reference of the World Health Organization. METHODS: E = 1171 kJ + 12 mg iron; M = 209 kJ + 12 mg iron; S = 104 kJ. Supplementation was given for 12 months. Evaluations of intake were made at baseline and every 2 months thereafter. RESULTS: For the 12-month-old cohort the mean increase in daily energy intake approximately 2931 kJ for E, approximately 1675 kJ for M, and approximately 837 kJ increase over the 6 months for the S group. For the 18-month-old cohort the changes were approximately 2512 kJ for E approximately 1675 for the M group and approximately 1047 for the S group.

Is it possible to predict the blood volume of a sick preterm infant?

OBJECTIVE: To investigate the relation between the measured intravascular blood volume (BV) and current methods of indirectly assessing BV status in sick preterm infants on the first day of life. METHODS: Thirty eight preterm infants of gestation 24-32 weeks (median 30) and weight 480-2060 g (median 1220) were studied. Red cell volume was measured by the fetal haemoglobin dilution method in six infants and by the biotin labelled autologous red cell dilution method in the remaining 32. Total BV was calculated by dividing red cell volume by packed cell volume. Indirect assessments of BV status using heart rate (HR), core-peripheral temperature difference, mean arterial pressure, base excess, and packed cell volume were recorded. RESULTS: The mean (SD) initial measured BV was 71 (12) ml/kg (range 53-105). The mean HR was 148 beats/min (range 130-180), which correlated positively (r = 0.39, p = 0.02) with BV (higher HR was associated with higher BV). The mean base excess was -3.19 mmol/l (range -18 to +6.2). The negative base excess correlated significantly positively (r = 0.41, p < 0.01) with BV (more acidotic babies tended to have higher BV). There was no significant correlation between core-peripheral temperature difference, mean arterial pressure, or packed cell volume and BV. Regression analysis showed that base excess and HR were significantly related to BV; base excess alone can predict variability in BV only to 17%, and base excess with HR can predict variability in BV to 29%. CONCLUSION: The conventional clinical and laboratory indices are poor predictors of measured blood volume.

Methods for improving the repeatability of automated ECG analysis.

Statistically-based smoothing techniques are described which have been applied to the existing framework of the Glasgow ECG Analysis program. These methods have been designed with the aim of improving repeatability in the computer interpretation of ECGs which have been recorded either several minutes or 24 hours apart from patients in a clinically stable condition. With respect to the ECG diagnosis of Left Ventricular Hypertrophy (LVH), these flexible methods have the effect to reducing the number of inconsistent day-to-day interpretations by 36% from 33 to 21 in 330 pairs of ECGs recorded one day apart. Similarly, when comparing agreement in the diagnosis of LVH in 249 pairs of ECGs which were recorded several minutes apart, the number of discordant computer interpretations was 6 using the new methodology, compared with 13 using conventional criteria, i.e. there was a 54% reduction in disagreements.

Prediction of caries increment in Scottish adolescents.

Salivary, clinical, and microbiological factors were compared with subsequent 2-yr caries increment in a group of 372 Scottish adolescents. The caries increment was significantly correlated with previous caries experience, salivary buffering capacity and counts of lactobacilli, mutans streptococci and candida. Veillonella levels and salivary flow rate were not correlated with caries increment. Significant improvements in the predictions were obtained when the results of more than one test were included using stepwise regression analysis. On an individual basis, using stepwise discriminant analysis, the caries increment group (low, medium, or high) was identified correctly in 49% of all subjects, but this was reduced to 45% if previous caries experience was excluded from the analysis.

Caries prevalence and microbiological and salivary caries activity tests in Scottish adolescents.

Salivary and microbiological caries activity tests were investigated on three occasions in a group of 372 Scottish adolescents. Counts of lactobacilli, mutans streptococci, and candida were consistently and significantly associated with caries prevalence, as either DS or DMFS score, and buffering capacity was consistently inversely related to DMFS score. However, veillonella counts and salivary flow rate were not correlated with caries prevalence. Significant improvements in the associations were obtained when the results of more than one test were included using stepwise regression analysis. On an individual basis, at most, stepwise discriminant analysis identified the DMFS group correctly in 49% of all subjects, and the DS group in 47%.

Salivary levels of mutans streptococci, Lactobacillus, Candida, and Veillonella species in a group of Scottish adolescents.

Salivary levels of mutans streptococci, Lactobacillus, Candida, and Veillonella species were investigated on three occasions at annual intervals in a group of 372 Scottish adolescents. Counts of the micro-organisms studied were logarithmically distributed, with Candida spp. being isolated from approximately half the subjects. Counts of lactobacilli, mutans streptococci, and candida were significantly intercorrelated, while veillonella were associated consistently with mutans streptococci alone. Levels of each of the four micro-organisms were significantly correlated over the three examinations, with levels of the Candida spp. being the most stable over the period studied.

Bovine acute phase response following turpentine injection.

The serum levels of five proteins, alpha 1 antitrypsin, ceruloplasmin, fibrinogen, haptoglobin and seromucoid, were measured daily in calves after the subcutaneous injection of oil of turpentine. Raised concentrations were detected on the second and third days after injection with peak levels occurring on the fourth to seventh days and returning to normal by the 17th day. Levels of four of these proteins, alpha 1 antitrypsin, ceruloplasmin, haptoglobin and seromucoid were compared in the same calves following three different doses of turpentine. Levels of haptoglobin and seromucoid varied with the dose whereas ceruloplasmin and alpha 1 antitrypsin levels did not.

Prognostic trees to aid prognosis in patients with cutaneous malignant melanoma. Scottish Melanoma Group.

OBJECTIVES: To design user friendly guides to prognosis for patients who have had invasive primary cutaneous malignant melanomas surgically excised. DESIGN: Adaptation of the classification tree method was used to derive prognostic trees for four different subgroups of malignant melanoma patients in whom known and possible prognostic variables interacted in different ways. SETTING: Scotland. SUBJECTS: Statistical modelling for prognostic trees was based on 1978 patients whose primary malignant melanoma was first diagnosed in 1979-86 for whom five year follow up and all relevant clinical pathological data were available. The resultant model was validated with 300 patients first diagnosed in 1987 for whom the same information was available. MAIN OUTCOME MEASURES: Actual and predicted rate of survival after diagnosis of primary cutaneous malignant melanoma. RESULTS: The four subgroups of patients were men and women with ulcerated and non-ulcerated cutaneous primary melanomas. Validation of the model showed excellent agreement between actual status of patients in the relevant subgroups and their status as predicted by the model. CONCLUSIONS: The prognostic trees are simple to use and give more accurate prognosis for individual patients than is currently available from tumour thickness alone.