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1.  Physical activity among adult survivors of childhood lower extremity sarcoma 
INTRODUCTION
Adult survivors of childhood lower-extremity sarcoma are largely physically inactive, a behavior which potentially compounds their health burden. Altering this behavior requires understanding those factors that contribute to their physical inactivity. Therefore, this investigation sought to identify factors associated with inactivity in this subpopulation of cancer survivors.
METHODS
Demographic, personal, treatment and physical activity information from adult survivors of childhood lower-extremity sarcomas was obtained from the Childhood Cancer Survivor Study (CCSS) cohort. Generalized linear models were used to identify variables that best identified those individuals who were physically inactive.
RESULTS
Only 41% of survivors met Center for Disease Control (CDC) activity guidelines. Survivors were 1.20 (95% CI 1.11–1.30) more likely compared to CCSS sibling cohort and 1.12 (95% CI 1.10–1.15) times more likely than the general population to fail to meet CDC guidelines. Significant predictors of physical inactivity included female sex, hemipelvectomy surgery, and platinum and vinca alkaloid chemotherapy.
CONCLUSIONS
The primary findings of this study are that survivors of childhood onset lower-extremity sarcoma are 1) highly likely to be physically inactive and 2) less likely than their siblings or the general population to regularly exercise. This study has identified treatment related risk factors associated with inactivity that will help health and wellness practitioners develop successful exercise interventions to help these survivors achieve recommended levels of physical activity for health.
IMPLICATIONS FOR CANCER SURVIVORS
These results suggest that physical activity interventions for adult survivors of childhood lower-extremity sarcomas should be sex specific and responsive to unique physical late effects experienced by these survivors.
doi:10.1007/s11764-011-0187-5
PMCID: PMC3248971  PMID: 21681405
Childhood cancer; physical activity; exercise; late-effects; sedentary
2.  Risk Factors for Obesity in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2011;30(3):246-255.
Purpose
Many Childhood Cancer Survivor Study (CCSS) participants are at increased risk for obesity. The etiology of their obesity is likely multifactorial but not well understood.
Patients and Methods
We evaluated the potential contribution of demographic, lifestyle, treatment, and intrapersonal factors and self-reported pharmaceutical use to obesity (body mass index ≥ 30 kg/m2) among 9,284 adult (> 18 years of age) CCSS participants. Independent predictors were identified using multivariable regression models. Interrelationships were determined using structural equation modeling (SEM).
Results
Independent risk factors for obesity included cancer diagnosed at 5 to 9 years of age (relative risk [RR], 1.12; 95% CI, 1.01 to 1.24; P = .03), abnormal Short Form–36 physical function (RR, 1.19; 95% CI, 1.06 to 1.33; P < .001), hypothalamic/pituitary radiation doses of 20 to 30 Gy (RR, 1.17; 95% CI, 1.05 to 1.30; P = .01), and paroxetine use (RR, 1.29; 95% CI, 1.08 to 1.54; P = .01). Meeting US Centers for Disease Control and Prevention guidelines for vigorous physical activity (RR, 0.90; 95% CI, 0.82 to 0.97; P = .01) and a medium amount of anxiety (RR, 0.86; 95% CI, 0.75 to 0.99; P = .04) reduced the risk of obesity. Results of SEM (N = 8,244; comparative fit index = 0.999; Tucker Lewis index = 0.999; root mean square error of approximation = 0.014; weighted root mean square residual = 0.749) described the hierarchical impact of the direct predictors, moderators, and mediators of obesity.
Conclusion
Treatment, lifestyle, and intrapersonal factors, as well as the use of specific antidepressants, may contribute to obesity among survivors. A multifaceted intervention, including alternative drug and other therapies for depression and anxiety, may be required to reduce risk.
doi:10.1200/JCO.2010.34.4267
PMCID: PMC3269951  PMID: 22184380
3.  Trends in the Risk of U.S. Polio Outbreaks and Poliovirus Vaccine Availability for Response 
Public Health Reports  2012;127(1):23-37.
SYNOPSIS
Objectives
The United States eliminated indigenous wild polioviruses (WPVs) in 1979 and switched to inactivated poliovirus vaccine in 2000, which quickly ended all indigenous live poliovirus transmission. Continued WPV circulation and use of oral poliovirus vaccine globally allow for the possibility of reintroduction of these viruses. We evaluated the risk of a U.S. polio outbreak and explored potential vaccine needs for outbreak response.
Methods
We synthesized information available on vaccine coverage, exemptor populations, and population immunity. We used an infection transmission model to explore the potential dynamics of a U.S. polio outbreak and potential vaccine needs for outbreak response, and assessed the impacts of heterogeneity in population immunity for two different subpopulations with potentially low coverage.
Results
Although the risk of poliovirus introduction remains real, widespread transmission of polioviruses appears unlikely in the U.S., given high routine coverage. However, clusters of un- or underimmunized children might create pockets of susceptibility that could potentially lead to one or more paralytic polio cases. We found that the shift toward combination vaccine utilization, with limited age indications for use, and other current trends (e.g., decreasing proportion of the population with immunity induced by live polioviruses and aging of vaccine exemptor populations) might increase the vulnerability to poliovirus reintroduction at the same time that the ability to respond may decrease.
Conclusions
The U.S. poliovirus vaccine stockpile remains an important resource that may potentially be needed in the future to respond to an outbreak if a live poliovirus gets imported into a subpopulation with low vaccination coverage.
PMCID: PMC3234395  PMID: 22298920
4.  Neurologic Manifestations Associated with an Outbreak of Typhoid Fever, Malawi - Mozambique, 2009: An Epidemiologic Investigation 
PLoS ONE  2012;7(12):e46099.
Background
The bacterium Salmonella enterica serovar Typhi causes typhoid fever, which is typically associated with fever and abdominal pain. An outbreak of typhoid fever in Malawi-Mozambique in 2009 was notable for a high proportion of neurologic illness.
Objective
Describe neurologic features complicating typhoid fever during an outbreak in Malawi-Mozambique
Methods
Persons meeting a clinical case definition were identified through surveillance, with laboratory confirmation of typhoid by antibody testing or blood/stool culture. We gathered demographic and clinical information, examined patients, and evaluated a subset of patients 11 months after onset. A sample of persons with and without neurologic signs was tested for vitamin B6 and B12 levels and urinary thiocyanate.
Results
Between March – November 2009, 303 cases of typhoid fever were identified. Forty (13%) persons had objective neurologic findings, including 14 confirmed by culture/serology; 27 (68%) were hospitalized, and 5 (13%) died. Seventeen (43%) had a constellation of upper motor neuron findings, including hyperreflexia, spasticity, or sustained ankle clonus. Other neurologic features included ataxia (22, 55%), parkinsonism (8, 20%), and tremors (4, 10%). Brain MRI of 3 (ages 5, 7, and 18 years) demonstrated cerebral atrophy but no other abnormalities. Of 13 patients re-evaluated 11 months later, 11 recovered completely, and 2 had persistent hyperreflexia and ataxia. Vitamin B6 levels were markedly low in typhoid fever patients both with and without neurologic signs.
Conclusions
Neurologic signs may complicate typhoid fever, and the diagnosis should be considered in persons with acute febrile neurologic illness in endemic areas.
doi:10.1371/journal.pone.0046099
PMCID: PMC3513310  PMID: 23226492
5.  Psychological Outcomes of Siblings of Cancer Survivors: A Report from the Childhood Cancer Survivor Study 
Psycho-oncology  2010;20(12):1259-1268.
Objective
To identify risk factors for adverse psychological outcomes among adult siblings of long-term survivors of childhood cancer.
Methods
Cross-sectional, self-report data from 3,083 adult siblings (mean age 29 years, range 18-56 years) of 5+ year survivors of childhood cancer were analyzed to assess psychological outcomes as measured by the Brief Symptom Inventory-18 (BSI-18). Sociodemographic and health data, reported by both the siblings and their matched cancer survivors were explored as risk factors for adverse sibling psychological outcomes through multivariable logistic regression.
Results
Self-reported symptoms of psychological distress, as measured by the global severity index of the BSI-18, were reported by 3.8% of the sibling sample. Less than 1.5% of siblings reported elevated scores on two or more of the subscales of the BSI-18. Risk factors for sibling depression included having a survivor brother (OR 2.22, 95% CI 1.42-3.55), and having a survivor with impaired general health (OR 2.15, 95% CI 1.18-3.78). Siblings who were younger than the survivor reported increased global psychological distress (OR 1.81, 95% CI 1.05-3.12), as did siblings of survivors reporting global psychological distress (OR 2.32, 95% CI 1.08-4.59). Siblings of sarcoma survivors reported more somatization than did siblings of leukemia survivors (OR 2.07, 95% CI 1.05-3.98).
Conclusions
These findings suggest that siblings of long-term childhood cancer survivors are psychologically healthy in general. There are, however, small subgroups of siblings at risk for long-term psychological impairment who may benefit from preventive risk-reduction strategies during childhood while their sibling with cancer is undergoing treatment.
doi:10.1002/pon.1848
PMCID: PMC3223600  PMID: 22114043
6.  Pain in Long-Term Adult Survivors of Childhood Cancers and Their Siblings: A Report from the Childhood Cancer Survivor Study 
Pain  2011;152(11):2616-2624.
Little is known about pain among long-term adult survivors of childhood cancers. The study investigated pain prevalence in this population compared with sibling controls and examined pain-related risk factors. Three self-reported pain outcomes including pain conditions, prescription analgesics used, and pain attributed to cancer and treatment were assessed among 10,397 cancer survivors and 3,034 sibling controls from the Childhood Cancer Survivor Study (CCSS). Pain conditions (pain/abnormal sensation, migraines, and other headaches) were reported by 12.3%, 15.5%, and 20.5% of survivors respectively; 16.7% of survivors reported use of prescription analgesics, and 21% attributed pain to cancer and treatment. Risks of reporting pain conditions and using prescription analgesics were higher among survivors than siblings adjusting for sociodemographic factors. Younger age at diagnosis and a history of non-Hodgkin lymphoma, Wilms tumor, or neuroblastoma (compared to leukemia) were associated with greater risk of reporting pain conditions. A history of bone cancer or soft tissue sarcoma (compared to leukemia) was associated with greater risks of using prescription analgesics and cancer-related pain attribution. Non-brain directed scatter irradiation was associated with elevated risk for migraines and cancer-related pain attribution. Female gender and lower educational attainment were associated with increased reports of all three pain outcomes; minority status, unemployment, and being single were associated with greater risks for reporting pain conditions. These findings contribute to the understanding of pain and associated risk factors among adult survivors of childhood cancer and suggest areas of focus for pain intervention.
doi:10.1016/j.pain.2011.08.006
PMCID: PMC3304496  PMID: 21907493
Long-term adult survivors of childhood cancer; Self-reported pain; Pain attribution; Risk factors
7.  Knowledge and attitudes of doctors regarding the provision of mental health care in Doddaballapur Taluk, Bangalore Rural district, Karnataka 
Background
Specialist mental health care is out of reach for most Indians. The World Health Organisation has called for the integration of mental health into primary health care as a key strategy in closing the treatment gap. However, few studies in India have examined medical practitioners’ mental health-related knowledge and attitudes. This study examined these facets of service provision amongst doctors providing primary health care in a rural area of Karnataka is Southern India.
Methods
A mental health knowledge and attitudes questionnaire was self- administered by participants. The questionnaire consisted of four sections; 1) basic demographics and practice information, 2) training in mental health, 3) knowledge of mental health, and self-perceived competence in providing mental health care, and 4) attitudes towards mental health. Data was analysed quantitatively, primarily using descriptive statistics.
Results
This study recruited 46 participants. The majority of participants (69.6%) felt competent in providing mental health services to their patients. However, there was a substantial level of endorsement for several statements that reflected negative attitudes. Almost one third of participants (28.0%) had not received any training in providing mental health care. Whilst three-quarters of participants correctly identified depression (76.1%) and psychosis (76.1%) in a vignette, fewer were able to name three common signs and symptoms of depression (50.0%) and psychosis (28.3%).
Conclusions
Integrating mental health into primary health care requires evidence-based up-skilling programs. Doctors in this study desired such training and would benefit from it, with a focus on both depth of knowledge and uncovering stigmatising attitudes towards people with mental health problems.
doi:10.1186/1752-4458-6-21
PMCID: PMC3499292  PMID: 22995756
8.  Physical, Mental and Neurocognitive Status and Employment Outcomes in the Childhood Cancer Survivor Study Cohort 
Introduction
We examined the relationship of physical, mental, and neurocognitive function with employment and occupational status in the Childhood Cancer Survivor Study.
Methods
We included survivors ≥25 years of age with available Short Form-36 (physical and mental health component scores), Brief Symptom Inventory (depression, anxiety and somatization), and Neurocognitive Questionnaire (task efficiency, emotional regulation, organization, and memory). We generated relative risks (RR) from generalized linear models for these measures on unemployment (N=5386) and occupation (N=3763) outcomes adjusted for demographic and cancer-related factors, and generated sex-stratified models.
Results
Poor physical health was associated with an almost 8-fold higher risk of health-related unemployment (p<0.001) compared to survivors with normal physical health. Male survivors with somatization and memory problems were approximately 50% (p<0.05 for both) more likely to report this outcome, while task efficiency limitations was significant for both sexes (males: RR=2.43, p<0.001; females: RR=2.28, p<0.001). Employed female survivors with task efficiency, emotional regulation, and memory limitations were 13%-20% (p<0.05 for all) less likely to work in professional or managerial occupations than unaffected females.
Conclusions
Physical problems may cause much of the health-related unemployment among childhood cancer survivors. While both male and female survivors with neurocognitive deficits – primarily in task efficiencies – are at risk for unemployment, employed female survivors with neurocognitive deficits may face poor occupational outcomes more often than males.
Impact
Childhood cancer survivors are at risk for poor employment outcomes. Screening and intervention for physical, mental and neurocognitive limitations could improve employment outcomes for this population.
doi:10.1158/1055-9965.EPI-11-0239
PMCID: PMC3266056  PMID: 21844244
pediatric cancer; employment status; physical health; mental health; neurocognitive function
9.  Unemployment among Adult Survivors of Childhood Cancer: A report from the Childhood Cancer Survivors Study 
Medical care  2010;48(11):1015-1025.
Background
Adult childhood cancer survivors report high levels of unemployment although it is unknown whether this is due to health or employability limitations.
Objectives
We examined two employment outcomes from 2002–2005 in the Childhood Cancer Survivor Study (CCSS): 1. health-related unemployment and 2. unemployed but seeking work. We compared survivors to a nearest-age CCSS sibling cohort and examined demographic and treatment-related risk groups for each outcome.
Methods
We studied 6339 survivors and 2280 siblings aged ≥25 years excluding those unemployed by choice. Multivariable generalized linear models evaluated whether survivors were more likely to be unemployed than siblings and whether certain survivors were at a higher risk for unemployment.
Results
Survivors (10.4%) reported health-related unemployment more often than siblings (1.8%; Relative Risk [RR] 6.07, 95% Confidence Interval [CI] 4.32–8.53). Survivors (5.0%) were more likely to report being unemployed but seeking work than siblings (2.7%; RR 1.90, 95% CI 1.43–2.54). Health-related unemployment was more common in female survivors than males (Odds Ratio [OR] 1.73, 95% CI 1.43–2.08). Cranial radiotherapy doses ≥25 Gy were associated with higher odds of unemployment (health-related: OR 3.47, 95% CI 2.54–4.74; seeking work: OR 1.77, 95% CI 1.15–2.71). Unemployed survivors reported higher levels of poor physical functioning than employed survivors, and had lower education and income and were more likely to be publicly insured than unemployed siblings.
Conclusions
Childhood cancer survivors have higher levels of unemployment due to health or being between jobs. High-risk survivors may need vocational assistance.
doi:10.1097/MLR.0b013e3181eaf880
PMCID: PMC3428202  PMID: 20940653
10.  Occurrence of Multiple Subsequent Neoplasms in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2011;29(22):3056-3064.
Purpose
Childhood cancer survivors experience an increased incidence of subsequent neoplasms (SNs). Those surviving the first SN (SN1) remain at risk to develop multiple SNs. Because SNs are a common cause of late morbidity and mortality, characterization of rates of multiple SNs is needed.
Patients and Methods
In a total of 14,358 5-year survivors of childhood cancer diagnosed between 1970 and 1986, analyses were carried out among 1,382 survivors with an SN1. Cumulative incidence of second subsequent neoplasm (SN2), either malignant or benign, was calculated.
Results
A total of 1,382 survivors (9.6%) developed SN1, of whom 386 (27.9%) developed SN2. Of those with SN2, 153 (39.6%) developed more than two SNs. Cumulative incidence of SN2 was 46.9% (95% CI, 41.6% to 52.2%) at 20 years after SN1. The cumulative incidence of SN2 among radiation-exposed survivors was 41.3% (95% CI, 37.2% to 45.4%) at 15 years compared with 25.7% (95% CI, 16.5% to 34.9%) for those not treated with radiation. Radiation-exposed survivors who developed an SN1 of nonmelanoma skin cancer (NMSC) had a cumulative incidence of subsequent malignant neoplasm (SMN; ie, malignancies excluding NMSC) of 20.3% (95% CI, 13.0% to 27.6%) at 15 years compared with only 10.7% (95% CI, 7.2% to 14.2%) for those who were exposed to radiation and whose SN1 was an invasive SMN (excluding NMSC).
Conclusion
Multiple SNs are common among aging survivors of childhood cancer. SN1 of NMSC identifies a population at high risk for invasive SMN. Survivors not exposed to radiation who develop multiple SNs represent a population of interest for studying genetic susceptibility to neoplasia.
doi:10.1200/JCO.2011.34.6585
PMCID: PMC3157966  PMID: 21709189
11.  Survivors of Childhood Cancer Have Increased Risk for Gastrointestinal Complications Later in Life 
Gastroenterology  2011;140(5):1464-1471.e1.
Background & Aims
Children who receive cancer therapy experience numerous acute gastrointestinal (GI) toxicities. However, the long-term GI consequences have not been extensively studied. We evaluated the incidence of adverse long-term GI outcomes and identified treatment-related risk factors.
Methods
Upper GI, hepatic, and lower GI adverse outcomes were assessed in cases randomly selected from participants in the Childhood Cancer Survivor Study, a study of 14,358 survivors of childhood cancer who were diagnosed between 1970 and 1986; data were compared with those from siblings. The median age at cancer diagnosis was 6.8 years (0–21.0 years), the median age at outcome assessment was 23.2 years (5.6–48.9 years) for survivors and 26.6 years (1.8–56.2 years) for siblings. Rates of self-reported, late complications of the GI tract (occurred 5 or more years after cancer diagnosis) were determined and associated with patient characteristics and cancer treatments, adjusting for age, sex, and race; data were compared with those from siblings.
Results
Compared with siblings, survivors had increased risk for late-onset complications of the upper GI tract (relative risk [RR]=1.8; 95% confidence interval [CI], 1.6–2.0), liver (RR=2.1; 95% CI, 1.8–2.5), and lower GI tract (RR=1.9; 1.7–2.2). The RR for requiring colostomy, ileostomy, or liver biopsy, or for developing liver cirrhosis were 5.6 (95% CI, 2.4–13.1), 24.1 (95% CI, 7.5–77.8), and 8.9 (95% CI, 2.0–40.0), respectively. Older age at diagnosis, intensified therapy, abdominal radiation, and abdominal surgery increased the risk of certain GI complications.
Conclusions
Individuals who received therapy for cancer during childhood have an increased risk of developing GI complications later in life.
doi:10.1053/j.gastro.2011.01.049
PMCID: PMC3081911  PMID: 21315721
tumor; chemotherapy; side effect; toxicity; pediatric
12.  Prospective Medical Assessment of Adults Surviving Childhood Cancer: Study Design, Cohort Characteristics, and Feasibility of the St. Jude Lifetime Cohort Study 
Pediatric blood & cancer  2010;56(5):825-836.
Background
To facilitate prospective medical assessment of adults surviving pediatric malignancies and advance knowledge about long-term childhood cancer survivor health, St. Jude Children’s Research Hospital (SJCRH) is establishing a lifetime cohort of survivors.
Methods
Eligibility criteria for inclusion in the St. Jude Lifetime Cohort (SJLIFE) study include: 1) diagnosis of childhood malignancy treated at SJCRH; 2) survival ≥ 10 years from diagnosis; and 3) current age ≥ 18 years. Three levels of participation are offered: 1) comprehensive evaluation on SJCRH campus; 2) limited home evaluation; or 3) completion of health surveys only. A systematic recruitment structure based upon blocks of 50 patients initially focused on leukemia and lymphoma survivors and patients eligible for pilot studies.
Results
As of 01/01/2010, 1625 (42%) of 3900 eligible ≥ 10 year survivors have been contacted. Among the first 1000 potentially eligible survivors selected for recruitment, 971 were subsequently confirmed to fulfill eligibility criteria. To date, 898/971 (92.5%) have been successfully contacted of whom 825 (91.8%) have agreed to participate. Among participants, 88.6% agreed to comprehensive medical evaluation, 0.4% limited local evaluation, and 11.0% survey only. Anticipated minimum overall participation rate for medical evaluation is 75.3% (731/971). Comparison of those contacted who agreed versus declined to participate revealed a greater proportion of males who declined participation (p = 0.001).
Conclusions
Early results of the SJLIFE study support its feasibility to recruit aging childhood cancer survivors to research investigations evaluating late health outcomes by medical assessments.
doi:10.1002/pbc.22875
PMCID: PMC3088729  PMID: 21370418
Childhood cancer; late effects; long-term follow-up
13.  PHYSICAL THERAPY AND CHIROPRACTIC USE AMONG CHILDHOOD CANCER SURVIVORS WITH CHRONIC DISEASE: IMPACT ON HEALTH-RELATED QUALITY OF LIFE 
Introduction
The use of rehabilitation services to address musculoskeletal, neurological and cardiovascular late effects among childhood cancer survivors could improve physical function and health-related quality-of-life (HRQL). We describe physical therapy (PT) and chiropractic utilization among childhood cancer survivors and their association with HRQL.
Methods
The sample included 5+ year survivors from the Childhood Cancer Survivor Study (N=9,289). Questions addressing use of PT or chiropractic services and HRQL (Medical Outcomes Survey Short Form (SF-36)) were evaluated. Multivariable regression models compared PT and/or chiropractic utilization between survivors and siblings, and by diagnosis, treatment and demographic characteristics; associations between chronic disease, PT/chiropractic use, and HRQL were similarly evaluated.
Results
Survivors were not more likely to use PT (OR 1.0; 95% CI 0.8-1.2) or chiropractic (OR 0.8; 95% CI 0.7-1.0) services than siblings. More survivors reported using chiropractic (12.4%) than PT (9.2%) services. Older age and having health insurance were associated with utilization of either PT or chiropractic services. Grade 3-4 chronic conditions and a CNS tumor or sarcoma history were associated with PT but not with chiropractic service utilization. Survivors with musculoskeletal (OR 1.8; 95% CI 1.1-2.9), neurological (OR 3.4; 95% CI 1.6-6.9), or cardiovascular (OR 3.3; 95% CI 1.6-6.9) chronic conditions who used PT/chiropractic services were more likely to report poor physical health than survivors who did not use services.
Conclusions
The reported prevalence of PT/chiropractic among survivors is consistent with that reported by siblings. Severity of late effects is associated with service use and with reporting poor physical health.
Implications for Cancer Survivors
Long-term childhood cancer survivors do not appear to utilize rehabilitation services to optimize physical function and support increased HRQL.
doi:10.1007/s11764-010-0151-9
PMCID: PMC3062253  PMID: 20922492
Physical therapy; chiropractic; childhood cancer survivor; health related quality of life
14.  Survival and long-term health and cognitive outcomes after low-grade glioma 
Neuro-Oncology  2010;13(2):223-234.
Long-term morbidity for children with low-grade glioma (LGG) requires exposure-specific characterization. Overall survival (OS) and progression-free survival (PFS) were estimated for 361 children diagnosed with LGG between 1985 and 2007 at a single institution. Five-year survivors (n = 240) received risk-based clinical assessment. Cumulative incidence of late effects 15 years from diagnosis were estimated. Risk factors for adverse health were identified using Fine and Gray's approach to Cox's proportional hazards model, accounting for death as a competing risk. OS at 15 years was 86% (95% confidence interval [CI] 82%–90%), and PFS was 55% (95% CI 51%–58%). Among the 240 5-year survivors, the 5-, 10-, and 15-year cumulative incidence of adverse outcomes included blindness: 10%, 13%, and 18%, respectively; hearing loss: 8%, 14%, and 22%; obesity/overweight: 18%, 35%, and 53%; hyperinsulinism: 1%, 5%, and 24%; growth hormone deficiency: 13%, 27%, and 29%;thyroid hormone deficiency: 16%, 28%, and 33%; and adrenocorticotropic hormone (ACTH) deficiency: 12%, 22%, and 26%. Multivariable models demonstrated radiation therapy to be a significant independent predictor of hearing loss, growth hormone deficiency, abnormal thyroid function, and ACTH deficiency. Diencephalic location was a statistically significant independent risk factor for blindness, growth hormone deficiency, abnormal thyroid function, and ACTH deficiency. Among the 182 5-year survivors assessed for intellectual function, 34% had an intelligence quotient (IQ) below average (<85), associated with younger age at diagnosis, epilepsy, and shunt placement. Survivors of childhood LGG experience substantial long-term adverse effects that continue to increase well beyond the 5-year survival time point.
doi:10.1093/neuonc/noq178
PMCID: PMC3064628  PMID: 21177781
cancer; glioma; pediatric; survivor
15.  HIV risk behaviours among injecting drug users in Northeast India following scale-up of a targeted HIV prevention programme 
BMC Public Health  2011;11(Suppl 6):S9.
Background
In the Northeast Indian states of Manipur and Nagaland there has been an ongoing HIV epidemic among injecting drug users (IDUs) since the mid-1990s. Project ORCHID is an Avahan-funded HIV prevention project that has been working in selected districts of Manipur and Nagaland since 2004. It supports local partner non-government organisations (NGOs) to deliver a range of harm reduction interventions, and currently reaches approximately 14,500 IDUs across the two states. To assess changes in HIV risk behaviours two Behavioural Tracking Surveys (BTS) were undertaken among IDUs in 2007 and 2009.
Methods
The BTS used respondent driven sampling (RDS) to recruit adult male IDUs (18 years of age and above) from Ukhrul and Chandel districts in Manipur, and Kiphire and Zunheboto districts in Nagaland. This paper reports on analysis of socio-demographics, drug use and injecting practices, sexual behaviour and condom use, knowledge of HIV, and exposure to interventions. Descriptive data were analysed using RDSAT, and odds ratios were calculated in SPSS.
Results
The proportion of IDUs reporting NOT sharing needles / syringes at last injection increased substantially in Ukhrul (59.6% to 91.2%) and Zunheboto (45.5% to 73.8%), remained high in Chandel (97.0% to 98.9%), and remained largely unchanged in Kiphire (63.3% to 68.8%). The use of condoms with regular partners was low in all districts at both time points. In Ukhrul, Kiphire and Zunheboto the proportion of IDUs using condoms during sexual intercourse with a casual partner increased substantially to approximately 70-85%, whilst in Chandel the increase was only marginal (57.4% to 63.6%). Exposure to NGO HIV prevention interventions was significantly associated (p<0.05) with lower odds of sharing needles during the previous month (Nagaland, OR=0.63; Manipur, OR 0.35).
Conclusion
Despite district-level differences, the results from this BTS study indicate that exposure to HIV prevention services, predominately delivered in this region by NGOs, is associated with a reduced likelihood of engaging in HIV risk behaviours. IDUs using HIV prevention services are more likely to engage in safe injecting and sexual practices, and effort is required to sustain / increase opportunities for IDUs to access these services. These outcomes are a noteworthy achievement in a very challenging context.
doi:10.1186/1471-2458-11-S6-S9
PMCID: PMC3287562  PMID: 22375900
16.  The Increasing Burden of Imported Chronic Hepatitis B — United States, 1974–2008 
PLoS ONE  2011;6(12):e27717.
Background
Without intervention, up to 25% of individuals chronically infected with hepatitis B virus (HBV) die of late complications, including cirrhosis and liver cancer. The United States, which in 1991 implemented a strategy to eliminate HBV transmission through universal immunization, is a country of low prevalence. Approximately 3,000–5,000 U.S.-acquired cases of chronic hepatitis B have occurred annually since 2001. Many more chronically infected persons migrate to the United States yearly from countries of higher prevalence. Although early identification of chronic HBV infection can reduce the likelihood of transmission and late complications, immigrants are not routinely screened for HBV infection during or after immigration.
Methods
To estimate the number of imported cases of chronic hepatitis B, we multiplied country-specific prevalence estimates by the yearly number of immigrants from each country during 1974–2008.
Results
During 1974–2008, 27.9 million immigrants entered the U.S. Sixty-three percent were born in countries of intermediate or high chronic hepatitis B prevalence (range 2%–31%). On average, an estimated 53,800 chronic hepatitis B cases were imported to the U.S. yearly from 2004 through 2008. The Philippines, China, and Vietnam contributed the most imported cases (13.4%, 12.5%, and 11.0%, respectively). Imported cases increased from an estimated low of 105,750 during the period 1974–1977 to a high of 268,800 in 2004–2008.
Conclusions
Imported chronic hepatitis B cases account for approximately 95% of new U.S. cases. Earlier case identification and management of infected immigrants would strengthen the U.S. strategy to eliminate HBV transmission, and could delay disease progression and prevent some deaths among new Americans.
doi:10.1371/journal.pone.0027717
PMCID: PMC3233539  PMID: 22163270
17.  Long-Term Effects of Radiation Exposure among Adult Survivors of Childhood Cancer: Results from the Childhood Cancer Survivor Study 
Radiation research  2010;174(6):840-850.
In the last four decades, advances in therapies for primary cancers have improved overall survival for childhood cancer. Currently, almost 80% of children will survive beyond 5 years from diagnosis of their primary malignancy. These improved outcomes have resulted in a growing population of childhood cancer survivors. Radiation therapy, while an essential component of primary treatment for many childhood malignancies, has been associated with risk of long-term adverse outcomes. The Childhood Cancer Survivor Study (CCSS), a retrospective cohort of over 14,000 survivors of childhood cancer diagnosed between 1970 and 1986, has been an important resource to quantify associations between radiation therapy and risk of long-term adverse health and quality of life outcomes. Radiation therapy has been associated with increased risk for late mortality, development of second neoplasms, obesity, and pulmonary, cardiac and thyroid dysfunction as well as an increased overall risk for chronic health conditions. Importantly, the CCSS has provided more precise estimates for a number of dose–response relationships, including those for radiation therapy and development of subsequent malignant neoplasms of the central nervous system, thyroid and breast. Ongoing study of childhood cancer survivors is needed to establish long-term risks and to evaluate the impact of newer techniques such as conformal radiation therapy or proton-beam therapy.
doi:10.1667/RR1903.1
PMCID: PMC3080029  PMID: 21128808
18.  Region-specific radiotherapy and neuropsychological outcomes in adult survivors of childhood CNS malignancies 
Neuro-Oncology  2010;12(11):1173-1186.
Childhood cancer survivors exposed to CNS irradiation are at increased risk for neurocognitive deficits; however, limited data exist linking outcomes with region-specific exposure to CNS irradiation. We report associations between region-specific radiation dose and self-reported neurocognitive and health-related quality of life (HRQOL) outcomes in 818 adult survivors of childhood central nervous system (CNS) malignancies from the Childhood Cancer Survivor Study. Survivors were compared with a sibling group and national normative samples to calculate standardized scores. Cumulative radiation dose was calculated for 4 specific brain regions. Logistic regression was used to estimate the association between radiation dose to specific brain regions and outcome measures of functional impairment adjusted for clinical and demographic factors, including sex and age at diagnosis. High radiation dose levels to temporal regions were associated with a higher risk for memory impairment (radiation doses ≥30 to <50 Gy: OR, 1.95; 95% CI, 1.01–3.78; dose ≥50 Gy: OR, 2.34; 95% CI, 1.25–4.39) compared with those with no radiation exposure. No such association was seen with radiation exposure to other regions. Exposure to temporal regions was associated with more social and general health problems, whereas exposure to frontal regions was associated with general health problems and physical performance limitations. Adult survivors of childhood CNS malignancies report higher rates of neuropsychological and HRQOL outcomes, which vary as a function of dose to specific neuroanatomical regions. Survivors with a history of radiation exposure to temporal brain regions are at increased risk for impairment in memory and social functioning.
doi:10.1093/neuonc/noq104
PMCID: PMC3098024  PMID: 20716593
CNS malignancies; Childhood Cancer Survivor Study (CCSS); health-related quality of life; neuropsychological functioning; radiation therapy
20.  A mental health training program for community health workers in India: impact on knowledge and attitudes 
Background
Unmet needs for mental health treatment in low income countries are pervasive. If mental health is to be effectively integrated into primary health care in low income countries like India then grass-roots workers need to acquire relevant knowledge and skills to be able to recognise, refer and support people experiencing mental disorders in their own communities. This study aims to provide a mental health training intervention to community health workers in Bangalore Rural District, Karnataka, India, and to evaluate the impact of this training on mental health literacy.
Methods
A pre-test post-test study design was undertaken with assessment of mental health literacy at three time points; baseline, completion of the training, and three month follow-up. Mental health literacy was assessed using the interviewer-administered Mental Health Literacy Survey. The training intervention was a four day course based on a facilitator's manual developed specifically for community health workers in India.
Results
70 community health workers from Doddaballapur, Bangalore Rural District were recuited for the study. The training course improved participants' ability to recognize a mental disorder in a vignette, and reduced participants' faith in unhelpful and potentially harmful pharmacological interventions. There was evidence of a minor reduction in stigmatizing attitudes, and it was unclear if the training resulted in a change in participants' faith in recovery following treatment.
Conclusion
The findings from this study indicate that the training course demonstrated potential to be an effective way to improve some aspects of mental health literacy, and highlights strategies for strengthening the training course.
doi:10.1186/1752-4458-5-17
PMCID: PMC3169476  PMID: 21819562
21.  Characteristics of Responders to a Request for a Buccal Cell Specimen Among Survivors of Childhood Cancer and Their Siblings 
Pediatric blood & cancer  2010;55(1):165-170.
Purpose
Analysis of biological samples in large cohort studies may provide insight into the mechanism of, and risk factors for, disease onset and progression.
Methods
This study describes the methods used to collect biological samples from a large multi-center cohort of childhood cancer survivors and siblings of childhood cancer survivors, and evaluates the predictors of a positive response among these individuals.
Results
Among survivors, female sex, white race/ethnicity, college graduation, never smoking, accessing the health care system in the past two years, and having a second malignant neoplasm were the strongest predictors of returning a sample. Among siblings, a similar demographic profile defined those likely to submit the requested sample.
Conclusion
To reduce selection bias and increase the value of these samples for future analysis, additional phone calls and reminders targeting non-responders are needed to improve response rates among those least likely to respond to a single mailed request.
doi:10.1002/pbc.22513
PMCID: PMC2909600  PMID: 20486182
neoplasm; pediatric; buccal mucosa; cohort study; DNA
22.  Long-term Survivors of Childhood Central Nervous System Malignancies: The Experience of the Childhood Cancer Survivor Study 
In the last four decades, advances in neurosurgical technique, delivery of radiation therapy (RT), supportive care, and use of chemotherapy have improved 5-year survival for children with central nervous system (CNS) malignancies. Currently, in the United States 74% of children will become 5-year survivors of their primary CNS malignancy. This improved outcome has resulted in a new and growing population of childhood cancer survivors. Surgery, RT and chemotherapy, while essential components of primary treatment for most childhood CNS malignancies, have also been associated with risk of long-term morbidity and late mortality. The Childhood Cancer Survivor Study, a retrospective cohort of over 14,000 survivors of childhood cancer diagnosed between 1970 and 1986, has been an important resource for quantification of associations between these therapeutic modalities and risk of long-term adverse health and quality of life outcomes. CNS malignancy survivors are at significant risk for late mortality, development of second neoplasms, as well as increased risk for multiple endocrinopathies and adverse neurologic health conditions. Importantly, the CCSS has identified a number of dose-response relationships between RT and development of subsequent malignant neoplasms of the central nervous system, abnormal timing of menarche and neurocognitive function. Ongoing study of childhood cancer survivors is needed to establish long-term risks and evaluate impact of newer techniques such as conformal RT or proton beam delivery that limit RT exposure and may reduce long-term effects.
doi:10.1016/j.ejpn.2009.12.006
PMCID: PMC2885448  PMID: 20110182
23.  Malaria in Kakuma refugee camp, Turkana, Kenya: facilitation of Anopheles arabiensis vector populations by installed water distribution and catchment systems 
Malaria Journal  2011;10:149.
Background
Malaria is a major health concern for displaced persons occupying refugee camps in sub-Saharan Africa, yet there is little information on the incidence of infection and nature of transmission in these settings. Kakuma Refugee Camp, located in a dry area of north-western Kenya, has hosted ca. 60,000 to 90,000 refugees since 1992, primarily from Sudan and Somalia. The purpose of this study was to investigate malaria prevalence and attack rate and sources of Anopheles vectors in Kakuma refugee camp, in 2005-2006, after a malaria epidemic was observed by staff at camp clinics.
Methods
Malaria prevalence and attack rate was estimated from cases of fever presenting to camp clinics and the hospital in August 2005, using rapid diagnostic tests and microscopy of blood smears. Larval habitats of vectors were sampled and mapped. Houses were sampled for adult vectors using the pyrethrum knockdown spray method, and mapped. Vectors were identified to species level and their infection with Plasmodium falciparum determined.
Results
Prevalence of febrile illness with P. falciparum was highest among the 5 to 17 year olds (62.4%) while malaria attack rate was highest among the two to 4 year olds (5.2/1,000/day). Infected individuals were spatially concentrated in three of the 11 residential zones of the camp. The indoor densities of Anopheles arabiensis, the sole malaria vector, were similar during the wet and dry seasons, but were distributed in an aggregated fashion and predominantly in the same zones where malaria attack rates were high. Larval habitats and larval populations were also concentrated in these zones. Larval habitats were man-made pits of water associated with tap-stands installed as the water delivery system to residents with year round availability in the camp. Three percent of A. arabiensis adult females were infected with P. falciparum sporozoites in the rainy season.
Conclusions
Malaria in Kakuma refugee camp was due mainly to infection with P. falciparum and showed a hyperendemic age-prevalence profile, in an area with otherwise low risk of malaria given prevailing climate. Transmission was sustained by A. arabiensis, whose populations were facilitated by installation of man-made water distribution and catchment systems.
doi:10.1186/1475-2875-10-149
PMCID: PMC3130698  PMID: 21639926
24.  Screening and surveillance for second malignant neoplasms in adult survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS) 
Annals of internal medicine  2010;153(7):442-451.
Background
Childhood cancer survivors may develop a second malignant neoplasm during adulthood and therefore require regular surveillance.
Objective
To examine adherence to population cancer screening guidelines by survivors at average risk of developing a second malignant neoplasm, and to cancer surveillance guidelines by survivors at high risk of developing a second malignant neoplasm.
Design
Retrospective cohort study.
Setting
The Childhood Cancer Survivor Study (CCSS), a 26 center study of long-term survivors of childhood cancer who were diagnosed between 1970 and 1986.
Patients
4,329 male and 4,018 female survivors of childhood cancer who completed a CCSS questionnaire assessing screening and surveillance for new cancers.
Measurements
Patient-reported receipt and timing of mammography, Papanicolaou smear, colonoscopy, or skin examination was categorized as adherent to the United States Preventive Services Task Force guidelines for survivors at average risk for breast or cervical cancer, or the Children’s Oncology Group guidelines for survivors at high risk for developing breast, colorectal or skin cancer as a result of their therapy.
Results
Among average risk female survivors, 2,743/3,392 (80.9%) reported a Papanicolaou smear within the recommended period, and 140/209 (67.0%) reported a mammogram within the recommended period. Among high risk survivors, rates of recommended mammography among females, and colonoscopy and complete skin exams among both genders were only 241/522 (46.2%), 91/794 (11.5%) and 1,290/4,850 (26.6%), respectively.
Limitations
Data were self report. CCSS participants are a select group of survivors and their compliance may not be representative of all childhood cancer survivors.
Conclusions
Female survivors at average risk for developing a second malignant neoplasm demonstrate reasonable rates of screening for cervical and breast cancer. However, surveillance for new cancers is very poor amongst survivors at highest risk for colon, breast or skin cancer, suggesting that survivors and their physicians need education about their risks and the recommended surveillance.
doi:10.1059/0003-4819-153-7-201010050-00007
PMCID: PMC3084018  PMID: 20921543
25.  Temporal Trends in Cause-Specific Late Mortality Among 5-Year Survivors of Childhood Cancer 
Journal of Clinical Oncology  2010;28(7):1224-1231.
Purpose
Five-year survival rates for childhood cancer have improved over the past four decades. However, it is unknown whether changes in primary cancer therapy have improved rates of long-term (> 5 years from diagnosis) durable remissions and reduced treatment-related deaths. We investigated changes in patterns of late mortality over time and cause-specific attribution of late-mortality among 5-year survivors.
Patients and Methods
Using data from the Surveillance, Epidemiology and End Results (SEER) population-based registry, we assessed all-cause and cause-specific (recurrence/progression of primary disease, external cause, and nonrecurrence/nonexternal cause) late mortality during four consecutive time periods from 1974 through 2000 among 26,643 5-year survivors of childhood cancer.
Results
All-cause late mortality improved during more recent eras, dropping from 7.1% (95% CI, 6.4% to 7.8%) among children diagnosed during 1974 to 1980 to 3.9% (95% CI, 3.3% to 4.4%) among children diagnosed during 1995 to 2000 (P < .001), largely because of reduced mortality from recurrence or progression. While there was no significant reduction in mortality attributable to other health conditions (including treatment-related health conditions), analysis controlling for demographic characteristics identified a trend toward reduced risk during more recent eras (P = .007). Disparity by race/ethnicity was identified, with higher mortality among non-Hispanic blacks than among non-Hispanic whites for all-cause and nonrecurrence/nonexternal -cause late mortality.
Conclusion
While overall patterns of mortality from other health conditions do not differ over time, adjustment for demographic characteristics provides evidence that risk of treatment-related mortality may be lower in more recent eras. Disparities in health care utilization among survivors should be explored.
doi:10.1200/JCO.2009.24.4608
PMCID: PMC3102544  PMID: 20124180

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