Hyaluronidase-facilitated subcutaneous immunoglobulin 10% as maintenance therapy for chronic inflammatory demyelinating polyradiculoneuropathy: The ADVANCE-CIDP 1 randomized controlled trial.

BACKGROUND AND AIMS: ADVANCE-CIDP 1 evaluated facilitated subcutaneous immunoglobulin (fSCIG; human immunoglobulin G 10% with recombinant human hyaluronidase) efficacy and safety in preventing chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse. METHODS: ADVANCE-CIDP 1 was a phase 3, double-blind, placebo-controlled trial conducted at 54 sites in 21 countries. Eligible adults had definite or probable CIDP and adjusted Inflammatory Neuropathy Cause and Treatment (INCAT) disability scores of 0-7 (inclusive), and received stable intravenous immunoglobulin (IVIG) for ≥12 weeks before screening. After stopping IVIG, patients were randomized 1:1 to fSCIG 10% or placebo for 6 months or until relapse/discontinuation. fSCIG 10% was administered at the same dose (or matching placebo volume) and interval as pre-randomization IVIG. The primary outcome was patient proportion experiencing CIDP relapse (≥1-point increase in adjusted INCAT score from pre-subcutaneous treatment baseline) in the modified intention-to-treat population. Secondary outcomes included time to relapse and safety endpoints. RESULTS: Overall, 132 patients (mean age 54.4 years, 56.1% male) received fSCIG 10% (n = 62) or placebo (n = 70). CIDP relapse was reduced with fSCIG 10% versus placebo (n = 6 [9.7%; 95% confidence interval 4.5%, 19.6%] vs n = 22 [31.4%; 21.8%, 43.0%], respectively; absolute difference: -21.8% [-34.5%, -7.9%], p = .0045). Relapse probability was higher with placebo versus fSCIG 10% over time (p = .002). Adverse events (AEs) were more frequent with fSCIG 10% (79.0% of patients) than placebo (57.1%), but severe (1.6% vs 8.6%) and serious AEs (3.2% vs 7.1%) were less common. INTERPRETATION: fSCIG 10% more effectively prevented CIDP relapse than placebo, supporting its potential use as maintenance CIDP treatment.

Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial.

BACKGROUND: Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations. METHODS: We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55-74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov, number NCT00047385. FINDINGS: Our cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371·88 [95% CI 337·97-408·26] per 100 000 person-years vs 661·23 [622·07-702·21]) and had lower lung cancer-related mortality (185·82 [95% CI 162·17-211·93] per 100 000 person-years vs 277·20 [252·28-303·90]). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0·34% (62 screen-detected cancers out of 18 121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1·0% (267 of 26 231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185·82 [95% CI 162·17-211·93] per 100 000 person-years to 212·14 [186·80-239·96]) over the course of the trial. INTERPRETATION: Participants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted. FUNDING: None.

Coronary Computed Tomography Angiography Versus Traditional Care: Comparison of One-Year Outcomes and Resource Use.

STUDY OBJECTIVE: Three large, multicenter, randomized, clinical trials have shown that coronary computed tomography (CT) angiography allows efficient evaluation and safe discharge of patients with low- to intermediate-risk chest pain who present to the emergency department (ED). We report 1-year event rates and resource use from the American College of Radiology Imaging Network-Pennsylvania 4005 multicenter trial. METHODS: Patients with low- to intermediate-risk chest pain and presenting to the ED were randomized in a 2:1 ratio to a coronary CT angiography care pathway or traditional care. Subjects were contacted by telephone at least 1 year after ED presentation. Medical record review was performed for all cardiac hospitalizations, procedures and diagnostic tests, and adverse cardiac events. Our main outcome was the composite of cardiac death and myocardial infarction within 1 year. The secondary outcome was resource use. RESULTS: One thousand three hundred sixty-eight patients enrolled and 1,285 (94%) had direct participant or proxy contact at 1 year. All others had record review or death index search. From index presentation through 1 year, there was no difference between patients in the coronary CT angiography arm versus traditional care with respect to major adverse cardiac event (1.4% versus 1.1%; difference 0.3%; 95% CI -5.5% to 6.0%). From hospital discharge through 1 year, there was also no difference in ED revisits (36% versus 38%; difference -2.1%; 95% CI -7.9% to 3.7%), hospital admissions (16% versus 17%; difference -0.9%; 95% CI -6.7% to 4.9%), or subsequent cardiac testing (13% versus 13%; difference -0.4%; 95% CI -6.2% to 5.5%). One of 640 subjects with a negative coronary CT angiography result had a major adverse cardiac event within 1 year of presentation (0.16%; 95% CI 0.004% to 0.87%). CONCLUSION: A coronary CT angiography-based strategy for evaluation of patients with low- to intermediate-risk chest pain who present to the ED does not result in increased resource use during 1 year. A negative coronary CT angiography result is associated with a less than 1% major adverse cardiac event rate during the first year after testing.

Airflow Limitation and Histology Shift in the National Lung Screening Trial. The NLST-ACRIN Cohort Substudy.

RATIONALE: Annual computed tomography (CT) is now widely recommended for lung cancer screening in the United States, although concerns remain regarding the potential harms, including those from overdiagnosis. OBJECTIVES: To examine the effect of airflow limitation on overdiagnosis by comparing lung cancer incidence, histology, and stage shift in a subgroup of the National Lung Screening Trial (NLST). METHODS: In an NLST subgroup (n = 18,714), screening participants were randomized to annual computed tomography (CT, n = 9,357) or chest radiograph (n = 9,357) screening and monitored for a mean of 6.1 years. After baseline prebronchodilator spirometry, to identify the presence of airflow limitation, 18,475 subjects (99%) were assigned as having chronic obstructive pulmonary disease (COPD) or no COPD. Lung cancer prevalence, incidence, histology, and stage shift were compared after stratification by COPD. MEASUREMENTS AND MAIN RESULTS: For screening participants with spirometric COPD (n = 6,436), there was a twofold increase in lung cancer incidence (incident rate ratio, 2.15; P < 0.001) and, when compared according to screening arm, no excess lung cancers and comparable histology. Compared with chest radiography, there was also a trend favoring reduced late-stage and increased early-stage cancers in the CT arm (P = 0.054). For those with normal baseline spirometry (n = 12,039), we found an excess of lung cancers during screening in the CT arm, almost exclusively early-stage adenocarcinoma-related cancers (histology shift and overdiagnosis). After correction for these excess cancers, stage shift was marginal (P = 0.077). CONCLUSIONS: In the CT arm of the NLST-ACRIN (American College of Radiology Imaging Network) cohort, COPD status was associated with a doubling of lung cancer incidence, no apparent overdiagnosis, and a more favorable stage shift.

Noninvasive Computed Tomography-based Risk Stratification of Lung Adenocarcinomas in the National Lung Screening Trial.

RATIONALE: Screening for lung cancer using low-dose computed tomography (CT) reduces lung cancer mortality. However, in addition to a high rate of benign nodules, lung cancer screening detects a large number of indolent cancers that generally belong to the adenocarcinoma spectrum. Individualized management of screen-detected adenocarcinomas would be facilitated by noninvasive risk stratification. OBJECTIVES: To validate that Computer-Aided Nodule Assessment and Risk Yield (CANARY), a novel image analysis software, successfully risk stratifies screen-detected lung adenocarcinomas based on clinical disease outcomes. METHODS: We identified retrospective 294 eligible patients diagnosed with lung adenocarcinoma spectrum lesions in the low-dose CT arm of the National Lung Screening Trial. The last low-dose CT scan before the diagnosis of lung adenocarcinoma was analyzed using CANARY blinded to clinical data. Based on their parametric CANARY signatures, all the lung adenocarcinoma nodules were risk stratified into three groups. CANARY risk groups were compared using survival analysis for progression-free survival. MEASUREMENTS AND MAIN RESULTS: A total of 294 patients were included in the analysis. Kaplan-Meier analysis of all the 294 adenocarcinoma nodules stratified into the Good, Intermediate, and Poor CANARY risk groups yielded distinct progression-free survival curves (P < 0.0001). This observation was confirmed in the unadjusted and adjusted (age, sex, race, and smoking status) progression-free survival analysis of all stage I cases. CONCLUSIONS: CANARY allows the noninvasive risk stratification of lung adenocarcinomas into three groups with distinct post-treatment progression-free survival. Our results suggest that CANARY could ultimately facilitate individualized management of incidentally or screen-detected lung adenocarcinomas.

Impact of lung cancer screening results on participant health-related quality of life and state anxiety in the National Lung Screening Trial.

BACKGROUND: Low-dose computed tomography (LDCT) lung screening has been associated with a 20% reduction in lung cancer mortality. A major barrier to the adoption of lung screening is the potential negative psychological impact of a false-positive (FP) screen, occurring in 20% to 50% of those screened. The objective of this study was to assess the impact of abnormal findings on health-related quality of life (HRQoL) and anxiety in the American College of Radiology (ACRIN)/National Lung Screening Trial (NLST). METHODS: The NLST was a randomized screening trial comparing LDCT with chest X-ray screening (CXR). This study was part of the original protocol. A total of 2812 participants at 16 of 23 ACRIN sites who had baseline HRQoL assessments were asked to complete the Short Form-36 and the State Trait Anxiety Inventory (form Y-1) questionnaires to assess short-term (1 month) and long-term (6 months) effects of screening. FP were lung cancer-free at 1 year, and true-positives (TP) were not. RESULTS: Of the total participants, 1024 (36.4%) participants were FP, 63 (2.2%) were TP, 344 (12.2%) had significant incidental findings (SIFs), and 1381 (49.1%) had negative screens. Participants had been randomized to LDCT (n = 1947) and CXR (n = 865). Short-term and long-term HRQoL and state anxiety did not differ across participants with FP, SIF, or negative screens. Short-term and long-term HRQoL were lower and anxiety was higher for TP participants compared to participants with FP, SIF, and negative screens. CONCLUSIONS: In a large multicenter lung screening trial, participants receiving a false-positive or SIF screen result experienced no significant difference in HRQoL or state anxiety at 1 or at 6 months after screening relative to those receiving a negative result.

Retinal Dystrophy Associated With RLBP1 Retinitis Pigmentosa: A Five-Year Prospective Natural History Study.

Purpose: To assess the progression in functional and structural measures over a five-year period in patients with retinal dystrophy caused by RLBP1 gene mutation. Methods: This prospective, noninterventional study included patients with biallelic RLBP1 mutations from two clinical sites in Sweden and Canada. Key assessments included ocular examinations, visual functional measures (best-corrected visual acuity [BCVA], contrast sensitivity [CS], dark-adaptation [DA] kinetics up to six hours for two wavelengths [450 and 632 nm], Humphrey visual fields [HVF], full-field flicker electroretinograms), and structural ocular assessments. Results: Of the 45 patients enrolled, 38 completed the full five years of follow-up. At baseline, patients had BCVA ranging from -0.2 to 1.3 logMAR, poor CS, HVF defects, and prominent thinning in central foveal thickness. All patients had extremely prolonged DA rod recovery of approximately six hours at both wavelengths. The test-retest repeatability was high across all anatomic and functional endpoints. Cross-sectionally, poorer VA was associated with older age (right eye, correlation coefficient [CC]: 0.606; left eye, CC: -0.578; P < 0.001) and HVF MD values decreased with age (right eye, CC: -0.672, left eye, CC: -0.654; P < 0.001). However, no major changes in functional or structural measures were noted longitudinally over the five-year period. Conclusions: This natural history study, which is the first study to monitor patients with RLBP1 RD for five years, showed that severely delayed DA sensitivity recovery, a characteristic feature of this disease, was observed in all patients across all age groups (17-69 years), making it a potentially suitable efficacy assessment for gene therapy treatment in this patient population.

Depressed mood in pregnancy: prevalence and correlates in two Cape Town peri-urban settlements.

BACKGROUND: The disability associated with depression and its impact on maternal and child health has important implications for public health policy. While the prevalence of postnatal depression is high, there are no prevalence data on antenatal depression in South Africa. The purpose of this study was to determine the prevalence and correlates of depressed mood in pregnancy in Cape Town peri-urban settlements. METHODS: This study reports on baseline data collected from the Philani Mentor Mothers Project (PMMP), a community-based, cluster-randomized controlled trial on the outskirts of Cape Town, South Africa. The PMMP aims to evaluate the effectiveness of a home-based intervention for preventing and managing illnesses related to HIV, TB, alcohol use and malnutrition in pregnant mothers and their infants. Participants were 1062 pregnant women from Khayelitsha and Mfuleni, Cape Town. Measures included the Edinburgh Postnatal Depression Scale (EPDS), the Derived AUDIT-C, indices for social support with regards to partner and parents, and questions concerning socio-demographics, intimate partner violence, and the current pregnancy. Data were analysed using bivariate analyses followed by logistic regression. RESULTS: Depressed mood in pregnancy was reported by 39% of mothers. The strongest predictors of depressed mood were lack of partner support, intimate partner violence, having a household income below R2000 per month, and younger age. CONCLUSIONS: The high prevalence of depressed mood in pregnancy necessitates early screening and intervention in primary health care and antenatal settings for depression. The effectiveness and scalability of community-based interventions for maternal depression must be developed for pregnant women in peri-urban settlements. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00972699.

Philani Plus (+): a Mentor Mother community health worker home visiting program to improve maternal and infants' outcomes.

Pregnant mothers in South African townships face multiple health risks for themselves and their babies. Existing clinic-based services face barriers to access, utilization, and human resource capacities. Home visiting by community health workers (CHW) can mitigate such barriers. The Philani Plus (+) Intervention Program builds upon the original Philani CHW home-visiting intervention program for maternal and child nutrition by integrating content and activities to address HIV, alcohol, and mental health. Pregnant Mothers at Risk (MAR) for HIV, alcohol, and/or nutrition problems in 24 neighborhoods in townships in Cape Town, South Africa (n = 1,239) were randomly assigned by neighborhood to an intervention (Philani Plus (+), N = 12 neighborhoods; n = 645 MAR) or a standard-care control condition of neighborhood clinic-based services (N = 12 neighborhoods; n = 594 MAR). Positive peer deviant "Mentor Mother" CHWs are recruited from the township neighborhoods and trained to deliver four antenatal and four postnatal home visits that address HIV, alcohol, nutrition, depression, health care regimens for the family, caretaking and bonding, and securing government-provided child grants. The MAR and their babies are being monitored during pregnancy, 1 week post-birth, and 6 and 18 months later. Among the 1,239 MAR recruited: 26% were HIV-positive; 27% used alcohol during pregnancy; 17% previously had low-birthweight babies; 23% had at least one chronic condition (10% hypertension, 5% asthma, 2% diabetes); 93% had recent sexual partners with 10% known to be HIV+; and 17% had clinically significant prenatal depression and 42% had borderline depression. This paper presents the intervention protocol and baseline sample characteristics for the "Philani Plus (+)" CHW home-visiting intervention trial.

Mamekhaya: a pilot study combining a cognitive-behavioral intervention and mentor mothers with PMTCT services in South Africa.

Nearly 30% of pregnant women in South Africa are estimated to be HIV seropositive, yet adherence to guidelines for the prevention of mother-to-child transmission of HIV (PMTCT) is often low. A pilot study was developed to see whether PMTCT services provided by the South African Government could be enhanced by the Mamekhaya program, a combination of the mothers2mothers peer-mentoring program and a culturally adapted cognitive-behavioral intervention (CBI) from the USA. Pregnant women attending two maternity clinics offering PMTCT in Gugulethu and Vanguard Townships, Cape Town, South Africa, were invited to participate in the study. Women at the intervention site (Gugulethu) received the support of a mentor mother and also attended an eight-session Mamekhaya CBI. At the control site (Vanguard), women received standard services provided by midwives and counselors. Baseline assessments were completed by all participants at enrollment (n=160), and follow-ups were completed six months later by 44% of participants. Self-reports of adherence to PMTCT practices were high across both sites (90% or more engaging in the core practices). Women at the Mamekhaya site showed significantly greater improvement in establishing social support and reducing depression scores than women at the control site. Mamekhaya participants also showed trends for better attendance at follow-up medical visits, and greater improvements in positive coping. The greatest effect of the Mamekhaya program was to increase HIV knowledge scores, particularly with regard to understanding the meaning and importance of viral load and CD4 test results. Results from this pilot study show promise that augmenting basic PMTCT services with mentor mothers and a culturally adapted CBI can be effective in conveying information and in improving the emotional outlook and hopefulness of HIV-positive pregnant women in South Africa.

Home visits by neighborhood Mentor Mothers provide timely recovery from childhood malnutrition in South Africa: results from a randomized controlled trial.

BACKGROUND: Child and infant malnourishment is a significant and growing problem in the developing world. Malnourished children are at high risk for negative health outcomes over their lifespans. Philani, a paraprofessional home visiting program, was developed to improve childhood nourishment. The objective of this study is to evaluate whether the Philani program can rehabilitate malnourished children in a timely manner. METHODS: Mentor Mothers were trained to conduct home visits. Mentor Mothers went from house to house in assigned neighborhoods, weighed children age 5 and younger, and recruited mother-child dyads where there was an underweight child. Participating dyads were assigned in a 2:1 random sequence to the Philani intervention condition (n = 536) or a control condition (n = 252). Mentor Mothers visited dyads in the intervention condition for one year, supporting mothers' problem-solving around nutrition. All children were weighed by Mentor Mothers at baseline and three, six, nine and twelve month follow-ups. RESULTS: By three months, children in the intervention condition were five times more likely to rehabilitate (reach a healthy weight for their ages) than children in the control condition. Throughout the course of the study, 43% (n = 233 of 536) of children in the intervention condition were rehabilitated while 31% (n = 78 of 252) of children in the control condition were rehabilitated. CONCLUSIONS: Paraprofessional Mentor Mothers are an effective strategy for delivering home visiting programs by providing the knowledge and support necessary to change the behavior of families at risk.

ACRIN 6684: Multicenter, phase II assessment of tumor hypoxia in newly diagnosed glioblastoma using magnetic resonance spectroscopy.

A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials.

Reduced Expiratory Flow Rate among Heavy Smokers Increases Lung Cancer Risk. Results from the National Lung Screening Trial-American College of Radiology Imaging Network Cohort.

RATIONALE: Although epidemiological studies consistently show that chronic obstructive pulmonary disease is associated with an increased risk of lung cancer, debate exists as to whether there is a linear relationship between the severity of airflow limitation and lung cancer risk. OBJECTIVES: We examined this in a large, prospective study of older heavy smokers from the American College of Radiology Imaging Network subcohort of the National Lung Screening Trial (ACRIN). Airflow limitation was defined by prebronchodilator spirometry subgrouped according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4. METHODS: In the National Lung Screening Trial-ACRIN cohort of 18,473 screening participants, 6,436 had airflow limitation (35%) and 12,037 (65%) had no airflow limitation. From these groups, 758 lung cancer cases were prospectively identified. Participants with airflow limitation were stratified according to GOLD groups 1 (n = 1,607), 2 (n = 3,528), 3 (n = 1,083), and 4 (n = 211). Lung cancer incidence at study end (mean follow-up, 6.4 yr) was compared between the GOLD groups and those with no airflow limitation (referent group). MEASUREMENTS AND MAIN RESULTS: Compared with those with no airflow limitation, where lung cancer incidence was 3.78/1,000 person years, incidence rates increased in a simple linear relationship: GOLD 1 (6.27/1,000 person yr); GOLD 2 (7.86/1,000 person yr); GOLD 3 (10.71/1,000 person yr); and GOLD 4 (13.25/1,000 person yr). All relationships were significant versus the reference group at a P value of 0.0001 or less. CONCLUSIONS: In a large prospective study of high-risk cigarette smokers, we report a strong linear relationship between increasing severity of airflow limitation and risk of lung cancer.

ACRIN 6684: Assessment of Tumor Hypoxia in Newly Diagnosed Glioblastoma Using 18F-FMISO PET and MRI.

PURPOSE: Structural and functional alterations in tumor vasculature are thought to contribute to tumor hypoxia which is a primary driver of malignancy through its negative impact on the efficacy of radiation, immune surveillance, apoptosis, genomic stability, and accelerated angiogenesis. We performed a prospective, multicenter study to test the hypothesis that abnormal tumor vasculature and hypoxia, as measured with MRI and PET, will negatively impact survival in patients with newly diagnosed glioblastoma. EXPERIMENTAL DESIGN: Prior to the start of chemoradiation, patients with glioblastoma underwent MRI scans that included dynamic contrast enhanced and dynamic susceptibility contrast perfusion sequences to quantitate tumor cerebral blood volume/flow (CBV/CBF) and vascular permeability (ktrans) as well as 18F-Fluoromisonidazole (18F-FMISO) PET to quantitate tumor hypoxia. ROC analysis and Cox regression models were used to determine the association of imaging variables with progression-free and overall survival. RESULTS: Fifty patients were enrolled of which 42 had evaluable imaging data. Higher pretreatment 18F-FMISO SUVpeak (P = 0.048), mean ktrans (P = 0.024), and median ktrans (P = 0.045) were significantly associated with shorter overall survival. Higher pretreatment median ktrans (P = 0.021), normalized RCBV (P = 0.0096), and nCBF (P = 0.038) were significantly associated with shorter progression-free survival. SUVpeak [AUC = 0.75; 95% confidence interval (CI), 0.59-0.91], nRCBV (AUC = 0.72; 95% CI, 0.56-0.89), and nCBF (AUC = 0.72; 95% CI, 0.56-0.89) were predictive of survival at 1 year. CONCLUSIONS: Increased tumor perfusion, vascular volume, vascular permeability, and hypoxia are negative prognostic markers in newly diagnosed patients with gioblastoma, and these important physiologic markers can be measured safely and reliably using MRI and 18F-FMISO PET. Clin Cancer Res; 22(20); 5079-86. ©2016 AACR.

When Life is a Drag: Depressive Symptoms Associated with Early Adolescent Smoking.

Adolescent nicotine use continues to be a significant public health problem. We examined the relationship between the age of youth reporting current smoking and concurrent risk and protective factors in a large state-wide sample. We analyzed current smoking, depressive symptoms, and socio-demographic factors among 4,027 adolescents, ages 12-17 years using multivariate logistic regression (see 2005 California Health Interview Survey (CHIS) Public Use File). Consistent with previous work, Latinos, girls, those whose family incomes were below the poverty level, and those with fair-poor health were more likely to display depressive symptoms. Males, whites, older teens and those in fair-poor health were more likely to be current smokers. In a multivariate analysis predicting depressive symptoms, the interaction between age and current smoking was highly significant (Wald Χ2=15.8, p<.01). At ages 12-14 years, the probability of depressive symptoms was estimated to be four times greater among adolescents who currently smoked, compared to those who were not current smokers. The likelihood of depressive symptoms associated with current smoking decreases with age and becomes non-significant by 17 years. Interventions to reduce smoking may be most useful among youth prior to age 12 years and must be targeted at multiple risks (e.g. smoking and depression).

Alcohol consumption among HIV-positive pregnant women in KwaZulu-Natal, South Africa: prevalence and correlates.

BACKGROUND: HIV-positive pregnant women who drink put their children at risk of both HIV and fetal alcohol spectrum disorders. The province of KwaZulu-Natal (KZN) has the highest prevalence of HIV in South Africa, but has not before been considered an area of high alcohol consumption among women. This paper analyzes a large sample of HIV+ pregnant women in KZN to examine alcohol consumption in that population. METHODS: Data came from assessments of women enrolled in Prevention of Mother-To-Child Transmission programs at 8 clinics in KZN. Descriptive statistics and logistic regressions were used to examine the prevalence and correlates of alcohol consumption and binge drinking. RESULTS: Of 1201 women assessed, 18% reported drinking during pregnancy, and 67% of drinkers usually binged when drinking (had 3+ drinks in one sitting). Over one-third of drinkers binged twice a month or more. Women living in urban and peri-urban locations were more likely to drink, as were those with indicators of higher economic status and greater social engagement. Married women were less likely to drink, while women who had poorer mental health, used tobacco, or had a greater history of sexual risk-taking were more likely to drink. CONCLUSION: Health care workers in KZN should be aware that pregnant women who drink are likely to do so at a level that is dangerous for their babies. Some factors associated with drinking indicate social/environmental influences that need to be counteracted by greater dissemination of information about the dangers of drinking, and greater support for abstinence or moderation.

Predictors of alcohol use prior to pregnancy recognition among township women in Cape Town, South Africa.

South Africa has the highest prevalence of Fetal Alcohol Spectrum Disorders (FASDs) in the world. The purpose of this study was to identify high risk factors associated with drinking alcohol prior to pregnancy recognition in 24 neighborhoods in the Cape Flats outside Cape Town, South Africa. An interviewer assessed risk among 619 pregnant Black/African women between the ages of 18 and 41 years. Logistic regression analyses explored factors associated with drinking alcohol post conception but prior to pregnancy recognition. Forced multiple logistic regression analysis revealed that drinking prior to pregnancy recognition was associated with being younger, single, having better living conditions, smoking, having a longer gestation prior to pregnancy recognition, having a greater number of sexual partners, and a higher incidence of intimate partner violence. Depressive symptoms tended to be higher among alcohol users. These risk factors were consistent with other research on the characteristics of South African women having children with a diagnosis of Fetal Alcohol Spectrum Disorders and/or of non pregnant women at high risk for an alcohol-exposed pregnancy. These findings highlight the need for women of child-bearing age to be routinely screened for alcohol use and its associated risk factors. Intervention efforts could be integrated into health initiatives already present in South Africa including the prevention and treatment of HIV/AIDS, tuberculosis, and malnutrition. Preconception care is particularly important since pregnancy recognition often occurs several weeks to months following conception and could be implemented by South African community health workers. These endeavors should facilitate national goals of healthier pregnancies and the elimination of FASDs in South Africa.

Project Masihambisane: a cluster randomised controlled trial with peer mentors to improve outcomes for pregnant mothers living with HIV.

BACKGROUND: Pregnant women living with HIV (WLH) face daily challenges maintaining their own and their babies' health and mental health. Standard Prevention of Maternal to Child Transmission (PMTCT) programs are not designed to address these challenges. METHODS/DESIGN: As part of a cluster randomized controlled trial, WLH are invited to attend four antenatal and four postnatal small group sessions led by a peer WLH (a Peer Mentor). The WLH and their babies are assessed during pregnancy and at one week, six months, and twelve months post-birth. Mobile phones are used to collect routine information, complete questionnaires and remain in contact with participants over time. Pregnant WLH (N = 1200) are randomly assigned by clinic (N = 8 clinics) to an intervention program, called Masihambisane (n = 4 clinics, n = 600 WLH) or a standard care PMTCT control condition (n = 4 clinics; n = 600 WLH). DISCUSSION: Data collection with cellular phones are innovative and effective in low-resource settings. Standard PMTCT programs are not designed to address the daily challenges faced by WLH; Peer Mentors may be useful in supporting WLH to cope with these challenges. TRIAL REGISTRATION: ClinicalTrials.gov registration # NCT00972699.