PNPLA3, Obesity, and Heavy Alcohol Use in Cirrhosis Patients May Exert a Synergistic Increase Hepatocellular Carcinoma Risk.

BACKGROUND & AIMS: In patients with cirrhosis, continued heavy alcohol consumption and obesity may increase risk of hepatocellular carcinoma (HCC). We examined whether germline susceptibility to hepatic steatosis not only independently predisposes to HCC but may also act synergistically with other risk factors. METHODS: We analyzed data from 1911 patients in 2 multicenter prospective cohort studies in the United States. We classified patients according to alcohol consumption (current heavy vs not current heavy), obesity (body mass index ≥30 vs <30 kg/m2), and PNPLA3 I148M variant status (carrier of at least one G risk allele vs noncarrier). We examined the independent and joint effects of these risk factors on risk of developing HCC using Cox regression with competing risks. RESULTS: Mean age was 59.6 years, 64.3% were male, 28.7% were Hispanic, 18.3% were non-Hispanic Black, 50.9% were obese, 6.2% had current heavy alcohol consumption, and 58.4% harbored at least 1 PNPLA3 G-allele. One hundred sixteen patients developed HCC. Compared with PNPLA3 noncarriers without heavy alcohol consumption, HCC risk was 2.65-fold higher (hazard ratio [HR], 2.65; 95% confidence interval [CI], 1.20-5.86) for carriers who had current heavy alcohol consumption. Compared with noncarrier patients without obesity, HCC risk was higher (HR, 2.40; 95% CI, 1.33-4.31) for carrier patients who were obese. PNPLA3 and alcohol consumption effect was stronger among patients with viral etiology of cirrhosis (HR, 3.42; 95% CI, 1.31-8.90). PNPLA3 improved 1-year risk prediction for HCC when added to a clinical risk model. CONCLUSIONS: The PNPLA3 variant may help refine risk stratification for HCC in patients with cirrhosis with heavy alcohol consumption or obesity who may need specific preventive measures.

An Electronic Health Record Model for Predicting Risk of Hepatic Fibrosis in Primary Care Patients.

BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease. AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes. METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic fibrosis (> 8 kPa). Possible predictors included data from the EHR for age, gender, diabetes, hypertension, FIB-4, body mass index (BMI), LDL, HDL, and triglycerides. RESULTS: Of 344 patients (56.4% women), 34 had any hepatic fibrosis, and 15 significant hepatic fibrosis. Three variables (BMI, FIB-4, diabetes) were identified from both approaches. When we used variable cut-offs defined by Youden's index, the final model predicting any hepatic fibrosis had an AUC of 0.75 (95% CI 0.67-0.84), NPV of 91.5% and PPV of 40.0%. The final model with variable categories based on standard clinical thresholds (i.e., BMI ≥ 30 kg/m2; FIB-4 ≥ 1.45) had lower discriminatory ability (AUC 0.65), but higher PPV (50.0%) and similar NPV (91.3%). We observed similar findings for predicting significant hepatic fibrosis. CONCLUSIONS: Our results demonstrate that standard thresholds for clinical risk factors/biomarkers may need to be modified for greater discriminatory ability among populations with high prevalence of obesity and diabetes.

Serum biomarker signature is predictive of the risk of hepatocellular cancer in patients with cirrhosis.

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor ß1, adipsin, fetuin-A, interleukin-1 ß, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors.

Concurrence of inflammatory bowel disease with multiple sclerosis or Hodgkin lymphoma.

BACKGROUND AND AIMS: Epidemiologic evidence suggests that Hodgkin lymphoma (HL) and multiple sclerosis (MS) share a common set of risk factors with Crohn's disease (CD) and ulcerative colitis (UC). It was hypothesized that such shared risk factors would lead to clustering of the 4 diagnoses in the same patients. METHODS: All patients with HL, MS, CD, or UC were identified in the veterans population from 2016-2020 and the Medicare population from 1986 to 1989. In a case-control study, the observed concurrences amongst these 4 diagnoses were compared with their expected frequencies in the overall veterans or Medicare population during the same time period by calculating odds ratios (OR) with their 95% confidence intervals (CI). RESULTS: The study included 6 million veterans and 35 million Medicare patients. In the veterans population, inflammatory bowel disease (IBD) was significantly associated with a concurrent diagnosis of HL (OR: 1.40, 95% CI: 1.15-1.71) and MS (1.34, 1.19-1.50). In the Medicare population, IBD was also significantly associated with HL (1.84, 1.07-3.17) and MS (2.31, 1.59-3.35). Similar trends were observed in CD or UC when analyzed separately in both datasets. In the veterans population, adjustment for the potentially confounding influence of ethnicity, sex, and age left all OR values largely unaffected and statistically significant. CONCLUSION: The concurrence of IBD with HL or MS could reflect on a common pathway in the etiology or pathogenesis of these 4 diseases.

Bioimpedance analysis predicts the etiology of cirrhosis in a prospective cohort study.

BACKGROUND: Obesity is associated with an increased risk of developing cirrhosis. However, body mass index (BMI) and waist-to-hip ratio (WHR) may not be indicative of body composition parameters that predispose to cirrhosis. Bioimpedance analysis (BIA) is a noninvasive cost-efficient method for more detailed estimation of body composition. METHODS: We examined patients with cirrhosis who underwent BIA as part of enrollment into a prospective cohort study. We examined the correlation between BIA variables, BMI, and WHR. We performed sex-adjusted and race-adjusted and race-specific multivariable logistic regression analyses to examine the association between anthropometric variables and risk factors [NAFLD, alcohol-associated liver disease (ALD), and HCV]. RESULTS: We analyzed data from 348 cirrhosis patients; 23.3% were women; 48.3% were non-Hispanic White; 19.3% were Hispanic; and 30.7% were African American. The cirrhosis etiology was 21.8% NAFLD, 56.9% HCV mostly cured, and 11.5% ALD. Several BIA variables correlated well with BMI, and others showed modest correlations, but none correlated well with WHR. Higher body fat mass and basal metabolic rate were positively associated, while higher lean body mass, dry lean mass, total body water, or skeletal muscle mass were negatively associated with NAFLD. Associations between these BIA parameters and ALD-related cirrhosis were in the opposite direction. These associations of BIA variables were seen only in Hispanic and non-Hispanic White patients but not non-Hispanic Blacks. BIA variables were more predictive of cirrhosis etiology than BMI or WHR. CONCLUSIONS: Among patients with cirrhosis, several BIA-derived measurements indicative of body fat and muscle are associated with NAFLD and ALD etiology. BIA variables show stronger associations, as well as race/ethnicity-specific associations, with cirrhosis etiology than those of BMI or WHR.

Environmental circadian disruption re-programs liver circadian gene expression.

Circadian gene expression is fundamental to the establishment and functions of the circadian clock, a cell-autonomous and evolutionary-conserved timing system. Yet, how it is affected by environmental-circadian disruption (ECD) such as shiftwork and jetlag, which impact millions of people worldwide, are ill-defined. Here, we provided the first comprehensive description of liver circadian gene expression under normal and after ECD conditions. We found that post-transcription and post-translation processes are dominant contributors to whole-cell or nuclear circadian proteome, respectively. Furthermore, rhythmicity of 64% transcriptome, 98% whole-cell proteome and 95% nuclear proteome is re-written by ECD. The re-writing, which is associated with changes of circadian cis-regulatory elements, RNA-processing and protein trafficking, diminishes circadian regulation of fat and carbohydrate metabolism and persists after one week of ECD-recovery.

Anti-human immunodeficiency virus-1 activity of MoMo30 protein isolated from the traditional African medicinal plant Momordica balsamina.

BACKGROUND: Plants are used in traditional healing practices of many cultures worldwide. Momordica balsamina is a plant commonly used by traditional African healers as a part of a treatment for HIV/AIDS. It is typically given as a tea to patients with HIV/AIDS. Water-soluble extracts of this plant were found to contain anti-HIV activity. METHODS: We employed cell-based infectivity assays, surface plasmon resonance, and a molecular-cell model of the gp120-CD4 interaction to study the mechanism of action of the MoMo30-plant protein. Using Edman degradation results of the 15 N-terminal amino acids, we determined the gene sequence of the MoMo30-plant protein from an RNAseq library from total RNA extracted from Momordica balsamina. RESULTS: Here, we identify the active ingredient of water extracts of the leaves of Momordica balsamina as a 30 kDa protein we call MoMo30-plant. We have identified the gene for MoMo30 and found it is homologous to a group of plant lectins known as Hevamine A-like proteins. MoMo30-plant is distinct from other proteins previously reported agents from the Momordica species, such as ribosome-inactivating proteins such as MAP30 and Balsamin. MoMo30-plant binds to gp120 through its glycan groups and functions as a lectin or carbohydrate-binding agent (CBA). It inhibits HIV-1 at nanomolar levels and has minimal cellular toxicity at inhibitory levels. CONCLUSIONS: CBAs like MoMo30 can bind to glycans on the surface of the enveloped glycoprotein of HIV (gp120) and block entry. Exposure to CBAs has two effects on the virus. First, it blocks infection of susceptible cells. Secondly, MoMo30 drives the selection of viruses with altered glycosylation patterns, potentially altering their immunogenicity. Such an agent could represent a change in the treatment strategy for HIV/AIDS that allows a rapid reduction in viral loads while selecting for an underglycosylated virus, potentially facilitating the host immune response.

The Prevalence and Determinants of NAFLD and MAFLD and Their Severity in the VA Primary Care Setting.

BACKGROUND & AIMS: A recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population. METHODS: We conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 dB/m was used to define NAFLD, whereas MAFLD was defined as controlled attenuation parameter median ≥290 dB/m and either body mass index ≥25 kg/m2 or diabetes, or 2 or more of the following: hypertension, high triglycerides, low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol. RESULTS: The mean age of participants was 50.9 years, 55.4% were women, 42.8% were white, and 43.8% were Black. The prevalence of NAFLD was 40.6% (82/202). All 82 patients with NAFLD had a body mass index ≥25 kg/m2, and therefore met our criteria for MAFLD (ie, 100% concordance). Compared with patients with no metabolic trait, patients with ≥3 traits had a 48-fold (adjusted odds ratio, 47.6; 95% confidence interval, 11.3-200) higher risk of NAFLD/MAFLD. Overall, 19 participants (9.4% of the total, 15.9% of those with NAFLD) had at least moderate fibrosis. CONCLUSIONS: NAFLD was present in 40% of Veterans registered in primary care; 9.4% of veterans had at least moderate hepatic fibrosis, with most having concurrent NAFLD. There was perfect concordance between NAFLD and the alternative MAFLD definition.

Identification of a Novel Anti-HIV-1 Protein from Momordica balsamina Leaf Extract.

Our lab investigates the anti-HIV-1 activity in Momordica balsamina (M. balsamina) leaf extract. Traditional Senegalese healers have used M. balsamina leaf extract as a part of a plant-based treatment for HIV/AIDS infections. Our overall goal is to define and validate the scientific basis for using M. balsamina leaf extract as a part of the traditional Senegalese treatment. As an initial characterization of this extract, we used activity-guided fractionation to determine the active ingredient's solubility and relative size. We found that M. balsamina leaf extract inhibits HIV-1 infection by >50% at concentrations of 0.02 mg/mL and above and is not toxic over its inhibitory range (0-0.5 mg/mL). We observed significantly more antiviral activity in direct water and acetonitrile extractions (p ≤ 0.05). We also observed significantly more antiviral activity in the aqueous phases of ethyl acetate, chloroform, and diethyl ether extractions (p ≤ 0.05). Though most of the antiviral activity partitioned into the aqueous layers, some antiviral activity was present in the organic layers. We show that the active agent in the plant extracts is at least 30 kD in size. Significantly more antiviral activity was retained in 3, 10, and 30 kD molecular weight cutoff filters (p ≤ 0.05). In contrast, most of the antiviral activity passed through the 100 kD filter (p ≤ 0.05). Because the active anti-HIV-1 agent presented as a large, amphiphilic molecule we ran the purified extract on an SDS-page gel. We show that the anti-HIV-1 activity in the leaf extracts is attributed to a 30 kDa protein we call MoMo30. This article describes how MoMo30 was determined to be responsible for its anti-HIV-1 activity.

A pretest-posttest design to assess the effectiveness of an intervention to reduce HIV-related stigma and discrimination in healthcare settings in Vietnam.

INTRODUCTION: Stigma and discrimination are important barriers to HIV epidemic control. We implemented a multi-pronged facility-level intervention to reduce stigma and discrimination at health facilities across three high-burden provinces. Key components of the intervention included measurement of stigma, data review and use, participatory training of healthcare workers (HCWs), and engagement of people living with HIV and key populations in all stigma reduction activities. METHODS: From July 2018 to July 2019, we assessed HIV-related stigma and discrimination among patients and HCWs at 10 facilities at baseline and 9 months following an intervention. A repeated measures design was used to assess the change in stigma and discrimination among HCWs and a repeated cross-sectional design assessed the change in stigma and discrimination experienced by PLHIV. HCWs at target facilities were invited at random and PLHIV were recruited when presenting for care during the two assessment periods. McNemar's test was used to compare paired proportions among HCWs, and chi-square test was used to compare proportions among PLHIV. Mixed models were used to compare outcomes before and after the intervention. RESULTS: Semi-structured interviews were conducted with 649 and 652 PLHIV prior to and following the intervention, respectively. At baseline, over the previous 12 months, 21% reported experiencing discrimination, 16% reported self-stigma, 14% reported HIV disclosure without consent and 7% had received discriminatory reproductive health advice. Nine months after the intervention, there was a decrease in reported stigma and discrimination across all domains to 15%, 11%, 7% and 3.5%, respectively (all p-values <0.05). Among HCWs, 672 completed the pre- and post-intervention assessment. At baseline, 81% reported fear of HIV infection, 69% reported using unnecessary precautions when caring for PLHIV, 44% reported having observed other staff discriminate against PLHIV, 54% reported negative attitudes towards PLHIV and 41% felt uncomfortable working with colleagues living with HIV. The proportions decreased after the intervention to 52%, 34%, 32%, 35% and 24%, respectively (all p-values <0.05). CONCLUSIONS: A multi-pronged facility-level intervention was successful at reducing healthcare-associated HIV-related stigma in Vietnam. The findings support the scale-up of this intervention in Vietnam and highlight key components potentially applicable in other settings.

210PO IN SOIL AND TOBACCO LEAVES IN QUANG XUONG, VIETNAM AND ESTIMATION OF ANNUAL EFFECTIVE DOSE TO SMOKERS.

210Po is the main radiotoxic chemical in tobacco smoke and one of the primary causes of lung cancer. Investigating 210Po concentration in tobacco is important in estimating the annual effective dose (AED) due to smoking. In this study, the 210Po concentrations in tobacco leaves and soil in Quang Xuong, Vietnam were measured using a high-resolution passivated and implanted planar silicon detector. Based on these data the AEDs to smokers were estimated. The 210Po activity concentration in tobacco varied significantly from 28.7 to 254.0 mBq g-1, whereas its variation in soil was insignificant. The AED due to smoking fresh tobacco leaves in Vietnam (average 565 µSv y-1) was significantly higher than the values reported for other countries (36-361 µSv y-1).

Facilitators and barriers to a family empowerment strategy to improve healthcare worker hand hygiene in a resource-limited setting.

OBJECTIVES: The World Health Organization recommends empowering patients/families to remind healthcare workers (HCWs) to perform hand hygiene (HH). We sought to understand acceptability of a family empowerment strategy in a Vietnamese pediatric intensive care unit (PICU). METHODS: With end-user input, we designed a tool to help families in a PICU in Vietnam to remind HCWs to perform HH. We conducted 3 preliminary focus group discussions (FGDs) with patients' family members (n = 8), physicians (n = 9), and nurses (n = 8) to understand acceptability of preliminary tools, attitudes towards HH and barriers to HH. Tools were then modified and implemented in a 5-week intervention study. We then conducted 3 more FGDs with families (n = 7), physicians (n = 7), and nurses (n = 8). Discussions were analyzed using qualitative directed content analysis. Families who used the tool were asked to complete written surveys. FINDINGS: Both family members and HCWs felt that HCWs had a responsibility to perform HH. Barriers to performing HH were identified, including forgetfulness and time constraints. Family members felt shy reminding HCWs to perform HH. However, the HH reminder tool was acceptable, and some felt it could overcome barriers to reminding HCWs to perform HH. HCWs felt embarrassed when reminded to perform HH, but felt that the reminder was useful. Nearly all (99%) survey respondents felt that family members should speak up if they noticed HCWs omitting HH. CONCLUSIONS: A tool given to families to remind HCWs to perform HH was largely acceptable in a pediatric ICU in Vietnam. Perceived benefits of improving HH were felt to surmount barriers to tool use.

A family empowerment strategy is associated with increased healthcare worker hand hygiene in a resource-limited setting.

BACKGROUND: Guidelines recommend empowering patients and families to remind healthcare workers (HCWs) to perform hand hygiene (HH). The effectiveness of empowerment tools for patients and their families in Southeast Asia is unknown. METHODS: We performed a prospective study in a pediatric intensive care unit (PICU) of a Vietnamese pediatric referral hospital. With family and HCW input, we developed a visual tool for families to prompt HCW HH. We used direct observation to collect baseline HH data. We then enrolled families to receive the visual tool and education on its use while continuing prospective collection of HH data. Multivariable logistic regression was used to identify independent predictors of HH in baseline and implementation periods. RESULTS: In total, 2,014 baseline and 2,498 implementation-period HH opportunities were observed. During the implementation period, 73 families were enrolled. Overall, HCW HH was 46% preimplementation, which increased to 73% in the implementation period (P < .001). The lowest HH adherence in both periods occurred after HCW contact with patient surroundings: 16% at baseline increased to 24% after implementation. In multivariable analyses, the odds of HCW HH during the implementation period were significantly higher than baseline (adjusted odds ratio [aOR], 2.94; 95% confidence interval [CI], 2.54-3.41; P < .001) after adjusting for observation room, HCW type, time of observation (weekday business hours vs evening or weekend), and HH moment. CONCLUSIONS: The introduction of a visual empowerment tool was associated with significant improvement in HH adherence among HCWs in a Vietnamese PICU. Future research should explore acceptability and barriers to use of similar tools in low- and middle-income settings.

Routine versus Targeted Viral Load Strategy among Patients Starting Antiretroviral in Hanoi, Vietnam.

INTRODUCTION: HIV viral load (VL) testing is recommended by the WHO as the preferred method for monitoring patients on antiretroviral therapy (ART). However, evidence that routine VL (RVL) monitoring improves clinical outcomes is lacking. METHODS: We conducted a prospective, randomized controlled trial of RVL monitoring every six months versus a targeted VL (TVL) strategy (routine CD4 plus VL testing if clinical or immunological failure) in patients starting ART between April 2011 and April 2014 at Bach Mai Hospital in Hanoi. Six hundred and forty-seven subjects were randomized to RVL (n = 305) or TVL monitoring (n = 342) and followed up for three years. Primary endpoints were death or WHO clinical Stage 4 events between six and thirty-six months of ART and rate of virological suppression at three years. RESULTS: Overall, 37.1% of subjects were female, median age was 33.4 years (IQR: 29.5 to 38.6), and 47% had a CD4 count ≤100 cells/mm3 at time of ART initiation. Approximately 44% of study events (death, LTFU, withdrawal, or Stage 4 event) and 68% of deaths occurred within the first six months of ART. Among patients on ART at six months, death or Stage 4 event occurred in 3.6% of RVL and 3.9% of TVL (p = 0.823). Survival analysis showed no significant difference between the groups (p = 0.825). Viral suppression at 36 months of ART was 97.2% in RVL and 98.9% in TVL (p = 0.206) at a threshold of 400 copies/mL and was 98.0% in RVL and 98.9% in TVL (p = 0.488) at 1000 copies/mL. In ITT analysis, 20.7% in RVL and 21.9% in TVL (p = 0.693) were unsuppressed at 1000 copies/mL. CONCLUSIONS: We found no significant difference in rates of death or Stage 4 events and virological failure in patients with RVL monitoring compared to those monitored with a TVL strategy after three years of follow-up. Viral suppression rates were high overall and there were few study events among patients alive and on ART after six months, limiting the study's power to detect a difference among study arms. Nonetheless, these data suggest that the choice of VL monitoring strategy may have less impact on patient outcomes compared to efforts to reduce early mortality and improve ART retention.

Factors associated with concurrent heroin use among patients on methadone maintenance treatment in Vietnam: A 24-month retrospective analysis of a nationally representative sample.

BACKGROUND: Methadone maintenance treatment (MMT) is highly effective for reducing heroin use and HIV transmission among people who inject opioids. We sought to measure and understand factors associated with continued heroin use, a critical factor affecting treatment outcome among MMT patients in Vietnam. METHOD: We collected data from medical charts of a nationally representative sample of patients who were on MMT from May 2008 to December 2013. We selected 10 MMT clinics using probability proportional to size and 50 patients/clinic by systematic random sampling. Concurrent heroin use was defined by self-report/positive urine test recorded in patient charts during month 3, 6, 12, and 24 after MMT initiation. We used multivariable logistic regression to identify factors associated with concurrent heroin use over the first 24 months in treatment. FINDINGS: All clients used heroin at baseline; concurrent heroin use was 55% at month 3; 19%, 14.6% and 15.2% at month 6, 12, and 24, respectively. Having no family emotional/financial support at baseline versus having this support (AOR = 2.03; 95% confidence interval [CI] = 1.17-3.53); using heroin for <15 years versus ≥15 years at baseline (AOR = 1.55; 95% CI = 1.01-2.38); being HIV-infected/not on antiretroviral treatment (ART; AOR = 1.79; 95% CI = 1.07-2.98) or being HIV infected/on ART (AOR = 2.39; 95% CI = 1.61-3.55), versus not being HIV infected; baseline methamphetamine use versus non-use (AOR = 2.68; 95% CI = 1.08-6.65), were associated with increased odds of concurrent heroin use among patients. CONCLUSION: The association between concurrent heroin use among MMT patients and lack of family emotional/financial support, highlights the critical importance of these types of support for successful treatment. Association with shorter heroin use history suggests motivational enhancement may reduce concurrent heroin use. Living with HIV, whether on ART or not, is associated with increased concurrent heroin use and suggests safe injection commodities and education, and drug-drug interaction management, are needed for this subgroup. Though few MMT clients reported baseline methamphetamine use, its association with later heroin use suggests the need for effective methamphetamine use interventions.

Sensitivity and specificity of two dried blood spot methods for HIV-1 viral load monitoring among patients in Hanoi, Vietnam.

The use of dried blood spot (DBS) specimens for HIV viral load (VL) monitoring is recommended to support the roll-out of routine VL monitoring in low and middle income countries (LMICs). To better understand the use of DBS for VL monitoring, we evaluated two DBS testing methods, Roche TaqMan® Free Virus Evolution protocol (DBS-FVE) and Roche TaqMan® SPEX protocol (DBS-SPEX)) in patients receiving ART at an HIV clinic in Hanoi, Vietnam. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each DBS testing method at the thresholds of 1000 and 5000 copies/ml compared to plasma VL. At a threshold of 1000 copies/ml, sensitivity, specificity, PPV and NPV of the DBS-SPEX method were 98.8% (95% CI: 93.3%-100%), 74.3% (95% CI: 70.8%-77.5%), 31.5% (95% CI: 25.8%-37.6%), and 99.8% (95% CI: 98.9%-100%), respectively. Increasing the VL threshold value to 5000 copies/ml improved specificity (97.9% CI: 96.6%-98.9%) and PPV (83.9% CI: 74.5%-90.9%). Using the DBS-FVE method, at the threshold of 1000 copies/ml and with a correction factor of +0.3 log copies/ml, sensitivity was 95.1% (87.8%-98.6%) and specificity was 98.8% (97.7%-99.5%). Sensitivity decreased at the threshold of 5000 copies/ml (65.8%, 95% CI: 54.3%-76.1%). With a correction factor of +0.7 log copies/ml, the sensitivity was 96.3% (89.6%-99.2%) and specificity was 98.2% (96.9%-99.1%) at the threshold of 1000 copies/ml. We found that the Roche DBS-FVE method, with a +0.7 log copies/ml correction factor, performed well with sensitivity and specificity greater than 96% at a VL threshold of 1000 copies/m. These findings add to the growing body of evidence supporting the use of DBS VL testing for ART monitoring. Future research should evaluate the association between VL results by DBS and clinical outcome measures such as HIV drug resistance, morbidity, and mortality.

Maternal report of fever from cold or flu during early pregnancy and the risk for noncardiac birth defects, National Birth Defects Prevention Study, 1997-2011.

BACKGROUND: As maternal fever affects approximately 6-8% of early pregnancies, it is important to expand upon previous observations of an association between maternal fever and birth defects. METHODS: We analyzed data from the National Birth Defects Prevention Study, a multistate, case-control study of major structural birth defects. Telephone interviews were completed by mothers of cases (n = 17,162) and controls (n = 10,127). Using multivariable logistic regression, we assessed the association between maternal self-report of cold or flu with fever and cold or flu without fever during early pregnancy and 30 categories of non-cardiac birth defects. RESULTS: Maternal report of cold or flu with fever was significantly associated with 8 birth defects (anencephaly, spina bifida, encephalocele, cleft lip with or without cleft palate, colonic atresia/stenosis, bilateral renal agenesis/hypoplasia, limb reduction defects, and gastroschisis) with elevated adjusted odds ratios ranging from 1.2 to 3.7. Maternal report of cold or flu without fever was not associated with any of the birth defects studied. CONCLUSIONS: This study adds to the evidence that maternal fever during early pregnancy is associated with an increased risk for selected birth defects. Elevated associations were limited to mothers who reported a fever, suggesting that it is fever that contributes to the excess risk rather than illnesses associated with it. However, fever may also serve as a marker for more severe infections.

Cigarette smoking is associated with high HIV viral load among adults presenting for antiretroviral therapy in Vietnam.

High HIV viral load (VL >100,000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132 cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100,000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1-10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15-3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75-2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100,000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use among HIV-infected patients.

Is there an association between short sleep duration and adolescent anxiety disorders?

OBJECTIVE: The purpose of this study is to provide the first data on the prospective, reciprocal association between short sleep duration and DSM-IV anxiety disorders among adolescents. METHODS: A community-based two-wave cohort study included 4175 youths aged 11-17 years at baseline, with 3134 of these followed up a year later, drawn from a metropolitan area with a population of over 4 million. Anxiety is defined as any DSM-IV anxiety disorder in the past year generalized anxiety: panic disorder, agoraphobia without panic, social phobia, and post-traumatic stress disorder. Short sleep duration is defined as ≤6 h of sleep per night. RESULTS/CONCLUSIONS: In multivariate analyses, short sleep duration every night at baseline predicted anxiety disorders at follow-up, controlling for anxiety at baseline. Examining the reciprocal association, anxiety disorders at baseline did not predict short sleep duration at follow-up. We are the first to examine the reciprocal effects for anxiety disorders and sleep duration among adolescents using prospective data. The data suggest that reduced quantity of sleep may increase risk for anxiety, but anxiety does not increase risk for decreased sleep duration.

Clinical characteristics of hand, foot and mouth disease in Daklak Province, Vietnam and associated factors of severe cases.

The Hand, Foot and Mouth Disease (HFMD) outbreaks occurred throughout Daklak province, Vietnam in 2011. This study reviewed all 744 medical records of HFMD patients admitted to Daklak Hospital in 2011 to describe the clinical characteristics of HFMD patients and determined factors associated with severe illness. Among 744 patients, 63 (8.5%) cases were severe. Most (695, 93.4%) of the cases were 3 years old or younger, and 464 (62.4%) were boys. The number of cases peaked between August and November. Most (726, 97.6%) recovered, 17 severe cases (2.3%) were transferred to higher level hospitals, and one death. Symptoms at admission included fever (93.5% had a fever ≥ 38.5 °C), blisters (99.1%), myoclonus (58.5%), and leukocytosis (> 11,300/mm3: 38.8%). Viral cultures were performed for 61 of 63 severe cases, of which 26.2% were positive for Enteroviruses. Multivariable analysis found that oral ulcers (Odds Ratio (OR) 3.74; 95% Confidence Interval (CI) 2.13-6.58), myoclonus (OR 44.75; 95% CI 6.04-331.66) and high white blood cell count (OR 1.08; 95% CI 1.01-1.16 per 1000/mm3 increase) were significantly associated with severe illness. HFMD mainly occurs in children younger than 3 years old and rainy season. Oral ulcers, myoclonus, and leukocytosis should be closely monitored to promptly detect severe cases of HFMD.