Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients

<p>Abstract</p> <p>Background</p> <p>Radiation-induced diarrhea is frequently observed during pelvic radiotherapy. This study was performed to determine the ability of a probiotic containing live lactobacillus acidophilus plus bifidobacterium bifidum to reduce the incidence of radiation-induced diarrhea in locally advanced cervical cancer patients.</p> <p>Methods</p> <p>Patients who were undergoing pelvic radiotherapy concurrent with weekly cisplatin were randomly assigned to a study drug or placebo, in a double-blind study. Diarrhea was graded weekly according the Common Toxicity Criteria (CTC) system. Stool consistency and white and red blood cell count in stool were also assessed. The primary endpoint was to reduce the incidence of diarrhea, defined by a CTC grade 2 or more, and the need for anti-diarrheal medication.</p> <p>Results</p> <p>A total of 63 patients were enrolled. Grade 2 -3 diarrhea was observed in 45% of the placebo group (n = 31) and 9% of the study drug group (n = 32) (p = 0.002). Anti-diarrheal medication use was significantly reduced in the placebo group (p = 0.03). The patients in the study drug group had a significantly improved stool consistency (p < 0.001).</p> <p>Conclusions</p> <p>Live lactobacillus acidophilus plus bifidobacterium bifidum reduced the incidence of radiation-induced diarrhea and the need for anti-diarrheal medication and had a significant benefits on stool consistency.</p

AIDS-defining events and deaths in HIV-infected children and adolescents on antiretrovirals: a 14-year study in Thailand

BACKGROUND: Data are scarce on the long-term clinical outcomes of perinatally HIV-infected children and adolescents receiving antiretroviral therapy (ART) in low/middle-income countries. We assessed the incidence of mortality before (early) and after (late) 6-month of ART and of the composite outcome of new/recurrent AIDS-defining-event or death >6 months after ART start (late AIDS/death) and their associated factors. METHODS: Study population was perinatally HIV-infected children (≤18 years) initiating ART within the Program for HIV Prevention and Treatment observational cohort (NCT00433030). Factors associated with late AIDS/death were assessed using competing risk regression models accounting for loss-to-follow-up, and included baseline and time-updated variables. RESULTS: Among 619 children, "early" mortality incidence was 99 deaths per 1000-PYFU (95%CI; 69-142) and "late" mortality 6 per 1000-PYFU (95%CI; 4-9). Of the 553 children alive >6 months after ART initiation, median age at ART initiation was 6.4 years, CD4% 8.2% and HIV-RNA 5.1 log10 copies/mL. 38 (7%) children developed late AIDS/death after median time of 3.3 years: 24 died and 24 experienced new/recurrent AIDS-defining-events (10 subsequently died). Factors independently associated with late AIDS/death were: current age ≥13 years (adjusted sub-distribution hazard-ratio 4.9; 95%CI; 2.4-10.1), HIV-RNA always ≥400 copies/mL (12.3; 4.0-37.6), BMI-z-score always <-2 SD (13.7; 3.4-55.7), and hemoglobin <8g/dL at least once (4.6; 2.0-10.5). CONCLUSIONS: After the initial 6 months of ART, being an adolescent, persistent viremia, poor nutritional status and severe anemia were associated with poor clinical outcomes. This supports the need for novel interventions that target children, particularly adolescents with poor growth and uncontrolled viremia

Associated factors for depressive disorder in patients with end-stage renal disease treated with continuous ambulatory peritoneal dialysis

Patrinee Traisathit,1 Kasiramart Moolkham,2 Narong Maneeton,2 Natthapat Thongsak,1 Benchalak Maneeton2 1Department of Statistics, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand; 2Department of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Background: The aim of this study was to primarily determine factors associated with the depressive disorders in continuous ambulatory peritoneal dialysis (CAPD).Methods: CAPD patients were recruited from the chronic kidney disease and CAPD Clinic of University Hospital. The stable CAPD patients for at least 3 months were included in the study. Sociodemographic data, renal conditions, and depressive disorder were evaluated. In addition to determining prevalence rate of depressive disorders, identification of factors associated with depressive disorders in CAPD patients were analyzed by using the multivariable logistic regression analysis with backward elimination procedure.Results: The eligible participants were 108 patients. The study found that 11% of CAPD patients were diagnosed with depressive disorders including, minor depressive, dysthymic, and major depressive disorders. Additionally, the depressive disorders were associated with the duration between the diagnosis date of the end-stage renal disease (ESRD) and the initial treatment date (P=0.043). Accordingly, the ESRD patients diagnosed in Conclusion: The rate of prevalence for depressive disorder is high in the CAPD patients. Additionally, the results of this study have shown the relationship between depressive disorder and time for diagnosis of ESRD. Specifically, the risk of depressive disorder increases when patients have a shorter duration between the dates of ESRD diagnosis and initial treatment. In addition to closed monitoring for those patients, the psychiatrists should be consulted for evaluation and treatment of depressive disorders for the suspected high risk patients. Keywords: peritoneal dialysis, depressive disorder, end-stage renal disease, cross-sectional study, prevalence of depression, chronic kidney disease, psychosocial factor, the patient health questionnair

Delirium after a traumatic brain injury: predictors and symptom patterns

Jutaporn Maneewong,1 Benchalak Maneeton,1 Narong Maneeton,1 Tanat Vaniyapong,2 Patrinee Traisathit,3 Natthanidnan Sricharoen,3 Manit Srisurapanont1 1Department of Psychiatry, 2Department of Surgery, Faculty of Medicine, 3Department of Statistics, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand Background: Delirium in traumatic brain injury (TBI) is common, may be predictable, and has a multifaceted symptom complex. This study aimed to examine: 1) the sum score of Glasgow Coma Scale (GCS) and if its component scores could predict delirium in TBI patients, and 2) the prominent symptoms and their courses over the first days after TBI. Methods: TBI patients were recruited from neurosurgical ward inpatients. All participants were hospitalized within 24&nbsp;hours after their TBI. Apart from the sum score of GCS, which was obtained at the emergency department (ED), the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria for delirium were applied daily. The severity of delirium symptoms was assessed daily using the Delirium Rating Scale &ndash; Revised-98 (DRS-R-98). Results: The participants were 54 TBI patients with a mean GCS score of 12.7 (standard deviation [SD]&nbsp;=2.9). A total of 25 patients (46.3%) met the diagnosis of delirium and had a mean age of 36.7&nbsp;years (SD&nbsp;=14.8). Compared with 29 non-delirious patients, 25 delirious patients had a significantly lower mean GCS score (P=0.04), especially a significantly lower verbal component score (P=0.03). Among 18 delirious patients, four symptoms of the DRS-R-98 cognitive domain (orientation, attention, long-term memory, and visuospatial ability) were moderate symptoms (score&nbsp;&ge;2) at the first day of admission. After follow-up, three cognitive (orientation, attention, and visuospatial ability) and two noncognitive symptoms (lability of affect and motor agitation) rapidly resolved. Conclusion: Almost half of patients with mild to moderate head injuries may develop delirium in the first 4&nbsp;days after TBI. Those having a low GCS score, especially the verbal component score, at the ED were likely to have delirium in this period. Most cognitive domains of delirium described in the DRS-R-98 were prominent within the first 4&nbsp;days of TBI with delirium. Three cognitive and two noncognitive symptoms of delirium decreased significantly. Keywords: Delirium Rating Scale Revised-98, DRS-R-98, brain injuries, traumatic, noncognitive symptoms, cognitive symptoms, Glasgow Coma Scale scor

Gestational age determination and prevention of HIV perinatal transmission

Objective: To compare different methods of gestational age (GA) measurement for ensuring effective zidovudine (ZDV) prophylaxis to prevent mother-to-child transmission of HIV. Methods: For 1398 HIV-infected women enrolled in a perinatal prevention trial, gestation durations were calculated based on GA estimated using ultrasound (US), date of last menstruation period (LMP), first fundal height (FH1), and a specific algorithm was developed to provide a "reference" GA. The performance of each GA estimate was evaluated by the percentage of women who would have received >= 8 weeks ZDV, if prophylaxis was initiated at 28 weeks. Results: The performances of the algorithm, US, LMP, and FH1 were 95.5%, 94.8%, 88.4%, and 83.7%, respectively. US and FH1 were significantly better when estimated before and after 24 weeks, respectively. Conclusion: In situations where no US is available and LMP is not or imprecisely known, FH1 can be used after 24 weeks to schedule ZDV initiation date. (c) 2005 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved

Hematological safety of perinatal exposure to Zidovudine in uninfected infants born to HIV Type 1-infected women in Thailand. Short communication

The evolution of hematological parameters in HIV-1-exposed uninfected infants according to various durations of perinatal zidovudine exposure was studied. We used data prospectively collected among 1122 HIV-uninfected formula-fed infants born to HIV-infected mothers who participated in a clinical trial to prevent perinatal transmission in Thailand (PHPT-1). Infants were exposed to different durations of zidovudine both in utero and after birth. Hemoglobin level and leukocyte, absolute neutrophil, and lymphocyte counts were measured at birth and at 6 weeks of age. The association between hematological parameters at birth and the duration of zidovudine exposure in utero was studied using a linear regression model, and changes between birth and 6 weeks of age and the duration of postnatal zidovudine exposure using mixed effects models. At birth, the hemoglobin level was lower in newborns exposed to zidovudine for more than 7.5 weeks in utero (adjusted regression coefficient: -0.6 g/dl; 95% confidence interval: -1.1 to -0.1). Six weeks after birth, the hemoglobin level had decreased faster in infants administered zidovudine for more than 4 weeks (adjusted regression coefficient: -0.1 g/dl; 95% confidence interval: -0.2 to -0.1). The duration of perinatal zidovudine exposure was not associated with the evolution of leukocyte, neutrophil, and lymphocyte counts. Despite the differences in hemoglobin levels, grade 3 or 4 anemia did not significantly differ by maternal or infant zidovudine duration. The clinical impact appeared modest, but longer exposure may warrant close monitoring

Long-term outcome of nevirapine or efavirenz based antiretroviral regimens in mothers exposed to single dose nevirapine

Exposure to single dose nevirapine during labor (SD-NVP) to prevent mother to child transmission of HIV (PMTCT) is associated with a lower likelihood of virologic suppression at six months of a nevirapine based antiretroviral therapy but long-term consequences of SD-NVP have not been studied. We analyzed data from women who received SD-NVP in the PHPT-2 PMTCT clinical trial. Following delivery, women initiated a regimen composed of nevirapine, lamivudine, and stavudine or zidovudine when their CD4 level declined to less than 250 cells/mm(3). HIV RNA load and CD4 cell counts were evaluated every six months. Failure was defined as a confirmed HIV RNA load > 400 copies/mL at least 6 months after therapy initiation, or death, and observations were censored at time of drop out or switch to a protease inhibitor based regimen. Survival analysis was performed using Kaplan-Meier estimates and Cox regression models. The 221 SD-NVP exposed women and 48 unexposed women had similar characteristics at baseline, except the time spent between delivery and initiation of therapy (6.1 and 14.9 months, respectively). At four years, 35% of the SD-NVP exposed and 14% of the unexposed women met the failure criteria (P=0.02). In the multivariable analysis, factors contributing to the failure consisted of exposure to SD-NVP (HR: 2.63, P=0.03), plasma HIV-1 RNA level above median (HR: 2.53, P<0.001), stage C of the CDC HIV clinical staging (HR: 2.12, P=0.04), platelets cell count above median (HR: 1.65, P=0.04) and early initiation of therapy after delivery (HR: 1.64, P=0.04). In this cohort, the impact of SD-NVP on further antiretroviral therapy was still significant after four years of therapy, justifying the use of strategies to prevent resistance mutations after exposure to SD-NVP

Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand

Objectives:Perinatal single-dose nevirapine (sdNVP) selects for resistance mutations. The objective of this trial was to compare two maternal sdNVP-sparing regimens with standard zidovudine (ZDV)/sdNVP prophylaxis.Design:PHPT-5 was a randomized, partially double-blind placebo-controlled, noninferiority trial in Thailand (NCT00409591). Study participants were women with CD4(+) of at least 250cells/l and their infants.Methods:All women received ZDV from 28 weeks' gestation and their newborn infants for one week. Women were also randomized to receive NVP-NVP (reference): maternal intrapartum sdNVP with a 7-day tail' of ZDV along with lamivudine, and infant NVP (one dose immediately, another 48h later); infant-only NVP: maternal placebos for sdNVP and the tail', with infant NVP; LPV/r: maternal LPV/r starting at 28 weeks. Infants were formula-fed. HIV-diagnosis was determined by DNA-PCR.Results:Four-hundred and thirty-five women were randomized between January 2009 and September 2010. Accrual was terminated prematurely following a change in Thai guidelines recommending antiretroviral combination therapy for all pregnant women. Data on 405 mothers and 407 live-born children were analyzed. Baseline characteristics were similar between arms. Intent-to-treat transmission rates were 3.8% (95% confidence interval: 1.2-8.6) in NVP-NVP, 1.6% (0.2-5.6) in infant-only NVP, and 1.4% (0.4-5.1) in LPV/r arms. As-treated rates were 2.2% (0.5-6.4), 3.2% (0.9-7.9), and 1.5% (0.2-5.2), respectively. Factors independently associated with transmission were prophylaxis duration less than 8 weeks (adjusted odds ratio 15.5; 3.6-66.1) and viral load at baseline at least 4log(10)copies/ml (adjusted odds ratio 10.9; 1.3-91.5). Regimens appeared well tolerated.Conclusion:Transmission rates in all arms were low but noninferiority was not proven. Antiretroviral prophylaxis for at least 8 weeks before delivery is necessary to minimize transmission risk

Modeling of in-utero and intra-partum transmissions to evaluate the efficacy of interventions for the prevention of perinatal HIV

Background Antiretroviral treatments decrease HIV mother-to-child transmission through pre/post exposure prophylaxis and reduction of maternal viral load. We modeled in-utero and intra-partum HIV transmissions to investigate the preventive role of various antiretroviral treatments interventions. Methods We analysed data from 3,759 women-infant pairs enrolled in 3 randomized clinical trials evaluating (1) zidovudine monotherapy, (2) zidovudine plus perinatal single-dose nevirapine or (3) zidovudine plus lopinavir/ritonavir for the prevention of mother-to-child transmission of HIV in Thailand. All infants were formula-fed. Non-linear mixed effect modeling was used to express the viral load evolution under antiretroviral treatments and the probability of transmission. Results Median viral load was 4 log(10) copies/mL (Interquartile range: 3.36-4.56) before antiretroviral treatments initiation. An Emaxmodel described the viral load time-course during pregnancy. Half of the maximum effect of zidovudine (28% decrease) and lopinavir/ritonavir (72% decrease) were achieved after 98 and 12 days, respectively. Adjusted on viral load at baseline (Odds ratio = 1.50 [95% confidence interval: 1.34, 1.68] per log(10) copies/mL increment), anti-retroviral treatments duration (OR = 0.80 [0.75, 0.84] per week increment) but not the nature of antiretroviral treatments were associated with in-utero transmission. Adjusted on gestational age at delivery (<37 weeks, OR = 2.37 [1.37, 4.10]), baseline CD4 (Odds ratio = 0.79 [0.72, 0.88] per 100 cells/mm(3) increment) and predicted viral load at delivery (OR = 1.47 [1.25, 1.64] per log(10) copies/mL increment), single-dose nevirapine considerably reduced intra-partum transmission (OR = 0.32 [0.2, 0.51]). Conclusion These models determined the respective contributions of various antiretroviral strategies on prevention of mother-to-child transmission. This can help predict the efficacy of new antiretroviral treatments and/or prevention of mother-to-child transmission strategies particularly for women with no or late antenatal care who are at high risk of transmitting HIV to their offspring