Implementation of tailored interventions in a statewide programme to reduce central line-associated bloodstream infections.

BACKGROUND: There have been few studies exploring implementation strategies to central line-associated bloodstream infections (CLABSIs) in low- or middle-income countries. AIM: To implement tailored interventions to reduce CLABSI rates in adult intensive care units. METHODS: The implementation strategy of the State Health Department was performed in São Paulo State, Brazil, over two cycles. Cycle 1 (56 hospitals) was exploratory and cycle 2 (77 hospitals) was designed to confirm the hypothesis generated by the first cycle, with three phases each (pre-intervention, intervention, post-intervention). Cycles included: evaluation of healthcare workers' knowledge, observation of practices, and CLABSI rates monthly report. In cycle 1, a log-normal mixed model was used to select variables significantly associated with the reduction of CLABSI. In cycle 2, CLABSI rates were evaluated. FINDINGS: Healthcare workers' practices improved after intervention. In cycle 1, reduction of CLABSI rates was more pronounced in hospitals with initial CLABSI rates >7.4 per 1000 catheter-days (P < 0.001) and those that introduced the use of peripherally inserted central catheters (P = 0.01). For hospitals with high CLABSI initial rates, simulation demonstrated that the rates were expected to decrease by 36% (95% CI: 9-63), no matter the type of intervention. In cycle 2, there was an overall decrease in CLABSI rates during the intervention period; whereas the mean rate fell further post-intervention, rates at the 90th percentile increased. CONCLUSION: The implementation strategy may have had an effect on infection rates independently of the specific interventions implemented; however, the sustainability of reduction in the post-intervention period remains a challenge.

Estimation of finite population parameters with auxiliary information and response error.

We use a finite population mixed model that accommodates response error in the survey variable of interest and auxiliary information to obtain optimal estimators of population parameters from data collected via simple random sampling. We illustrate the method with the estimation of a regression coefficient and conduct a simulation study to compare the performance of the empirical version of the proposed estimator (obtained by replacing variance components with estimates) with that of the least squares estimator usually employed in such settings. The results suggest that when the auxiliary variable distribution is skewed, the proposed estimator has a smaller mean squared error.

Use of hyaluronidase for cervical ripening: a randomized trial.

OBJECTIVE: To investigate the action of intracervical administration of hyaluronidase (HAase) as an inductor of cervical ripening on an outpatient basis. METHODS: A randomized double-blind trial was conducted with 168 pregnant women at term, Bishop score (BS)<5, normal fetal vitality and no uterine contractions. An evaluation was performed at the first visit, when either 20,000 UI of lyophilized HAase (5 ml) or placebo was administered via cervical injection. After 48 h, if the BS remained<5, a second dose was administered. The primary outcome was the BS after 48 h or 96 h. The outcome was considered positive when BS>/=5. RESULTS: The results indicate that the proportion of positive response for the HAase group (55%) after 48 h is significantly higher (p<0.0001) than the corresponding proportion for the placebo group (7%) with an absolute risk reduction (ARR) of 48%=55-7% (95%CI=40-56%). After 96 h, these proportions are 93% in the Haase group and 22% in the placebo group (p<0.0001, ARR=71%, 95%CI=61-81%). The average duration of labour for the nulliparae in the HAase group (6.5h) is significantly smaller (p<0.0001) than for those under placebo (12.0 h) with an absolute difference of 5.5h (95%CI=4.6-6.4h). For the multiparae, the results are 4.3h for the HAase patients versus 9.5h for the placebo patients (p<0.0001) with an absolute difference of 5.2h (95%CI=4.1-6.3h). The proportion of vaginal deliveries for women who received HAase was 82% versus 51% for the placebo group (p=0.0007, ARR=31%, 95%CI=19-44%). The proportion of vaginal deliveries for patients with prior cesareans in the HAase group (69%) was also significantly higher (p<0.0001) than that corresponding to the placebo group (13%) with ARR=56% (95%CI=26-86%). No uterine hyper stimulation occurred in the study. CONCLUSION: We detected significant associations between intracervical injection of HAase and ripening of the cervix, as well as with shorter duration of labour and larger chance of vaginal delivery, suggesting that this is a simple, effective and safe method even for women with prior cesarean.

Holistic processing unites face parts across time.

When complementary halves of different familiar faces are combined into a new face, there is interference in the identification of either half. This "composite face effect" has been taken as strong evidence that faces are processed holistically. Here, we demonstrate that this effect can persist when the two parts of a face are separated by up to 80 ms of visual noise, showing that the parts of a face interact not only spatially but also temporally. We suggest that the processing underlying robust identification accepts an accumulation of evidence over time.

Air pollution and child mortality: a time-series study in São Paulo, Brazil.

Although most available evidence relating air pollution and mortality was obtained for adults, pollution has been also associated with increased mortality in children, but in a significantly smaller number of studies. This study was designed to evaluate the association between child mortality and air pollution in the city of São Paulo, Brazil, from 1994 to 1997. Daily records of mortality due to respiratory diseases for children under 5 years of age were obtained from the municipal mortality information improvement program. Daily concentrations of sulfur dioxide (SO(2)), carbon monoxide (CO), inhalable particulate matter less than 10 microm in diameter (PM(10)), and ozone were obtained from the state air pollution controlling agency. Information on minimum daily temperature and on relative humidity were obtained from the Institute of Astronomy and Geophysics of the University of São Paulo. Statistical analysis was performed through generalized additive models considering a Poisson response distribution and a log link. Explanatory variables were time, temperature, humidity, and pollutant concentrations. The loess smoother was applied to time (in order to model seasonality) and temperature. Significant associations between mortality and concentrations of CO, SO(2), and PM(10) were detected. The coefficients (and standard errors) of these three pollutants were 0.0306 (0.0076), 0.0055 (0.0016), and 0.0014 (0.0006), respectively. The observed associations were dose dependent and quite evident after a short period of exposure (2 days). According to the proposed model and considering the mean of the pollutant concentration during the period of the study, the estimated proportions of respiratory deaths attributed to CO, SO(2), and PM(10), when considered individually, are around 15, 13, and 7%, respectively.

Suppressors of mdm20 in yeast identify new alleles of ACT1 and TPM1 predicted to enhance actin-tropomyosin interactions.

The actin cytoskeleton is required for many aspects of cell division in yeast, including mitochondrial partitioning into growing buds (mitochondrial inheritance). Yeast cells lacking MDM20 function display defects in both mitochondrial inheritance and actin organization, specifically, a lack of visible actin cables and enhanced sensitivity to Latrunculin A. mdm20 mutants also exhibit a temperature-sensitive growth phenotype, which we exploited to isolate second-site suppressor mutations. Nine dominant suppressors selected in an mdm20/mdm20 background rescue temperature-sensitive growth defects and mitochondrial inheritance defects and partially restore actin cables in haploid and diploid mdm20 strains. The suppressor mutations define new alleles of ACT1 and TPM1, which encode actin and the major form of tropomyosin in yeast, respectively. The ACT1 mutations cluster in a region of the actin protein predicted to contact tropomyosin, suggesting that they stabilize actin cables by enhancing actin-tropomyosin interactions. The characteristics of the mutant ACT1 and TPM1 alleles and their potential effects on protein structure and binding are discussed.

Radiobiological prediction of normal tissue toxicities and tumour response in the radiotherapy of advanced non-small-cell lung cancer.

A number of randomized studies have been carried out in the UK and USA to determine the optimal radiotherapy dose schedule for advanced non-small-cell lung cancer (NSCLC). We have examined eight radiotherapy regimens from data taken from four randomized phase III studies carried out in the UK (1264 patients): 10 Gy single fraction; 17 Gy in two fractions over 8 days; 30 Gy in ten fractions over 14 days; 22.5 Gy in five fractions in 5 days; 27 Gy in six fractions over 11 days; 30 Gy in six fractions over 11 days; 36 Gy in 12 fractions over 16 days; and 39 Gy in 13 fractions over 17 days. We compared the clinical results in palliation, toxicity and survival with four regimens taken from one randomized study from the USA (365 patients): 40 Gy in 20 fractions over 4 weeks; 40 Gy 'split course' in ten fractions in 4 weeks; 50 Gy in 25 fractions over 5 weeks; and 60 Gy in 30 fractions over 6 weeks. Using the linear-quadratic (LQ) radiobiological model, we have calculated the radiobiological equivalent dose (BED) for acute-reacting tissues (BED10), late-reacting tissues (BED1.7) and tumour (BED25), and related the predicted response to the observed response in each tissue. There was a good correlation between the predicted response and the reported response in the case of late-reacting tissue toxicity and tumour response. The model confirmed that, in good performance status patients, a higher value for BED25 correlated with a higher degree of local control and survival and that radiotherapy regimens with a higher value for BED1.7 were associated with five cases of cord myelopathy, if the spinal cord was not shielded. In poor performance status patients the model suggested that the optimal regimen was a single fraction of 10 Gy because this resulted in an equivalent degree of symptom control as other regimens, needed only one hospital visit and was less likely to result in cord damage, thus, allowing for the possibility of retreatment at a later date.

Association between air pollution and intrauterine mortality in São Paulo, Brazil.

The associations among daily counts of intrauterine mortality and pollutant concentrations (NO2, SO2, CO, O3, and particulate matter (3/4)10 microm) were investigated for the period ranging from January 1991 to December 1992 in the city of São Paulo, Brazil. We used Poisson regression techniques, adjusted for season and weather. The association between intrauterine mortality and air pollution was strong for NO2 (coefficient = 0.0013/ microg/m3; p<0.01) but lesser for SO2 (coefficient = 0.0005/ microg/m3; p<0.10) and CO (coefficient = 0.0223/ppm; p<0.10). A significant association was observed when an index that combined these three pollutants was considered in the models instead of considering each pollutant individually (p<0.01). These associations exhibited a short time lag, not over 5 days. In addition, some evidence of fetal exposure to air pollution was obtained by disclosing a significant association between the levels of carboxyhemoglobin of blood sampled from the umbilical cord and ambient CO levels in children delivered by nonsmoking pregnant women in the period from May to July 1995. Our results suggest that air pollution in São Paulo may promote adverse health effects on fetuses.

The pharmacokinetics and metabolism of ifosfamide during bolus and infusional administration: a randomized cross-over study.

In a randomized cross-over trial, 11 patients received ifosfamide (IFOS) in 21-day cycles, which alternated between 3 g m(-2) x (2 or 3) days given as a 1-h bolus doses, or the same total dose as a continuous infusion. Patients who received four or more cycles also alternated between two cycles on dexamethasone 4 mg 8 hourly for 3 days starting 8 h before IFOS, and two cycles off dexamethasone. A total of 34 patient cycles were studied and serum and urinary levels of IFOS, 2 dechloroethylifosfamide (2DC), 3 dechloroethylifosfamide (3DC), carboxyifosfamide (CX) and isophosphoramide mustard (IPM) were measured by thin-layer chromatography. No significant differences could be detected in the areas under the curve (AUCs) of serum concentration, nor in the proportion of IFOS or its metabolites found in the urine. There was no significant effect of dexamethasone on IFOS metabolism. These results indicate that there is no identifiable pharmacokinetic basis for insistence on either bolus or infusional methods of IFOS administration.

The influence of a mineralizing mouthrinse on the mineral contents and on the pH of dental plaque.

The main objective of this study was to evaluate the effects of a single use of a mineralizing mouthrinse on dental plaque pH and on its mineral contents: an additional objective was to examine the effects of an oral prophylaxis and scaling on the same response variables. A total of 22 volunteer dental students (14 female and 8 male) participated in the study. The mineralizing mouthrinse contained calcium, phosphate, strontium and fluoride ions. Following a 48-hour period without oral hygiene and 2 hours after breakfast, dental plaque was collected twice from each participant for the evaluation of the effects of the oral prophylaxis and scaling, and twice more for the evaluation of the effects of the mineralizing mouthrinse. The pH was measured in vitro with a microelectrode and the mineral contents were determined by atomic emission spectrometry. The results demonstrate that the average post-prophylaxis pH was higher than the average pre-prophylaxis pH, and that a variation of the average contents of some minerals in the dental plaque was also observed after prophylaxis compared to the contents prior to prophylaxis. Although there was a significant reduction in the Fe content after the rinse with the mineralizing solution, no significant variation on the average pH was detected.

Effect of gustatory stimulation on flow rate and protein content of human parotid saliva according to the side of preferential mastication.

Unstimulated and citric acid-stimulated parotid saliva from the left- and right-hand sides of 20 females, was collected separately to compare the corresponding flow rates, total protein and electrophoretic protein profiles. Individuals having the left-hand side as the preferential side of mastication presented significantly greater flow rates for the ipsilateral glands than for the contralateral ones. Although the data suggested that the left-hand side average protein concentrations were greater for the group with the right-hand side of preferential mastication, the results were not statistically significant. Some minor differences in electrophoretic protein profiles were detected by scanning densitometry.

Urinary proton magnetic resonance studies of early ifosfamide-induced nephrotoxicity and encephalopathy.

Ifosfamide is an oxazophosphorine widely used in the treatment of cancer in children and adults. Nephrotoxicity and neurotoxicity are major side effects. The aim of this study was to use high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy of urine to identify novel biochemical markers of ifosfamide-induced toxicity. Urine samples were collected from 10 nonencephalopathic patients (who had not previously received nephrotoxic chemotherapy) immediately prior to the first ifosfamide dose and at timed intervals for up to four treatment cycles. The findings were compared with those for urine samples collected from five patients during acute encephalopathic episodes. 1H NMR urinalysis identified a series of characteristic time-related changes in the excretion profiles of low molecular weight endogenous metabolites during ifosfamide therapy. These changes included a decreased excretion of hippurate and an increased excretion of glycine, histidine, glucose, lactate, and trimethylamine-N-oxide. Two nonencephalopathic patients had marked but transient glutaric or adipic aciduria during the second cycle of ifosfamide treatment. Urinary retinol-binding protein rose acutely after each treatment cycle but usually returned to baseline levels. Maximum renal toxicity was observed by the fourth treatment cycle. The ratio of the urinary excretion of the uroprotectant mesna (active form) to dimesna (inactive form) correlated with the degree of renal toxicity. For the encephalopathic patients, the ifosfamide-induced changes in the urinary low molecular weight metabolite profile were similar to those for the nonencephalopathic group. In contrast to previous reports, none of the encephalopathic group developed glutaric aciduria, and i.v. methylene blue did not reverse neurotoxicity in the two patients who received it. The results suggest that ifosfamide nephrotoxicity involves both cortical and medullary regions of the nephron and that the urinary mesna:dimesna ratio may be important in assessing the degree of cytoprotection. This study demonstrates that 1H NMR can provide novel biochemical information on ifosfamide-induced toxicity and will be of value in the optimization of ifosfamide therapy.

The effect of training on the ability of children to use dental floss.

The effect of training on the ability to use dental floss was evaluated in a study involving forty-eight children in the 6.5 to 7.5 age-group. Using a dental plaque index for the proximal surfaces, we observed significantly superior average results for the trained group (five weekly sessions) relative to the group with no training. We also observed a significant average difference favoring the male trained group relative to the female trained group.

Supratentorial low grade gliomas in adults. A retrospective analysis of 43 cases treated with surgery and radiotherapy.

Forty-three adults with histologically verified low grade gliomas, treated with post-operative radiotherapy between 1983 and 1991, were reviewed. Previous studies have identified age and extent of surgery as prognostic factors for survival. In this series, there was no significant difference between patients under 40 years of age and those 40 and over, nor was there a survival difference between those who had open biopsy and those who underwent subtotal/total resection. Patients with seizures preoperatively showed improvement in epileptic control at one year post-radiation. Clinical performance status and neurological deficit scoring indicated good preservation of function one year after radiation.

VAPEC-B chemotherapy in the treatment of aggressive non-Hodgkin's lymphoma: a retrospective analysis of 45 patients.

We performed a retrospective analysis on 45 patients who, between January 1989 and October 1993, received VAPEC-B chemotherapy for high and intermediate grade non-Hodgkin's lymphoma. The aim was to assess response and tolerance to treatment. The weekly regimen consisted of: doxorubicin 35 mg/m2 i.v. weeks 1,3,5,7,9,11; cyclophosphamide 350 mg/m2 i.v. weeks 1, 5, 9; etoposide 100 mg/m2 p.o. daily for 5 days, weeks 3, 7, 11; vincristine 1.4 mg/m2 i.v. (2 mg max.) weeks 2, 4, 6, 8, 10; bleomycin 10 mg/m2 i.v. weeks 2, 6, 10; methotrexate 12.5 mg i.t. weeks 1, 5, 9; prednisolone 50 mg p.o. daily for 6 weeks, reduced to 25 mg daily for 6 weeks. The patients treated were aged 22-71 years, 34 (75%) had high grade (Working Formulation) non-Hodgkin's lymphoma (NHL); 11 (24%) had intermediate grade NHL; 25 had Stage III/IV disease; and 14 (31%) had marrow involvement. The majority of patients (76%) received VAPEC-B as first line chemotherapy; the remainder received it for relapsing disease. Follow-up time from completion of VAPEC-B chemotherapy ranged from 6 months to 50 months (median 25). VAPEC-B, as first line therapy, induced a complete response (CR) and partial response (PR) in 79% and 18% respectively, whilst 3% had no response to treatment. VAPEC-B used for relapsing disease produced CR and PR in 64% and 27% respectively, whilst 9% failed to respond. Six patients in PR and five patients in CR have subsequently undergone an autologous bone marrow transplant or a peripheral blood stem cell transplant. In the group who received VAPEC-B first line but did not proceed to transplant (27 patients), five relapsed (three with CNS disease who had not had CNS prophylaxis). Tolerance to treatment was measured by WHO toxicity scores. The haemoglobin (Hb) toxicity median score for all patients was grade 1 (Hb 9.5-10.9 g/dl), and the white cell count (WCC), toxicity score was grade 2 (WCC 2.0-2.9 x 10(9)/l). No platelet toxicity was observed. Ten per cent of patients suffered grade 3 severity infections requiring antibiotics and there was one treatment related death. The majority of patients received VAPEC-B on time, however, 24% patients had a 2-week delay. VAPEC-B chemotherapy is an effective regimen for malignant lymphoma, either as a first line or as a salvage treatment. Although chemotherapy was given weekly, the tolerance to treatment was acceptable, thus making this short regimen a good alternative to CHOP chemotherapy.

Association between air pollution and mortality due to respiratory diseases in children in São Paulo, Brazil: a preliminary report.

This work presents the results of a time series study relating air pollution and respiratory mortality in children under 5 years of age in the metropolitan area of São Paulo, Brazil. Daily records of mortality (excluding neonatal mortality) for the period May 1990 to April 1991 were collected along with daily records of relative humidity, temperature, SO2, CO, particulates (PM10), O3, and NOx concentrations. Using multiple regression methods we demonstrated a significant association between mortality due to respiratory diseases and the NOx levels. After controlling for weather and season effects, the odds of dying due to respiratory diseases, considering the mean levels of NOx in São Paulo, was estimated at 1.3 (+/- 0.13). This result is in accord with previous animal studies conducted by our group and indicates that air pollution in São Paulo has reached levels high enough to have adverse health effects on the exposed population.

The successful use of radiotherapy for osteoblastoma.

We report a case of osteoblastoma arising in the petrous temporal bone of a 16-year-old boy. Attempts at surgical resection were unsuccessful. The patient was treated with radiotherapy and is now well 10 years later. A review of the literature indicates that radiotherapy has been used rarely for this tumour and some have felt it to be detrimental. Our report illustrates a case where planned radiotherapy has been successful when full surgical resection had not been possible.

Effectiveness of three mouthrinses to inhibit acid formation by dental plaque under home-use conditions.

A study was conducted to assess the effectiveness of three mouthrinses (Plax, Cepacol and Fluordent) to inhibit acid formation from plaque collected from 21 volunteer dental students. Plaque was collected on each side of the mouth, two hours after breakfast, once-a-week, after a period of 48 hours without any oral hygiene other than the use of the mouthrinses. Initial pH and the change in pH of plaque incubated with sucrose were recorded up to 120 min. Excepting Cepacol for the first week only, no inhibitory effect on acid formation was observed.

Larvicidal activity of Tagetes minuta (marigold) toward Aedes aegypti.

The steam distilled oils of 3 species of marigold, Tagetes patula, T. erecta and T. minuta, were tested for larvicidal activity toward third instar Aedes aegypti; activity at 10 ppm was demonstrated only for T. minuta. The larvicidal property of the whole oil dispersed in water persisted for at least 9 days. The terpene, ocimenone, which is a part of the whole oil, was found to be larvicidal only at a higher concentration than the whole oil and to lose its activity within 24 h after dispersal in water. These results suggest a potential utilization of oil of T. minuta or its components for the control of Ae. aegypti and other species of mosquitoes.

A single-dose study of the efficacy and safety of FS 205-397 (250 mg or 500 mg) versus aspirin and placebo in the treatment of postsurgery dental pain.

The efficacy and safety of two dose levels of FS 205-397 (either 250 or 500 mg) were compared with the efficacy and safety of aspirin 650 mg and placebo in a 6-hour, single-dose, double-blind study in 161 patients who had undergone extraction of third molars. Each of the doses of FS 205-397, as well as aspirin, produced analgesia. However, the analgesic effects of both the 500 mg dose of FS 205-397 and aspirin were at times significantly better and more prolonged than those produced by the lower dose of FS 205-397. On the other hand, both doses of FS 205-397 had a significantly faster onset of action than aspirin. Side effects, reported by 17% of the 161 patients, did not differ significantly among the four treatment groups with respect to frequency, type, or severity. The most commonly reported side effects were nausea (7%) and drowsiness (6%). The results indicated that FS 205-397, administered in single doses of either 500 or 250 mg, is a safe and effective analgesic for the relief of pain following dental surgery, and may offer particular advantages in terms of onset of effects.