INTRODUCTION:The relationship between cancers and thromboembolic events is well established. In our study, we aim to determine the burden of thromboembolic events in patients with solid tumors and identify the risk factors related to their development. MATERIALS & METHODS:Data on patients with solid tumors and thromboembolism between January 2013 and September 2014 were collected and analyzed. RESULTS:During the study period 174 patients were identified. Of which, 172 (98.9%) had venous thrombus embolism, 137 (79%) were diagnosed with deep vein thromboses, 67 (38.5%) with pulmonary embolism, 84 (48.3%) were symptomatic and 90 (51.7) were incidental at diagnosis. The most common patients and disease characteristics were female sex, high body mass index (BMI), metastatic stage, colorectal and breast primaries, and anti-neoplastic therapy. CONCLUSION:Our study confirmed the high burden of thromboembolic events in cancer patients and the relevant factors associated with its development.

Background: Both everolimus and peptide receptor radionuclide therapy (PRRT) are approved as monotherapies for advanced neuroendocrine tumors (NETs). Research in animal models showed synergism between the two treatment modalities. This study aimed to evaluate the safety and efficacy of combining everolimus and PRRT in the treatment of unresectable NETs.Methods: Adult patients (>= 18 years) with progressing and unresectable histologically confirmed grade 1-2 NETs of all origins were enrolled. Everolimus was started at a 5 mg daily dose and was increased after the initial three patients to 10 mg daily. Patients were treated concurrently with Lu-177-DOTATATE at an 8-week interval, with planned four cycles. Safety was the primary endpoint, with response rate and progression-free survival (PFS) being secondary.Results: Eleven patients were enrolled. The trial was terminated early for poor accrual. The median age was 51 years (18-64), and 4 were males. The median number of cycles of Lu-177-DOTATATE was 3, and the median cumulative dose was 300 mCi. The most frequent grade 1-2 toxicities were stomatitis (90.9%) and nausea (72.7%). Less frequent were fatigue (63.6%), anorexia, diarrhea, and skin changes (each at a 36.4% rate). Grade 3 toxicities occurred in 36% (fatigue, infection, pneumonitis, neutropenia, and stroke). No patient developed grade 4 toxicity. Treatment was stopped because of progression in three patients, and toxicity in another three patients, in addition, in four patients due to therapy interruption and in one patient who developed stroke. One patient achieved partial response, and nine had stable disease. One patient developed disease progression. At a median follow-up of 18.9 months, three died and one was lost to follow-up. The median PFS was 23.3 months.Conclusions: The combination of everolimus at a dose of 10 mg daily and Lu-177-DOTATATE appears not to be feasible. A larger trial at a lower dose of everolimus is warranted.

Background Informed consent (IC) is a healthcare standard emphasizing the meaning of human dignity as clarified in the Universal Declaration of Human Rights. Data about IC practices in Egypt is insufficient. This study aimed to assess the Egyptian patients’/guardians’ experiences about IC and their expectations about its practices’ purposes in general and according to the type of the healthcare facility. Methods Self-administered questionnaire was carried out for 1092 participants who had undergone or were scheduled to a procedure requiring an IC at three studied types for Egyptian health care facilities. Ten statements were ranked twice by the participants to reflect their perception of IC purpose as per what is currently practiced and what they believe should be practiced. Results IC implementation varies significantly (p<0.05) across the health care facilities in Egypt. The percentage of its implementation at the non-governmental facilities, governmental facilities, and university hospital was 85.9%, 77.8%, and 63.8 respectively. The first three ranked purposes of the current IC practices were: “Helping patient/guardian decide (64.9%)”, “Documenting patient’s/guardian’s decision (59.3%)”, and “Having shared decision (57.3%)”. The perceived purposes of IC to be practiced were: “Informing the patient/guardian (68.4%)”, “Making sure patient/guardian understand (65.3%)” and “Documenting patients/guardians decisions (65.1%)”. “Being a meaningless routine” was reported by the majority to be ranked as a low purpose for IC current and preferred practices. Conclusion The practice of IC is common within the Egyptian medical community. Participants believe that information disclosure “Making sure patients understand” has to help in IC decision making and its main purpose. However, unfortunately, this is not perceived as a current purpose of IC. There was consensus agreement that documenting the patient’s/guardian’s decision and informing the patient/guardian are perceived as both important current and preferred purposes for IC practices.

Background Surgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here, we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC. Patients and methods Patients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of capecitabine, oxaliplatin, irinotecan, and bevacizumab. Patients were given 5–8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity, or patient request. All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and 2 monthly intervals thereafter. Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy. Results Fifty-three patients were enrolled. The median age was 52 years (range 23–74), 29 (55%) were males, ECOG PS 0-1 was 13 (66%), 11 (42%) had a right-sided tumor, 29 (55%) had resection of their primary tumor, 22 (42%) had a single metastatic site, and 8 (15.1%) had a liver-limited disease. Thirteen patients (24.5%) underwent surgical resection of residual metastatic disease +/− the primary tumor with 10 (18.9%) of them were R0. The surgical group had a higher incidence of males compared to the non-surgical group (69.3% vs 47.2%, p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p = 0.09), higher mutant Kras (53.8% vs 34.2%, p = 0.3), and higher response rate (84.6% vs 56.2%, p = 0.3). With a median follow-up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI) 9.1–20] and the median OS was 28.2 months (95% CI 22.5–53.3). The median PFS for the surgery group was 18.9 months (95% CI 12.6–not reached) compared to 9.6 months (95% CI 7.0–18.3) for the non-surgical group, log-rank p = 0.0165. The median OS for both groups was not reached (95% CI 53.3–not reached) and 23.2 months (95% CI 17.0–28.4) respectively, log-rank p = 0.0006. Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively. Conclusions Patients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible. Trial registration Clinicaltrials.gov , NCT01311050 , registered March 6, 2011, retrospectively registered.

PURPOSE:Antiangiogenic tyrosine kinase inhibitors have been the mainstay first-line therapy for metastatic renal cell carcinoma (mRCC). We reviewed the efficacy of first-line therapy with sunitinib in patients with mRCC in an Arab population.METHODS:Medical records of patients with mRCC treated at a tertiary care center in Saudi Arabia, during the period from 2007 to 2016, were reviewed. Demographic data, treatment received, response, and prognostic factors were analyzed.RESULTS:Fifty-five patients who received sunitinib were identified. The median age was 60 years (range, 18 to 78 years), and 42 of the 55 patients were men (76.3%). International Metastatic RCC Diagnostic Consortium prognostic scores for favorable/intermediate/poor were 14.5%/43.6%/38.2%, respectively. The median performance status was 1, and the median Charlson comorbidity index score was 9. Thirty-seven patients (67.2%) had cytoreductive nephrectomy. Thirty-seven patients (67.2%) had clear cell histology. Twenty-two patients (40%) underwent dose reduction. Twenty-seven patients (49%) received second-line therapy, and seven patients (12.7%) received third-line therapy. Response rates were complete response in one patient (1.8%), partial response in 17 (30.9%), stable disease in 10 (18.1), and disease progression in 20 (36.3%). Progression-free survival (PFS) and overall survival (OS) were 6.0 and 24.7 months, respectively. Univariate analysis showed statistically improved PFS for dose reduction (P = .015) and the development of hypothyroidism (P = .03). It also showed statistically improved OS for dose reduction (P = .035), hypothyroidism (P = .0002), and cytoreductive nephrectomy (P = .0052). Multivariate analysis showed statistically improved PFS for dose reduction (P = .01) and OS for development of hypothyroidism (P = .007).CONCLUSION:Our data for sunitinib in mRCC show significantly lower PFS than expected. The absence of prognostic value of the International Metastatic RCC Diagnostic Consortium scoring system and pathologic subtype warrant further investigation and possible inclusion of genetic scoring in this ethnic group of patients.

Objective: To assess the usefulness of serum ferritin and soluble interleukin-2 receptor (sIL-2r) levels as markers of disease activity in childhood systemic lupus erythematosus (cSLE) and their role in screen for subclinical macrophage activation syndrome (MAS). Patients and methods: This is a cross-sectional analysis of prospectively collected data. Consecutive children who met the Systemic Lupus International Collaborating Clinics (SLICC) criteria were enrolled between June 2015 and June 2017. All patients interviewed and assessed for disease activity using SLE disease activity index (SLEDAI). Biochemical and serological tests including markers of disease activity and MAS were measured by standard laboratory procedure. Results: A total of 31 (25 female; 6 male) consecutive cSLE patients with a mean age of 10.6 (±3.2) years were included. The most frequent manifestations were mucocutaneous and musculoskeletal (84%) followed by hematological (64.5%) then renal involvement (58%). Twenty-two patients had active disease (SLEDAI ≥ 4), with a mean of 9.8. Mean serum ferritin and sIL-2r were 555 (±1860) and 2789 (±1299) respectively. Both correlated significantly with leucocyte, platelet count, transferrin, C3 and SLEDAI (p < 0.05). Additionally, sIL-2r had positive correlation with ANA, ds-DNA and C4. Both ferritin and sIL-2r had weak correlation with ESR, but no correlation with CRP. Twelve patients had a recent infection. However, they were comparable to patients without infection with regard to all clinical and laboratory features. Three patients had MAS proved by bone marrow aspiration. Conclusion: Measurement of serum ferritin and sIL-2r might help in assessing disease activity of cSLE. Both might be good screening markers for MAS in cSLE. A larger prospective study is required to allow more definitive conclusions.

Background: Classical MMA, caused by methylmalonyl-CoA mutase deficiency, may result in late-onset dysfunction in several organ systems. To date, 10 cases of optic neuropathy have been reported. The prevalence of optic neuropathy in visually asymptomatic patients has not been determined. This study sought to identify overt and subclinical optic neuropathy in a cohort with classical MMA.Methods and Materials: Neuroophthalmic examinations were performed on 21 patients identified with classical MMA, older than 10years. Diagnosis of optic neuropathy was determined by a combination of visual acuity, optic nerve appearance and electrodiagnostic tests. Tabulated data were analyzed for association of variables using SAS software. Significance was set at p < .05.Results: Two-thirds were Saudi nationals and one third, Syrian. Age range was 11-29years. Eleven (52.4%) patients had optic neuropathy. Nine (81.8%) of these were bilateral, seven (57.9% to 63.6%) reported decreased vision and four (33.1% to 36.4%) were asymptomatic. Two patients had catastrophic vision loss, following acute metabolic crises. Sixteen patients had chronic renal impairment while three had renal hypertension. Seventeen patients had short stature and eight, chronic pancreatitis. Methylmalonic acid levels ranged from 82 to 3,324µmol/L (Normal<1µmol/L). There was a significant association between optic neuropathy and female gender (p = .011) and none with age, nationality, renal impairment, pancreatitis or specific genotype.Conclusion: Optic neuropathy was a frequent finding in classical MMA. It was often bilateral and some cases were sub-clinical, lacking visual symptoms. These findings have important management implications. Full ophthalmic evaluations should be performed early and regularly in patients with MMA, even when patients are asymptomatic.

Background/Aims: Evidence of increased risk of osteoporosis and osteopenia in chronic liver disease and cirrhosis is inconsistent. This study aims to investigate this relationship and to identify the predictors of increased loss of bone mineral density in Saudi patients. Patients and Methods: One hundred and sixty-four patients and controls who are age and gender matched, were included in this study with 1:1 ratio. Patients' included in this study were adults with confirmed liver cirrhosis. Bone mineral densitometry (BMD) at both lumbar spine (LS) and femoral neck (FN) were collected for both groups. Univariate and multivariate regression analyses were performed to identify predictors of BMD loss. Results: Results showed that cirrhotic patients are at higher risk of developing osteoporosis or osteopenia at LS (OR 2.23, 95% CI [1.19–4.19], P = 0.01) but not at FN, when compared to control sample. Patients with cirrhosis were found to have lower vitamin D and PTH levels (P = 0.0005) and (P = 0.006), respectively. Of the possible predictors tested (gender, age, body mass index [BMI], phosphorus, calcium, parathyroid hormone (PTH), vitamin D, and Model for End Stage Liver Disease [MELD] score), female gender was the main predictor of loss of BMD at LS only (OR 4.80, 95% CI [1.47–15.73], P = 0.01). Conclusions: The study showed that cirrhotic patients are at increased susceptibility of having decreased BMD, particularly at the LS and it highlights the need for preventive measures, especially for female patients.

BACKGROUND:In Saudi Arabia, a diet for life policy has been adopted in the management of amino acid metabolism disorders for years. However, the specially designed low protein products/medical foods - which are one of the important treatment tools - were not available up until several years ago in Saudi Arabia (SA). Our aim was to measure the compliance and quality of life in patients affected with these disorders followed in the metabolic nutrition clinic at King Faisal Specialist Hospital & Research Centre (KFSH&RC), Riyadh, SA. METHODOLOGY:We used a non-randomized retrospective/prospective study which utilized the growth parameters, biochemical data of patients plus questionnaires collected from patients and their family/caregivers. A total of n = 182 patients affected with selected amino acid metabolism disorders were enrolled. Some were excluded n = 84 for various reasons. Sample analyzed were: Phenylketonuria (PKU) (44), Maple Syrup Urine Disease (MSUD) (30), Tyrosinemia (TYR) (17) and Homocystinuria (HCU) (7). Tandem Mass Spectrometry (TMS) used to quantitate plasma amino acid concentrations. Data was obtained using (COMPLE) Microsoft-Access which was designed by the metabolic nutrition clinic at KFSH&RC-Riyadh. Student's paired t-test was used to investigate relationship between variables. RESULTS:The main findings were the improvement of selected amino acid levels pre and post the usage of medical foods. In PKU patients, the TMS Phenylalanine (PHE) levels post usage was significantly decreased (P value < .0001). This was also the case in MSUD patients with significant decrease in Leucine & Isoleucine levels (P value .0008) but not in Valine levels (P value .1148) as 36.7% of them received Valine supplements while enrolled in the study. CONCLUSION:Low protein products availability was successful in improving outcomes for selected amino acid metabolic disorders. However, due to compliance issues and impracticality of the diet, the results were not significant in all enrolled patients.

Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplant (allo-HCT) is challenging. Data on extramedullary relapse (EMR) after allo-HCT are limited. We analyzed 215 patients with AML who underwent allo-HCT in our institution between January 2005 and December 2015. We limited this retrospective review to patients who received a MA conditioning, were in complete remission (CR) at the time of transplant and who received a matched sibling transplant, all other patients were excluded to avoid heterogeneity. Seventy-seven (35.8%) patients experienced disease relapse, 45 had BMR, and 32 had EMR. The only variable that was statistically associated with EMR post allo-HCT was male sex (OR = 3.2 (1.2, 8.2), p-value = 0.01); there was a trend for association between transplant in >CR2 and EMR (OR = 0.38 (0.14, 1.06), p-value = 0.06). The median overall survival (OS) after relapse for all relapses was 10 months (95% CI 4.839–15.161). The median OS for BMR group was 8 months (95% CI 2.850–13.150) and 14 months for the EMR group (95% CI 5.776–22.224); however, this was not statistically significant, p-value = 0.4. Multivariate analysis revealed that gender, treatment modality, and time from allo-HCT to relapse (≥12 vs. <12 months) have significant association with the post-relapse death. Male gender was the only significant factor associated with EMR.

Background: Culturally conservative patients may feel uncomfortable when examined by opposite sex of EP (Emergency Physician).Objective: To determines the preferred EP gender among ED (Emergency Department) patients and investigates which characteristics affect their choice Design: Observational cross-sectional study.Setting: Four major emergency departments. Patients: Adults patients attending emergency departments.Main outcome measures: Randomly selected patients answered a structured questionnaire detailing socio-demographic information and cultural status.Patients were asked about the preferred gender of EP in critical and non-critical presentation and the diverse characteristics of EP.Categorical variables were summarized as frequencies, percentages and compared by Chi-square test.Univariate and multivariate logistic regression was used to assess the impact of important variables over gender preference.The level of statistical significance was set at P <.05. Results:The interviewed 407 patients (56% females) reflected a wide range of age, educational level, marital status, and occupation.In non-critical conditions, 41% of female patients preferred female EP which was statistically significant (p<0.004).In critical conditions, 27% of female patients preferred female EP.Experience, concerning, trustfulness and making the patient comfortable were the major characteristic features among EP.Using univariate logistic regression in non-critical conditions for female EP preference; the significant factors are: origin (P=.02), gender (P <.0001), age (p=0.006), and occupation (P=.01).While in multivariate logistic regression only gender and age was found to be significant (p<.0001), (P =.01) respectively.Univariate logistic regression in critical conditions for female EP preference found the significant factors are: gender (P<.0001), occupation (P<.0001), and religion commitment (P=.03).While in multivariate logistic regression only gender and occupation were found to be significant (P<.0001), (P=.004) respectively.Conclusions: Both genders of EP are needed in emergency departments, however, more female EPs are needed for the delivery of high-quality gender-sensitive healthcare in ED.

BACKGROUND: Optic atrophy (OA) represents permanent retinal ganglion cell loss warranting study to establish etiology.OBJECTIVES: To describe neurogenic causes of OA.DESIGN: Prospective, observational.SETTING: Tertiary care center, Riyadh, Saudi Arabia.PATIENTS AND METHODS: We included consecutive patients of all ages with OA caused by lesions affecting the visual pathways who were referred over a 9-month period (November 2013 to July 2014). Diagnosis was based on visual acuity, ophthalmoscopic features and ancillary tests. Patient demographics, results of a clinical examination, test data and etiology were recorded. For each cause of OA, both gender and age group were analyzed as potential risk factors using simple univariate logistic regression. OA associated with glaucoma and retinal diseases was excluded.MAIN OUTCOME MEASURE: Description of causes of OA.RESULTS: Two hundred and four patients and 353 eyes met inclusion criteria. The median age was 27 years (range 3 months-77 years; interquartile range, 27 years) among 111(54.4%) females and 93(45.6%) males, with no statistically significant difference in age of presentation between the genders. The majority of lesions were bilateral (n=151, 74%). Tumors were the most common cause, accounting for 127 (62.2%) cases. These occurred mostly in adults (72.4%) compared to the pediatric group (OR=3.3, 95% CI: 1.79-6.03; P<.001). Hereditary neoplasia (OR=5.55; 95% CI: 1.67-18.42; P=. 005) and metabolic diseases (OR=17.57; 95% CI: 2.15-143.62; P=. 007) were more common causes in the pediatric group. There were no significant associations between gender or visual acuity and etiology of OA. In developed nations, OA is frequently the result of ischemia and neuritis. We found many other causes, especially orbital and intracranial tumors.CONCLUSIONS: The frequency of tumors as the cause of OA may represent a higher incidence of aggressive tumors coupled with poor recognition/acknowledgement of symptoms and limited access, resulting in late presentations.LIMITATIONS: These findings may reflect bias from selective referrals to a tertiary center and may not represent all of Saudi Arabia.

Background Vitamin D deficiency has been linked to an increased risk of osteoporosis. Vitamin D deficiency has reached high levels in the Saudi population, but there is conflicting evidence both in the Saudi population, and worldwide, regarding the existence of a correlation between these low vitamin D levels and reduced BMD (bone mineral density), or osteoporosis. Objective The objective of this study was primarily to determine whether there was a correlation between vitamin D deficiency and osteoporosis in the Saudi population. We aimed to investigate whether the high levels of vitamin D deficiency and insufficiency would translate to higher prevalence of osteoporosis, and whether there is a correlation between vitamin D levels and bone mineral density. Materials and methods This was a community based cross sectional study conducted in the Family Medicine Clinics at King Faisal Specialist Hospital and Research Centre in Riyadh, Saudi Arabia. Electronic records of 1723 patients were reviewed. Laboratory and radiology results were collected, including vitamin D levels, calcium levels, and bone mineral density scan results. Results Among the whole population, 61.5% had moderate to severe vitamin D deficiency with levels less than 50nmol/L. 9.1% of the population had osteoporosis, and 38.6% had osteopenia. Among the whole population, there was no significant correlation between spine or total femoral BMD and serum 25(OH) D. Conclusion Vitamin D deficiency is prevalent in the Saudi population. However, no correlation has been found between vitamin D deficiency and reduced bone mineral density in any age group, in males or females, Saudis or Non-Saudis, in our population in Riyadh, Saudi Arabia.

Understanding the attitudes of cancer patients towards different cancer-related issues is very important for the health care provider in order to deliver an optimal care. This survey was designed to collect data about the initial patient’s perception and reaction to the diagnosis of cancer, the patient’s preference regarding the disclosure of diagnosis, and prevalence and pattern of complementary and alternative medicine (CAM) use. Between January and December 2011, of 234 cancer patients, 42.2 % believed that eye of evil/envy was the cause of their cancers. In 18.3 % of cases, relatives refused to inform the patient about the diagnosis. Participants liked to be the first to be informed, either with relatives at the same time (44.21 %) or alone (33.48 %). Only 7.7 % of participants liked to totally leave decisions to their doctors and/or relatives. There were 53.4 % tried CAM before starting treatment, and 46.7 % continued using CAM during treatment and most of them used more than one type of CAM. Treatment with the Holy Qur’an or Ruqia was widely reported by the study population (92 %). Our survey confirmed that the patient’s preference is towards disclosure while the public attitude is, relatively, still against full disclosure. This situation poses a special challenge to the physicians in Kingdom of Saudi Arabia (KSA) when it comes to discussing the disease and treatment. Educational efforts are required to emphasize the curative role of conventional treatment, especially surgery, in many cases. Such efforts should also address the wrong beliefs and misconceptions regarding CAM.

BACKGROUND:Patient attendance in the emergency department (ED) is inherently variable and unpredictable. Resources might be better allocated if use of the ER could be predicted during the month of fasting (Ramadan), healthy adult Muslims do not eat or drink from dawn to sunset and in the Middle East, social activities occur mostly during night. There is no published data that has reported changes in local ED attendance pattern during Ramadan.OBJECTIVES:Determine if there are differences in tertiary care ed attendance during Ramadan compared to other times of the year.DESIGN:Retrospective, using data from the hospital integrated clinical information system.SETTING:Tertiary care institution in Riyadh, Saudi Arabia.PATIENTS AND METHODS:All ED visits during the Islamic calendar years of 1431-1434 (December 18, 2009-October 13, 2013) were analyzed.MAIN OUTCOME MEASURES:Patient volume, acuity, demographics and admission rate variability between Ramadan and other months.RESULTS:During the study period of 4 years, of 226075 ED patients, 129178 (57.14%) patients were seen during the day shift (07:00 to 18:59). During Ramadan, 10 293 (60%) patients presented during the night shift compared with the day shift (P < .0001). This trend was seen consistently with no statistically significant differences in admissions 7%, triage acuity or when compared with other months.CONCLUSION:During Ramadan, ED attendance changes as more patients present during the night shift. In Saudi Arabia and possibly other Muslim countries, appropriate resources should be allocated during Ramadan to manage the nocturnal ED patient surge.LIMITATIONS:We believe that the majority of our patients fast, but it is not known how many ED patients were actually fasting during the study period. This study was conducted in a tertiary care hospital and the patient population presenting to our ed is predominantly Muslim; therefore, the results may not be generalized to populations that are not predominantly Muslim.

Iron overdose remains a significant public health threat to young children. Unit dose packaging of potent iron supplements is expected to reduce the frequency of severe pediatric iron overdose incidents. Interna - tional regulations require child-resistant iron packages. We aim to know if iron is dispensed in child-resistant containers (CRCs) and to emphasize the importance of using them. A prospective cross-sectional observational study assessing the proper dispensing of ferrous sulfate tablets in CRCs from major city pharmacies. Forty government and private pharmacies were visited. Ferrous sulfates with a total of 600 to 6500 mg elemental iron per package were found. The package of 6000 mg was the most commonly found. Most of the packages with high concentrations are dispensed from the government hospitals and primary healthcare centers pharmacies. None of the pharmacies dispensed iron in CRCs. To conclude, pharmacies dispensed iron in non-CRCs. Public health efforts on increasing awareness and improving packaging are highly needed. Authority regulations to use child-resistant iron packaging are required.

Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.