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Prospective Monitoring (prospective + monitoring)
Selected AbstractsProspective Monitoring of Polyomavirus BK Replication and Impact of Pre-Emptive Intervention in Pediatric Kidney RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007F. Ginevri Polyoma BK virus (BKV)-associated nephropathy (PVAN) is a relevant cause of poor renal allograft survival. In a prospective analysis, we monitored BKV DNA in blood and urine samples from 62 consecutive pediatric kidney recipients. In patients with BKV replication, we analyzed the impact of reduction of maintenance immunosuppression on viral load kinetics and PVAN in patients with BKV replication. BKV-specific immunity was concomitantly evaluated on blood samples of viremic patients, by measuring the frequency of BKV-specific interferon-,-producing and cytotoxic T cells, and BKV IgG antibody levels. At a median follow-up of 24 months, BK viruria was observed in 39 of 62 patients, while BK viremia developed in 13 patients (21%). In all viremic patients, immunosuppression reduction resulted in the clearance of viremia, and prevented development of PVAN, without increasing the rate of acute rejection or causing graft dysfunction. As a consequence of immunosuppression adjustment, an expansion of BKV-specific cellular immunity was observed that coincided with viral clearance. We conclude that treating pediatric kidney transplant patients pre-emptively with immunosuppression reduction guided by BKV DNA in blood is safe and effective to prevent onset of PVAN. BKV-specific cellular immunity may be useful to guide this intervention. [source] Increased rate of prematurity associated with antenatal antiretroviral therapy in a German/Austrian cohort of HIV-1-infected womenHIV MEDICINE, Issue 1 2008I Grosch-Woerner Objective The aim of the study was to assess the risk of adverse pregnancy outcomes after antenatal antiretroviral therapy in a well-defined prospective cohort of nontransmitting HIV-infected women. Methods Prospective monitoring of 183 mother,child pairs from 13 centres in Germany and Austria, delivering between 1995 and 2001, was carried out. Following German,Austrian guidelines recommending an elective Caesarean section (CS) at 36 weeks, prematurity was defined as <36 weeks' gestation for these analyses. Results Of 183 mother,child pairs, 42% were exposed to antenatal monotherapy and 17% to dual therapy. Of the 75 women exposed to highly active antiretroviral therapy (HAART), 21 (28%) received protease inhibitor (PI)-based HAART and the remaining 54 received nonnucleoside reverse transcriptase inhibitor-based HAART. In multivariable analysis (176 pregnancies), PI-based HAART exposure during pregnancy was associated with an increased risk of premature delivery [adjusted odds ratio 3.40; 95% confidence interval (CI) 1.13,10.2; P=0.029, compared with monotherapy]. Congenital abnormalities affected 3.3% infants. Perinatally, 18.9% of children (34 of 179) had respiratory problems requiring interventions, which were associated with prematurity but not with type of treatment exposure. From adjusted regression analysis, the mean birth weight z -score for children exposed to HAART with PI (+0.46; 95% CI 0.01,0.92; P=0.047) or dual therapy (+0.43; 95% CI 0.03,0.82; P=0.034) was slightly but significantly higher than that for those exposed to monotherapy; head circumference was appropriate for gestational age and there were no significant differences between treatment groups. Conclusions Use of antenatal PI-based HAART initiated before or during pregnancy was associated with a significantly increased risk of premature delivery at <36 weeks' gestation. The overall crude prematurity rate was 34% (63 of 183; 95% CI 28,42). [source] Prospective monitoring of lipid profiles in children receiving pravastatin preemptively after renal transplantationPEDIATRIC TRANSPLANTATION, Issue 6 2005Lavjay Butani Abstract:, Hyperlipidemia is common after renal transplantation (Tx) and contributes to the increased cardiovascular morbidity seen in the post-transplant period. Limited data are available on the utility of the statins in children after renal Tx. This 12-month prospective study was undertaken to determine the efficacy of pravastatin in reducing dyslipidemia after renal Tx in children and to determine predictors of dyslipidemia after Tx. From August 2001 to April 2004, all 17 newly transplanted pediatric renal transplant recipients at our center were preemptively treated with pravastatin from the immediate post-transplant period. Fasting lipid profiles were obtained at 1, 3, 6 and 12 months after Tx. Trends in the lipid profile were analyzed using the repeated measures general linear model (GLM). A historical cohort of pediatric renal-transplant recipients not treated with pravastatin was used as the control population. The mixed effects GLM was used for multivariable logistic regression analyses to determine the independent effect of age, pretransplant cholesterol (Chol), body mass index (BMI), creatinine clearance (CrCl), and corticosteroid and tacrolimus doses on the development of dyslipidemia. The mean age of the children at Tx was 8.7 yr. The GLM analysis showed that with time, there was a significant decline in the total Chol, serum triglyceride (TG), LDL and also HDL-Chol (p-value <0.05 for each). Compared with the controls, the mean serum Chol was lower at all time points post-transplant in the treated patients. However, despite treatment, the prevalence of hypercholesterolemia increased from 31% pretransplant to 53% at 1-month, but declined thereafter to 6% at 3 and 6 months and 0% at 1 yr. Multivariable regression analyses showed the prednisone dose, pretransplant Chol and age to be the most important risk factors for the development of dyslipidemia. No child developed complications related to therapy. In summary, pravastatin is safe in the post-transplant period in children and reduces serum Chol, LDL-Chol and TG. An unexpected finding in our study was the decline in HDL-Chol after Tx. Whether the preemptive use of the statins will result in lower cardiovascular morbidity, especially considering the concomitant reduction in HDL-Chol remains to be determined. [source] Prospective monitoring of BCR-ABL1 transcript levels in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia undergoing imatinib-combined chemotherapyBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2008Masamitsu Yanada Summary The clinical significance of minimal residual disease (MRD) is uncertain in patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) treated with imatinib-combined chemotherapy. Here we report the results of prospective MRD monitoring in 100 adult patients. Three hundred and sixty-seven follow-up bone marrow samples, collected at predefined time points during a uniform treatment protocol, were analysed for BCR-ABL1 transcripts by quantitative reverse transcription polymerase chain reaction. Ninety-seven patients (97%) achieved complete remission (CR), and the relapse-free survival (RFS) rate was 46% at 3 years. Negative MRD at the end of induction therapy was not associated with longer RFS or a lower relapse rate (P = 0·800 and P = 0·964 respectively). Twenty-nine patients showed MRD elevation during haematological CR. Of these, 10 of the 16 who had undergone allogeneic haematopoietic stem cell transplantation (HSCT) in first CR were alive without relapse at a median of 2·9 years after transplantation, whereas 12 of the 13 who had not undergone allogeneic HSCT experienced a relapse. These results demonstrate that, in Ph+ ALL patients treated with imatinib-combined chemotherapy, rapid molecular response is not associated with a favourable prognosis, and that a single observation of elevated MRD is predictive of subsequent relapse, but allogeneic HSCT can override its adverse effect. [source] The mechanisms of resistance to antimalarial drugs in Plasmodium falciparumFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2003Jacques Le Bras Abstract Drug-resistant malaria is primarily caused by Plasmodium falciparum, a species highly prevalent in tropical Africa, the Amazon region and South-east Asia. It causes severe fever or anaemia that leads to more than a million deaths each year. The emergence of chloroquine resistance has been associated with a dramatic increase in malaria mortality among inhabitants of some endemic regions. The rationale for chemoprophylaxis is weakening as multiple-drug resistance develops against well-tolerated drugs. Plasmodium falciparum drug-resistant malaria originates from chromosome mutations. Analysis by molecular, genetic and biochemical approaches has shown that (i) impaired chloroquine uptake by the parasite vacuole is a common characteristic of resistant strains, and this phenotype is correlated with mutations of the Pfmdr1, Pfcg2 and Pfcrt genes; (ii) one to four point mutations of dihydrofolate reductase (DHFR), the enzyme target of antifolates (pyrimethamine and proguanil) produce a moderate to high level of resistance to these drugs; (iii) the mechanism of resistance to sulfonamides and sulfones involves mutations of dihydropteroate synthase (DHPS), their enzyme target; (iv) treatment with sulphadoxine,pyrimethamine selects for DHFR variants Ile(51), Arg(59), and Asn(108) and for DHPS variants Ser(436), Gly(437), and Glu(540); (v) clones that were resistant to some traditional antimalarial agents acquire resistance to new ones at a high frequency (accelerated resistance to multiple drugs, ARMD). The mechanisms of resistance for amino-alcohols (quinine, mefloquine and halofantrine) are still unclear. Epidemiological studies have established that the frequency of chloroquine resistant mutants varies among isolated parasite populations, while resistance to antifolates is highly prevalent in most malarial endemic countries. Established and strong drug pressure combined with low antiparasitic immunity probably explains the multidrug-resistance encountered in the forests of South-east Asia and South America. In Africa, frequent genetic recombinations in Plasmodium originate from a high level of malaria transmission, and falciparum chloroquine-resistant prevalence seems to stabilize at the same level as chloroquine-sensitive malaria. Nevertheless, resistance levels may differ according to place and time. In vivo and in vitro tests do not provide an adequate accurate map of resistance. Biochemical tools at a low cost are urgently needed for prospective monitoring of resistance. [source] Prospective community-based cluster census and case-control study of stillbirths and neonatal deaths in the West Bank and Gaza StripPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 4 2008Henry D. Kalter Summary Obstetric complications and newborn illnesses amenable to basic medical interventions underlie most perinatal deaths. Yet, despite good access to maternal and newborn care in many transitional countries, perinatal mortality is often not monitored in these settings. The present study identified risk factors for perinatal death and the level and causes of stillbirths and neonatal deaths in the West Bank and Gaza Strip. Baseline and follow-up censuses with prospective monitoring of pregnant women and newborns from September 2001 to August 2002 were conducted in 83 randomly selected clusters of 300 households each. A total of 113 of 116 married women 15,49 years old with a stillbirth or neonatal death and 813 randomly selected women with a surviving neonate were interviewed, and obstetric and newborn care records of women with a stillbirth or neonatal death were abstracted. The perinatal and neonatal mortality rates, respectively, were 21.2 [95% confidence interval (CI) 16.5, 25.9] and 14.7 [95% CI 10.2, 19.2] per 1000 livebirths. The most common cause (27%) of 96 perinatal deaths was asphyxia alone (21) or with neonatal sepsis (5), while 18/49 (37%) early and 9/19 (47%) late neonatal deaths were from respiratory distress syndrome (12) or sepsis (9) alone or together (6). Constraint in care seeking, mainly by an Israeli checkpoint, occurred in 8% and 10%, respectively, of 112 pregnancies and labours and 31% of 16 neonates prior to perinatal or late neonatal death. Poor quality care for a complication associated with the death was identified among 40% and 20%, respectively, of 112 pregnancies and labour/deliveries and 43% of 68 neonates. (Correction added after online publication 5 June 2008: The denominators 112 pregnancies, labours, and labour/deliveries, and 16 and 68 neonates were included; and 9% of labours was corrected to 10%.) Risk factors for perinatal death as assessed by multivariable logistic regression included preterm delivery (odds ratio [OR] = 11.9, [95% CI 6.7, 21.2]), antepartum haemorrhage (OR = 5.6, [95% CI 1.5, 20.9]), any severe pregnancy complication (OR = 3.4, [95% CI 1.8, 6.6]), term delivery in a government hospital and having a labour and delivery complication (OR = 3.8, [95% CI 1.2, 12.0]), more than one delivery complication (OR = 4.4, [95% CI 1.8, 10.5]), mother's age >35 years (OR = 2.9, [95% CI 1.3, 6.8]) and primiparity in a full-term pregnancy (OR = 2.6, [1.1, 6.3]). Stillbirths are not officially reportable in the West Bank and Gaza Strip and this is the first time that perinatal mortality has been examined. Interventions to lower stillbirths and neonatal deaths should focus on improving the quality of medical care for important obstetric complications and newborn illnesses. Other transitional countries can draw lessons for their health care systems from these findings. [source] Prospective screening by a panfungal polymerase chain reaction assay in patients at risk for fungal infections: implications for the management of febrile neutropeniaBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2000Holger Hebart Invasive fungal infections are a major cause of mortality in neutropenic cancer patients. To determine whether a polymerase chain reaction (PCR)-based assay enabled the identification of patients at risk for invasive fungal infections, a prospective monitoring once per week was performed during 92 neutropenic episodes in patients receiving chemotherapy for acute leukaemia or high-dose therapy followed by allogeneic or autologous stem cell transplantation, with the investigators blinded to clinical and microbiological data. PCR positivity was documented in 34 out of 92 risk episodes. All patients developing proven invasive fungal infection were found PCR positive, and PCR was found to be the earliest indicator of invasive fungal infection preceding clinical evidence by a mean of 5·75 d (range 0,14 d). In febrile neutropenic patients without a prior history of invasive fungal infection, a sensitivity of 100% and a specificity of 73% of the PCR assay for the development of proven or probable invasive fungal infection was documented. In conclusion, panfungal PCR performed prospectively once a week enabled the identification of patients at high risk for invasive fungal infections. [source] | ||||||||||