Prevalence of depressive symptoms and excessive daytime sleepiness in a cohort of Saudi doctors under training: A cross sectional study.

OBJECTIVES: Recent studies have highlighted an increasing prevalence of depression and sleep problems among physicians during their residency training in the medical field. The study aims to explore the prevalence of depressive symptoms and sleepiness among the residents of different medical specialties in the two regions of KSA and describe the factors that potentially cause depression and sleepiness. METHODS: A survey was distributed to the residents of King Abdulaziz Medical City in the Riyadh province, and to the residents of King Fahad Specialist Hospital Buraidah and Maternity and Children's Hospital Buraidah in the Qassim province. The Patients' Health Questionnaire-2 was used to determine the prevalence of depression and the Epworth Sleepiness Scale was used to measure sleepiness. RESULTS: One hundred and eighty-one residents completed the survey. While depressive symptoms were prevalent among 93% of the residents, 49% of the residents reported excessive daytime sleepiness. Depressive symptoms were more common in the residents of King Abdulaziz Medical City, with the prevalence being 94.5%. There was a significant association between depressive symptoms and excessive sleepiness (p = 0.046). CONCLUSION: Depressive symptoms and excessive sleepiness are highly prevalent in postgraduate trainees. Residents with depression were found to be sleepier during their work. Given the negative effect on patient safety, the high prevalence of both depressive symptoms and sleepiness is alarming. There is an urgent need to improve residents' wellness through well-structured well-being programs.

Travel burden and geographic access to health care among children with cancer in Saudi Arabia.

BACKGROUND: Travel burden has a substantial psychosocial impact and financial strain on childhood cancer patients and their families. AIMS: To study the geographic distribution of childhood cancer and assess the travel burden for care in Saudi Arabia. METHODS: This was a cross-sectional multi-institutional study that enrolled 1657 children with cancer who were diagnosed between 2011 and 2014. Cancer type/stage, city/region of residence, and city/region of treating centre were recorded. Travel burden was measured based on a 1-way distance in kilometres from the city centre to the treatment institution. This study was supported by Sanad Children's Cancer Support Association. RESULTS: Diagnosis was leukaemia (45.2%), non-CNS solid tumours (30.2%), lymphoma (12.3%), CNS tumours (11.8%) and histiocytosis (0.5%). Childhood cancer centres were in the same city as where the patients lived in 652 (39.3%) cases, same region but different city in 308 (18.6%), different regions in 613 (37%), and not known in 84 (5.1%). The mean 1-way travel distance for patients who lived in different regions was 790 (range, 116-1542) km. A total of 536 (32%) patients lived ≥ 400 km and 216 (13%) > 1000 km from the treatment centre. Among 642 patients with acute lymphoblastic leukaemia who required 2-3 years of therapy, 197 (31%) lived ≥ 400 km and 94 (15%) >1000 km from the treatment centre. CONCLUSIONS: Nearly two thirds of patients with childhood cancer lived in different cities than the treatment centres, including one third of patients who lived ≥ 400 km away. There is a need to develop strategies to improve access to childhood cancer care.

Frequency of pathogenic/likely pathogenic germline variants in cancer-related genes among children with acute leukemia in Saudi Arabia.

BACKGROUND: The frequency of pathogenic/likely pathogenic (P/LP) germline mutations in cancer-related genes among children with cancer in highly consanguineous populations is not well studied. METHODS: Whole-exome sequencing of germline DNA was performed in 60 children with acute leukemia. We used the St. Jude Pediatric Cancer Variant Pathogenicity Information Exchange (PeCanPIE) data portal for the classification of germline variants by the St. Jude Medal Ceremony pipeline. RESULTS: Fifty-seven patients had acute lymphoblastic leukemia (ALL) and three patients had acute myeloid leukemia. Parental consanguinity was present in 27 (45%) patients. All patients were of Arab ancestry. Three patients (5%) had a history of cancer in their siblings. Five patients (8.3%) had P/LP germline mutations in cancer-related genes. Three patients with B-ALL had heterozygous pathogenic mutations in TP53, BRCA1, and BRCA2; one patient with B-ALL had homozygous pathogenic mutation in PMS2; and one patient with T-ALL had LP homozygous mutation in AK2 that was associated with reticular dysgenesis. Among patients who had history of parental consanguinity, three (11%) had P/LP germline mutations compared with two (8%) in the absence of parental consanguinity. Fourteen (23%) patients had gold medal variants in cancer-related genes, 13 were heterozygous, and one was homozygous. Silver medal variants were present in 35 (58%) patients; all were heterozygous except one homozygous. CONCLUSIONS: Children with acute leukemia in Saudi Arabia had low frequency of P/LP mutations in cancer-related genes despite the high rate of consanguinity. Larger studies using whole-genome sequencing are needed to further explore the heritability of childhood leukemia.

Identifying Prognostic Factors That Influence Outcome of Childhood Acute Myeloid Leukemia in First Relapse in Saudi Arabia: Results of the Multicenter SAPHOS Study.

BACKGROUND: The outcome of childhood acute myeloid leukemia (AML) in first relapse (rAML) remains poor. Reported overall survival (OS) rates vary between high-income developed countries and those with fewer resources. The OS of rAML in high-income developing countries (HIDCs) has not been reported. PATIENTS AND MATERIALS: A multicenter study was performed in an HIDC. The outcome of patients with relapsed non-M3/non-Down syndrome AML was evaluated. Three-year OS was computed using the Kaplan-Meier method, and predictors of OS were analyzed using a Cox proportional hazards model. RESULTS: A total of 88 patients with non-M3/non-Down syndrome AML diagnosed between January 2005 and December 2012 with a first relapse were identified. Their 3-year OS was 22.6% ± 5.4%. Patients with inv(16) and t(8;21) had an OS of 75.0% ± 21.7% and 36.0% ± 16.1%, respectively. Worse outcomes were associated with "other intermediate" and 11q23 rearrangement AML (OS of 9.4% ± 8.7% and 10.7% ± 9.6%, respectively). Patients experiencing time to relapse (TTR) less than 1 year had shorter OS than those with a longer TTR (14.6% ± 5.4% vs. 41.1% ± 11.5%; P = .006). The outcome of patients after stem cell transplantation (SCT) in second complete remission (CR2) was superior compared with no SCT (50.9% ± 11.2% vs. 7.7% ± 4.6%; P = .001). TTR, risk group, CR2, and SCT in CR2 were the most significant predictors for survival. CONCLUSIONS: rAML remains a clinical challenge. Genetic variability in outcomes was observed. A majority of patients with inv(16) were successfully salvaged post-relapse, whereas patients with 11q23 rearrangement had a poor prognosis. Only one-third of those with t(8;21) rAML survived. Better access to SCT in HIDCs is needed.

A study of resident duty hours and burnout in a sample of Saudi residents.

BACKGROUND: Work hour restrictions in residency programs have been implemented over the last several decades in Europe, USA, and Canada. To best of our knowledge, there is no study of resident duty hours in the Kingdom of Saudi Arabia. In addition, few studies have looked at the prevalence of burnout amongst Saudi residents. The present study explored resident duty hours and burnout amongst residents in Saudi Arabia. METHODS: A paper-based questionnaire was designed to survey resident duty hours in Saudi Arabia and was administered along with the Maslach Burnout Inventory. The questionnaires were administered to residents in medical and surgical residency programs at King Abdulaziz Medical City-Riyadh and two hospitals in Buraidah, Qassim Province. RESULTS: A total of 181 residents from the three hospitals participated in the survey. In terms of average number of work hours per week, 50% of all residents reported working 60-79 h while 30% reported working 80 or more hours per week. The prevalence of burnout was 81%. There was no association between higher number of working hours and the prevalence of burnout. CONCLUSION: This was the first study describing resident duty hours and exploring the relationship between duty hours and burnout in Saudi Arabia. Our main findings were that the majority of residents work 60 or more hours per week, and there was a very high degree of burnout amongst residents. A larger multi-centre study of resident duty hours and its effect on patient safety and resident well-being is needed to develop work hour regulations in Saudi Arabia. In addition, there is an urgent need to develop programs that address resident burnout.

Prevalence of hereditary cancer susceptibility syndromes in children with cancer in a highly consanguineous population.

BACKGROUND & AIM: Hereditary cancer susceptibility syndromes (HCSS) are reported in up to one-third of children with cancer. Diagnosis of HCSS is crucial for implementation of surveillance protocols. We identified children who fulfilled criteria for HCSS in Saudi Arabia using the American College of Medical Genetics and Genomics (ACMG) guidelines, addressing the utility of these guidelines in a highly consanguineous population. METHODS: This multi-center cross-sectional study recruited 1858 children with cancer between January 2011 and December 2014. HCSS criteria were based on the ACMG guidelines. RESULTS: Seven hundred and four (40.4%) out of 1742 eligible patients fulfilled criteria for HCSS. Consanguinity was reported in 629 (38%) patients, with 50 (2.9%) first-degree, 535 (30.7%) second-degree, and 272 (15.6%) third-degree relatives affected with cancer. Two hundred and eighty eight (17.4%) leukemia and 87 (5.3%) brain tumour patients fulfilled HCSS criteria, with parental consanguinity being the most frequent criterion in both (leukemia 85.4%, brain tumors 83.9%). However, leukemia was less frequent in patients of consanguineous parents (p = 0.023). CONCLUSION: Four out of 10 children with cancer fulfilled criteria for HCSS, most often due to consanguinity. This higher than expected prevalence suggests the need to validate consanguinity as a criterion for HCSS in highly consanguineous populations.

Clinical characteristics and outcome of childhood acute promyelocitic leukemia (APL) in Saudi Arabia: a multicenter SAPHOS leukemia group study.

BACKGROUND: Acute promyelocytic leukemia (APL) is a rare form of acute myelogenous leukemia (AML). Survival rates exceed 80% in developed countries. Successful treatments rely on all-trans retinoic acid with anthracycline-based chemotherapy. Availability of modern care and public knowledge play important roles in pediatric APL survival. METHOD: A cytogenetic diagnosis of APL was confirmed in 30 (14.5%) out of 207 children consecutively diagnosed with de novo AML between January 2005 and December 2012 at nine cancer care centers in Saudi Arabia. Patients were treated based on the standard protocol used by the center following the PETHEMA or the C9710 treatment protocols. We modeled 5-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) vs. treatment and potential covariates of age at diagnosis, involvement of central nervous system (CNS), and white blood cell (WBC) levels. RESULTS: The median age was 10.4 years with a male:female ratio of 1.9. WBC was 10 × 109/l or greater in 57% and CNS involvement was confirmed in 13%. OS, EFS, and CIR were 74 ± 12%, 55 ± 19%, and, 36 ± 17% respectively. No significant difference was found by treatment protocol. WBC levels were significantly prognostic for all negative events, but treatment with C9710 significantly ameliorated negative WBC effects. Overall outcomes were comparable to those reported in developed countries. CONCLUSIONS: Access to modern care is likely to be a critical factor in successful and comparable outcomes of childhood APL across the globe. In the present study, utilizing a cytarabine-containing protocol improved outcome of high-risk pediatric patients with APL.

Treatment results in children with myeloid leukemia of Down syndrome in Saudi Arabia: A multicenter SAPHOS leukemia group study.

Despite the high incidence of Down syndrome (DS) in Arab countires, the incidence and outcomes of myeloid leukemia of DS (ML-DS) have not been studied. We evaluated 206 pediatric acute myeloid leukemia (AML) patients diagnosed between 2005 and 2012 and identified 31 (15%) ML-DS. The incidence of ML-DS was 48 per 100,000 compared to 0.6 per 100,000 for AML in non-DS children. Thus, patients with DS had 80-fold increased risk of ML-DS compared to AML in non-DS children. The median age at diagnosis was 1.8 years, male/female ratio was 1.2, majority (84%) of patients had FAB-M7 subtype, and the cytogenetic abnormalities were normal karyotype (constitutional trisomy 21) in 48%, additional trisomy in 23%, and other aberrations in 29%. Complete remission, cumulative incidences of relapse (CIR), toxic-death, and 5-year event-free survival (EFS) rates were 96.8%, 19.4%, 13.1%, and 67.7±8.4%; respectively. In the present study, multivariate analysis revealed favorable outcome (5-year EFS 86.7±8.8%) for patients with normal karyotype. The incidence and clinical characteristics of ML-DS in Saudi patients were comparable to other reports. However, there is a need to optimize risk stratification and treatment intensity to reduce CIR and toxic death rates to further improve outcomes of patients with ML-DS.

Serologic evidence of Toxoplasma gondii infection among cancer patients. A prospective study from Qassim region, Saudi Arabia.

OBJECTIVES: To determine the frequency of antibody seropositivity of Toxoplasma gondii  infection in a cancer patient population. We also explored on association of Toxoplasma gondii seropositivity with selected variables. Methods: This is a prospective cross-sectional study conducted at  Prince Faisal bin Bandar cancer center, Qassim, Saudi Arabia, from November 2014 to  March 2015. One hundred thirty seven patients were involved in the study. Demographic data was collected using structured questionnaire, and clinical information was retrieved from the patient's medical reports. Enzyme-linked immunosorbent assay technique was used for antibody assay. Results:   The frequency of seropositivity for Toxoplasma gondii infection was 30.6%. The patient's age range from 1.5-84 years with a geometric mean of 42.7 years. The seropositivity was significantly higher (p<0.05) among the 40-80 years age group (71.4%) as compared  to  0-39 years one (28.6%).   Conclusion: The prevalence of Toxoplasma gondii increases with increasing age among cancer patients in this region of central Saudi Arabia. More research is advisable for better understanding of ageing in pathogenesis of toxoplasmosis among patients with malignancies.

Clinical characteristics and outcome of childhood de novo acute myeloid leukemia in Saudi Arabia: A multicenter SAPHOS leukemia group study.

Geographic variation and ethnicity have been implicated to influence the outcome of pediatric acute myeloid leukemia (AML). Furthermore, survival outcomes from developing countries are reported to be inferior to developed nations. We hypothesized that risk- and response-based outcome in high-income resource-rich developing countries would be comparable to developed nations as access to care and supportive measures would be similar. A total of 193 children diagnosed with de novo AML between January 2005 and December 2012 were identified, of those 175 were evaluable for outcome. Patients were stratified into low-risk (LR), intermediate-risk (IR), or high-risk (HR) groups. The complete remission (CR), early death, and induction failure rates were: 85.7%, 2.3%, and 12%; respectively. The 5-year cumulative incidences of relapse (CIR) and non-relapse mortality (NRM) were 43.1% and 9.8% respectively; overall survival (OS) was 58.8±4% and event-free survival (EFS) 40.9±4.1%. The 5-year OS for LR, IR, and HR groups were 72.0±6.9%, 59.8±6.2%, and 45.1±7.4%; respectively (p=0.003); and EFS 50.5±8.0%, 46.3±6.4%, and 23.3±6.4%; respectively (p=0.001). This study demonstrated comparable outcomes to those reported from developed countries. This suggests that utilization of risk- and response-based protocols in developing countries can overcome ethnic and geographic variation, if access to care and supportive measures were similar.