Retinoblastoma in Asia: Clinical Presentation and Treatment Outcomes in 2112 Patients from 33 Countries.

PURPOSE: To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia. DESIGN: Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter. PARTICIPANTS: A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries. INTERVENTIONS: Chemotherapy, radiotherapy, enucleation, and orbital exenteration. MAIN OUTCOME MEASURES: Enucleation and death. RESULTS: Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively. CONCLUSIONS: At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Comprehensive genetic analyses of childhood acute leukemia in Iraq using next-generation sequencing.

Background: Molecular analyses in hematological malignancies provide insights about genetic makeup. Probable etiological factors in leukemogenesis could also be disclosed. Since genetic analyses are still primitive in Iraq, a country of repeated wars, we conceived of performing next-generation sequencing (NGS), to disclose the genomic landscape of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) among a cohort of Iraqi children. Methods: Dried blood samples were collected from Iraqi children with ALL (n=55), or AML (n=11), and transferred to Japan where NGS was done. Whole-exome, whole-genome, and targeted gene sequencings were performed. Results: Somatic point mutations and the copy number variations among Iraqi children with acute leukemia were comparable with those in other countries, and cytosine-to-thymine nucleotide alterations were dominant. Strikingly, TCF3-PBX1 was the most recurrent fusion gene (22.4%) in B-cell precursor ALL (B-ALL), and acute promyelocytic leukemia (AML-M3) was subtyped in 5 AML cases. Additionally, a high frequency of RAS signaling pathway mutations was detected in children with B-ALL (38.8%), along with 3 AML cases that carried oncogenic RAS. Conclusions: Apart from disclosing the high frequency of TCF3-PBX1, NGS confirmed our previous finding of recurrent RAS mutations in Iraqi childhood acute leukemia. Our results suggest that the biology of Iraqi childhood acute leukemia is in part characteristic, where the war-aftermath environment or geography might play a role.

Comprehensive global collaboration in the care of 1182 pediatric oncology patients over 12 years: The Iraqi-Italian experience.

BACKGROUND: Iraq's health care system has gradually declined after several decades of wars, terrorism, and UN economic sanctions. The Oncology Unit at Children's Welfare Teaching Hospital (CWTH) in Baghdad was lacking basic facilities and support. To address this shortcoming, a humanitarian and educational partnership was established between CWTH and Sapienza University of Rome (SUR). METHODS: We investigated the outcomes of 80 online and 16 onsite educational sessions and 142 teleconsultation sessions from 2006 to 2014. We also determined the outcomes of pathology reviews by SUR of 1216 tissue specimens submitted by CWTH from 2007 until 2019 for second opinions. The primary outcomes were discordance, concordance, and changes among clinical diagnoses and pathology review findings. The measures included the frequency of teleconsultation and tele-education sessions, the topics discussed in these sessions, and the number of pathology samples requiring second opinions. FINDINGS: A total of 500 cases were discussed via teleconsultations during the study period. The median patient age was 7 years (range, 24 days to 16·4 years), and the cases comprised 79 benign tumors, 299 leukemias, 120 lymphomas, and 97 solid tumors. The teleconsultation sessions yielded 27 diagnostic changes, 123 confirmed diagnoses, and 13 equivocal impacts. The pathology reviews by SUR were concordant for 996 (81·9%) cases, discordant for 186 (15·3%), and inconclusive for 34 (2·8%). The major cause of discordance was inadequate immunohistochemical staining. The percentage of discordance markedly decreased over time (from 40% to 10%). The cause of the improvement is multifactorial: training of two CWTH pathologists at SUR, better immunohistochemical staining, and the ongoing clinical and pathologic telemedicine activities. The partnership yielded 12 publications, six posters, and three oral presentations by CWTH investigators. INTERPRETATION: The exchange of knowledge and expertise across continental boundaries meaningfully improved the diagnoses and management of pediatric cancer at CWTH.

Childhood acute promyelocytic leukemia in a pediatric cancer referral center in Baghdad, Iraq. Improved results with ATRA extended consolidation.

Modern treatments have dramatically improved the prognosis of childhood acute promyelocytic leukemia (APL). This progress has not yielded equivalent benefit in developing countries, where biological studies and supportive cares are insufficient and often unavailable. Since 2003, an all-trans retinoic (ATRA)-based, risk-adapted protocol was initiated in Baghdad. Patients were defined: high-risk with WBC ≥10 × 109/L and standard-risk with WBC <10 × 109/L. ATRA was included in induction and maintenance and, from 2010, in consolidation. Of 429 pediatric acute myeloid leukemia (September 2003-August 2019), 118 (27.5%) were APL. Six children died before therapy, 4 refused; 94/108 (87%) achieved a remission; 12 (11%) died early and 2 abandoned. The 5-year overall survival and event-free survival are 61.8% and 55.5% for all patients, 51.7% and 43.6% for first protocol, 68.4% and 63.9% for second one. Baseline WBC count was a risk factor for induction mortality; early hemorrhagic death remains a major cause of failure. ATRA extended consolidation improved results.

Pediatric oncology infrastructure and workforce training needs: a report from the Pediatric Oncology East and Mediterranean (POEM) Group.

BACKGROUND: Inadequate numbers of trained healthcare providers (HCPs), contribute to poor pediatric oncology (PO) outcomes, particularly in low- and lower middle-income countries (L/LMICs). An understanding of the characteristics of the workforce challenges are vital for addressing these problems. METHODS: The Pediatric Oncology East and Mediterranean (POEM) Group surveyed PO centers in countries of the North Africa, Middle East, Central Asia and Indian subcontinent on infrastructure and workforce capacity, service availability, and training opportunities for HCPs. Participating centers were categorized by the World Bank income levels for their countries and correlated with services, workload and staffing characteristics, and training needs. RESULTS: Fifty of 82 member-centers (61%) from 21 countries responded to the survey. 299 pediatric oncologists and 1,176 nurses treated 12,496 new PO patients/year, with a 1,451 beds utilization. The majority (71%) of new cases occurred in L/LMICs. The availability of HCPs correlated with country income level, as did pediatric subspecialty access, while availability of support services was unrelated. Twenty-five centers in 11 countries offered PO fellowship training for physicians, whereas 13 PO nurse training centers in 9 countries had the capacity to train 273 nurses annually. The survey respondents indicated that, among their existing workforce, an average of 3·5 physicians and 14 nurses per institution would benefit from additional PO training opportunities. CONCLUSIONS: The participating centers exhibited intra-regional heterogeneity in financial resources, infrastructure, workload, workforce, and medical services. Our findings provide insight into the disparities and regional resources available to POEM, which can be mobilized to rectify specific deficiencies. This article is protected by copyright. All rights reserved.

Evaluating Pain Management Practices for Cancer Patients among Health Professionals: A Global Survey.

Background: Cancer incidence in the world is predicted to increase in the next decade. While progress has been in diagnosis and treatment, much still remains to be done to improve cancer pain therapy, mainly in underserved communities in low-income countries. Objective: To determine knowledge, beliefs, and barriers regarding pain management in both high- and low-income countries (according to the WHO classification); and to learn about ways to improve the current state of affairs. Design: Descriptive survey. Setting/Subjects: Fifty-six countries worldwide; convenience sample of 1639 consisted of 36.8% physicians; 45.1% nurses, and 4.5% pharmacists employed in varied settings. Results: Improved pain management services are key elements. Top barriers include religion factors, lack of appropriate education and training at all levels, nonadherence to guidelines, patients' reluctance to report on pains, over regulation associated with prescribing and access to opioid analgesics, fear of addiction to opioids, and lack of discussions around prognosis and treatment planning. Conclusion: The majority of patients with cancer in low-income countries are undertreated for their pain. Promoting cancer pain accredited program of training and education on pain management for physicians and nurses is crucial, as well as advocating policymakers and the public at large.

Treatment of childhood acute lymphoblastic leukemia in Iraq: a 17-year experience from a single center.

We performed a retrospective analysis of 1415 acute lymphoblastic leukemia children diagnosed between January 2000 and December 2016 at Children Welfare Teaching Hospital, Baghdad, Iraq. Patients were divided into three cohorts according to treatment period (2000-2005; 2006-2011; 2012-2016). Treatments were based on modified-UKALL protocols; a steroid-pre-phase was introduced from September 2008. The overall complete remission was 86%, increased from 80% to 91% in the last period. Early deaths occurred in 10%, decreasing to 6%, overtime. Relapses were 23%; toxic deaths and abandonment 8% and 13%, respectively. At a median follow-up of 65.3 months, with abandonment considered as an event, the 5-year overall survival (OS) and event-free survival were 62.2% and 46.3%, statistically influenced by treatment period (5-year OS 62.6%, 59.1%, 66.3%; p=.057, respectively). Though pediatric ALL survival in Iraq is still below that observed in high income countries, survival rates progressively improved. Toxic deaths remain an important cause of failure.

Pediatric oncology infrastructure and workforce training needs: A report from the Pediatric Oncology East and Mediterranean (POEM) Group.

BACKGROUND: Inadequate numbers of trained health care providers (HCPs) contribute to poor pediatric oncology (PO) outcomes, particularly in low- and lower middle-income countries (L/LMICs). An understanding of the characteristics of the workforce challenges is vital for addressing these problems. METHODS: The Pediatric Oncology East and Mediterranean (POEM) Group surveyed PO centers in countries of North Africa, Middle East, Central Asia, and Indian subcontinent on infrastructure and workforce capacity, service availability, and training opportunities for HCPs. Participating centers were categorized by the World Bank income levels for their countries and correlated with services, workload and staffing characteristics, and training needs. RESULTS: Fifty of 82 member centers (61%) from 21 countries responded to the survey. Two hundred ninety-nine pediatric oncologists and 1176 nurses treated 12 496 new PO patients/year, with a 1451-bed utilization. The majority (71%) of new cases occurred in L/LMICs. The availability of HCPs correlated with country income level, as did pediatric subspecialty access, while availability of support services was unrelated. Twenty-five centers in 11 countries offered PO fellowship training for physicians, whereas 13 PO nurse training centers in nine countries had the capacity to train 273 nurses annually. The survey respondents indicated that, among their existing workforce, an average of 3.5 physicians and 14 nurses per institution would benefit from additional PO training opportunities. CONCLUSIONS: The participating centers exhibited intraregional heterogeneity in financial resources, infrastructure, workload, workforce, and medical services. Our findings provide insight into the disparities and regional resources available to POEM, which can be mobilized to rectify specific deficiencies.

Childhood cancer care in the Middle East, North Africa, and West/Central Asia: A snapshot across five countries from the POEM network.

BACKGROUND: The Pediatric Oncology East and Mediterranean (POEM) network, through this report, provides a snapshot view of an expected child's treatment journey in five countries in the region. METHODS: Pediatric oncologists from cancer centers in Egypt, Lebanon, Iraq, Jordan, and Pakistan provided input on referral pathways, barriers to care, and patient outcomes, based on personal experience and published data. Outcome data were extracted from institutional registries. A literature review of articles and meeting abstracts was conducted, and results summarized. RESULTS: Countries across the Middle Eastern, North African, and West Asian region face common difficulties relating to the provision of pediatric oncology care. National registries are largely lacking, with unavailability of outcome data. Economic barriers are a common theme, leading to delays in patient diagnosis, and interruptions and abandonment of therapy. Insufficient infrastructure and human resources, high rates of toxic deaths, and lack of common national protocols are common. The establishment of successful fundraising organizations linked to specific cancer hospitals showcase several success stories, enhancing services, improving patient access, and leading to outcomes comparable to those in developed countries. All identified published literature is institution-based and from only one or a few hospitals. Therefore, outcomes at a national level likely differ due to disparate cancer care capabilities. CONCLUSION: Well-designed national registries are essential for identifying gaps, and clear referral networks are needed to address delays to diagnosis and therapy. National and transversal programs to improve infrastructure, facilitate knowledge transfer, and promote advocacy, are needed to accelerate progress in the region.

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs.

Follicular dendritic cells display microvesicle-associated LMP1 in reactive germinal centers of EBV+ classic Hodgkin lymphoma.

Expression of the latent membrane protein-1 (LMP1) of Epstein-Barr virus (EBV) was investigated in 153 cases of EBV+ classic Hodgkin lymphoma (cHL); 120 cases were pediatric patients (< 14 years of age) from Iraq, and 33 cases were adult patients from Italy. We describe for the first time the presence of LMP1 protein in EBV-encoded RNA (EBER)-negative follicular dendritic cells (FDCs) of reactive germinal centers (GC) associated with EBV+ cHL. Presence of LMP1+ GCs was independent of geographic region and age of patients. Variable numbers of reactive GCs were present in 22.2% of cases (34 of 153), whereas LMP1 staining of FDCs was present in about a third of cases (10 of 34) with reactive GC. Most cases with LMP1+ GC were mixed-cellularity (MC) subtype, but some nodular sclerosis (NS) was also present. GC cells with LMP1+ FDCs were surrounded by numerous EBV-infected cells which were positive for EBER, LMP1, and CD30. Double immunolocalization analysis revealed that LMP1 was associated with CD63, an exosomal marker, and with CD21. The possibility is discussed that peri-follicular EBV-infected cells release LMP1 protein, perhaps through exosomes, and that the protein is then captured by FDCs and is presented to EBER-negative GC B cells.

Long-term results with the adapted LMB 96 protocol in children with B-cell non Hodgkin lymphoma treated in Iraq: comparison in two subsequent cohorts of patients.

Since 2000, an adapted LMB 96 protocol was implemented at the Children-Welfare-Teaching-Hospital in Baghdad for the treatment of childhood B-cell non-Hodgkin lymphoma. The first experience (2000-2005) demonstrated efficacy and feasibility of this protocol in Iraq. In 2006, further adjustments were made in an attempt to reduce therapy-related toxicities. The outcome of the second cohort of 190 children (2006-2010) and the comparison with the previous study are hereby reported. Out of the 180 treated patients, 120 achieved a complete response; during treatment 51 died and 9 abandoned. The 60-month overall survival (OS) and event-free survival (EFS) were 64.7 and 56.3%, respectively. No differences were observed in the 24-month OS and EFS between the 2000-2005 and 2006-2010 cohorts (66.3% vs. 65.1%; p = .89 and 53.3% vs. 57.3%; p = .28, respectively). Therapeutic group-B in the second cohort showed better outcome, although not significant, compared to the first one (EFS 62.9% vs. 53.8%; p = .088). Therapy-related mortality remained high.

Correction to: Human Development Index and its association with staff spiritual care provision: a Middle Eastern oncology study.

Incorrect family name of Layth Mula-Hussain.

Human Development Index and its association with staff spiritual care provision: a Middle Eastern oncology study.

BACKGROUND: Although staff spiritual care provision plays a key role in patient-centered care, there is insufficient information on international variance in attitudes toward spiritual care and its actual provision. METHODS: A cross-sectional survey of the attitudes of Middle Eastern oncology physicians and nurses toward eight examples of staff provision of spiritual care: two questionnaire items concerned prayer, while six items related to applied information gathering, such as spiritual history taking, referrals, and encouraging patients in their spirituality. In addition, respondents reported on spiritual care provision for their last three advanced cancer patients. RESULTS: Seven hundred seventy responses were received from 14 countries (25% from countries with very high Human Development Index (HDI), 41% high, 29% medium, 5% low). Over 63% of respondents positively viewed the six applied information gathering items, while significantly more, over 76%, did so among respondents from very high HDI countries (p value range, p < 0.001 to p = 0.01). Even though only 42-45% overall were positively inclined toward praying with patients, respondents in lower HDI countries expressed more positive views (p < 0.001). In interaction analysis, HDI proved to be the single strongest factor associated with five of eight spiritual care examples (p < 0.001 for all). Significantly, the Middle Eastern respondents in our study actually provided actual spiritual care to 47% of their most recent advanced cancer patients, compared to only 27% in a parallel American study, with the key difference identified being HDI. CONCLUSIONS: A country's development level is a key factor influencing attitudes toward spiritual care and its actual provision. Respondents from lower ranking HDI countries proved relatively more likely to provide spiritual care and to have positive attitudes toward praying with patients. In contrast, respondents from countries with higher HDI levels had relatively more positive attitudes toward spiritual care interventions that involved gathering information applicable to patient care.

Training for awareness of one's own spirituality: A key factor in overcoming barriers to the provision of spiritual care to advanced cancer patients by doctors and nurses.

OBJECTIVE: When patients feel spiritually supported by staff, we find increased use of hospice and reduced use of aggressive treatments at end of life, yet substantial barriers to staff spiritual care provision still exist. We aimed to study these barriers in a new cultural context and analyzed a new subgroup with "unrealized potential" for improved spiritual care provision: those who are positively inclined toward spiritual care yet do not themselves provide it. METHOD: We distributed the Religion and Spirituality in Cancer Care Study via the Middle East Cancer Consortium to physicians and nurses caring for advanced cancer patients. Survey items included how often spiritual care should be provided, how often respondents themselves provide it, and perceived barriers to spiritual care provision.ResultWe had 770 respondents (40% physicians, 60% nurses) from 14 Middle Eastern countries. The results showed that 82% of respondents think staff should provide spiritual care at least occasionally, but 44% provide spiritual care less often than they think they should. In multivariable analysis of respondents who valued spiritual care yet did not themselves provide it to their most recent patients, predictors included low personal sense of being spiritual (p < 0.001) and not having received training (p = 0.02; only 22% received training). How "developed" a country is negatively predicted spiritual care provision (p < 0.001). Self-perceived barriers were quite similar across cultures.Significance of resultsDespite relatively high levels of spiritual care provision, we see a gap between desirability and actual provision. Seeing oneself as not spiritual or only slightly spiritual is a key factor demonstrably associated with not providing spiritual care. Efforts to increase spiritual care provision should target those in favor of spiritual care provision, promoting training that helps participants consider their own spirituality and the role that it plays in their personal and professional lives.

Burkitt lymphoma in Iraqi children: A distinctive form of sporadic disease with high incidence of EBV+ cases and more frequent expression of MUM1/IRF4 protein in cases with head and neck presentation.

Epstein-Barr virus (EBV)-related lymphoproliferative disorders are relatively common in Iraqi children. Burkitt lymphoma (BL) accounted for 40% of lymphoma cases. The mean age of 125 BL cases was 5.9 ± 3.1 years, and the male-to-female ratio was 3.6:1. Clinical presentation was abdominal in 66% and head and neck in 34%. Bone marrow involvement was higher (P < 0.001) in children with head and neck disease. Tumor cells had MYC translocation (96%) and were CD20+ /CD10+ /MYC+ /BCL2- . MUM1/IRF4 staining was expressed by a fraction of tumor cells in 19 of 125 cases (15%) and was more frequent (P < 0.007) in head and neck disease (12/42; 29%). EBV-encoded RNA was positive in 100 of 125 (80%) BL cases.

Molecular and epidemiologic characterization of Wilms tumor from Baghdad, Iraq.

BACKGROUND: Wilms tumor (WT) is the most common childhood kidney cancer worldwide, yet its incidence and clinical behavior vary according to race and access to adequate healthcare resources. To guide and streamline therapy in the war-torn and resource-constrained city of Baghdad, Iraq, we conducted a first-ever molecular analysis of 20 WT specimens to characterize the biological features of this lethal disease within this challenged population. METHODS: Next-generation sequencing of ten target genes associated with WT development and treatment resistance (WT1, CTNNB1, WTX, IGF2, CITED1, SIX2, p53, N-MYC, CRABP2, and TOP2A) was completed. Immunohistochemistry was performed for 6 marker proteins of WT (WT1, CTNNB1, NCAM, CITED1, SIX2, and p53). Patient outcomes were compiled. RESULTS: Mutations were detected in previously described WT "hot spots" (e.g., WT1 and CTNNB1) as well as novel loci that may be unique to the Iraqi population. Immunohistochemistry showed expression domains most typical of blastemal-predominant WT. Remarkably, despite the challenges facing families and care providers, only one child, with combined WT1 and CTNNB1 mutations, was confirmed dead from disease. Median clinical follow-up was 40.5 months (range 6-78 months). CONCLUSIONS: These data suggest that WT biology within a population of Iraqi children manifests features both similar to and unique from disease variants in other regions of the world. These observations will help to risk stratify WT patients living in this difficult environment to more or less intensive therapies and to focus treatment on cell-specific targets.

Paediatric cancer care in a limited-resource setting: Children's Welfare Teaching Hospital, Medical City, Baghdad.

There has been a lot of news coming out of Iraq in recent decades, but most of it ignores the situation for people on the ground: ordinary men, women and children who continue trying to live their lives in spite of wars, economic sanctions, violence, and social, political and cultural collapse. The challenges of maintaining and sustaining health in an environment where everything-the human spirit, education and health care systems and the health-sustaining infrastructures of housing, water purification and the electric grid-is damaged or broken are enormous.

Middle Eastern Conflicts: Implications for Refugee Health in the European Union and Middle Eastern Host Countries.

Until very recently, health care in conflict settings was based on a model developed in the second half of the twentieth century. Things have changed, and present civil wars, such as those that are currently taking place in the Middle East, do not address the complexity of the ongoing armed conflicts in countries such as Syria, Iraq, and Afghanistan. These conflicts have caused a significant increase in the number of refugees in the region, as well as in Europe. Hundreds of thousands of refugees succeed in settling in mid- and north-European countries, and their health issues are becoming of great importance. Refugees in Europe in the twenty-first century do not suffer so much from infectious diseases but more from noninfectious chronic diseases such as diabetes, cardiac disease, and cancer. These facts profoundly alter the demographics and disease burden of hostility-derived migrants. Thus, host European countries face situations they have never faced before. Hence, new approaches and strategies are urgently needed to cope with this new situation. The efforts to absorb refugees of different traditions and cultural backgrounds often cause increasing ethnic and religious tensions, which frequently escort the emergence of social violence. To date, little attention has been paid to the overall load of distress being experienced, especially among the first-generation refugees. The current ongoing hostilities in the Middle East induce a long-term health impact on people expelled from their homes, communities, traditions, and cultural environment. The realization of collective suffering forces communities and governmental health agencies to develop new programs that include social determinants to overcome the severe cultural gaps of the newcomers in their new European host countries.