Miracle-dz/UniFAR-FTUs huggingface dataset:
Human cytomegalovirus-specific T cell reconstitution in young patients receiving T cell-depleted, allogeneic hematopoietic stem cell transplantation.

BACKGROUND Reconstitution of human cytomegalovirus (HCMV) T cell-specific immunity is of crucial relevance in patients receiving a hematopoietic stem cell transplant (HSCT). Scarce data on this subject are available for children receiving a T cell-depleted HSCT. METHODS We investigated HCMV-specific T cell recovery in 48 recipients of a T cell-depleted HSCT from a human leukocyte antigen (HLA)-disparate relative. Autologous HCMV-infected dendritic cells were used to stimulate HCMV-specific CD8+ and CD4+ T cells producing interferon-gamma (IFN). RESULTS The 1-year cumulative incidence of both HCMV infection and specific T cell reconstitution was 83% among the 23 HCMV-seropositive patients and 4% and 8%, respectively, among the 25 HCMV-seronegative patients (P < .01). HCMV-specific T cell reconstitution was significantly delayed in patients receiving T cell-depleted grafts, compared with patients receiving unmanipulated HSCTs (median time to reconstitution, 75 vs. 47 days, respectively; P < .01). The median time from HCMV infection to immune recovery in recipients of T cell-depleted grafts was 47 days. Detection of HCMV-specific T cells correlated with control of HCMV infection. The number of residual T cells in the graft predicted earlier T cell recovery (P = .02). CONCLUSIONS Latent HCMV in the recipient was the major cause of HCMV reactivation and also promoted specific T cell reconstitution in patients given a T cell-depleted HSCT from an HLA-disparate relative. Routine immunologic monitoring is valuable in identifying patients with early HCMV-specific T cell reconstitution.
Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation.

BACKGROUND Invasive pneumococcal disease is a life-threatening complication after allogeneic stem cell transplantation, and at least 20% of cases occur within 1 year after transplantation. The 23-valent pneumococcal polysaccharide vaccine (PPV23) has limited efficacy, especially during the first year after transplantation. The immune response to the conjugated vaccines is expected to be better than that to the polysaccharide vaccine, but the optimal timing of vaccination is not defined. Our objective was to show that a 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) was not inferior when first given 3 months after transplantation, compared with when first given 9 months after transplantation. METHODS We performed a multicenter, randomized, noninferiority study involving 158 patients from 13 European Group for Blood and Marrow Transplantation centers who were randomly allocated at approximately 100 days after myeloablative stem cell transplantation to receive a series of vaccinations (3 doses of PCV7 given 1 month apart) that was started immediately (i.e., 3 months after transplantation) or 6 months later (i.e., 9 months after transplantation). The primary evaluation criterion was the rate of response (antibody level, > or = 0.15 microg/mL for each of the 7 serotypes) at 1 month after the third dose of PCV7. The noninferiority margin was 20%. All patients were followed up for 24 months after transplantation or until death, whichever occurred first. RESULTS We found that the response rate was not lower after early vaccination (79% [45 of 57 patients]) than after late vaccination (82% [47 of 57 patients]) (difference, -3.5%; 90% confidence interval, -15.6 to 8.6; not significant). CONCLUSIONS We conclude that PCV7 vaccination at 3 months after stem cell transplantation is not inferior to PCV7 vaccination at 9 months after transplantation. Because invasive pneumococcal disease can occur early, we recommend starting the PCV7 vaccination series at 3 months after transplantation to ensure earlier protection against Streptococcus pneumoniae. However, the early vaccination may result in only short-lasting response and may not prime for a 23-valent pneumococcal polysaccharide vaccine boost as efficiently as the late vaccination.
Factors in Mental Health Problems among Japanese Dialysis Patients Living in Heavily Damaged Prefectures Two Years after the Great East Japan Earthquake

This study examined the prevalence of mental health problems and related factors among dialysis patients living in prefectures that were heavily damaged by the Great East Japan Earthquake. Research was conducted two years following the disaster, and data of 1500 residents of the prefectures were analyzed. This study examined disaster related stressors, gender, socioeconomic status, health problems prior the earthquake, and social support, all of which have been identified as aggravating/mitigating factors in previous research on disaster survivors. We also examined advanced awareness of emergency planning as a dialysis specific factor. Mental health problems after the disaster were categorized into three types: PTSD and depression comorbidity, PTSD only, and depression only. Results indicated that people with comorbidity, PTSD, and depression comprised 7.5%, 25.0%, and 2.9% of the sample, respectively. Not only disaster related stressors but also health problems prior to the disaster had an aggravating direct effect on comorbidity and PTSD. In addition, social support and advanced awareness of disaster planning had a mitigating effect on comorbidity. These results suggest that advanced awareness of disaster planning is a dialysis specific factor that could decrease the occurrence of comorbidity among dialysis patients following a disaster.
Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study.

BACKGROUND Tenofovir is one of the most widely used antiretroviral drugs. Tenofovir undergoes renal clearance by a combination of glomerular filtration and active tubular secretion. Although rare, the mechanism by which tenofovir causes renal damage is not well characterized. We have explored the association between kidney tubular dysfunction (KTD) and polymorphisms in genes encoding drug transporters. METHODS All consecutive, human immunodeficiency virus (HIV)-infected patients receiving tenofovir-containing antiretroviral regimens who were seen at a single institution during the first trimester of 2008 were enrolled in the study. KTD was defined by the presence of at least 2 of the following abnormalities: nondiabetic glucosuria, urine phosphate wasting, hyperaminoaciduria, beta2-microglobulinuria, and increased fractional excretion of uric acid. Twelve single-nucleotide polymorphisms in the ABCC2, ABCC4, SCL22A6, SLC22A11, and ABCB1 genes were analyzed using TaqMan 5'-nuclease assays. RESULTS A total of 115 HIV-infected patients were examined, of whom 19 (16.5%) had KTD. The percentage of patients with KTD was higher among those with genotype CC at position -24 of ABCC2 than among those with genotypes CT and TT (24% [16 of 68 patients] vs. 6% [3 of 47 patients]; P = .020). In a multivariate analysis, older age (odds ratio [OR], 1.1; 95% confidence interval [CI], 1.0-1.2; P = .024), lower body weight (OR, 0.9; 95% CI, 0.8-0.9; P = .048), and genotype CC at ABCC2 position -24 (OR, 5; 95% CI, 1.2-21; P = .027) were independently associated with KTD. CONCLUSIONS Approximately 17% of HIV-infected patients treated with tenofovir had KTD. Homozygosity for the C allele at position -24 of the ABCC2 gene was strongly associated with KTD in this population. This polymorphism may help to identify patients at greater risk for developing tenofovir-associated tubulopathy, and close monitoring of renal function is warranted for these patients.
Effectiveness of Antiretroviral Therapy in Individuals Who for Economic Reasons Were Switched From a Once-Daily Single-Tablet Regimen to a Triple-Tablet Regimen

Background:To assess the impact on virological outcomes of a switch from branded single-tablet regimen (STR) including tenofovir, efavirenz, and emtricitabine (STR-TEE) to generic triple-tablet regimen (TTR), including tenofovir, efavirenz, and lamivudine (TTR-TEL), which was implemented on April 1, 2011 to obtain economic savings. Methods and Findings:From the Capital Region of Denmark (covering two-thirds of the Danish HIV patients), we included combination antiretroviral therapy (cART)–naive patients who administered STR-TEE from April 1, 2010 to March 31, 2011 (n = 111) or TTR-TEL from April 1, 2011 to March 31, 2012 (n = 56) and cART-experienced HIV patients who were on STR-TEE from April 1, 2010 (n = 356) or were switched from STR-TEE to TTR-TEL after April 1, 2011 (n = 512). We estimated the fraction with detectable HIV-RNA, development of the 184V/I resistance mutations, and time to switch of cART. Approximately 96.2% of cART-experienced patients on STR-TEE were shifted to TTR-TEL after April 1, 2011. For the naive STR-TEE and TTR-TEL patients, the fractions with detectable HIV-RNA at week 48 were 7.0% and 8.3% and for the cART experienced 4.0% and 4.4%, respectively. The 184V/I resistance mutation was detected in 1 cART-experienced patient on TTR-TEL with virological failure. The risk of switch to a new cART regimen was slightly increased in the cART-experienced population (difference in 1-year risk: 1.5%; 95% confidence interval: −2.4% to 5.4%). Conclusions:In settings comparable with the Danish health care system, the estimated economic savings from a switch from STR-TEE to TTR-TEL can be realized with negligible short-term risk of adverse outcomes.
Safety of Cotrimoxazole in Pregnancy: A Systematic Review and Meta-Analysis

Introduction:Cotrimoxazole is widely prescribed to treat a range of infections, and for HIV-infected individuals it is administered as prophylaxis to protect against opportunistic infections. Some reports suggest that fetuses exposed to cotrimoxazole during early pregnancy may have an increased risk of congenital anomalies. We carried out this systematic review to update the evidence of cotrimoxazole safety in pregnancy. Methods:Three databases and 1 conference abstract site were searched in duplicate up to October 31, 2013, for studies reporting adverse maternal and infant outcomes among women receiving cotrimoxazole during pregnancy. This search was updated in MEDLINE via PubMed to April 28, 2014. Studies were included irrespective of HIV infection status or the presence of other coinfections. Our primary outcome was birth defects of any kind. Secondary outcomes included spontaneous abortions, terminations of pregnancy, stillbirths, preterm deliveries, and drug-associated toxicity. Results:Twenty-four studies were included for review. There were 232 infants with congenital anomalies among 4196 women receiving cotrimoxazole during pregnancy, giving an overall pooled prevalence of 3.5% (95% confidence interval: 1.8% to 5.1%; &tgr;2 = 0.03). Three studies reported 31 infants with neural tube defects associated with first trimester exposure to cotrimoxazole, giving a crude prevalence of 0.7% (95% confidence interval: 0.5% to 1.0%) with most data (29 neural tube defects) coming from a single study. The majority of adverse drug reactions were mild. The quality of the evidence was very low. Conclusions:The findings of this review support continued recommendations for cotrimoxazole as a priority intervention for HIV-infected pregnant women. It is critical to improve data collection on maternal and infant outcomes.
Challenges in the Detection, Prevention, and Treatment of HIV-Associated Malignancies in Low- and Middle-Income Countries in Africa

Abstract:Cancers associated with immunosuppression and infections have long been recognized as a major complication of HIV/AIDS. More recently, persons living with HIV are increasingly diagnosed with a wider spectrum of HIV-associated malignancies (HIVAM) as they live longer on combination antiretroviral therapy. This has spurred research to characterize the epidemiology and determine the optimal management of HIVAM with a focus on low-and middle-income countries (LMICs). Given background coinfections, environmental exposures, host genetic profiles, antiretroviral therapy usage, and varying capacities for early diagnosis and treatment, one can expect the biology of cancers in HIV-infected persons in LMICs to have a significant impact on chronic HIV care, as is now the case in high-income countries. Thus, new strategies must be developed to effectively prevent, diagnose, and treat HIVAM in LMICs; provide physical/clinical infrastructures; train the cancer and HIV workforce; and expand research capacity—particularly given the challenges posed by the limitations on available transportation and financial resources and the population's general rural concentration. Opportunities exist to extend resources supported by the President's Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, Tuberculosis, and Malaria to improve the health-care infrastructure and train the personnel required to prevent and manage cancers in persons living with HIV. These HIV chronic care infrastructures could also serve cancer patients regardless of their HIV status, facilitating long-term care and treatment for persons who do not live near cancer centers, so that they receive the same degree of care as those receiving chronic HIV care today.
Quadrant root planing versus same-day full-mouth root planing. I. Clinical findings.

OBJECTIVES: The aim of this study was to test the hypothesis that same-day full-mouth scaling and root planing (FM-SRP) resulted in greater clinical improvement compared to quadrant scaling and root planing (Q-SRP) in chronic periodontitis patients over a period of 6 months. MATERIAL AND METHODS: Forty patients were recruited into this study. Subjects were randomised into two groups. The FM-SRP group received full-mouth scaling and root planing completed within the same day, while the Q-SRP group received quadrant root planing at 2-weekly intervals over four consecutive sessions. Whole-mouth clinical measurements were recorded with a manual periodontal probe at baseline (BAS) and at reassessment 1 (R1) (approximately 6 weeks after the completion of therapy), and at reassessment 2 (R2) (6 months after the initiation of therapy). Selected site analyses were performed on the deepest site in each quadrant before and after therapy (R1 and R2) and clinical indices were recorded with an electronic pressure sensitive probe. In addition, during the active phase of treatment clinical data were collected at 2-weekly intervals from the remaining untreated quadrants in the Q-SRP group only. RESULTS: Both therapies resulted in significant improvements in all clinical indices both at R1 and R2. A continuous clinical improvement was seen for both treatment groups during the experimental period, which reached peak levels at 6 months (DeltaPD=1.8 mm, DeltaCAL=1.1 mm, p<0.001; PD: pocket depth; CAL: clinical attachment level). The selected-site analysis revealed no significant differences in any clinical index between the two treatment groups at R2 (DeltaPD=2.8 mm, DeltaRAL=1.1 mm; RAL: relative attachment level). At the selected sites, the analysis of the deep pockets (<7 mm) showed a significantly greater gain in RAL for the FM-SRP group compared to the Q-SRP group at R2 (p<0.05). The results of this analysis however, should be interpreted with care due to the small number of deep pockets. Data from the Q-SRP group provided an insight into how treated and untreated quadrants responded during the initiation of plaque control measures. There were significant reductions in PD, suppuration (SUP), modified gingival index (MGI) and plaque index (PI) in the remaining untreated quadrants in the Q-SRP group during the initial phase of treatment (p<0.05), while minimum changes in RALs and bleeding on probing (BOP) occurred. Nevertheless, the improvement in PD was clearly inferior to that seen after scaling and root planing. CONCLUSION: Following both therapeutic modalities, there were marked clinical improvements at both R1 and R2 (6 months) from baseline. The current study, in contrast to previous findings, failed to show that FM-SRP is a more efficacious periodontal treatment modality compared to Q-SRP. However, both modalities are efficacious and the clinician should select the treatment modality based on practical considerations related to patient preference and clinical workload.
Contribution of Women to Henna Cultivation in Rajasthan

In agriculture, women are active partners in all operations sharing work between 20-80% in certain cases and almost 100% especially in arduous repetitive work (Singh et al. 2013). Gender issues assume great importance in Indian agricultural scenario keeping in view that large diversity exists in the status of women which is influenced mostly by social and religious taboos, economic status and farm production systems. Henna can be grown on a wide variety of soil and climatic conditions. Henna is cultivated in about 44000 ha area in the form of field, hedges on bunds and as ornamentals in the gardens in India. Out of this Pali district of Rajasthan occupies around 39800 ha area (Anon., 2012). In 2003-04 trade of henna leaves was 19430 tons which doubled in 2011-12 (38431 tones) with a significant annual compound growth rate of 9.8% (Chand, 2012). Women play a major role in henna farming but we do not know enough about what this means for technology development, adoption and further impact on productivity. Hence, issues relating to both research coverage and impact in terms of gender need careful study. Therefore, the present study was undertaken with specific objective to assess the extent of participation of men and women in different henna farming operations.
Patterns and Correlates of PrEP Drug Detection Among MSM and Transgender Women in the Global iPrEx Study

Background:Adherence to pre-exposure prophylaxis (PrEP) is critical for efficacy. Antiretroviral concentrations are an objective measure of PrEP use and correlate with efficacy. Understanding patterns and correlates of drug detection can identify populations at risk for nonadherence and inform design of PrEP adherence interventions. Methods:Blood antiretroviral concentrations were assessed among active arm participants in iPrEx, a randomized placebo-controlled trial of emtricitabine/tenofovir in men who have sex with men and transgender women in 6 countries. We evaluated rates and correlates of drug detection among a random sample of 470 participants at week 8 and a longitudinal cohort of 303 participants through 72 weeks of follow-up. Results:Overall, 55% of participants (95% confidence interval: 49 to 60) tested at week 8 had drug detected. Drug detection was associated with older age and varied by study site. In longitudinal analysis, 31% never had drug detected, 30% always had drug detected, and 39% had an inconsistent pattern. Overall detection rates declined over time. Drug detection at some or all visits was associated with older age, indices of sexual risk, including condomless receptive anal sex, and responding “don't know” to a question about belief of PrEP efficacy (0–10 scale). Conclusions:Distinct patterns of study product use were identified, with a significant proportion demonstrating no drug detection at any visit. Research literacy may explain greater drug detection among populations having greater research experience, such as older men who have sex with men in the United States. Greater drug detection among those reporting highest risk sexual practices is expected to increase the impact and cost-effectiveness of PrEP.
The Efficacy, Pharmacokinetics, and Safety of a Nevirapine to Rilpivirine Switch in Virologically Suppressed HIV-1–Infected Patients

Abstract:This prospective, open-label nonrandomized controlled trial evaluated the efficacy, safety, and pharmacokinetics of substituting nevirapine/emtricitabine/tenofovir for rilpivirine/emtricitabine/tenofovir in 50 suppressed HIV-1 switchers. One hundred thirty-nine nonswitchers remained on nevirapine as controls. Week 12 HIV-1 RNA was <50 copies per milliliter in 92.0% of switchers and was <50 copies per milliliter at week 24 in 88.0% of switchers and 90.6% of nonswitchers (difference 2.6%, 95% confidence interval: −7.6% to 12.8%). Week 3 geometric mean nevirapine concentration was undetectable and week 1 geometric mean rilpivirine concentration (0.083 mg/L) was comparable with phase 3 trial (P = 0.747). Substituting nevirapine for rilpivirine resulted in ongoing virological suppression and did not have clinically relevant pharmacokinetic effects by cytochrome P450 interactions.
Maternal HIV Status Associated With Under-Five Mortality in Rural Northern Malawi: A Prospective Cohort Study

Background:Under-five mortality is decreasing but with little change in neonatal mortality rates. We examined the effect of maternal HIV status on under-five mortality and cause of death since widespread availability of antiretroviral therapy in rural Malawi. Methods:Children born in 2006–2011 in the Karonga demographic surveillance area were included. Maternal HIV status was available from HIV serosurveys. Age-specific mortality rate ratios for children born to HIV-positive and HIV-negative mothers were obtained by fitting a Poisson model accounting for child clustering by mother and adjusting for potential confounders. Cause of death was ascertained by verbal autopsy. Findings:There were 352 deaths among 6913 under-five singleton children followed for 20,754 person-years (py), giving a mortality rate of 17.0/1000 py overall, 218/1000 py (16.5/1000 live births) in neonates, 20/1000 py (17.4/1000 live births) in postneonatal infants, and 8/1000 py in 1–4 years old. Comparing those born to HIV-positive and HIV-negative mothers, the rate ratio adjusted for child age, sex, maternal age, parity, and drinking water source was 1.5 (95% confidence interval [CI]: 0.6 to 3.7) in neonates, 11.5 (95% CI: 7.2 to 18.5) in postneonatal infants, and 4.6 (95% CI: 2.7 to 7.9) in 1–4 years old. Birth injury/asphyxia, neonatal sepsis, and prematurity contributed >70% of neonatal deaths, whereas acute infections, malaria, diarrhea, and pneumonia accounted for most deaths in older children. Conclusions:Maternal HIV status had little effect on neonatal mortality but was associated with much higher mortality in the postneonatal period and among older children. Greater attention to HIV care in pregnant women and mothers should help improve child survival, but broader interventions are needed to reduce neonatal mortality.