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Background: Several observational studies have reported the prevalence of cerebral microbleeds (CMBs) and their risk factors in an elderly population. Any information in this regard is currently lacking from India. Aim of this study was to estimate the prevalence, risk factors of CMBs, and association with cognition in an Indian urban population aged 50 years and above. Methods: Household surveys were conducted as part of ongoing Longitudinal Cognition and Aging Research on Population of the National Capital Region (LoCARPoN) study in areas of urban Delhi. Magnetic resonance imaging of the brain was performed in 2599 participants. Using standard neuropsychological battery, mean Z-scores for each domain (memory, executive, information) were derived. Binary and stepwise logistic regression models were used to determine associated risk factors for the presence of CMB and its association with cognitive domains. Results: The prevalence of CMBs was 14.42% (95% confidence interval [CI]: 13.06-15.73). Of these, 203 (7.81%) participants had single CMBs and 172 (6.61%) had multiple microbleeds (≥2). Higher prevalence was observed in older age (6070 years: odds ratio [OR]: 1.25 [95% CI: 0.93-1.67]; 70-80 years: OR: 2.05 [95% CI: 1.48-2.84]; ≥80 years: OR: 3.27 [95% CI: 1.97-5.44]) compared to individuals in the age group 50-60 years. History of stroke (OR: 2.97 [95% CI: 1.56-5.66]), hypertension (OR: 1.36 [95% CI: 1.05-1.75]), and smoking (OR: 1.43 [95% CI: 1.11-1.85]) was associated with at least one CMB. Multiple CMBs were associated with worse scores in memory and executive domains. Conclusion: Older age, hypertension, history of stroke, and history of smoking emerged as important risk factors for the presence of multiple CMBs. Follow-up study is required to determine implications of CMBs. [ABSTRACT FROM AUTHOR]

Mastectomy serves as the main surgical treatment for both invasive and in situ breast carcinoma and large phyllodes tumors. It is associated with skin necrosis, seroma, and surgical site infection in up to 30% of patients. In the present trial, we compared the complications in patients undergoing skin flap elevation by one of the 4 techniques: thick skin flap raised by scalpel(group1), thin skin flap raised with scalpel (group 2), thick skin flap raised with diathermy (group 3), and thin skin flap raised with diathermy (group 4). A randomized trial with superiority hypothesis and 2 × 2 factorial design was conducted at All India Institute of Medical Sciences New Delhi. Mastectomy skin flap necrosis (MSN) was recorded as the main outcome of interest. MSN was noted in 2.5% in group1, 10% in group 2, 7.5% in group 3, and 30% in group 4. MSN was observed in 5% cases with thick flap compared to 20% cases with a thin skin flap (p = 0.007). Raising the flap with scalpel was associated with MSN in 6.25% compared to 18.75% in the diathermy group (p = 0.029). We conclude that raising a thick flap with scalpel is associated with lowest risk of skin flap necrosis. Trial Registration: Clinical Trial Registry- India CTRI/2014/09/004978 [ABSTRACT FROM AUTHOR]

Objective: To assess the efficacy and safety of fixed-dose combinations (FDC) of triple-drug dapagliflozin, sitagliptin, and metformin (DSM) compared with FDC of two-drug sitagliptin and metformin (SM), in Indian adult patients with type 2 diabetes (T2D). Methods: A multicentric, randomized, double-blind, active-controlled, Phase 3 study (CTRI/2021/10/037461) was conducted on 274 Indian adult patients with T2D. Patients were randomized (1:1) to receive either an FDC of triple-drug (n = 137) dapagliflozin propanediol 10 mg, sitagliptin phosphate 100 mg, and metformin hydrochloride 1000 mg extended-release (DSM) or FDC of two-drug (n = 137) sitagliptin phosphate 100 mg and metformin hydrochloride 1000 mg sustained-release (SM), for 16 weeks. The primary endpoint was a change in HbA1c, while the secondary endpoints were changes in fasting plasma glucose (FPG), postprandial glucose (PPG), body weight, and safety. Results: Both DSM and SM FDCs reduced HbA1c significantly (-1.45% and -1.00%, respectively, both p < 0.0001), however, HbA1c lowering was superior with DSM (∆ -0.45%; p = 0.0005) compared to SM, at week 16. Similarly, both DSM and SM FDCs reduced FPG and PPG significantly, however, FPG (∆ -12.4 mg/dl; p = 0.003) and PPG reduction (∆ -18.45 mg/dl; p = 0.01) were significantly superior to DSM compared to SM, respectively. No significant reduction in body weight was observed between the two arms. Both FDCs were well tolerated. Conclusion: FDC of DSM was superior to SM in reducing HbA1c, FPG, and PPG in Indian adults with T2D. Both triple and dual FDCs had optimal safety profiles. [ABSTRACT FROM AUTHOR]

Aims and Objectives: Our goal is to describe the association between total quantitative blood loss (QBL) and risk of obstetric haemorrhage‐related morbidity (OBH‐M) to assess the utility of the current definition of obstetric haemorrhage (OBH). Methods: This was a retrospective cohort study completed of all patients who had a live delivery at the only urban safety‐net hospital over a 2‐year period from 2018 to 2019. We categorized deliveries into 10 equally sized deciles based on QBL and compared the proportion with OBH‐M in each. Among the two deciles with the highest proportions of OBH‐M, we stratified deliveries into seven groups of ascending intervals of 250cc QBL. Finally, we compared the positive predictive value (PPV) of the standard definition of OBH (QBL ≥ 1000cc) to a definition extrapolated from our stratified analysis. The primary outcome was proportion of deliveries within each QBL decile affected by OBH‐M. The secondary outcome was PPV. Results: We found a significant increase in OBH‐M from decile 9 (895–1201cc QBL) to decile 10 (1205–8325cc QBL) (p < 0.001). In our stratified analysis, we found QBL of 1500cc to be an inflection point for an increased proportion of OBH‐M. Our secondary analysis showed an increased PPV for OBH‐M using QBL of 1500cc (20.5%) compared with that of QBL 1000cc (9.8%). Conclusions: Our findings suggest that a higher QBL threshold than the currently accepted definition of OBH is more predictive of OBH‐M. [ABSTRACT FROM AUTHOR]

Background: All women with hyperglycemia in pregnancy (HIP) require optimal care. With western Uttarakhand alone recording a HIP prevalence of 9.7%, the successful implementation of HIP guidelines pan-India at primary healthcare level becomes paramount. Aim and objective: The present cross-sectional study aimed to assess the baseline awareness of medical undergraduates regarding HIP management protocols assuming higher their knowledge better the successful implementation of these guidelines within the community. Methodology: A descriptive study was carried out among 309 medical undergraduates at a private teaching institute in Uttarakhand. Data was collected using a selfadministered, pre-tested questionnaire. Based on individual knowledge scores, participants were subdivided into: good (score≥24), moderate (score 12-24), and poor (score<12) knowledge categories. Data were analyzed using Statistical Package for Social Sciences. Results: Most subjects (92.2%) reported reading Indian textbooks on obstetrics; despite this, only 3.6% of subjects had good awareness of the protocols. Sub-domain analysis showed while 90.0% of respondents had a fair understanding of the disease basics, more than two-thirds lagged in recollecting its standard diagnostic and management protocols including the role of health workers. Conclusion: Most medical undergraduates have overall poor-to-moderate awareness of HIP management especially the diagnostic and management protocols including the role of health workers. [ABSTRACT FROM AUTHOR]

Recent studies have found increasing rates of overweight and obesity in bulimia nervosa (BN). However, the relationships between body mass index (BMI) and BN symptoms and other clinically relevant constructs are unknown. Participants (N = 152 adults with BN) were assigned to three groups by BMI: group with no overweight or obesity (NOW-BN; BMI <25; N = 32), group with overweight (OW-BN; BMI ≥25 and <30; N = 66), and group with obesity (O-BN; BMI ≥30; N = 54). We compared the groups on demographics, diet and weight histories, body esteem, BN symptoms, and depression using chi square, analysis of variance, analysis of covariance, and Poisson regression models. The O-BN group was older (d = 0.57) and OW-BN and O-BN groups had greater proportions of race/ethnic minorities than NOW-BN group. The O-BN group was significantly younger at first diet (d = 0.41) and demonstrated significantly higher cognitive dietary restraint (d = 0.31). Compared to NOW-BN, O-BN participants had lower incidence of objective binge eating (incidence rate ratio [IRR] = 4.86) and driven exercise (IRR = 7.13), and greater incidence of vomiting (IRR = 9.30), laxative misuse (IRR = 4.01), and diuretic misuse (d = 2.08). O-BN participants also experienced higher shape (d = 0.41) and weight (d = 0.42) concerns than NOW-BN and OW-BN, although NOW-BN experienced higher shape (d = 0.44) and weight (d = 0.39) concerns than OW-BN. Groups did not differ on depression scores. These results were replicated when examining BMI as a continuous predictor across the full sample, with the exception of objective binge eating and driven exercise, which were not significantly associated with BMI. Individuals with BN and comorbid obesity have distinct clinical characteristics. Existing interventions may need to be adapted to meet clinical needs of these individuals. [ABSTRACT FROM AUTHOR]

Determine the temporal and spatial characteristics of stairs versus elevator use in a university residence hall to inform future physical activity promotion efforts. All residents and visitors for a single, four-story residence hall dormitory building located on a college campus in Orange, CA. Smart mat systems capable of detecting pedestrian traffic were placed in front of the stairs and elevators on each floor plus a basement. Generalized additive mixed models (GAMMs) were used to compare stair versus elevator usage at different times of the day and on different floors. Stair versus elevator use varied much more throughout the day on floors nearest to the ground floor, with stair use most common in the morning. Overall, the elevator was used more frequently on higher floors, with less variation throughout the day. To be most effective, future stair promotion interventions should target residents on higher floors and in the morning. [ABSTRACT FROM AUTHOR]

Background: Alcohol dependence is a wide and extending social and physical problem in the world. It affects a person at the individual, family, and society levels. The aim is to study and compare the influence of motivational enhancement therapy (MET) and behavioral couple therapy on the level of motivation in a person with alcohol dependence. Methodology: Pre- and post-test with control group design was used. A total number of 60 subjects were selected using a purposive sampling method. The sample comprised twenty subjects in the behavioral couple therapy treatment as usual (Behavioral couple therapy BCT + TAU) group, twenty subjects in the control (TAU) group, and twenty subjects in the (MET + TAU) group, respectively. The subjects recruited were in the age range of 21-60 years, educated up to primary level and above, with no comorbid psychiatric, neurological disorder, physical problem, multiple substance use coming to outpatient department and inpatient department Department of Psychiatry IMS, BHU, Varanasi, and wife having age above 18 years, married for at least 1 year, educated up to primary level and above. Tools: sociodemographic datasheets, alcohol use disorder identification test, general health questionnaire-12, and stages of change readiness and treatment eagerness scale were utilized. Results: Psychotherapeutic intervention such as MET and behavioral couple therapy plays an effective role in raising motivation to change in alcohol-dependent person to quit alcohol, which is indicated by the significant rise in motivation for the change of alcohol-dependent person's recognition (F = 4.42, P < 0.05) and taking steps (F==3.78, P < 0.05). Conclusion: The present study suggests that combining pharmacological treatment with appropriate psychosocial therapies give fruitful result in the form of a desire to quit alcohol dependence. [ABSTRACT FROM AUTHOR]

Background: The Stanford Youth Diabetes Coaching Program (SYDCP) is an evidence-based program led by health care professionals to teach healthy youth who then coach family members with diabetes or other chronic conditions. This purpose of this study is to evaluate a Community Health Worker (CHW)-led implementation of the SYDCP for low-income Latinx students from underserved agricultural communities. Method: CHWs were trained and virtually led 10 training sessions virtually during the COVID-19 for Latinx students who were recruited from high schools in agricultural regions of Washington state. Feasibility measures include recruitment, retention, class attendance, and successful coaching of a family member or friend. Acceptability was measured by responses on the post-training survey. Effectiveness was evaluated by pre-post changes in measures used in prior studies of the SYDCP such as level of activation and diabetes knowledge. Results: Thirty-four students were recruited, 28 completed the training and 23 returned both pre- and post-surveys. Over 80% of students attended 7 or more classes. All met with a family or friend and 74% met with them weekly. Approximately 80% of the students rated the program's usefulness as "very good" or "excellent." Pre-post increases in diabetes knowledge, nutrition-related behaviors, resilience, and activation were significant and similar to those observed in prior published studies of the SYDCP. Conclusions: Findings support the feasibility, acceptability, and effectiveness of a CHW-led implementation of the SYDCP in underserved Latinx communities using a virtual remote model. [ABSTRACT FROM AUTHOR]

In the modern era of dentistry, role modeling/roleplaying is one of the most prevalent and recommended methods of dental education. Working on video production projects and using student-centred learning also help students create feelings of ownership and self-esteem. This study aimed to compare students' perceptions of roleplay videos among genders, different disciplines of dentistry, and different levels of dental students. This study included 180 third- and fourth-year dental students registered in courses such as 'Introduction to Dental Practice' and 'Surgical management of oral and maxillofacial diseases', respectively, at the College of Dentistry at Jouf University. Four groups of recruited participants were pre-tested using a questionnaire about their clinical and communication skills. The students were tested again using the same questionnaire at the end of the workshop to evaluate improvements in their skills. The students were then assigned to create roleplay videos with respect to demonstrated skills related to all three disciplines (Periodontics, Oral Surgery, and Oral Radiology) in a week's time. Students' perceptions of the roleplay video assignments were collected through a questionnaire survey. The Kruskal–Wallis test was used to compare responses for each section of the questionnaire (p < 0.05). Improvements in problem-solving and project management skills during video production were reported by 90% of the participants. No significant difference (p > 0.05) in the mean scores of the responses was found with respect to the type of discipline involved in the process. There was a significant difference in the mean scores of the responses between male and female students (p < 0.05). The fourth year participants demonstrated increased mean scores and significantly higher (p < 0.05) mean scores than third-year participants. Students' perceptions of roleplay videos differed by gender and the level of the students, but not by the type of discipline. [ABSTRACT FROM AUTHOR]

Objective: The objective was to evaluate the clinical experience and treatment patterns of generic dapagliflozin usage in different patient profiles in Indian settings. Materials and Methods: A retrospective, multicentric, real-world study included patients with type 2 diabetes mellitus (T2DM) (aged >18 years), inadequately controlled by existing antidiabetic therapy and receiving generic dapagliflozin as an add-on to existing oral antidiabetic drug(s) with or without insulin or switch therapy. Baseline characteristics and treatment-related outcomes were retrieved from the medical records and analyzed. Results: A total of 1935 patients were included, of which 1279 (66.1%) were males. The mean age was 57.4 years, and around half of the patients (51.4%) were aged from 45 to 60 years. Hypertension (55.9%) and dyslipidemia (19.8%) were the common comorbidities. The majority (n = 1122; 60%) of patients received dapagliflozin in combination with one or two antihyperglycemic drugs. More than half of the patients received metformin (56.8%) or sulfonylurea (52.3%) in combination with dapagliflozin. A dose of 10 mg (93.4%) was the most commonly used dose of dapagliflozin. The mean levels of glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose were significantly reduced to 1.1% (1.0-1.1), 30.5 mg/dL (29.2-31.9), and 57.5 mg/dL (55.1-59.9), respectively, after the initiation of dapagliflozin. A total of 1935 patients experienced weight changes during the treatment, of which 90.5% of patients showed weight loss. Hypoglycemic events were reported in 12.5% of patients. Physician global evaluation of efficacy and tolerability showed a majority of patients on a good-to-excellent scale (97.3% and 97.1%). Conclusion: Generic dapagliflozin showed a significant improvement in glycemic parameters and reduced body weight with low hypoglycemic events. The administration of dapagliflozin provided a good-to-excellent efficacy and tolerability profile in patients with T2DM. To the best of our knowledge, this is the first study confirming the efficacy, safety, and usefulness of generic dapagliflozin in patients with T2DM. [ABSTRACT FROM AUTHOR]

Recognition of β-cell antigens by autoreactive T cells is a critical step in the initiation of autoimmune type1 diabetes. A complete protection from diabetes development in NOD mice harboring a point mutation in the insulin B-chain 9-23 epitope points to a dominant role of insulin in diabetogenesis. Generation of NOD mice lacking the chromogranin A protein (NOD.ChgA-/-) completely nullified the autoreactivity of the BDC2.5 T cell and conferred protection from diabetes onset. These results raised the issue concerning the dominant antigen that drives the autoimmune process. Here we revisited the NOD.ChgA-/- mice and found that their lack of diabetes development may not be solely explained by the absence of chromogranin A reactivity. NOD.ChgA-/- mice displayed reduced presentation of insulin peptides in the islets and periphery, which corresponded to impaired T-cell priming. Diabetes development in these mice was restored by antibody treatment targeting regulatory T cells or inhibiting transforming growth factor-β and programmed death-1 pathways. Therefore, the global deficiency of chromogranin A impairs recognition of the major diabetogenic antigen insulin, leading to broadly impaired autoimmune responses controlled by multiple regulatory mechanisms. [ABSTRACT FROM AUTHOR]

BACKGROUND: Human-Robot Interaction (HRI) has become a prominent solution to improve the robustness of real-time service provisioning through assisted functions for day-to-day activities. The application of the robotic system in security services helps to improve the precision of event detection and environmental monitoring with ease. OBJECTIVES: This paper discusses activity detection and analysis (ADA) using security robots in workplaces. The application scenario of this method relies on processing image and sensor data for event and activity detection. The events that are detected are classified for its abnormality based on the analysis performed using the sensor and image data operated using a convolution neural network. This method aims to improve the accuracy of detection by mitigating the deviations that are classified in different levels of the convolution process. RESULTS: The differences are identified based on independent data correlation and information processing. The performance of the proposed method is verified for the three human activities, such as standing, walking, and running, as detected using the images and sensor dataset. CONCLUSION: The results are compared with the existing method for metrics accuracy, classification time, and recall. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to characterize the prevalence and risk of pain, pain interference, and recurrent pain in adult survivors of childhood cancer in comparison with siblings.Methods: This study analyzed longitudinal data from survivors (n = 10,012; 48.7% female; median age, 31 years [range, 17-57 years]; median time since diagnosis, 23 years) and siblings (n = 3173) from the Childhood Cancer Survivor Study. Survivors were diagnosed between 1970 and 1986 at 1 of 26 participating sites. Associations between risk factors (demographics, cancer-related factors, and psychological symptoms) and pain, pain interference, and recurrent pain (5 years apart) were assessed with multinomial logistic regression. Path analyses examined cross-sectional associations between risk factors and pain outcomes.Results: Twenty-nine percent of survivors reported moderate to severe pain, 20% reported moderate to extreme pain interference, and 9% reported moderate to severe recurrent pain. Female sex, a sarcoma/bone tumor diagnosis, and severe/life-threatening chronic medical conditions were associated with recurrent pain. Depression and anxiety were associated with increased risk for all pain outcomes. Poor vitality mediated the effects of anxiety on high pain and pain interference (root mean square error of approximation, 0.002).Conclusions: A large proportion of adult survivors report moderate to severe pain and pain interference more than 20 years after their diagnosis. Increased screening and early intervention for pain interference and recurrent pain are warranted. [ABSTRACT FROM AUTHOR]

Rationale: Neuroendocrine cell hyperplasia of infancy (NEHI) is an important form of children's interstitial and diffuse lung disease for which the diagnostic strategy has evolved. The prevalence of comorbidities in NEHI that may influence treatment has not been previously assessed.Objectives: To evaluate a previously unpublished NEHI clinical score for assistance in diagnosis of NEHI and to assess comorbidities in NEHI.Methods: We performed a retrospective chart review of 199 deidentified patients with NEHI from 11 centers. Data were collected in a centralized Research Electronic Data Capture registry and we performed descriptive statistics.Results: The majority of patients with NEHI were male (66%). The sensitivity of the NEHI Clinical Score was 87% (95% confidence interval [CI], 0.82-0.91) for all patients from included centers and 93% (95% CI, 0.86-0.97) for those with complete scores (e.g., no missing data). Findings were similar when we limited the population to the 75 patients diagnosed by lung biopsy (87%; 95% CI, 0.77-0.93). Of those patients evaluated for comorbidities, 51% had gastroesophageal reflux, 35% had aspiration or were at risk for aspiration, and 17% had evidence of immune system abnormalities.Conclusions: The NEHI Clinical Score is a sensitive tool for clinically evaluating NEHI; however, its specificity has not yet been addressed. Clinicians should consider evaluating patients with NEHI for comorbidities, including gastroesophageal reflux, aspiration, and immune system abnormalities, because these can contribute to the child's clinical picture and may influence clinical course and treatment. [ABSTRACT FROM AUTHOR]

Background: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target.Methods: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer. Two doses, 100 mg or 200 mg, were delivered transorally every hour for 3 hours. Blood and saliva were collected before and 1 hour, 2 hours, 3 hours, and 24 hours after treatment. Electrocardiograms and blood tests did not demonstrate any toxicity.Results: Treatment with APG-157 resulted in circulating concentrations of curcumin and analogs peaking at 3 hours with reduced IL-1β, IL-6, and IL-8 concentrations in the salivary supernatant fluid of patients with cancer. Salivary microbial flora analysis showed a reduction in Bacteroidetes species in cancer subjects. RNA and immunofluorescence analyses of tumor tissues of a subject demonstrated increased expression of genes associated with differentiation and T-cell recruitment to the tumor microenvironment.Conclusions: The results of the current study suggested that APG-157 could serve as a therapeutic drug in combination with immunotherapy.Lay Summary: Curcumin has been shown to suppress tumor cells because of its antioxidant and anti-inflammatory properties. However, its effectiveness has been limited by poor absorption when delivered orally. Subjects with oral cancer were given oral APG-157, a botanical drug containing multiple polyphenols, including curcumin. Curcumin was found in the blood and in tumor tissues. Inflammatory markers and Bacteroides species were found to be decreased in the saliva, and immune T cells were increased in the tumor tissue. APG-157 is absorbed well, reduces inflammation, and attracts T cells to the tumor, suggesting its potential use in combination with immunotherapy drugs. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, few studies to date have examined long-term neurocognitive outcomes in survivors of childhood soft-tissue sarcoma.Methods: A total of 150 survivors (41% of whom were female with a mean current age of 33 years [SD, 8.9 years] and a time since diagnosis of 24 years [SD, 8.7 years]) and 349 community controls (56% of whom were female with a mean current age of 35 years [SD, 10.2 years]) completed comprehensive neuropsychological testing, echocardiography, electrocardiography, pulmonary function tests, endocrine evaluation, and physical examination. Patient-reported outcomes of health-related quality of life (HRQOL) and social attainment were collected. Survivors were compared with norms and controls on neurocognitive outcomes using general linear models, and on HRQOL and social attainment using modified Poisson models. The impacts of treatment and chronic health conditions on outcomes were examined using multivariable general linear models (effect size was expressed as unstandardized β estimates that reflected the unit of change from a mean of 0 and an SD of 1) and modified Poisson models (effect size expressed as relative risks).Results: Compared with controls and population norms, survivors demonstrated lower performance on measures of verbal reasoning (mean z score, -0.45 [SD, 1.15]; P < .001) mathematics (mean z score, -0.63 [SD, 1.07]; P < .001), and long-term memory (mean z score, -0.37 [SD, 1.14]; P < .001). Cumulative anthracycline exposure (per 100 mg/m2 ) was found to be associated with poorer verbal reasoning (β = -0.14 z scores; P = .04), reading (β = -0.09 z score; P = .04), and patient-reported vitality (relative risk, 1.32; 95% CI, 1.09-1.59). Neurologic and neurosensory chronic conditions were associated with poorer mathematics (neurologic conditions: β = -0.63 z score [P = 0.02]; and hearing impairment: β = -0.75 z scores [P < 0.01]). Better cognitive performance was associated with higher social attainment.Conclusions: Long-term survivors of soft-tissue sarcoma are at risk of neurocognitive problems and poor HRQOL associated with anthracycline treatment and chronic health conditions. [ABSTRACT FROM AUTHOR]

This randomized double-blind placebo-controlled trial evaluated the effects of early postnatal oral vitamin A supplementation (VAS) in 196 inborn very-low birth weight (VLBW) infants requiring respiratory support at 24 h of age. Eligible infants were randomized to receive aqueous syrup of vitamin A (10,000 IU of retinol/dose; n = 98) or placebo (n = 98) on alternate days for 28 days. Primary outcome variable was composite incidence of all-cause mortality and/or oxygen requirement for 28 days. Secondary outcome variables were safety/tolerability of VAS, serum retinol concentration at recruitment and day 28, duration of oxygen requirement and respiratory support and incidences of complications. On intention-to-treat analysis, composite incidence of all-cause mortality and oxygen requirement for 28 days was significantly lower in vitamin A group (relative risk (95% confidence interval), 0.440 (0.229-0.844); p < 0.05, number needed to benefit, 7). Requirement and duration of oxygen supplementation and non-invasive respiratory support, incidences of late-onset sepsis, patent ductus arteriosus, and duration of hospital stay were also significantly lower in vitamin A group. Serum retinol concentration improved significantly after VAS. No major adverse effect was observed.Conclusions: Early postnatal oral VAS was associated with better composite outcome of all-cause mortality and oxygen requirement without any major adverse effects.Clinical Trial Registration: Clinical Trials Registry of India (CTRI/2017/03/008131). What is Known: • Postnatal intramuscular vitamin A supplementation improves the survival, respiratory outcome and other morbidities in very low birth weight neonates without major adverse effects. • Limited studies on oral vitamin A supplementation did not document substantial benefits. What is New: • Early postnatal alternate-day oral vitamin A supplementation at the dose of 10,000 IU/dose for 28 days improves the composite outcome of death and oxygen requirement in very low birth weight neonates with respiratory distress • No major adverse effects were documented. [ABSTRACT FROM AUTHOR]

Purpose: This study describes the prevalence and predisposing factors for potentially modifiable unmet emotional, care/support, and information needs among adult survivors of childhood malignancies.Methods: A randomly selected/stratified sample of participants in the Childhood Cancer Survivor Study (CCSS) responded to the CCSS-Needs Assessment Questionnaire (CCSS-NAQ) (n = 1189; mean [SD] current age, 39.7 [7.7], range = 26-61 years; 60.9 % women; mean [SD] years since diagnosis, 31.6 [4.7]). Survivors self-reported demographic information, health concerns, and needs; diagnosis/treatment data were obtained from medical records. Adjusted proportional risk ratios (prevalence ratios, PRs) were used to evaluate 77 separate needs.Results: Fifty-four percent of survivors reported unmet psycho-emotional, 41 % coping, and 35 % care/support needs; 51, 35, and 33 %, respectively, reported unmet information needs related to cancer/treatment, the health care system, and surveillance. Female sex and annual income <$60K were associated with multiple needs; fewer needs were linked to diagnosis/years since/or age at diagnosis. Having moderate/extreme cancer-related anxiety/fear was associated with all needs, including a >6-fold increased prevalence for help dealing with "worry" (PR = 6.06; 95 % confidence interval [CI], 3.79-9.69) and anxiety (PR = 6.10; 95 % CI, 3.82-9.72) and a >5-fold increased prevalence for "needing to move on with life" (PR = 5.56; 95 % CI, 3.34-9.25) and dealing with "uncertainty about the future" (PR = 5.50; 95 % CI, 3.44-8.77). Radiation exposure and perceived health status were related to 42 and 29 needs, respectively.Conclusions: Demographic factors, disease/treatment characteristics, and intrapersonal factors can be used to profile survivors' unmet emotional, care/support, and information needs.Implications For Cancer Survivors: These data can be used to enhance provider-survivor communication, identify at-risk subsamples, and appraise core intervention content. [ABSTRACT FROM AUTHOR]

Background: Prevalence of emotional, behavioral, and psychiatric outcomes in child and adolescent survivors of childhood acute lymphoblastic leukemia treated on a chemotherapy-only protocol were not well defined.Methods: Self- and parent-reported emotional and behavioral symptoms were assessed for 161 survivors of childhood acute lymphoblastic leukemia (51.0% female; mean [SD] age 12.1[2.6] years; 7.5[1.6] years post-diagnosis). Age- and sex-adjusted scores were calculated for standardized measures and compared with 90th percentile of norms. Frequencies of survivor psychiatric disorders from structured diagnostic interviews with parents were compared with the general population. Parent emotional distress and post-traumatic stress symptoms were assessed. Associations between child symptoms/disorders and parent distress were examined with log-binomial models, adjusting for highest parent education.Results: Compared with population expectations (10%), more survivors self-reported symptoms of inattention (27.9; 95% CI, 21.0%-35.7%), hyperactivity/impulsivity (26.0%; CI, 19.2%-33.6%), and oppositional-defiant behavior (20.1%; CI, 14.1%-27.3%). Parents reported survivors with more symptoms of inattention (23.6%; CI, 17.2%-31.0%), higher frequencies of obsessive-compulsive disorder (10.3% vs 2%) and oppositional defiant disorder (16.0% vs 9.5%), but not attention-deficit/hyperactivity disorder (7.1% vs 7.8%) or generalized anxiety disorder (3.2% vs 4.1%), compared with national norms. Parent-report of child anxiety disorders was associated with parent self-reported emotional distress but not survivor self-report of anxiety.Conclusion: A significant minority of survivors have long-term psychiatric morbidity, multi-informant assessment is important to understand these symptom profiles and to inform selection of appropriate interventions. Interventions targeting inattention and oppositional behavior in children and emotional distress in parents are warranted in families with survivors who display behavioral problems. [ABSTRACT FROM AUTHOR]

Background: Children with non-Hodgkin lymphoma (NHL) undergo treatment with central nervous system-directed therapy, the potentially neurotoxic effects of which have not been reported in NHL survivors.Methods: NHL survivors (n = 187) participating in the St. Jude Lifetime Cohort who were 10 or more years from their diagnosis and were 18 years old or older underwent neurocognitive, emotional distress (Brief Symptom Inventory 18), and health-related quality of life (HRQOL) assessments (36-Item Short Form Health Survey). Age-adjusted z scores were compared with community controls (n = 181) and normative data. Treatment exposures were abstracted from medical records. Models adjusted for the age, sex, and time from diagnosis were used to calculate the risk of impairment.Results: The mean ages at evaluation were similar for the survivors and the controls (35.7 ± 8.9 vs 35.5 ± 11.0 years; P = .86). Survivors were 25.2 ± 8.8 years from their diagnosis: 43 (23%) received cranial radiation, 70 (37%) received high-dose methotrexate, 40 (21%) received high-dose cytarabine, and 151 (81%) received intrathecal chemotherapy. Survivors' intelligence and attention were within normal limits; however, their memory, executive function, processing speed, and academics were impaired in comparison with both population norms and community controls (P values < .05). Treatment-related exposures were not associated with neurocognitive function; however, neurocognitive impairment was associated with lower educational attainment, unemployment, and occupational status (P values < .03). Slower processing speed and worse self-reported executive function were associated with symptoms of depression (P values ≤ .003) and poorer HRQOL (P values < .05).Conclusions: Adult survivors of childhood NHL experience impaired neurocognitive function, which is associated with lower social attainment and poor HRQOL. Early-detection and intervention strategies are recommended. Cancer 2017. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: To examine the potential mediating role of body image dissatisfaction on the association between treatment-related scarring/disfigurement and psychological distress in adult survivors of childhood cancer.Methods: Participants included 1714 adult survivors of childhood cancer (mean [SD] age at evaluation = 32.4 [8.0] years, time since diagnosis = 24.1 [8.1] years) enrolled in the St. Jude Lifetime Cohort Study. Survivors completed measures of body image, emotional distress, and posttraumatic stress symptoms (PTSS). Body image dissatisfaction (BID) was categorized into 2 groups (cancer-related and general) based on factor analysis. Using causal mediation analysis, we estimated the proportion of psychological distress associated with treatment-related scarring/disfigurement that could be eliminated by resolving BID through a hypothetical intervention.Results: Among survivors with scarring/disfigurement of the head, a sizable proportion of the relative excess of psychological distress could be eliminated if BID was successfully treated (males: [cancer-related BID: depression: 63%; anxiety: 100%; PTSS: 52%]; [general BID: depression: 70%; anxiety: 100%; PTSS: 42%]; females: [cancer-related BID: depression: 20%; anxiety; 36%; PTSS: 23%]; [general BID: depression: 32%; anxiety: 87%; PTSS: 38%]). The mediating effect of BID was less pronounced for the association between scarring/disfigurement of the body and psychological distress for both males and females.Conclusions: Body image dissatisfaction mediates the association treatment-related scarring/disfigurement and psychological distress among adult survivors of childhood cancer, particularly among survivors with scarring/disfigurement of the head and male survivors. Successful treatment of body image dissatisfaction has the potential to eliminate a substantial proportion of psychological distress related to scarring/disfigurement among adult survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors treated with chest-directed radiotherapy have substantially elevated risk for developing breast cancer. Although genetic susceptibility to breast cancer in the general population is well studied, large-scale evaluation of breast cancer susceptibility after chest-directed radiotherapy for childhood cancer is lacking.Methods: We conducted a genome-wide association study of breast cancer in female survivors of childhood cancer, pooling two cohorts with detailed treatment data and systematic, long-term follow-up: the Childhood Cancer Survivor Study and St. Jude Lifetime Cohort. The study population comprised 207 survivors who developed breast cancer and 2774 who had not developed any subsequent neoplasm as of last follow-up. Genotyping and subsequent imputation yielded 16 958 466 high-quality variants for analysis. We tested associations in the overall population and in subgroups stratified by receipt of lower than 10 and 10 or higher gray breast radiation exposure. We report P values and pooled per-allele risk estimates from Cox proportional hazards regression models. All statistical tests were two-sided.Results: Among survivors who received 10 or higher gray breast radiation exposure, a locus on 1q41 was associated with subsequent breast cancer risk (rs4342822, nearest gene PROX1 , risk allele frequency in control subjects [RAF controls ] = 0.46, hazard ratio = 1.92, 95% confidence interval = 1.49 to 2.44, P = 7.09 × 10 -9 ). Two rare variants also showed potentially promising associations (breast radiation ≥10 gray: rs74949440, 11q23, TAGLN , RAF controls = 0.02, P = 5.84 × 10 -8 ; <10 gray: rs17020562, 1q32.3, RPS6KC1 , RAF controls = 0.0005, P = 6.68 × 10 -8 ). Associations were restricted to these dose subgroups, with consistent findings in the two survivor cohorts.Conclusions: Our study provides strong evidence that germline genetics outside high-risk syndromes could modify the effect of radiation exposure on breast cancer risk after childhood cancer. [ABSTRACT FROM AUTHOR]

Background: Blood-based biomarkers for early detection of pancreatic ductal adenocarcinoma (PDAC) are urgently needed. Current biomarkers lack high sensitivity and specificity for population screening. The gold-standard biomarker, CA 19-9, also fails to demonstrate the predictive value necessary for early detection.Methods: To validate a functional genomics-based plasma migration signature biomarker panel, plasma tissue factor pathway inhibitor (TFPI), tenascin C (TNC-FN III-C), and CA 19-9 levels were measured by enzyme-linked immunosorbent assays in three early-stage PDAC plasma cohorts, including two independent blinded validation cohorts containing a total of 43 stage I, 163 stage II, 86 chronic pancreatitis, 31 acute biliary obstruction, and 108 controls. Logistic regression models developed classification rules combining TFPI and/or TNC-FN III-C with CA 19-9 for patient cases and control subjects, with or without adjustment for age and diabetes status. Model classification performance was evaluated and analyses repeated among subpopulations without diabetes and pancreatitis history. Two-sided P values were calculated using bootstrap method.Results: The TFPI/TNC-FN III-C/CA 19-9 panel improved CA 19-9 performance in all early-stage cohorts, including discriminating stage IA/IB/IIA, stage IIB, and all early-stage cancer from healthy controls. Statistical significance was reached for a number of subcohorts, including for all early-stage cancer vs healthy controls (cohort 1 AUC = 0.92, 95% CI = 0.86 to 0.96, P  = .04; cohort 3 AUC = 0.83, 95% CI = 0.76 to 0.89, P  = .045). Among subcohorts without diabetes and pancreatitis history, the panel approaches potential clinical utility for early detection to discriminate early-stage PDAC from healthy controls including an area under the curve (AUC) of 0.87 (95% CI = 0.77 to 0.95) for stage I/IIA, an AUC of 0.93 (95% CI = 0.87 to 0.98) for stage IIB, and a statistically significant AUC of 0.89 (95% CI = 0.82 to 0.95) for all early-stage cancer ( P  = .03).Conclusions: TFPI/TNC-FN III-C migration signature adds statistically significantly to CA 19-9's predictive power to detect early-stage PDAC and may have clinical utility for early detection of surgically resectable PDAC, as well as for enhanced survival from this routinely lethal cancer. [ABSTRACT FROM AUTHOR]

Background: Urinary neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-beta-D-glucosaminidase (NAG), and interleukin 18 (IL-18) were found to be useful for early detection of acute kidney injury (AKI). The objective of this study was to determine the predictive ability of biomarkers for mortality and variation in levels in relation to different stages of AKI, need for dialysis, etiologies, and with duration of hospital stay. Methods: Urinary NGAL, NAG, and IL-18 levels were measured in 50 children with AKI and 30 age- and gender-matched healthy controls. AKI was classified as per pediatric Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. Results: Median NGAL, NAG, and IL-18 values were significantly increased in AKI patients compared with controls ( p < 0.001), with significant increase among risk, injury, and failure stages. Nonsurvivors had significantly higher median levels of NGAL ( p = 0.008) and NAG ( p = 0.018) than survivors. NGAL had highest area under the curve (AUC) at 0.750 [confidence interval (CI) 0.580-0.920], followed by NAG at 0.724 (CI 0.541-0.907), with sensitivity and specificity of 75 % each; and IL-18 (AUC 0.688, CI 0.511-0.864), with sensitivity 62.5 % and specificity 70.8 %, for predicting mortality. Values were significantly higher in patients who required peritoneal dialysis (PD) than in those in whom it was not indicated. Levels were comparable among different etiologies. Only NGAL level was found to be a significant risk factor associated with longer duration of hospital stay. Conclusions: Urinary NGAL and NAG had modest predictive ability for mortality. Children requiring dialysis had significantly raised levels, and the NGAL level had significant association with duration of hospital stay. [ABSTRACT FROM AUTHOR]

Objectives Lack of insight and neurocognitive deficits are often seen in schizophrenia patients. While there are several studies investigating the relationship between suicidal ideation, executive function and insight, there are relatively fewer investigating the triangular relationship between suicide intent, insight and cognitive competence in schizophrenia. The aim of our study was to address this issue. Methods One hundred seventy five subjects with DSM-IV TR diagnoses of schizophrenia or schizoaffective disorder were enrolled and the diagnosis was established using the Hindi version of the Diagnostic Interview for Genetic Studies and other available information in consultation with a Board certified senior Psychiatrist. All the subjects were interviewed on Beck's cognitive insight scale and tested on the Trail Making Test. All the subjects who had lifetime history of suicide attempt were interviewed on Pierce's suicide intent scale. Results Ever attempters scored significantly higher on Beck's cognitive insight scale (p = 0.012) and outperformed non-attempters on Trail Making Test A and B (p = 0.026 and p = 0.012 respectively), indicating better executive functions in the former. However among ever attempters, significant relationship was not found between executive functions, insight and severity of suicide intent. Conclusion Our study suggests that good insight and better executive functioning may be significantly correlated with suicide attempts at some time during the course of illness. Patients with schizophrenia should be evaluated for potential suicidality once denial, neurocognitive deficits and other factors associated with poor insight abate. [ABSTRACT FROM AUTHOR]

Background: The integrity of connections between the hippocampus and the anterior cingulate cortex (ACC) is critical for adaptive cognitive and emotional processing; these connections may be compromised in posttraumatic stress disorder (PTSD). However, there is a lack of PTSD research that combines structural and functional connectivity data, and no studies have examined whether abnormal ACC-hippocampal connectivity is associated with genetic variability, particularly for polymorphisms of a gene that has been previously associated with PTSD, FKBP5. This was the goal of the present study.Methods: Fifty-four women with and without PTSD underwent diffusion tensor imaging and resting-state MRI. Probabilistic tractography was used to examine ACC-hippocampal structural connectivity; mean fractional anisotropy (FA) values were extracted from connectivity streamlines, which represent the cingulum bundle. Genotype data were collected for a single nucleotide polymorphism (SNP) of FKBP5, rs1360780.Results: Participants with PTSD demonstrated poorer structural connectivity (lower cingulum FA) compared to traumatized controls (F1, 50 = 6.77, P < .05). An interaction of FKBP5 genotype and diagnostic group was also observed (F1, 37 = 4.52, P = .04), indicating lower cingulum FA in carriers of two risk alleles for this SNP, compared to other diagnostic and genotype groups. Carriers of two FKBP5 risk alleles also demonstrated poorer hippocampus-ACC connectivity at rest (P < .05). When cingulum FA was used a regressor in a brain-wide, seed-based regression analysis, significant associations were found between the hippocampus and dorsal regions of the ACC (P < .05).Conclusions: Individuals with PTSD demonstrated compromised structural connectivity of the hippocampus-ACC pathway. Altered hippocampus-ACC connectivity may represent a highly salient intermediate neural phenotype for PTSD. [ABSTRACT FROM AUTHOR]

Teachers and school nurses partner together to help ensure students stay healthy and engaged in school. The purpose of this study is to generate a deeper understanding of teachers’ perceptions on the benefits and challenges of working with full- or part-time school nurses. We conducted a qualitative analysis of open-ended survey responses from 129 teachers in nine low-income, ethnically diverse urban schools. These schools were part of a multiyear project that placed full-time nurses in four schools, while five schools with part-time nurses were used as a comparison group. Findings indicate that teachers had strong appreciation for the wide range of responsibilities undertaken by the school nurse. Teachers’ level of satisfaction was linked to the number of hours the nurse is on-site, where teachers reported greater satisfaction with nurses who worked on campus full time. Results point to factors that may improve working relations between teachers and nurses. [ABSTRACT FROM PUBLISHER]

Background/aims: The formation of advanced glycation end products (AGEs) is accelerated in patients with diabetic nephropathy. The aim of this study was to ascertain if the urinary excretion of proteins modified by advanced glycation can be used as biomarkers for albuminuria in individuals with type 1 or type 2 diabetes.Methods: Community-based patients with type 1 (n = 68) or type 2 diabetes (n = 216) attending a diabetes clinic of a tertiary referral hospital were classified as having normoalbuminuria (Normo, albumin excretion rate (AER) <20 μg/min), microalbuminuria (Micro, AER 20-200 μg/min) or macroalbuminuria (Macro, AER ≥200 μg/min). Serum and urine AGE-modified proteins were measured.Results: In patients with both type 1 diabetes and type 2 diabetes, there was a clear association between the degree of albuminuria and urinary AGE-modified proteins (p < 0.0001). Exclusive to patients with type 1 diabetes, urinary excretion of the AGE carboxymethyllysine correlated with AER, whereas patients with type 2 diabetes and macroalbuminuria had an increase in urinary methylglyoxal, an AGE intermediate. These changes were independent of isotopic glomerular filtration rate levels. Serum concentrations of AGEs or soluble receptor for AGEs were not consistently associated with albuminuria in either type 1 or type 2 diabetes.Conclusions: Urinary excretion of proteins modified by AGEs may be useful biomarkers of albuminuria in individuals with type 1 and type 2 diabetes, warranting prospective investigation in larger diabetic cohorts. [ABSTRACT FROM AUTHOR]

Background: Gastric carcinogenesis has been well documented in the step-wise histopathological model, known as Correa pathway. Several biomarkers including CD44, Musashi-1 and CD133 have been reported as putative stem cell (PSC) markers.Methods: We investigated expression of PSC markers CD44, Musashi-1 and CD133 in relation to gastric carcinogenesis and prognosis and chemoresponse. Immunohistochemistry staining was performed in gastric cancer (GC) clinical specimens representing different steps of the Correa pathway. Gastric cancer samples taken before and after neoadjuvant chemotherapy with docetaxel, cisplatin and capecitabine (DCX) were also evaluated for PSC marker expression.Results: We showed that the expression of three PSC markers was significantly elevated in GC relative to normal gastric mucosa (P<0.001 for each marker). Precancerous lesions, including intestinal metaplasia and dysplasia, demonstrated increased expression of CD44 and Musashi-1. CD133 was predominantly expressed along the border between intramucosal carcinoma and connective tissue at later stages. High CD44 and CD133 expression showed prognostic value for worse patient survival (P=0.014 and P=0.019, respectively). A small number of tumours with high expression of CD44 and CD133 showed pathological response to DCX-based neoadjuvant chemotherapy.Conclusion: CD44 and Musashi-1 are frequently expressed in both premalignant gastric lesions and invasive GC, whereas CD133 expression is restricted mainly to neoplastic tissues. [ABSTRACT FROM AUTHOR]

Natural killer (NK)-cell malignancies are among the most aggressive lymphoid neoplasms with very poor prognosis. We performed array comparative genomic hybridization analysis on a number of NK cell lines and primary tumors to gain better understanding of the pathogenesis and tumor biology of these malignancies. We also obtained transcriptional profiles of genes residing in these regions and compared them with normal and activated NK cells. Only 30-50% of the genes residing in the gained or deleted regions showed corresponding increased or decreased expression. However, many of the upregulated genes in regions of gain are functionally important for the proliferation and growth of the neoplastic population. Genes downregulated in regions of loss included many transcription factors or repressors, tumor suppressors or negative regulators of the cell cycle. The minimal common region of deletion in 6q21 included three known genes (PRDM1, ATG5 and AIM1) showing generally low expression. Mutations resulting in truncated PRDM1 and changes in conserved amino-acid sequences of AIM1 were detected. Highly methylated CpG islands 5' of PRDM1 and AIM1 correlated with low expression of the transcripts. Reversal of methylation by Decitabine induced expression of PRDM1 and cell death. In conclusion, we have shown a general tumor-promoting effect of genetic alterations and have identified PRDM1 as the most likely target gene in del6q21. ATG5, an essential gene for autophagy and AIM1, a gene implicated in melanoma, may also participate in the functional abnormalities. [ABSTRACT FROM AUTHOR]

Trimidox (3,4,5-trihydroxybenzamidoxime), a newly synthesized analog of didox (N,3,4-trihydroxybenzamide) reduced the activity of ribonucleotide reductase (EC 1.17.4.1) in extracts of L1210 cells by 50% (50% growth-inhibitory concentration, IC50) at 5 microM, whereas hydroxyurea, the only ribonucleotide reductase inhibitor in clinical use, exhibited an IC50 of 500 microM. Ribonucleotide reductase activity was also measured in situ by incubating L1210 cells for 24 h with trimidox at 7.5 microM, a concentration that inhibits cell proliferation by 50% (IC50) or at 100 microM for 2 h; these concentrations resulted in a decrease in enzyme activity to 22% and 50% of the control value, respectively. Trimidox and hydroxyurea were cytotoxic to L1210 cells with IC50 values of 7.5 and 50 microM, respectively. Versus ribonucleotide reductase, trimidox and hydroxyurea yielded IC50 values of 12 and 87 microM, respectively. A dose-dependent increase in life span was observed in mice bearing intraperitoneally transplanted L1210 tumors. Trimidox treatment (200 mg/kg; q1dx9) significantly increased the life span of mice bearing L1210 leukemia (by 82% in male mice and 112% in female mice). The anti-tumor activity appeared more pronounced in female mice than in male mice. Viewed in concert, these findings suggest that trimidox is a new and potent inhibitor of ribonucleotide reductase and that it is a promising candidate for the chemotherapy of cancer in humans. [ABSTRACT FROM AUTHOR]

Objective: To assess whether participation in Stanford Youth Coaches Programs (SYCP) increases patient activation scores and patient activation levels for vulnerable youth from low income communities.Methods: From 2016 to 18, seven high schools and four residency programs in California, Alabama, Kansas and Missouri participated in SYCPs. Enrolled youth participants completed online pre and post-participation surveys including the Patient Activation Measure (PAM®10). We used paired T-tests, chi square tests, and linear multivariate models to compare pre-and post-scores and levels.Results: 143 participants completed pre- and post-participation surveys. The PAM®10 mean pre-test score was 64.5 and post-test was 69.37, with mean difference 4.89 (p=.002). Participants showed significant improvement in patient activation levels after participation. 60 % participants in lowest activation Level 1; 63 % in Level 2; and 32 % in Level 3 moved to a higher level of activation after participation; 46 % who started in Level 4 moved down to Level 3 after participation.Conclusion and Practice Implications: Participation in SYCPs has potential to significantly increase patient activation for vulnerable youth which could lead to lifelong improvements in health outcomes and decrease in healthcare costs. [ABSTRACT FROM AUTHOR]

Background: Community-acquired pneumonia is a leading cause of pediatric morbidity. Administrative data are often used to conduct comparative effectiveness research (CER) with sufficient sample sizes to enhance detection of important outcomes. However, such studies are prone to misclassification errors because of the variable accuracy of discharge diagnosis codes.Objective: The aim of this study was to develop an automated, scalable, and accurate method to determine the presence or absence of pneumonia in children using chest imaging reports.Methods: The multi-institutional PHIS+ clinical repository was developed to support pediatric CER by expanding an administrative database of children's hospitals with detailed clinical data. To develop a scalable approach to find patients with bacterial pneumonia more accurately, we developed a Natural Language Processing (NLP) application to extract relevant information from chest diagnostic imaging reports. Domain experts established a reference standard by manually annotating 282 reports to train and then test the NLP application. Findings of pleural effusion, pulmonary infiltrate, and pneumonia were automatically extracted from the reports and then used to automatically classify whether a report was consistent with bacterial pneumonia.Results: Compared with the annotated diagnostic imaging reports reference standard, the most accurate implementation of machine learning algorithms in our NLP application allowed extracting relevant findings with a sensitivity of .939 and a positive predictive value of .925. It allowed classifying reports with a sensitivity of .71, a positive predictive value of .86, and a specificity of .962. When compared with each of the domain experts manually annotating these reports, the NLP application allowed for significantly higher sensitivity (.71 vs .527) and similar positive predictive value and specificity .Conclusions: NLP-based pneumonia information extraction of pediatric diagnostic imaging reports performed better than domain experts in this pilot study. NLP is an efficient method to extract information from a large collection of imaging reports to facilitate CER. [ABSTRACT FROM AUTHOR]

Altered cellular metabolism is a hallmark of cancer. Metabolic rewiring in cancer cells occurs due to the activation of oncogenes, inactivation of tumor suppressor genes, and/or other adaptive changes in cell signaling pathways. Furthermore, altered metabolism is also reported in tumor-corrupted stromal cells as a result of their interaction with cancer cells or due to their adaptation in the dynamic tumor microenvironment. Metabolic alterations are associated with dysregulation of metabolic enzymes and tumor-stromal metabolic crosstalk is vital for the progressive malignant journey of the tumor cells. Therefore, several therapies targeting metabolic enzymes have been evaluated and/or are being investigated in preclinical and clinical studies. In this review, we discuss some important metabolic enzymes that are altered in tumor and/or stromal cells, and focus on their role in supporting tumor growth. Moreover, we also discuss studies carried out in various cancers to target these metabolic abnormalities for therapeutic exploitation. [ABSTRACT FROM AUTHOR]

Background: The effect of a brief analytical treatment interruption (ATI) on the HIV-1 latent reservoir of individuals who initiate antiretroviral therapy (ART) during chronic infection is unknown.Methods: We evaluated the impact of transient viremia on the latent reservoir in participants who underwent an ATI and at least 6 months of subsequent viral suppression in a clinical trial testing the effect of passive infusion of the broadly neutralizing Ab VRC01 during ATI.Results: Measures of total HIV-1 DNA, cell-associated RNA, and infectious units per million cells (IUPM) (measured by quantitative viral outgrowth assay [QVOA]) were not statistically different before or after ATI. Phylogenetic analyses of HIV-1 env sequences from QVOA and proviral DNA demonstrated little change in the composition of the virus populations comprising the pre- and post-ATI reservoir. Expanded clones were common in both QVOA and proviral DNA sequences. The frequency of clonal populations differed significantly between QVOA viruses, proviral DNA sequences, and the viruses that reactivated in vivo.Conclusions: The results indicate that transient viremia from ATI does not substantially alter measures of the latent reservoir, that clonal expansion is prevalent within the latent reservoir, and that characterization of latent viruses that can reactivate in vivo remains challenging.Trial Registration: ClinicalTrials.gov NCT02463227FUNDING. Funding was provided by the NIH. [ABSTRACT FROM AUTHOR]

Background: Uveal melanoma is a rare tumour with no established treatments once metastases develop. Although a variety of immune-based therapies have shown efficacy in metastatic cutaneous melanoma, their use in ocular variants has been disappointing. Recently, adoptive T-cell therapy has shown salvage responses in multiple refractory solid tumours. Thus, we sought to determine if adoptive transfer of autologous tumour-infiltrating lymphocytes (TILs) could mediate regression of metastatic uveal melanoma.Methods: In this ongoing single-centre, two-stage, phase 2, single-arm trial, patients (aged ≥16 years) with histologically confirmed metastatic ocular melanoma were enrolled. Key eligibility criteria were an Eastern Cooperative Oncology Group performance status of 0 or 1, progressive metastatic disease, and adequate haematological, renal, and hepatic function. Metastasectomies were done to procure tumour tissue to generate autologous TIL cultures, which then underwent large scale ex-vivo expansion. Patients were treated with lymphodepleting conditioning chemotherapy (intravenous cyclophosphamide [60 mg/kg] daily for 2 days followed by fludarabine [25 mg/m2] daily for 5 days, followed by a single intravenous infusion of autologous TILs and high-dose interleukin-2 [720 000 IU/kg] every 8 h). The primary endpoint was objective tumour response in evaluable patients per protocol using Response to Evaluation Criteria in Solid Tumors, version 1.0. An interim analysis of this trial is reported here. The trial is registered at ClinicalTrials.gov, number NCT01814046.Findings: From the completed first stage and ongoing expansion stage of this trial, a total of 21 consecutive patients with metastatic uveal melanoma were enrolled between June 7, 2013, and Sept 9, 2016, and received TIL therapy. Seven (35%, 95% CI 16-59) of 20 evaluable patients had objective tumour regression. Among the responders, six patients achieved a partial response, two of which are ongoing and have not reached maximum response. One patient achieved complete response of numerous hepatic metastases, currently ongoing at 21 months post therapy. Three of the responders were refractory to previous immune checkpoint blockade. Common grade 3 or worse toxic effects were related to the lymphodepleting chemotherapy regimen and included lymphopenia, neutropenia, and thrombocytopenia (21 [100%] patients for each toxicity); anaemia (14 [67%] patients); and infection (six [29%] patients). There was one treatment-related death secondary to sepsis-induced multiorgan failure.Interpretation: To our knowledge, this is the first report describing adoptive transfer of autologous TILs to mediate objective tumour regression in patients with metastatic uveal melanoma. These initial results challenge the belief that metastatic uveal melanoma is immunotherapy resistant and support the further investigation of immune-based therapies for this cancer. Refinement of this T-cell therapy is crucial to improve the frequency of clinical responses and the general applicability of this treatment modality.Funding: Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. [ABSTRACT FROM AUTHOR]

Background: The magnitude of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma is not known. Using medically ascertained data, we applied the cumulative burden metric to compare chronic cardiovascular health conditions in survivors of Hodgkin's lymphoma and general population controls.Methods: For this study, participant data were obtained from two ongoing cohort studies at St Jude Children's Research Hospital: the St Jude Lifetime Cohort Study (SJLIFE) and the St Jude Long-term Follow-up Study (SJLTFU). SJLIFE is a cohort study initiated on April 27, 2007, to enable longitudinal clinical evaluation of health outcomes of survivors of childhood cancer treated or followed at St Jude Children's Research Hospital, and SJLTFU is an administrative system-based study initiated in 2000 to collect outcome and late toxicity data for all patients treated at the hospital for childhood cancer. The patient cohort for our study was defined as patients treated at St Jude Children's Research Hospital who reached 18 years of age and were at least 10 years post-diagnosis of pathologically confirmed primary Hodgkin's lymphoma. Outcomes in the Hodgkin's lymphoma survivors were compared with a sample of SJLIFE community control participants, aged 18 years or older at the time of assessment, frequency-matched based on strata defined by 5-year age blocks within each sex, who were selected irrespective of previous medical history. All SJLIFE participants underwent assessment for 22 chronic cardiovascular health conditions. Direct assessments, combined with retrospective clinical reviews, were used to assign severity to conditions using a modified Common Terminology Criteria of Adverse Events (CTCAE) version 4.03 grading schema. Occurrences and CTCAE grades of the conditions for eligible non-SJLIFE participants were accounted for by multiple imputation. The mean cumulative count (treating death as a competing risk) was used to estimate cumulative burden.Findings: Of 670 survivors treated at St Jude Children's Research Hospital, who survived 10 years or longer and reached age 18 years, 348 were clinically assessed in the St Jude Lifetime Cohort Study (SJLIFE); 322 eligible participants did not participate in SJLIFE. Age and sex frequency-matched SJLIFE community controls (n=272) were used for comparison. At age 50 years, the cumulative incidence of survivors experiencing at least one grade 3-5 cardiovascular condition was 45·5% (95% CI 36·6-54·3), compared with 15·7% (7·0-24·4) in community controls. The survivor cohort at age 50 experienced a cumulative burden of 430·6 (95% CI 380·7-480·6) grade 1-5 and 100·8 (77·3-124·3) grade 3-5 cardiovascular conditions per 100 survivors; these numbers were appreciably higher than those in the control cohort (227·4 [192·7-267·5] grade 1-5 conditions and 17·0 [8·4-27·5] grade 3-5 conditions per 100 individuals). Myocardial infarction and structural heart defects were the major contributors to the excess grade 3-5 cumulative burden in survivors. High cardiac radiation dose (≥35 Gy) was associated with an increased proportion of grade 3-5 cardiovascular burden, whereas increased anthracyline dose was not.Interpretation: The true effect of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin's lymphoma is reflected in the cumulative burden. Survivors aged 50 years will experience more than two times the number of chronic cardiovascular health conditions and nearly five times the number of more severe (grade 3-5) cardiovascular conditions compared with community controls and, on average, have one severe, life-threatening, or fatal cardiovascular condition. The cumulative burden metric provides a more comprehensive approach for assessing overall morbidity compared with currently used cumulative incidence based analytic methodologies, and will assist clinical researchers when designing future trials and refining general practice screening guidelines.Funding: US National Cancer Institute, St Baldrick's Foundation, and American Lebanese Syrian Associated Charities. [ABSTRACT FROM AUTHOR]