Characterization of the complications associated with plasma exchange for thrombotic thrombocytopaenic purpura and related thrombotic microangiopathic anaemias: a single institution experience.

BACKGROUND: Plasma exchange (PEX) is a life-saving therapeutic procedure in patients with thrombotic thrombocytopaenic purpura (TTP) and other thrombotic microangiopathic anaemias (TMAs). However, it may be associated with significant complications, exacerbating the morbidity and mortality in this patient group. STUDY DESIGN AND METHODS: We reviewed all PEX procedures over a 72-month period, following the exclusive introduction of solvent-detergent double viral-inactivated plasma in high-volume users, such as TTP, in the United Kingdom (UK). We documented allergic reactions to plasma, citrate reactions, complications relating to central venous access insertion and venous thrombotic events (VTE) in 155 patient episodes and >2000 PEX procedures. RESULTS: The overall complication rate was low. Allergic plasma reactions occurred in 6·45% of the cohort with only one episode of acute anaphylaxis. Similarly, VTEs were 6·45%, not significantly greater than in medical patients receiving thromboprophylaxis, despite added potential risk factors in TTP. Citrate reactions were the most frequent complication documented, but toxicity was significantly reduced by administration of further calcium infusions during the PEX procedure. There were no serious central line infections and no catheter thrombosis. CONCLUSION: Our data confirms that PEX continues to be a life-saving procedure in the acute TTP setting and, the procedure was not associated with an increased mortality and limited morbidity.

The effect of advanced treatment of sewage effluents on metal speciation and (bio)availability.

The bioavailability of metals can be strongly influenced by dissolved organic carbon (DOC). Wastewater treatment effluents add considerable quantities of DOC and metals to receiving waters, and as effluent controls become more stringent advanced effluent treatments may be needed. We assessed the effects of two types of advanced treatment processes on metal availability in wastewater effluents. Trace metal availability was assessed using diffuse gradients in thin films and predicted through speciation modelling. The results show little difference in metal availability post-advanced treatment. EDTA-like compounds are important metal complexants in the effluents.

ESHAP and G-CSF is a superior blood stem cell mobilizing regimen compared to cyclophosphamide 1.5 g m(-2) and G-CSF for pre-treated lymphoma patients: a matched pairs analysis of 78 patients.

Cyclophosphamide 1.5 g m(-2) followed by granulocyte colony-stimulating factor (G-CSF) is an effective peripheral blood stem cell (PBSC) mobilizing regimen, but has limited anti-lymphoma activity. We therefore assessed the mobilizing potential of ESHAP (etoposide, ara-C, methylprednisolone and cisplatin), a potent second-line lymphoma regimen followed by G-CSF. The results were compared in 78 patients with relapsed or resistant lymphomas with the use of cyclophosphamide 1.5 g m(-2) followed by G-CSF in a matched pairs analysis, matching the ESHAP recipients (for predetermined prognostic factors) from a cohort of 178 lymphoma patients mobilized with cyclophosphamide and G-CSF. The total numbers of mononuclear cells collected at apheresis was similar with both regimens but ESHAP plus G-CSF resulted in a significantly higher percentage of CD34+ cells, absolute number of CD34+ cells and GM-CFC (all with P-values < 0.001). The number of patients requiring only one apheresis harvest to achieve a CD34+ cell yield of > 2.0 x 10(6) kg(-1) was greatly increased in the ESHAP recipients (56/78 vs 17/78, P < 0.001). The total number of progenitor cells collected was not significantly different with the two mobilization regimens because of this higher number of apheresis in the cyclophosphamide group. The proportion of patients who failed to achieve a minimum CD34+ cell target of 1 x 10(6) kg(-1) with the pooled harvests was less in the ESHAP arm (four patients vs nine patients) despite an increased number of aphereses in the cyclophosphamide recipients. ESHAP plus G-CSF is well tolerated and is an excellent mobilization regimen in patients with pre treated lymphoma.

Peripheral blood stem cell versus autologous bone marrow transplantation for Hodgkin's disease: equivalent survival outcome in a single-centre matched-pair analysis.

A matched-pair retrospective analysis was used to compare 70 patients who had undergone peripheral blood stem cell transplantation (PBSCT) with 70 who had undergone autologous bone marrow transplantation (ABMT) for Hodgkin's disease. All transplants took place at a single centre using the same conditioning regimen (BEAM). Patients were matched for sex, previous chemotherapy and relapse status: factors which have previously been shown to have prognostic significance for transplant outcome in Hodgkin's disease at this centre. The two groups were also generally comparable for unmatched patient and disease characteristics. Toxic deaths and 90 d outcome were not different between the two groups. Three-year overall survival was 68.6% for the ABMT group and 78.2% for the PBSCT group (P = 0.078); progression-free survival was 59.4% for the ABMT group and 58.1% for the PBSCT group (P = 0.255), and relapse rates were 36.9% and 42.6% respectively (P = 0.30). Within the limitations of retrospective analysis, we conclude that there is no major overall or progression-free survival advantage for PBSCT compared to ABMT in Hodgkin's disease.

Back-up bone marrow is frequently ineffective in patients with poor peripheral-blood stem-cell mobilization.

PURPOSE: To assess hematologic recovery and procedure-related mortality in patients who received high-dose therapy with stem-cell support, in whom the peripheral-blood stem-cell (PBSC) collection fails (CD34+ cells < 1 x 10(6)/kg). The predictive value of granulocyte-monocyte colony-forming cell (GM-CFC) measurements and the value of bone marrow obtained after PBSC collection failure was assessed. PATIENTS AND METHODS: The study group comprised 324 consecutive patients mobilized with granulocyte colony-stimulating factor (G-CSF) and cyclophosphamide (273 patients), G-CSF with other chemotherapy (37 patients), and G-CSF alone (14 patients). Between one and four aphereses were performed. RESULTS: In 51 of 324 patients, there was failure to obtain 1 x 10(6)/kg CD34+ cells. Twenty-three patients had greater than 1 x 10(5)/kg GM-CFC; 22 patients proceeded to high-dose therapy. Neutrophil recovery occurred within 21 days, but platelet independence was delayed (> 28 days) in eight patients. Of 28 patients with less than 1 x 10(5)/kg GM-CFC, six received high-dose therapy with PBSC alone and five had delayed engraftment. Twelve patients with less than 1 x 10(5)/kg GM-CFC received high-dose therapy supported by bone marrow collected after PBSC collection failure. Eleven patients were assessable for engraftment; four patients had slow (> 21 days) or delayed (> 28 days) neutrophil recovery and eight patients had delayed platelet recovery. In the group of patients who received less than 1 x 10(5)/kg GM-CFC, there were five procedure-related deaths. CONCLUSION: This study shows that delayed hematologic recovery is frequent if less than 1 x 10(6)/kg CD34+ cells are infused after high-dose therapy, particularly with GM-CFC less than 1 x 10(5)/kg. The procedure-related mortality in this latter group is high. In most patients whose PBSC collection contains less than 1 x 10(5)/kg GM-CFC, the use of bone marrow cells does not improve engraftment, which suggests that poor PBSC mobilization usually indicates poor marrow function.

Evaluation of clinical scale CD34+ cell purification: experience of 71 immunoaffinity column procedures.

Seventy-one mobilised PBSC collections were subject to CD34+ cell purification using the CEPRATE SC stem cell concentration system. The overall median purity of CD34+ cells was 69% (6-93%). CD34+ cell, and GM-CFC recoveries were 52% (8-107%) and 36% (3-118%). Purity was logarithmically related to the input percentage of CD34+ cells and starting requirements were established of 1% CD34 cell content for optimal purity and a minimum of 2 x 10(6)/kg CD34+ cells to ensure recovery of our minimum engraftment threshold of 1 x 10(6)/kg CD34+ cells. Reduction of the washing steps reduced non-specific cell losses and shortened the procedure but did not affect progenitor cell recovery. Purified CD34+ cells were reinfused following high-dose therapy in 35 patients. The median time to neutrophil recovery of 0.5 x 10(9)/l was 12 (10-23) days and to the attainment of platelet independence was 13 (7-100) days. The risks of delayed platelet recovery were related to the CD34+ cell dose infused and were identical to the risks when non-purified PBSC collections were used. In conclusion, purification of CD34+ cells using the CEPRATE device is reliable and the purified product results in prompt engraftment. The cell losses that occur do however restrict its use in many patients.

Randomized clinical trial of the effect of prenatal fluoride supplements in preventing dental caries.

This randomized, double-blind study tested the caries-preventive efficacy of prenatal fluoride supplementation in 798 children followed until age 5. Initially, 1,400 women in the first trimester of pregnancy residing in communities served by fluoride-deficient drinking water were randomly assigned to one of two groups. During the last 6 months of pregnancy the treatment group received 1 mg fluoride daily in the form of a tablet and the control group received a placebo. Both treatment and control subjects were encouraged to use postnatal dietary fluoride supplements. Caries was measured in children at age 3 and 5 while fluorosis was assessed at age 5. Caries activity was very low in both study groups: 92% of children remained caries-free in the treatment group and 91% remained caries-free in the placebo group. Fluorosis was observed in 26 subjects, all classified as very mild. Overall, there were no statistically significant differences in the study groups with respect to caries and fluorosis in deciduous teeth. The study had sufficient power to detect an absolute risk reduction of 5.1% while only a 1.5% reduction was observed. These findings do not support the hypothesis that prenatal fluoride has a strong caries-preventive effect.

Interexaminer agreement for readings of dip slide tests for salivary mutans streptococci and lactobacilli.

This study reports the interexaminer agreement of three pairs of evaluators of salivary dip slide tests for mutans streptococci and lactobacilli. 717 Cariescreen SM and Bactotest LB dip slides were available for assessment by 2 dentists and 1 dental hygienist. A single calibration session was held prior to the onset of the study. Each dip slide was read once by each examiner independently. Among the three pairs of examiners, Pearson R values ranged from 0.84 to 0.90 for Cariescreen and from 0.78 to 0.87 for Bactotest. Kappa statistic values ranged from 0.56 to 0.61 for Cariescreen and from 0.70 to 0.74 for Bactotest. The range of agreement was from 72.2 to 76.9% for Cariescreen and from 86.4 to 88.3% for Bactotest. The majority of disagreements were of one category in magnitude, though there were a few disagreements of greater magnitude. This study found moderately strong agreement among the three examiners; it suggests that multiple examiners of dip slide tests carefully calibrated initially and periodically to ensure a high level of agreement.

Caries risk assessment in a longitudinal discrimination study.

Our objective was to develop and perfect a model for the assessment of risk of dental caries onset in children. Even though dental caries prevalence in children is continuing to decline, there is still a significant minority for whom it is a problem. In this study, we sought to ascertain whether a set of variables selected in a previous cross-sectional study could be used to differentiate between caries-free six-year-olds who would or would not subsequently present with clinically-detectable caries. A total of 472 caries-free six-year-olds--286 from a fluoridated community and 186 from a fluoride-deficient community--was selected. Clinical examinations for DMFS, dental fluorosis, and plaque were conducted. Stimulated whole saliva was collected for analysis of mutants streptococci, lactobacilli, total viable flora, and fluoride, calcium, and phosphate concentrations. A questionnaire was used for collection of demographic data as well as information on prior fluoride exposure, dietary habits, and oral hygiene practices. By means of linear discriminant analyses, it was possible to predict correctly which children would develop caries within six to 12 months (sensitivity) in 82.8% of cases and which children would not develop caries during that period (specificity) in 82.4% of cases.

Caries risk assessment by a cross-sectional discrimination model.

Although the prevalence of dental caries is continuing to decline, it still affects a majority of the US population and can be a serious problem for those afflicted. The objective of this project was to develop and perfect a model for assessment of risk of dental caries onset in children. In the first study, reported herein, a set of clinical, microbiological, biochemical, and socio-demographic variables was identified that distinguished, with an acceptable level of sensitivity and specificity, between children who had no previous caries experience and children who had high caries levels. A total of 313 children--age 12-15 years, 140 from a fluoridated community and 173 from a fluoride-deficient community--was selected on the basis of previous caries experience, either zero DMFS or high DMFS (> or = 6 in the fluoridated or > or = 8 in the fluoride-deficient community). Clinical exams for DMFS, dental fluorosis, and plaque were conducted. Stimulated whole saliva was collected for analysis of mutans streptococci, lactobacilli, total viable flora, and fluoride concentration. A questionnaire was used for collection of demographic data as well as information on prior fluoride exposure, dietary habits, and oral hygiene practices. By means of discriminant analyses, with use of seven key clinical and laboratory variables, it was possible for zero-DMFS subjects to e classified correctly (specificity) in 77.6% of cases in the fluoridated community and in 86.1% of cases in the fluoride-deficient community. High-caries subjects were classified as such (sensitivity) in 79.3% and 88.1% of cases, respectively.

Associations of microbiological factors and plaque index with caries prevalence and water fluoridation status.

Plaque indices, numbers of mutans streptococci, lactobacilli and total viable flora in plaque and saliva were assessed as part of a large-scale cross-sectional study designed to determine the factors that are associated with high caries activity in children. Subjects, 12 to 15 years old, residing in areas where the water supplies were either fluoridated (n = 140) or fluoride-deficient (n = 173) were studied. Mutans streptococci and lactobacilli numbers in saliva were positively correlated with plaque index. Plaque indices were significantly higher in the high-caries group than in the zero-caries group of the fluoride-deficient community. In the fluoridated community, there was no difference in the plaque index between the zero- or high-caries groups. In each community, pooled dental plaque and saliva harbored fewer mutans streptococci and lactobacilli in the zero-caries than the high-caries group. Greater numbers of mutans streptococci were found in the dental plaque and saliva of the zero-caries subjects in the fluoridated community than in the fluoride-deficient community, suggesting that a greater caries challenge can coexist with zero-caries status in the fluoridated community.

Correlations between numbers of microflora in plaque and saliva.

An epidemiologic investigation to reliably identify caries-susceptible subjects by microbiological and chemical assessment of plaque and saliva is currently in progress. As part of that study, the numerical relationships of mutans streptococci, lactobacilli and total viable microflora in plaque and saliva among 12- to 15-year-old children in a fluoridated community were determined. Paraffin-stimulated whole saliva and pooled dental plaque were collected. Each sample was suspended in reduced transport fluid, chilled on ice, and assayed. The bivariate normal distribution was found to be a suitable model for the distribution of the pairs [numbers of bacteria in plaque (log10), numbers of bacteria in saliva (log10)]. Statistically significant positive correlations were found between numbers of mutans streptococci in plaque and saliva, and between lactobacilli in plaque and saliva.

Effectiveness of mouthrinsing with fluoride solutions in preventing coronal and root caries.

Fluoride mouthrinses have been used extensively for the past 15 years to prevent dental caries in children. Their use has been especially widespread in organized school-based programs in the US. Nearly three dozen clinical studies of fluoride mouthrinses, both with and without placebo controls, have been reported in the literature since the early 1960s. The overwhelming majority of those studies report statistically significant caries inhibition from the use of the products. Most of the studies were published prior to the knowledge of a decline in caries prevalence during the past 30 years. Consequently, the results of those studies lacking a placebo control group have been challenged. Even randomized clinical trials with appropriate control groups appear to be reporting declining differences between test and control groups. Using a model based on annual caries increments from published studies, the conclusion is reached that future use of fluoride mouthrinses is unlikely to result in annual savings in DMF increment greater than 0.4 surfaces, regardless of age of rinsers.

Assessing diagnostic reliability and estimating incidence rates associated with a strictly progressive disease: dental caries.

This paper presents a general approach for simultaneously assessing, from serial data, diagnostic consistency, interrater reliability and incidence of a strictly progressive disease. Observed data are viewed as incomplete: diagnostic errors are not distinguished from true diagnoses. We introduce a broad class of models to separate rater errors from underlying patterns of disease incidence. The analysis can include covariates and risk factors. We provide variance expressions for parameter estimates. Categorical data for estimating the incidence of dental caries serve as an example.

Retention of sealants over carious and sound tooth surfaces.

Bacteriologic and clinical studies suggest that sealants can be used therapeutically on incipient caries of the enamel. The present study was designed to explore this approach further by determining whether there is a difference in retention rates on sound or carious tooth surfaces sealed for the first time as well as resealed surfaces. A total of 1766 teeth were sealed for subjects 12-14 yr of age of which 120 were judged to be carious. Mouths were divided sagittally on a random basis and an ultraviolet light activated resin with a filler or an autopolymerizing resin without a filler was placed on contralateral surfaces of all molar and premolar teeth. The effects of sealant type, caries status, arch and tooth type on retention over a 2-yr period were tested using Mantel-Haenszel statistics. At the end of 1 yr, 88% of the teeth sealed with the autopolymerizing resin were judged to be completely intact compared to 82% of the teeth filled with the ultraviolet light resin. At the end of the second year the retention rates were 84% and 75% respectively. The retention rates for carious and sound teeth at the end of both years were almost identical. Overall, premolars had a 15% more favorable retention rate than molars. There were minimal differences between arches although maxillary premolars had approximately a 5% higher retention rate than mandibular premolars. The reverse was true for molar teeth. Retention of sealants at the end of the second year (resealed after 1 yr) was 4% less than comparable teeth sealed initially.