Search

Hotspots difficult to confidently assess for CHIP

Supplementary Methods and Supplementary Figures

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by detectable hematopoietic-associated gene mutations in a person without evidence of hematologic malignancy. We sought to identify additional cancer-presenting mutations usable for CHIP detection by performing a data mining analysis of 48 somatic mutation landscape studies reporting mutations at diagnoses of 7,430 adult and pediatric patients with leukemia or other hematologic malignancy. Following extraction of 20,141 protein-altering mutations, we identified 434 significantly recurrent mutation hotspots, 364 of which occurred at loci confidently assessable for CHIP. We then performed an additional large-scale analysis of whole-exome sequencing data from 4,538 persons belonging to three noncancer cohorts for clonal mutations. We found the combined cohort prevalence of CHIP with mutations identical to those reported at blood cancer mutation hotspots to be 1.8%, and that some of these CHIP mutations occurred in children. Our findings may help to improve CHIP detection and precancer surveillance for both children and adults.Significance:This study identifies frequently occurring mutations across several blood cancers that may drive hematologic malignancies and signal increased risk for cancer when detected in healthy persons. We find clonal mutations at these hotspots in a substantial number of individuals from noncancer cohorts, including children, showcasing potential for improved precancer surveillance.See related commentary by Spitzer and Levine, p. 192.

PDF file - 75K, PROMIS Global Health Scale unadjusted means for cancer survivors and adults with no cancer history

Background: Despite extensive data on health-related quality of life (HRQOL) among cancer survivors, we do not yet have an estimate of the percentage of survivors with poor mental and physical HRQOL compared with population norms. HRQOL population means for adult-onset cancer survivors of all ages and across the survivorship trajectory also have not been published.Methods: Survivors (N = 1,822) and adults with no cancer history (N = 24,804) were identified from the 2010 National Health Interview Survey. The PROMIS® Global Health Scale was used to assess HRQOL. Poor HRQOL was defined as 1 SD or more below the PROMIS® population norm.Results: Poor physical and mental HRQOL were reported by 24.5% and 10.1% of survivors, respectively, compared with 10.2% and 5.9% of adults without cancer (both P < 0.0001). This represents a population of approximately 3.3 million and 1.4 million U.S. survivors with poor physical and mental HRQOL. Adjusted mean mental and physical HRQOL scores were similar for breast, prostate, and melanoma survivors compared with adults without cancer. Survivors of cervical, colorectal, hematologic, short-survival, and other cancers had worse physical HRQOL; cervical and short-survival cancer survivors reported worse mental HRQOL.Conclusion: These data elucidate the burden of cancer diagnosis and treatment among U.S. survivors and can be used to monitor the impact of national efforts to improve survivorship care and outcomes.Impact: We present novel data on the number of U.S. survivors with poor HRQOL. Interventions for high-risk groups that can be easily implemented are needed to improve survivor health at a population level. Cancer Epidemiol Biomarkers Prev; 21(11); 2108–17. ©2012 AACR.

Arab populations are largely understudied, notably their genetic structure and history. Here we present an in-depth analysis of 6,218 whole genomes from Qatar, revealing extensive diversity as well as genetic ancestries representing the main founding Arab genealogical lineages of Qahtanite (Peninsular Arabs) and Adnanite (General Arabs and West Eurasian Arabs). We find that Peninsular Arabs are the closest relatives of ancient hunter-gatherers and Neolithic farmers from the Levant, and that founder Arab populations experienced multiple splitting events 12–20 kya, consistent with the aridification of Arabia and farming in the Levant, giving rise to settler and nomadic communities. In terms of recent genetic flow, we show that these ancestries contributed significantly to European, South Asian as well as South American populations, likely as a result of Islamic expansion over the past 1400 years. Notably, we characterize a large cohort of men with the ChrY J1a2b haplogroup (n = 1,491), identifying 29 unique sub-haplogroups. Finally, we leverage genotype novelty to build a reference panel of 12,432 haplotypes, demonstrating improved genotype imputation for both rare and common alleles in Arabs and the wider Middle East., Arab populations are relatively understudied, especially their genetic architecture and historical relationship with early founders of the ancient Near East. Here, the authors examine 6,218 Qatari whole genomes, revealing insights on migration, population history and genetic structure of populations across the Middle Eastern region.

Research Objective: The objective of this study was to evaluate the insurance, employment, and financial experiences of young (age ≤ 39 years) female breast cancer patients and assess factors associated with any changes in their financial situation. Previous literature has shown that younger women are more likely to be diagnosed with late-stage disease that requires more-intensive treatments, while significant medical expenditures, productivity losses, financial hardship, and changes in employment and work productivity have been found in patients of all ages. Methods: A sample of women who were diagnosed with breast cancer between the ages of 18 and 39 years and residing in the states of California, Florida, Georgia, and North Carolina were identified. The sample included women who were (1) diagnosed with ductal carcinoma in situ (D05.90; 8500/2) or invasive breast cancer (C50; 8500/3) between January 2013 and December 2014; (2) between the ages of 18 and 39 years at the time of diagnosis; and (3) alive at the time of data extraction. We contacted 3,659 women by mail; 2,927 were alive with deliverable addresses. Of those, 830 women returned completed surveys, yielding a response rate of 28.4%. The survey instrument included 66 questions on demographics, insurance status, employment history, out-of-pocket cost, and overall financial well-being. Multivariate analysis was used to identify factors associated with financial decline. Principal Findings: About half of the women (47.4%) reported that treatment expenditures were higher than anticipated, and almost two-thirds (65.3%) had not discussed treatment costs with their care team. Almost a third of the patients (31.8%) reported treatment nonadherence due to cost. Factors associated with not receiving recommended care included very young age ( Citation Format: Florence Tangka, Sujha Subramanian, Madeleine Jones, Patrick Edwards, Tim Flanigan, Jenya Kaganova, Kevin Smith, Cheryll Thomas, Nikki Hawkins, Temeika Fairley, Gery Guy, Juan Rodriguez. Insurance coverage, employment status, and financial wellbeing of young women diagnosed with breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-45.

Obesity, a major risk factor for metabolic disorders, is highly prevalent in Qatari population. Maternal transmission of obesity traits can be significant; for example, X haplogroup is known to be associated with lower BMI and body fat mass in Northern Europeans and T haplogroup which is a sister haplogroup of J is known to be associated with obesity in Caucasian subjects from Austria and Southern Italy. We aimed to delineate the mitochondrial haplogroups and variants associated with obesity in Qatari population. Mitochondrial genomes of 864 Qatari individuals were extracted from whole exome sequencing data with an average coverage of 77X. We distributed the participants into 2 sub-cohorts: obese (BMI ≥ 30) and non-obese (BMI P = 0.0038; the Bonferroni adjusted P value threshold is 0.0041), whereas the individuals with haplogroup X were at low risk of obesity (OR 0.387; 95% CI 0.175–0.857; P = 0.019). Further, a set of 38 mitochondrial variants were found to be associated (at P ≤ 0.05) with obesity in models adjusted for age, sex and haplogroup.

PURPOSE: Breast cancer is the leading cause of cancer-related deaths in women younger than 40 years. We aim to evaluate cost as a barrier to care among female breast cancer patients diagnosed between 18 to 39 years. METHODS: In early 2017, we distributed a survey to women diagnosed with breast cancer between the ages of 18 and 39 years, as identified by the central cancer registries of California, Georgia, North Carolina, and Florida. We used multivariable statistics to explore cost-related barriers to receiving breast cancer care for the 830 women that completed the survey. RESULTS: About half of the women (47.4%) reported spending more on breast cancer care than expected, and almost two-thirds (65.3%) had not discussed costs with their care team. A third of the patients (31.8%) indicated forgoing care due to cost. Factors associated with not receiving anticipated care due to cost included age less than35 years at diagnosis, self-insurance, comorbid conditions, and late-stage diagnosis. CONCLUSION: Previous studies using breast cancer registry data have not included detailed insurance information and care received by young women. Young women with breast cancer frequently forgo breast cancer care due to cost. Our results highlight the potential for policies that facilitate optimal care for young breast cancer patients which could include the provision of comprehensive insurance coverage.

Oral health is influenced by social determinants of health (SDH), predisposing people and communities to greater risk of developing caries. This study evaluated the association between caries risk in adults and SDH such as ZIP Codes, systemic diseases, payment methods, and race or ethnicity.The BigMouth Dental Data Repository (n = 57,211) was used to extract clinical and SDH data from patients' dental electronic health records for 2019. Caries risk categories were used as ZIP Code data was merged with the Social Deprivation Index, a composite measure of area-level deprivation based on 7 demographic characteristics collected in the American Community Survey.The results showed that the odds of being in the high caries risk group were higher for people in the 49- to 64-year age group (adjusted odds ratio [aOR], 2.24; 95% CI, 2.08 to 2.40; P ≤ .001), men (aOR, 1.19; 95% CI, 1.13 to 1.25; P ≤ .001), people who had comorbidities (diabetes: aOR, 1.16; 95% CI, 1.08 to 1.24; P ≤ .001; cardiovascular disease: aOR, 1.40; 95% CI, 1.32 to 1.50), and people with an Social Deprivation Index score above the 75th percentile (aOR, 2.39; 95% CI, 2.21 to 2.58; P ≤ .001). In addition, Hispanic and Black people had higher odds of being at high caries risk than other races or ethnicities (Hispanic: aOR, 3.05; 95% CI, 2.32 to 4.00; Black: aOR, 2.05; 95% CI, 1.02 to 4.01).This study shows the association of caries risk with higher social deprivation, reinforcing the role of structural and upstream factors in oral health. This study is unique in using recorded ZIP Code information and assessing caries risk levels for those regions.The physical and structural environment should be considered contributors to caries risk in people.

The collection and evaluation of family health history in a clinical setting presents an opportunity to discuss cancer risk, tailor cancer screening recommendations, and identify people with an increased risk of carrying a pathogenic variant who may benefit from referral to genetic counseling and testing. National recommendations for breast and colorectal cancer screening indicate that men and women who have a first-degree relative affected with these types of cancers may benefit from talking to a healthcare provider about starting screening at an earlier age and other options for cancer prevention. The prevalence of reporting a first-degree relative who had cancer was assessed among adult respondents of the 2015 National Health Interview Survey who had never had cancer themselves (n = 27,999). We found 35.6% of adults reported having at least one first-degree relative with cancer at any site. Significant differences in reporting a family history of cancer were observed by sex, age, race/ethnicity, educational attainment, and census region. Nearly 5% of women under age 50 and 2.5% of adults under age 50 had at least one first-degree relative with breast cancer or colorectal cancer, respectively. We estimated that 5.8% of women had a family history of breast or ovarian cancer that may indicate increased genetic risk. A third of U.S. adults who have never had cancer report a family history of cancer in a first-degree relative. This finding underscores the importance of using family history to inform discussions about cancer risk and screening options between healthcare providers and their patients.

Among people with HIV, histoplasmosis represents an important cause of mortality. Previous studies provided estimates of the disease incidence. Here, we compared those estimates with the results obtained from a screening program implemented in Guatemala, which included histoplasmosis detection for people with HIV. To compare the results of this program with previous estimations, a literature search was performed and reports concerning histoplasmosis incidence were analyzed. The screening program enrolled 6366 patients. The overall histoplasmosis incidence in the screening program was 7.4%, which was almost double that estimated in previous studies. From 2017 to 2019, the screening program showed an upward trend in histoplasmosis cases from 6.5% to 8.8%. Histoplasmosis overall mortality among those who were newly HIV diagnosed showed a decrease at 180 days from 32.8% in 2017 to 21.2% in 2019. The screening approach using rapid diagnostic assays detects histoplasmosis cases more quickly, allowing a specific treatment to be administered, which decreases the mortality of the disease. Therefore, the use of these new techniques, especially in endemic areas of histoplasmosis, must be implemented. This work was supported by Global Action Fund for Fungal Infections and JYLAG, a charity Foundation based in Switzerland (E.A. received this funding under the proposal: “Minimising HIV deaths through rapid fungal diagnosis and better care in Guatemala”). Other contributions came from Intrahealth International and the Ministry of health in Guatemala (MSPAS). Sí

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by detectable hematopoietic-associated gene mutations in a person without evidence of hematologic malignancy. We sought to identify additional cancer-presenting mutations usable for CHIP detection by performing a data mining analysis of 48 somatic mutation landscape studies reporting mutations at diagnoses of 7,430 adult and pediatric patients with leukemia or other hematologic malignancy. Following extraction of 20,141 protein-altering mutations, we identified 434 significantly recurrent mutation hotspots, 364 of which occurred at loci confidently assessable for CHIP. We then performed an additional large-scale analysis of whole-exome sequencing data from 4,538 persons belonging to three noncancer cohorts for clonal mutations. We found the combined cohort prevalence of CHIP with mutations identical to those reported at blood cancer mutation hotspots to be 1.8%, and that some of these CHIP mutations occurred in children. Our findings may help to improve CHIP detection and precancer surveillance for both children and adults. Significance: This study identifies frequently occurring mutations across several blood cancers that may drive hematologic malignancies and signal increased risk for cancer when detected in healthy persons. We find clonal mutations at these hotspots in a substantial number of individuals from noncancer cohorts, including children, showcasing potential for improved precancer surveillance. See related commentary by Spitzer and Levine, p. 192.

Opportunistic infections (OIs) and advanced HIV disease (AHD) contribute to HIV-related mortality. Here, we analyzed the situation of AHD and OIs in a cohort of newly diagnosed HIV patients from Guatemala. We included 2127 adult patients from 13 facilities across the country during 2017 to 2018. Patients were screened for tuberculosis (TB), nontuberculous mycobacteria (NTM), histoplasmosis, and cryptococcal disease, independently of their CD4 cell count. Of the 2127 enrolled patients, 1682 (79.1%) had a CD4 cell count available, of which 52% presented with AHD. Of the Mayan population, 65% had AHD. The overall OI incidence was 21%. Histoplasmosis was the most frequent OI (7.9%), followed by TB (7.1%), 94.4% of these infections occurred in patients with a CD4 &lt, 350 cells/mm3. Mortality at 180 days was significantly higher in those with OIs than without OIs (29.7% vs. 5.9%, p &lt, 0.0001). In one year, this program decreased the OI mortality by 7% and increased the OI treatment by 5.1%. Early OI diagnosis and appropriate therapy reduced OI mortality among newly diagnosed HIV patients in Guatemala. Screening for OIs should be considered in all newly diagnosed HIV patients who have a CD4 cell count &lt, 350 cells/mm3 or those without a CD4 cell count available. To improve results, interventions such as early HIV detection and access to flucytosine and liposomal amphotericin B are required.

PURPOSE: Women undergoing diagnosis and treatment for breast cancer may face challenges in employment. We investigated the impact of demographic, clinical, workplace, and psychosocial characteristics on loss of employment after a breast cancer diagnosis and treatment. We further describe changes in work status and work environment for cancer survivors who sustain employment. METHODS: We analyzed responses from a survey of breast cancer survivors from the Sister Study and the Two Sister Study cohorts who reported being employed at the time of their breast cancer diagnosis and who reported employment status (lost vs. sustained employment) at the time of survey administration. Multivariate logistic regression was used to identify the effects of lymphedema, neuropathy, problems with memory or attention, social support, health insurance, and sick leave on lost employment, adjusting for demographic characteristics, cancer stage, treatment, and general health. RESULTS: Of the 1675 respondents who reported being employed at the time of diagnosis, 83.5% reported being ‘currently’ employed at the time of the survey. Older age, peripheral neuropathy, lack of sick leave, late stage at diagnosis, a recurrence or a new cancer, problems with memory or attention, and poor general health were significantly associated with lost employment. CONCLUSIONS: The long-term effects of breast cancer treatment and workplace provisions for leave and accommodation may have a substantial effect on women’s ability to sustain employment. The findings from this study highlight challenges reported by cancer survivors that may inform clinical and occupational interventions to support survivors’ return to work.

Background Data from a nationwide sample of US breast cancer survivors were used to examine associations between patient characteristics (breast cancer clinical features, prognostic factors, and treatments) and health-related quality of life (HRQOL). Associations between postdiagnosis HRQOL and mortality were then evaluated. Methods The authors identified female breast cancer survivors (n = 2453) from the Sister Study or Two Sister Study who were at least 1 year from breast cancer diagnosis and who had responded to a survivorship survey in 2012. HRQOL was assessed with the Patient-Reported Outcomes Measurement Information System (PROMIS) Global 10 measures. Multivariable linear regression was used to assess predictors associated with HRQOL. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between HRQOL and all-cause mortality. Results HRQOL, assessed an average of 4.9 years after the cancer diagnosis (standard deviation of 1.9 years), was negatively associated with a higher cancer stage at diagnosis; a higher comorbidity score at the survey; experience of surgical complications; dissatisfaction with breast surgery; and experience of any recent recurrence, metastasis, or secondary malignancy. Since the completion of the survey, there were 85 deaths (3.5%) during a mean follow-up of 4 years (standard deviation of 0.5 years). In multivariate models, decreases in PROMIS physical T scores and mental T scores were associated with increased mortality (HR for physical T scores, 1.08; 95% CI, 1.05-1.11; HR for mental T scores, 1.03; 95% CI, 1.01-1.06). Conclusions Prognostic and cancer treatment-related factors affect HRQOL in breast cancer survivors and may inform targeted survivorship care. PROMIS global health measures may offer additional insights into patients' well-being and mortality risk. Lay summary Findings from a study suggest that prognostic and cancer treatment-related factors affect health-related quality of life (HRQOL) in breast cancer survivors and that poor HRQOL may increase the mortality risk. The evaluation of HRQOL is important because it may hold potential as a tool for optimizing survivorship care.

The main goal of this collaborative effort is to provide genome wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for the public data release. DNBSEQ-G50 sequences, and genotypes by an Illumina GWAS chip were cross-validated on multiple samples, and additionally referenced to one sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage. The genome data has been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, CNVs, SNPs and microsatellites. This study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for historic and medical research in a large understudied population. While most of the common variation is shared with other European populations, this survey of population variation contributes a number of novel SNPs and structural variants that have not been reported in the gnomAD/1KG databases representing global distribution of genomic variation. These endemic variants will become a valuable resource for designing future population and clinical studies, help address questions about ancestry and admixture, and will fill a missing place in the puzzle characterizing human population diversity in Eastern Europe. Our results indicate that genetic diversity of the Ukrainian population is uniquely shaped by the evolutionary and demographic forces, and cannot be ignored in the future genetic and biomedical studies. This data will contribute a wealth of new information bringing forth different risk and/or protective alleles. The newly discovered low frequency and local variants can be added to the current genotyping arrays for genome wide association studies, clinical trials, and in genome assessment of proliferating cancer cells.

BackgroundThe main goal of this collaborative effort is to provide genome-wide data for the previously underrepresented population in Eastern Europe, and to provide cross-validation of the data from genome sequences and genotypes of the same individuals acquired by different technologies. We collected 97 genome-grade DNA samples from consented individuals representing major regions of Ukraine that were consented for public data release. BGISEQ-500 sequence data and genotypes by an Illumina GWAS chip were cross-validated on multiple samples and additionally referenced to 1 sample that has been resequenced by Illumina NovaSeq6000 S4 at high coverage.ResultsThe genome data have been searched for genomic variation represented in this population, and a number of variants have been reported: large structural variants, indels, copy number variations, single-nucletide polymorphisms, and microsatellites. To our knowledge, this study provides the largest to-date survey of genetic variation in Ukraine, creating a public reference resource aiming to provide data for medical research in a large understudied population.ConclusionsOur results indicate that the genetic diversity of the Ukrainian population is uniquely shaped by evolutionary and demographic forces and cannot be ignored in future genetic and biomedical studies. These data will contribute a wealth of new information bringing forth a wealth of novel, endemic and medically related alleles.

The economic burden of breast cancer for women under 50 in the United States remains largely unexplored, in part because young women make up a small proportion of breast cancer cases overall. To address this knowledge gap, we conducted a web-based survey to compare data from breast cancer survivors 18–39 years of age at first diagnosis and 40–49 years of age at first diagnosis. We administered a survey to a national convenience sample of 416 women who were 18–49 years of age at the time of their breast cancer diagnosis. We analyzed factors associated with financial decline using multivariate regression. Survivors 18–39 years of age at first diagnosis were more likely to report Stage II–IV breast cancer (P<0.01). They also quit their jobs more often (14.6%) than older survivors (4.4%; P<0.01) and faced more job performance issues (55.7% and 42.8%, respectively; P=0.02). For respondents in both groups, financial decline was more likely if the survivor had at least one comorbid condition (odds ratios: 2.36–3.21) or was diagnosed at Stage II–IV breast cancer (odds ratios: 2.04–3.51).

Objectives: We evaluated the comparative performance of different assays used in a Diagnostic Laboratory Hub that linked 13 HIV healthcare facilities for the diagnosis of tuberculosis (TB), histoplasmosis, and cryptococcosis, and describing its functions in Guatemala compared with other National Reference Laboratories. Methods: The following diagnostic techniques were analyzed in 24 months (2017-2018) in a cohort of patients with HIV: smear microscopy, mycobacterial and fungal cultures, isolator blood culture, PCR assays, and antigen detection tests. Results: A total of 4245 patients were included, 716 (16.2%) had an opportunistic infection: 249 (34.7%) TB, 40 (5.6%) nontuberculous mycobacteria, 227 (31.7%) histoplasmosis, 138 (19.3%) cryptococcosis, and 62 (8.6%) had multiple opportunistic infections. Two hundred sixty-three [92.6%; 95% confidence interval (CI), 89-95.1] of TB cases were diagnosed by PCR. Urine antigen assay detected 94% (95% CI, 89-96) of the disseminated histoplasmosis cases. A lateral flow assay to detect cryptococcal antigen diagnosed 97% (95% CI, 93.3-98.7%) of the cryptococcal cases. In 85 patients (51.5%) with a cerobrospinal fluid sample, cryptococcal meningitis was diagnosed in 55 (64.7%), of which 18 (32.7%) were only detected by cryptococcal antigen. Conclusion: Validated commercial antigen tests, as used in this program, should be the new gold standard for histoplasmosis and cryptococcosis diagnosis. In their absence, 35% of disseminated histoplasmosis and 32.7% of cryptococcal meningitis cases would have been missed. Patients with multiple opportunistic infections were frequently diagnosed and strategies should be designed to screen patients irrespective of their clinical presentation. In low resource settings, Diagnostic Laboratory Hubs can deliver quality diagnostics services in record time at affordable prices. This work was supported by Global ActionFund for Fungal Infections and JYLAG, a charity 270Foundation based in Switzerland (E.A. received this funding under the proposal: “Minimising 271HIV deaths through rapid fungal diagnosis and better care in Guatemala”). Other 272contributions came from AIDS Health Foundation (AHF) Guatemala, Intrahealth 273International and Ministry of health in Guatemala (MSPAS). Sí

Public health plays an important role in ensuring access to interventions that can prevent disease, including the implementation of evidence-based genomic recommendations. We used the Centers for Disease Control and Prevention (CDC) Science Impact Framework to trace the impact of public health activities and partnerships on the implementation of the 2009 Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Lynch Syndrome screening recommendation and the 2005 and 2013 United States Preventive Services Task Force (USPSTF) BRCA1 and BRCA2 testing recommendations. The EGAPP and USPSTF recommendations have each been cited by >300 peer-reviewed publications. CDC funds selected states to build capacity to integrate these recommendations into public health programs, through education, policy, surveillance, and partnerships. Most state cancer control plans include genomics-related goals, objectives, or strategies. Since the EGAPP recommendation, major public and private payers now provide coverage for Lynch Syndrome screening for all newly diagnosed colorectal cancers. National guidelines and initiatives, including Healthy People 2020, included similar recommendations and cited the EGAPP and USPSTF recommendations. However, disparities in implementation based on race, ethnicity, and rural residence remain challenges. Public health achievements in promoting the evidence-based use of genomics for the prevention of hereditary cancers can inform future applications of genomics in public health.

Objective: To show how state health agencies can plan and evaluate activities to strengthen the evidence base for public health genomics, we mapped state cancer genomics activities to the Doyle et al. [Genet Med. 2018;20(9):995–1003] implementation science outcome framework. Methods: We identified state health agency activities addressing hereditary breast and ovarian cancer and Lynch syndrome by reviewing project narratives from Centers for Disease Control and Prevention Cancer Genomics Program funding recipients, leading discussions with state health agencies, and conducting an environmental scan. Results: State health agencies’ cancer genomics activities included developing or adding to state surveillance systems, developing educational materials, bidirectional reporting, promoting health plan policy change, training providers, and promoting recommendations and standards. To address health disparities, programs have tracked group differences, developed culturally appropriate educational materials, and promoted access to services for underserved populations. Conclusion: State health agencies can use the Doyle et al. [Genet Med. 2018;20(9):995–1003] performance objectives and outcome measures to evaluate proposed and ongoing activities. By demonstrating whether activities result in improved outcomes, state health agencies can build the evidence for the implementation of cancer genomics activities.

Background: Ovarian cancer is the fifth most common cause of cancer death among women in the United States. Failure to receive optimal treatment and poorer survival rates have been reported for older women, African-American women, women with low income, and women with public health insurance coverage or no coverage. Additionally, regional differences in geographic access influence the type of treatment women may seek. This paper explores geographic accessibility and sociodemographic vulnerability in Georgia, which influence receipt of optimal ovarian cancer treatment. Methods: An enhanced two-step floating catchment area (E2SFCA), defining physical access, was created for each census tract and gynecologic oncologist clinic. Secondly, sociodemographic variables reflecting potential social vulnerability were selected from U.S. Census and American Community Survey data at the tract level. These two measures were combined to create a measure of Geosocial Vulnerability. This framework was tested using Georgia ovarian cancer mortality records. Results: Geospatial access was higher in urban areas with less accessibility in suburban and rural areas. Sociodemographic vulnerability varied geospatially, with higher vulnerability in urban citers and rural areas. Sociodemographic measures were combined with geospatial access to create a Geosocial Vulnerability Indicator, which showed a significant positive association with ovarian cancer mortality. Conclusions: Spatial and sociodemographic measures pinpointed areas of healthcare access vulnerability not revealed by either spatial analysis or sociodemographic assessment alone. Whereas lower healthcare accessibility in rural areas has been well described, our analysis shows considerable heterogeneity in access to care in urban areas where the disadvantaged census tracts can be easily identified.

Although annual breast magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer as an adjunct to screening mammography, breast MRI use remains low. We examined factors associated with breast MRI use in a cohort of women with a family history of breast cancer but no personal cancer history. Study participants came from the Sister Study cohort, a nationwide, prospective study of women with at least 1 sister who had been diagnosed with breast cancer but who themselves had not ever had breast cancer (n = 17 894). Participants were surveyed on breast cancer beliefs, cancer worry, breast MRI use, provider communication, and genetic counseling and testing. Logistic regression was used to assess factors associated with having a breast MRI overall and for those at high risk. Breast MRI was reported by 16.1% and was more common among younger women and those with higher incomes. After adjustment for demographics, ever use of breast MRI was associated with actual and perceived risk. Odds ratios (OR) were 12.29 (95% CI, 8.85-17.06), 2.48 (95% CI, 2.27-2.71), and 2.50 (95% CI, 2.09-2.99) for positive BRCA1/2 test, lifetime breast cancer risk ≥ 20%, and being told by a health care provider of higher risk, respectively. Women who believed they had much higher risk than others or had higher level of worry were twice as likely to have had breast MRI; OR = 2.23 (95% CI, 1.82-2.75) and OR = 1.76 (95% CI, 1.52-2.04). Patterns were similar among women at high risk. Breast cancer risk, provider communication, and personal beliefs were determinants of breast MRI use. To support shared decisions about the use of breast MRI, women could benefit from improved understanding of the chances of getting breast cancer and increased quality of provider communications.

To assess the implementation of evidence-based genomic medicine and its population-level impact on health outcomes and to promote public health genetics interventions, in 2015 the Roundtable on Genomics and Precision Health of the National Academies of Sciences, Engineering, and Medicine formed an action collaborative, the Genomics and Public Health Action Collaborative (GPHAC). This group engaged key stakeholders from public/population health agencies, along with experts in the fields of health disparities, health literacy, implementation science, medical genetics, and patient advocacy. In this paper, we present the efforts to identify performance objectives and outcome metrics. Specific attention is placed on measures related to hereditary breast ovarian cancer (HBOC) syndrome and Lynch syndrome (LS), two conditions with existing evidence-based genomic applications that can have immediate impact on morbidity and mortality. Our assessment revealed few existing outcome measures. Therefore, using an implementation research framework, 38 outcome measures were crafted. Evidence-based public health requires outcome metrics, yet few exist for genomics. Therefore, we have proposed performance objectives that states might use and provided examples of a few state-level activities already under way, which are designed to collect outcome measures for HBOC and LS.

Purpose There is limited research linking data sources to evaluate the multifactorial impacts on the quality of treatment received and financial burden among young women with breast cancer. To address this gap and support future evaluation efforts, we examined the utility of combining patient survey and cancer registry data. Patient and Methods We administered a survey to women, aged 18–39 years, with breast cancer from four U.S. states. We conducted a systematic response-rate analysis and evaluated differences between racial groups. Survey responses were linked with cancer registry data to assess whether surveys could reliably supplement registry data. Results A total of 830 women completed the survey for a response rate of 28.4 %. Blacks and Asian/Pacific Islanders were half as likely to respond as white women. Concordance between survey and registry data was high for demographic variables (Cohen’s kappa [k]: 0.879 to 0.949), moderate to high for treatments received (k: 0.467 to 0.854), and low for hormone receptor status (k: 0.167 to 0.553). Survey items related to insurance status, employment, and symptoms revealed racial differences. Conclusion Cancer registry data, supplemented by patient surveys, can provide a broader understanding of the quality of care and financial impacts of breast cancer among young women.

Problem/Condition Genetic testing for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene mutations can identify women at increased risk for breast and ovarian cancer. These testing results can be used to select preventive interventions and guide treatment. Differences between nonmetropolitan and metropolitan populations in rates of BRCA testing and receipt of preventive interventions after testing have not previously been examined. Period Covered 2009–2014. Description of System Medical claims data from Truven Health Analytics MarketScan Commercial Claims and Encounters databases were used to estimate rates of BRCA testing and receipt of preventive interventions after BRCA testing among women aged 18–64 years with employer-sponsored health insurance in metropolitan and nonmetropolitan areas of the United States, both nationally and regionally. Results From 2009 to 2014, BRCA testing rates per 100,000 women aged 18–64 years with employer-sponsored health insurance increased 2.3 times (102.7 to 237.8) in metropolitan areas and 3.0 times (64.8 to 191.3) in nonmetropolitan areas. The relative difference in BRCA testing rates between metropolitan and nonmetropolitan areas decreased from 37% in 2009 (102.7 versus 64.8) to 20% in 2014 (237.8 versus 191.3). The relative difference in BRCA testing rates between metropolitan and nonmetropolitan areas decreased more over time in younger women than in older women and decreased in all regions except the West. Receipt of preventive services 90 days after BRCA testing in metropolitan versus nonmetropolitan areas throughout the period varied by service: the percentage of women who received a mastectomy was similar, the percentage of women who received magnetic resonance imaging of the breast was lower in nonmetropolitan areas (as low as 5.8% in 2014 to as high as 8.2% in 2011) than metropolitan areas (as low as 7.3% in 2014 to as high as 10.3% in 2011), and the percentage of women who received mammography was lower in nonmetropolitan areas in earlier years but was similar in later years. Interpretation Possible explanations for the 47% decrease in the relative difference in BRCA testing rates over the study period include increased access to genetic services in nonmetropolitan areas and increased demand nationally as a result of publicity. The relative differences in metropolitan and nonmetropolitan BRCA testing rates were smaller among women at younger ages compared with older ages. Public Health Action Improved data sources and surveillance tools are needed to gather comprehensive data on BRCA testing in the United States, monitor adherence to evidence-based guidelines for BRCA testing, and assess receipt of preventive interventions for women with BRCA mutations. Programs can build on the recent decrease in geographic disparities in receipt of BRCA testing while simultaneously educating the public and health care providers about U.S. Preventive Services Task Force recommendations and other clinical guidelines for BRCA testing and counseling.

Language contact is not just about language. It extends to a whole complex set of sociocultural and historical formations that characterize life in intersecting communities of language users. It is a space of linguistic as well as sociocultural reproduction and transformation. Early anthropologists and linguists focused narrowly on how languages, understood here as structural codes, influence each other, producing lexical, phonological, and morphosyntactic changes. The discipline of linguistics has largely continued this line of inquiry and focused on issues of variation and structural change. In conducting empirical ethnographic studies, sociolinguists and linguistic anthropologists have exposed the constructedness of the static, bounded notions of “languages” and “communities” of monolingual speakers. They have also increasingly emphasized the embeddedness of language in its sociocultural and historical context (see Foundational Texts). Anthropology of language contact, accordingly, investigates changing practices of language use, unequal acquisition, socialization, and development of linguistic norms. This article highlights the dynamic relationship between the use and conceptualization of language. It includes works on multilingual and dialectal practices (see Multilingual Practices and Discursive Construction of Identity), and how linguistic differences function, produce, and perpetuate forms of social inequality (see Linguistic Differences and Social Inequality). It also addresses the historical, sociocultural, and interactional contexts of encounters and power dynamics. As such, we examine the context of colonialism and missionization (see Language and Colonialism) and the rise of nation-states in which standard language has been taken to be coterminous with the polity (see Language Contact and Nation-Building). Nationalism based on an association between nation and language is important in understanding the processes of language endangerment and revitalization (see Language Endangerment, Documentation, and Revitalization). This article also covers the flow of people and commodities, as well as industrialization, urbanization, and the introduction of new technologies (see Language Contact, Migration, and Globalization). Such flows and movements occur at different scales, from face-to-face interaction to global trade, and transform boundaries between languages (or what counts as such) and the communities that use them. Notwithstanding the fluidity of global communication, the school has been the most important site of the reproduction of standard and monolingual ideologies, closely connected to the process of nation-building, colonization, and the reproduction of privilege and inequality (see Education and Social (Re)production). The final section gathers works that highlight the poetic function of language and individual creative choice in multilingual verbal arts (see Verbal Play and Aesthetics of Contact).

Male infertility affects 7% of all men worldwide, yet for the majority the underlying cause is not found. From the very first identified karyotyping abnormalities to the very recent discovery of point mutations disrupting spermatogenesis, it is clear that a substantial number of patients suffer from genetic abnormalities. However, the discovery of these causes has largely been limited by the resolutions of the technologies used for patient assessment. In recent years, the advent of better tools and more comprehensive databases of genetic variations has led to profound discoveries of genes and pathways underlying male infertility. This chapter reviews these technologies and the discoveries they have led to and sets the scene for the transformation of infertile patient care in the era of next-generation sequencing.

Background: The economic cost of breast cancer is a major personal and public health problem in the United States. This study aims to evaluate the insurance, employment, and financial experiences of young female breast cancer survivors and to assess factors associated with financial decline. Methods: We recruited 830 women under 40 years of age diagnosed with breast cancer between January 2013 and December 2014. The study population was identified through California, Florida, Georgia, and North Carolina population-based cancer registries. The cross-sectional survey was fielded in 2017 and included questions on demographics, insurance, employment, out-of-pocket costs, and financial well-being. We present descriptive statistics and multivariate analysis to assess factors associated with financial decline. Results: Although 92.5% of the respondents were continuously insured over the past 12 months, 9.5% paid a “higher price than expected” for coverage. Common concerns among the 73.4% of respondents who were employed at diagnosis included increased paid (55.1%) or unpaid (47.3%) time off, suffering job performance (23.2%), and staying at (30.2%) or avoiding changing (23.5%) jobs for health insurance purposes. Overall, 47.0% experienced financial decline due to treatment-related costs. Patients with some college education, multiple comorbidities, late stage diagnoses, and self-funded insurance were most vulnerable. Conclusions: The breast cancer diagnosis created financial hardship for half the respondents and led to myriad challenges in maintaining employment. Employment decisions were heavily influenced by the need to maintain health insurance coverage. Impact: This study finds that a breast cancer diagnosis in young women can result in employment disruption and financial decline.

Aim: To assess whether DNA methylation of monocytes play a role in the development of acute diabetic Charcot foot (CF). Patients & methods: We studied the whole methylome (WM) of circulating monocytes in 18 patients with Type 2 diabetes (T2D) and acute CF, 18 T2D patients with equivalent neuropathy and 18 T2D patients without neuropathy, using the enhanced reduced representation bisulfite sequencing technique. Results & conclusion: WM analysis demonstrated that CF monocytes are differentially methylated compared with non-CF monocytes, in both CpG-site and gene-mapped analysis approaches. Among the methylated genes, several are involved in the migration process during monocyte differentiation into osteoclasts or are indirectly involved through the regulation of inflammatory pathways. Finally, we demonstrated an association between methylation and gene expression in cis- and trans-association.

Contralateral prophylactic mastectomy (CPM) rates have been increasing in the US, and although high levels of satisfaction with CPM have been reported, few studies have evaluated the long-term effects on body image, comparing CPM with breast-conserving surgery (BCS) and unilateral mastectomy (UM). We analyzed responses from a survey of women with both a personal and family history of breast cancer who were enrolled in the Sister Study (n = 1176). Among women who underwent mastectomy, we examined satisfaction with the mastectomy decision, as well as variation in the use of reconstruction and experience of complications. Five survey items, evaluated individually and as a summed total score, were used to compare body image across surgery types (BCS, UM without reconstruction, CPM without reconstruction, UM with reconstruction, and CPM with reconstruction). Participants were, on average, 3.6 years post-diagnosis at the time of survey (standard deviation 1.7). The majority of women (97% of CPM, 89% of UM) were satisfied with their mastectomy decision. Reconstruction was more common after CPM than after UM (70 vs. 47%), as were complications (28 vs. 19%). Body image scores were significantly worse among women who underwent CPM than among women who underwent BCS, with the lowest scores among women who underwent CPM without reconstruction. In our sample, most women were highly satisfied with their mastectomy decision, including those who elected to undergo CPM. However, body image was lower among those who underwent CPM than among those who underwent BCS. Our findings may inform decisions among women considering various courses of surgical treatment.

Purpose This study used population-based data to estimate the percentage of cancer survivors in the United States reporting current medication use for anxiety and depression and to characterize the survivors taking this type of medication. Rates of medication use in cancer survivors were compared with rates in the general population. Methods We analyzed data from the National Health Interview Survey, years 2010 to 2013, identifying cancer survivors (n = 3,184) and adults with no history of cancer (n = 44,997) who completed both the Sample Adult Core Questionnaire and the Adult Functioning and Disability Supplement. Results Compared with adults with no history of cancer, cancer survivors were significantly more likely to report taking medication for anxiety (16.8% v 8.6%, P < .001), depression (14.1% v 7.8%, P < .001), and one or both of these conditions combined (19.1% v 10.4%, P < .001), indicating that an estimated 2.5 million cancer survivors were taking medication for anxiety or depression in the United States at that time. Survivor characteristics associated with higher rates of medication use for anxiety included being younger than 65 years old, female, and non-Hispanic white, and having public insurance, a usual source of medical care, and multiple chronic health conditions. Survivor characteristics associated with medication use for depression were largely consistent with those for anxiety, with the exceptions that insurance status was not significant, whereas being widowed/divorced/separated was associated with more use. Conclusion Cancer survivors in the United States reported medication use for anxiety and depression at rates nearly two times those reported by the general public, likely a reflection of greater emotional and physical burdens from cancer or its treatment.

Although many efforts in cancer prevention and control have routinely focused on behavioral risk factors, such as tobacco use, or on the early detection of cancer, such as colorectal cancer screening, advances in genetic testing have created new opportunities for cancer prevention through evaluation of family history and identification of cancer-causing inherited mutations. Through the collection and evaluation of a family cancer history by a trained health care provider, patients and families at increased risk for a hereditary cancer syndrome can be identified, referred for genetic counseling and testing, and make informed decisions about options for cancer risk reduction (1). Although hereditary cancers make up a small proportion of all cancers, the number of affected persons can be large, and the level of risk among affected persons is high. Two hereditary cancer syndromes for which public health professionals have worked to reduce the burden of morbidity and mortality are hereditary breast and ovarian cancer syndrome (HBOC) and Lynch syndrome.

Previous research describing how informal cancer caregiving impacts employment has been conducted in small samples or a single disease site. This paper provides population-based estimates of the effect of informal cancer caregiving on employment and characterizes employment changes made by caregivers. The samples included cancer survivors with a friend or family caregiver, participating in either the Medical Expenditure Panel Survey Experiences with Cancer Survivorship Survey (ECSS) (n = 458) or the LIVESTRONG 2012 Survey for People Affected by Cancer (SPAC) (n = 4706). Descriptive statistics characterized the sample of survivors and their caregivers’ employment changes. Multivariable logistic regression identified predictors of caregivers’ extended employment changes, comprising time off and changes to hours, duties, or employment status. Among survivors with an informal caregiver, 25 % from the ECSS and 29 % from the SPAC reported that their caregivers made extended employment changes. Approximately 8 % of survivors had caregivers who took time off from work lasting ≥2 months. Caregivers who made extended employment changes were more likely to care for survivors: treated with chemotherapy or transplant; closer to diagnosis or end of treatment; who experienced functional limitations; and made work changes due to cancer themselves compared to caregivers who did not make extended employment changes. Many informal cancer caregivers make employment changes to provide care during survivors’ treatment and recovery. This study describes cancer caregiving in a prevalent sample of cancer survivors, thereby reflecting the experiences of individuals with many different cancer types and places in the cancer treatment trajectory.

Introduction Breast cancer in women aged 18–44 years accounts for approximately 27,000 newly diagnosed cases and 3,000 deaths annually. When tumors are diagnosed, they are usually aggressive, resulting in expensive treatment costs. The purpose of this study is to estimate the prevalent medical costs attributable to breast cancer treatment among privately insured younger women. Methods Data from the 2006 MarketScan® database representing claims for privately insured younger women were used. Costs for younger breast cancer patients were compared with a matched sample of younger women without breast cancer, overall and for an active treatment subsample. Analyses were conducted in 2013 with medical care costs expressed in 2012 U.S. dollars. Results Younger women with breast cancer incurred an estimated $19,435 (SE=$415) in additional direct medical care costs per person per year compared with younger women without breast cancer. Outpatient expenditures comprised 94% of the total estimated costs ($18,344 [SE=$396]). Inpatient costs were $43 (SE=$10) higher and prescription drug costs were $1,048 (SE=$64) higher for younger women with breast cancer than in younger women without breast cancer. For women in active treatment, the burden was more than twice as high ($52,542 [SE=$977]). Conclusions These estimates suggest that breast cancer is a costly illness to treat among younger, privately insured women. This underscores the potential financial vulnerability of women in this age group and the importance of health insurance during this time in life.

Islands have been used as model systems for studies of speciation and extinction since Darwin published his observations about finches found on the Galapagos. Amazon parrots inhabiting the Greater Antillean Islands represent a fascinating model of species diversification. Unfortunately, many of these birds are threatened as a result of human activity and some, like the Puerto Rican parrot, are now critically endangered. In this study we used a combination of de novo and reference-assisted assembly methods, integrating it with information obtained from related genomes to perform genome reconstruction of three amazon species. First, we used whole genome sequencing data to generate a new de novo genome assembly for the Puerto Rican parrot (Amazona vittata). We then improved the obtained assembly using transcriptome data from Amazona ventralis and used the resulting sequences as a reference to assemble the genomes Hispaniolan (A. ventralis) and Cuban (Amazona leucocephala) parrots. Finally, we, annotated genes and repetitive elements, estimated genome sizes and current levels of heterozygosity, built models of demographic history and provided interpretation of our findings in the context of parrot evolution in the Caribbean.

Introduction: Women facing complex and uncertain situations such as cancer in their families may seek information from a variety of sources to gain knowledge about cancer risk and reduce uncertainty. We describe and assess the relative importance of information sources about familial breast cancer at the individual, family, and healthcare provider levels influencing women's reporting they had enough information to speak with daughters about breast cancer. This outcome we refer to as being informed about breast cancer. Materials and Methods: Sister Study participants, a cohort of women with a family history of breast cancer, were surveyed on family cancer history, family communication, social support, and interactions with healthcare providers (n = 11,766). Adjusted percentages and 95% confidence intervals for being informed about breast cancer versus not being informed were computed for individual-, family-, and provider-level characteristics in three steps using multivariate logistic regression models. Results: We found 65% of women reported being informed about breast cancer while 35% did not. Having a trusted person with whom to discuss cancer concerns, having a lower versus higher perceived risk of breast cancer, having undergone genetic counseling, and being satisfied with physician discussions about breast cancer in their families were predictors of being informed about breast cancer. Conclusions: Although acquiring objective risk information, such as through genetic counseling, may contribute to a basic level of understanding, communication with providers and within other trusted relationships appears to be an essential component in women's reporting they had all the information they need to talk with their daughters about breast cancer.

Introduction Although dietary habits can affect colorectal cancer (CRC) survivors’ health, it is unclear how familiar survivors are with dietary guidelines, what they believe about healthy eating and alcohol consumption, and what hinders healthy dietary habits after cancer. This study assessed CRC survivors’ familiarity with dietary guidelines, their eating and drinking habits, and perceived facilitators and barriers to healthy eating after cancer, including social support and self-efficacy for maintaining a healthy diet and limiting alcohol. Methods A total of 593 individuals (50% female; mean age, 74 years) diagnosed with CRC approximately 6 years prior to study entry in early 2010 were identified through California Cancer Registry records and participated in a cross-sectional mailed survey assessing health behavior after cancer (46% adjusted response rate). Analyses were conducted in 2014–2015. Results Survivors were most familiar with—and most likely to follow—recommendations to choose low-fat foods; 15% had never heard of recommendations to limit alcohol. Survivors were more aware of recommendations involving messages to limit/avoid versus approach/choose certain foods. The most common barrier to a healthy diet involved the effort required (26%). Survivors received more family/friend support and provider recommendations for healthy eating than limiting alcohol. Conclusions Results provide an overview of awareness of and adherence to dietary recommendations among CRC survivors, highlighting the need for increasing awareness of recommendations that are especially relevant for survivors. Suggestions are made for modifying diet-related messages to facilitate comprehension and recall among CRC survivors, and increasing awareness among groups with the lowest awareness levels.

Introduction Disseminated histoplasmosis, a disease that often resembles and is mistaken for tuberculosis, is a major cause of death in patients with advanced HIV disease. Histoplasma antigen detection tests are an important addition to the diagnostic arsenal for patients with advanced HIV disease and should be considered for inclusion on the World Health Organization Essential Diagnostics List. Objective Our objective was to systematically review the literature to evaluate the diagnostic accuracy of Histoplasma antigen tests in the context of advanced HIV disease, with a focus on low- and middle-income countries. Methods A systematic review of the published literature extracted data on comparator groups, type of histoplasmosis, HIV status, performance results, patient numbers, whether patients were consecutively enrolled or if the study used biobank samples. PubMed, Scopus, Lilacs and Scielo databases were searched for published articles between 1981 and 2018. There was no language restriction. Results Of 1327 screened abstracts we included a total of 16 studies in humans for further analysis. Most studies included used a heterogeneousgroup of patients, often without HIV or mixing HIV and non HIV patients, with disseminated or non-disseminated forms of histoplasmosis. Six studies did not systematically use mycologically confirmed cases as a gold standard but compared antigen detection tests against another antigen detection test. Patient numbers were generally small (19–65) in individual studies and, in most (7/10), no confidence intervals were given. The post test probability of a positive or negative test were good suggesting that this non invasive diagnostic tool would be very useful for HIV care givers at the level of reference hospitals or hospitals with the infrastructure to perform ELISA tests. The first results evaluating point of care antigen detection tests using a lateral flow assay were promising with high sensitivity and specificity. Conclusions Antigen detection tests are promising tools to improve detection of and ultimately reduce the burden of histoplasmosis mortality in patients with advanced HIV disease., Author summary Disseminated histoplasmosis, a disease that often resembles and is mistaken for tuberculosis, is a major cause of death in patients with advanced HIV disease. Histoplasma antigen detection tests are an important addition to the diagnostic arsenal for patients with advanced HIV disease and should be considered for inclusion on the World Health Organization Essential Diagnostics List. Our objective was to systematically review the literature to evaluate the diagnostic accuracy of Histoplasma antigen tests in the context of advanced HIV disease, with a focus on low- and middle-income countries. Systematic review of the published literature extracted data on comparator groups, type of histoplasmosis, HIV status, performance results, patient numbers, whether patients were consecutively enrolled or if the study used biobank samples. At the end of the screening process we included a total of 16 studies in humans for further analysis. Most studies included used a heterogeneous group of patients, often without HIV or mixing HIV and non HIV patients, with disseminated or non-disseminated forms of histoplasmosis. Patient numbers were generally small in individual studies and, in most of these, no confidence intervals were given. When considering the diagnostic accuracy of Histoplasma antigen detection tests evaluated among consecutive HIV-infected patients with confirmed histoplasmosis, the performance of the tests was good. These non invasive diagnostic tools would be very useful for HIV care givers at the level of reference hospitals or hospitals with the infrastructure to perform ELISA tests. Antigen detection tests are promising tools to improve detection of and ultimately reduce the burden of histoplasmosis mortality in patients with advanced HIV disease.