Undergraduate research in medical schools in Pakistan: Relevance, Needs, and Importance.

Recent trends in medical education demand practicing physicians to be competent in playing multiple roles. Life-long learning skills underpinned by research & scholarly activity will enable them to play these roles adequately. Therefore, the introduction of structured training in research during early undergraduate years is pivotal. This would enable trainee physicians to develop essential skills; the institutions will grow in terms of visibility & ranking; the trainers and supervisors will be satisfied in terms of research productivity and, most importantly the patients will benefit in terms of improved clinical outcomes.

Nurses' job burnout and its association with work environment, empowerment and psychological stress during COVID-19 pandemic.

AIM: The aim of this study was to assess the influence of perceived work environment, empowerment and psychological stress on job burnout among nurses working at the time of the COVID-19 pandemic. BACKGROUND: Nurses experienced high levels of job burnout during the pandemic, which impacted their mental health and well-being. Studies investigating the influence of work environment, empowerment and stress on burnout during the time of COVID-19 are limited. DESIGN: The study utilized a cross-sectional design. METHODS: Data were collected from 351 nurses in Oman between January and March 2021. The Maslach Burnout Inventory, the Practice Environment Scale of the Nursing Work Index, the Conditions of Work Effectiveness Questionnaire and the Perceived Stress Scale were used to assess study variables. RESULTS: About two-thirds of the nurses (65.6%) reported high levels of job burnout. Nurse managers' ability, leadership and support; staffing and resources adequacy; and nurses' access to support were significant factors associated with a reduced level of burnout. CONCLUSION: Supporting nurses during the crisis, ensuring adequate staffing levels and providing sufficient resources are critical to lower job burnout. Creating a positive and empowered work environment is vital to enhance nurses' retention during the pandemic.

Interprofessional collaboration as a mediator in the relationship between nurse work environment, patient safety outcomes and job satisfaction among nurses.

BACKGROUND: As an important organisational feature, the nurse work environment has been associated with increased work effectiveness, reduced patient safety issues and improved care quality. However, the mechanism underlying this association remains unexplored. AIM: This study aims to assess the mediating role of interprofessional collaboration in the relationships between nurse work environment, select patient safety outcomes and job satisfaction. METHODS: This cross-sectional, descriptive study used five standardized scales and included 881 clinical nurses employed in select teaching hospitals in Oman. RESULTS: Nurses who worked in teaching hospitals in Oman perceived their work environment as highly favourable. Nurse work environment was directly and indirectly associated with nurse-assessed quality of care, adverse patient events and job satisfaction, through interprofessional collaborations. CONCLUSION: Findings of the study suggest that enhancing nurse work environments can be a potential strategy to foster interprofessional collaboration and improve job satisfaction and patient safety outcomes. IMPLICATIONS FOR NURSING MANAGEMENT: Organisational strategies to improve patient safety outcomes and job satisfaction in nurses can be facilitated by improving nurses' work conditions and enhancing interprofessional collaboration through supportive leadership, theory-driven approaches, obtaining hospital accreditation/certification and relevant workplace policies.

Beliefs and Perceptions About Cancer Diagnosis and Treatment-Seeking and Decision-Making Behaviors Among Omani Patients with Cancer: A Single-Center Study.

A cancer diagnosis is associated with anxiety and psychological distress. Cultural and societal factors greatly affect the complex process of coping mechanisms and decision making. Omani patients receiving cancer treatment at Sultan Qaboos University Hospital in Oman were interviewed about their perceptions regarding cancer, treatment, outcome, and decision making. Out of a total of 360 approached, 216 patients consented. The median age was 42 years. The results showed that 60.6% of patients considered cancer diagnosis as a test from God, 13.9% considered it as a result of an evil eye, 40% believed prayers treat cancer. Fifty-six percent of participants wanted to make treatment decisions themselves, while 2.3% preferred their family to make decisions. Our findings suggest that perceptions about cancer in Oman are specific and are associated with religion and sociocultural background.

Prevalence of BRCA1 and BRCA2 pathogenic sequence variants in ovarian cancer patients in the Gulf region: the PREDICT study.

BACKGROUND: Patients with pathogenic sequence variants (PSVs) in BRCA1/BRCA2 are at high risk of developing ovarian cancer (OC). However, genetic testing for BRCA1/BRCA2 PSVs is still not a routine practice in the Middle East. With the lack of epidemiological studies in the region, we aim to describe the prevalence of BRCA1/BRCA2 PSVs in patients with OC across different countries in the Gulf region. METHODS: The PREDICT study was an observational, prospective, epidemiological study, which consecutively recruited women with ovarian, primary peritoneal, and fallopian tube cancers from the following Gulf countries over the period from July 2017 to July 2019; United Arab Emirates (UAE), Kuwait, and Oman. The study was approved by the local ethics committee of participating centers. The BRCA1/BRCA2 PSVs were assessed by tissue genetic testing using next-generation sequencing (NGS). RESULTS: A total of 105 women were included with a median age at diagnosis of 52 years (IQR 44.5 - 61.0). Nearly 11.4% of patients reported a family history of ovarian or breast cancer, while 4.7% of patients reported a family history of other cancers. Most of the patients (70.3%) had advanced disease (FIGO stage III/IV) at presentation. Eighty-eight patients (84%) were successfully tested for somatic BRCA1/BRCA2 PSVs. Fifteen patients (17%) were found to have PSVs in either BRCA1, BRCA2, or both genes; of them, 10 patients (11.2%) had BRCA1 somatic PSVs alone, eight patients (9.1%) had BRCA2 somatic PSVs, while three patients (2.9%) had both PSVs. Five patients with BRCA1/BRCA2 somatic PSVs had germline PSVs tests, and three of them tested positive. Concerning treatment, 87.6% of patients received perioperative chemotherapy and 6.6% as first-line palliative chemotherapy. Eighty-seven (82.9%) patients underwent debulking surgery, with no residual disease in 42.5% of patients. CONCLUSION: Our study showed that the prevalence of BRCA1/BRCA2 somatic PSVs in patients with OC is higher than the reported global figures (2-8%). However, more studies are warranted to further elucidate the prevalence of BRCA1/BRCA2 somatic and germline PSVs, as well as other relevant genetic alterations, to better understand their impact on OC patient outcomes in Gulf countries. TRIAL REGISTRATION: NCT03082976 .

Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis.

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.

Authentic leadership and nurses' motivation to engage in leadership roles: The mediating effects of nurse work environment and leadership self-efficacy.

BACKGROUND: Leadership styles of a nurse manager have a profound influence on staff nurses' motivation to engage in formal nursing leadership roles; however, the mechanism underlying this pattern of influence remains unknown. AIM: To assess the direct and indirect effect of nurse managers' authentic leadership on staff nurses' motivation to engage in formal leadership roles, through the intermediary role of nurse work environment and leadership self-efficacy. METHODS: This cross-sectional study involved 1534 nurses from 24 acute care hospitals in the Sultanate of Oman. FINDINGS: Nurse managers' authentic leadership was associated with staff nurses' motivation to engage in formal leadership roles. Nurse practice environment and leadership self-efficacy mediated partially the association between authentic leadership and motivation to engage in formal leadership roles. CONCLUSION: Results of this study underscore the value of authentic leadership in creating a healthy work environment and fostering nurses' leadership self-efficacy, resulting in greater motivation to engage in nursing leadership roles. IMPLICATIONS FOR NURSING MANAGEMENT: Organizational strategies to attract nurses to undertake leadership roles should include measures to bolster authentic leadership behaviours in nurse managers through theory-driven leadership development programmes or interventions, continuing education, effective succession planning and creating a supportive work environment.

Authentic leadership, nurse-assessed adverse patient events and quality of care: The mediating role of nurses' safety actions.

BACKGROUND: Authentic leadership has been consistently cited as a strong precursor of sustained job performance and work effectiveness in nurses; however, studies linking authentic leadership with nurses' safety actions, nurse-assessed adverse patient events and nursing care quality are scarce. AIM: To examine whether nurses' safety actions mediate the relationship between authentic leadership, nurse-assessed adverse events and nursing care quality. METHODS: A multi-centre, cross-sectional study involving 1,608 nurses employed in acute care facilities in Oman. Multi-stage regression analysis was conducted in testing for the mediation model. FINDINGS: Nurse managers in Oman were perceived to be highly authentic by their staff nurses. Authentic leadership significantly predicted nurses' safety actions (ß = 0.168, p < .001), decrease in nurse-assessed adverse events (ß = -0.017, p = .024) and increase in care quality (ß = 0.121, p < .001). Further, the association between authentic leadership and nurse-assessed adverse events (ß = -0.063, p = .057) and care quality (ß = 0.038, p = .002) was mediated by nurses' safety actions. CONCLUSION: Results suggest the importance of developing nurse managers' authentic leadership to foster nurses' safety actions and reduce adverse patient outcomes and promote nursing care quality. IMPLICATIONS FOR NURSING MANAGEMENT: Organizational efforts to address patient safety issues should be directed towards developing authentic leadership in nurse managers through leadership programmes, periodic evaluation of leadership competencies (e.g., 360-degree or a bottom-up performance evaluation), and a creation of a safe culture in which nurses can openly report safety concerns for corrective action.

FAT4 silencing promotes epithelial-to-mesenchymal transition and invasion via regulation of YAP and ß-catenin activity in ovarian cancer.

BACKGROUND: The adhesion molecule, FAT4, has a tumor suppressor function with a critical role in the epithelial-to-mesenchymal-transition (EMT) and anti-malignant growth in several cancers. No study has investigated yet its role in epithelial ovarian cancer (EOC) progression. In the present study, we examined the role of FAT4 in proliferation and metastasis, and its mechanisms of interaction in these processes. METHODS: We have performed cell viability, colony formation, and invasion assays in ovarian cancer cells treated with siRNA to knockdown FAT4 gene expression. The regulatory effects of FAT4 on proteins involved in apoptotic, Wnt, Hippo, and retinoblastoma signaling pathways were evaluated by Western blotting following FAT4 repression. Also, 426 ovarian tumor samples and 88 non-tumor samples from the Gene Expression Profiling Interactive Analysis (GEPIA) database were analyzed for the expression of FAT4. Pearson's correlation was performed to determine the correlation between FAT4 and the E2F5, cyclin D1, cdk4, and caspase 9 expressions. RESULTS: Lower expression of FAT4 was observed in ovarian cancer cell lines and human samples as compared to non-malignant tissues. This down-regulation seems to enhance cell viability, invasion, and colony formation. Silencing FAT4 resulted in the upregulation of E2F5, vimentin, YAP, ß-catenin, cyclin D1, cdk4, and Bcl2, and in the downregulation of GSK-3-ß, and caspase 9 when compared to control. Furthermore, regulatory effects of FAT4 on the EMT and aggressive phenotype seem to occur through Hippo, Wnt, and cell cycle pathways. CONCLUSION: FAT4 downregulation promotes increased growth and invasion through the activation of Hippo and Wnt-ß-catenin pathways.

Low doses of colony-stimulating factors lead to resolution of neutropenia in cancer patients through increased levels of dihydrofolate reductase.

Low doses of granulocyte- colony stimulating factor (G-CSF) and granulocyte macrophage- colony stimulating factor (GM-CSF) have been shown to be beneficial in reducing duration of systemic antibiotic therapy and in-patient hospitalization by decreasing the period of neutropenia in cancer patients undergoing chemotherapy. Since the underlying mechanism is unclear, the aim of this study was to investigate whether the administration of G-CSF and GM-CSF in two different doses (low dose and standard dose) would result into resolution of neutropenia with concomitant increase in multiple forms of dihydrofolate reductase (DHFR, a pivotal enzyme in the pathway of de novo DNA synthesis). Thirty seven cancer patients (26 males and 11 females; age 14-73 years) having chemotherapy-induced neutropenia (absolute neutrophil counts <500/µl) were treated with colony stimulating factor (CSF) in the following manner: 11 received GM-CSF (7 received a dose 250 µg/m2 and 4 received a dose of 100 µg/m(2)); 26 received G-CSF (14 received a dose of 5 µg/kg and 12 received a dose of 2.5 µg/kg). CSFs was given every day till the absolute neutrophil count was more than 1,000/µl. Ten ml blood was collected from each patient and analyzed for total leukocyte count (TLC) and active DHFR and immunoreactive nonfunctional form of DHFR (IRE) in the cytoplasm of blood leukocytes by using methotrexate binding assay and enzyme-linked immunosorbent assay (ELISA). A significant increase (p<0.05) in concentrations of both active DHFR and IRE following stimulation with low as well as standard doses of CSFs was observed along with increase in the TLC. There was no significant difference in number of days to resolution of neutropenia at these two doses, indicating that even low doses of CSFs are clinically effective. Along with an increase in TLC, the levels of DHFR increased even at low doses of CSF suggesting that this might be one of the mechanisms for CSF-induced proliferation of leukocytes in neutropenic cancer patients.

Enhancing Postgraduate Medical Education: Upscaling and Recognition of Pakistan's Training.

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Artificial Intelligence and the Gartner Cycle: Time to Introduce in Undergraduate Medical Education.

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Managing the Adverse Events Associated with Pembrolizumab and Lenvatinib Therapy in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynaecological cancer. The combination of lenvatinib and pembrolizumab has exhibited efficacy as the second line treatment for advanced EC, with a significant benefit in terms of progression free survival (PFS) and overall survival, but the adverse events (AE) profile is complex. AEs associated with the treatment may represent a limitation to this combination. Here, we report the case of a 38-year-old female patient diagnosed with stage IV EC elsewhere, whose disease progressed after the first line of treatment and was referred to a specialised cacncer centre in Muscat, Oman, in 2021. We treated her with the combination of lenvatinib and pembrolizumab. During the course of the treatment, she developed hand-foot syndrome grade III and hypothyroidism grade II. The AEs were managed with supportive medications, dose interruptions, dose reductions and multidisciplinary care, which allowed the continuation of the treatment. The patient achieved a good partial response and an ongoing PFS of more than 12 months.

An Unusual Presentation of Choriocarcinoma in a Postmenopausal Woman: A case report.

Choriocarcinoma (CC) is a malignant neoplasm of the trophoblastic tissue, with a potential to metastasise to distant organs. Limited case of gestational CC develops after a long latent period. We report a 52-year-old postmenopausal woman who developed metastatic choriocarcinoma presumably of gestational origin, 8 years after the last pregnancy and 2 years after the last menstrual period. The patient was brought to the emergency room of a tertiary care centre in Muscat, Oman, in 2022 and was diagnosed with CC metastatic to the brain, spleen, lung and the kidney. The ß-human chorionic gonadotrophin level was found to be raised (1,292,867 mIU/mL). The International Federation of Gynecologic Oncology risk score was calculated to be 14 (very high risk). The patient was initially treated with whole-brain radiotherapy and splenic artery embolisation because of a hemoperitoneum. Afterwards the patient received systemic treatment using the standard EMA/CO regimen till complete serological remission.

Successful Treatment of a Case of Crescentic Glomerulonephritis in a Patient with Primary Peritoneal Carcinoma: A case report.

Crescentic glomerulonephritis has been associated with several solid tumour malignancies. Only a few cases of nephropathy have been reported in association with tubo-ovarian/peritoneal malignancies. We report a 55-year-old female patient who presented to a tertiary care centre, Muscat, Oman, in 2022. She developed combined immune complex-mediated glomerulonephritis and pauci-immune necrotising crescentic vasculitis simultaneously with the diagnosis of tubo-ovarian/peritoneal cancer. The baseline estimated glomerular filtration rate (eGFR) was 13 mL/min. The patient received two doses of rituximab and three doses of pulse corticosteroids, leading to significant improvement in renal function and the disappearance of her proteinuria. The eGFR improved to >60mL/min; her proteinuria gradually resolved after 10 weeks of treatment. She was then given a combination chemotherapy treatment for tubo-ovarian/peritoneal cancer leading to a normalisation of her CA-125 after three months of therapy.

Clinicopathological Features and Outcomes of Endometrial Cancer: A single institution experience.

Objectives: This study aimed to report the demographic features, clinical presentation, pathological types and long-term outcomes of patients diagnosed with endometrial cancer (EC) in Oman. EC is the sixth most common cancer in women worldwide and the fifth most common cancer in women in Oman. Survival outcomes of EC have not been reported previously from Oman. Methods: This retrospective study was carried out on consecutive patients treated at the Sultan Qaboos University Hospital, Muscat, Oman, between 2008 and 2020. Survival was estimated using the Kaplan and Meier method. Results: A total of 50 patients with EC were included. The median age was 61 years (range: 31-86 years), and 72% of the patients had type I histology. Most patients were diagnosed with stage IA and IB EC (49% and 20%, respectively), and the majority had grade 1 or 2 tumours (40% and 34%, respectively). Overall, the 5-year survival and 10-year survival rates were estimated to be 70% and 56%, respectively. Weight (>75 kg) and body mass index (>30 kg/m2) were significantly associated with better survival. Tumour histology (type I versus type II or carcinosarcoma), grade (1 versus 2 versus 3) and stage (IA or IB versus II-IV) were associated with better overall survival (P = 0.007, P <0.0001 and P <0.0003, respectively). Patients diagnosed with EC with co-morbidities, other than obesity, had inferior survival compared to those without co-morbidities. Conclusion: Median age at presentation, histological sub-type, clinical stage and outcomes are comparable to the published literature. Almost two-thirds of the patients were obese. These data could be used as a benchmark for outcomes of EC in the region.

Durable Response to Pazopanib in a Patient with Fumarate Hydratase-Mutant Tubulocystic Renal Cell Carcinoma.

Tubulocystic carcinoma of the kidney (TC-RCC) is a rare renal tumor and has been recently included as a distinct entity in WHO classification of renal neoplasms. We report the case of a patient with metastatic tubulocystic RCC whose disease progressed through standard of care treatment for nonclear RCC. However, genetic analysis revealed a germline pathogenic variant of fumarate hydratase (FH) gene, and the patient had a sustained and durable response to pazopanib.

A Step towards Personalised Cancer Treatment in Lower Middle-income Countries (LMICS): Molecular Tumour Boards.

Tumour boards are meetings where physicians from various disciplines treating cancer patients meet to recommend evidence-based or the best possible treatment plan. These meetings have evolved with time and now, in every part of the world; site-specific multi-disciplinary tumour boards are established. These meetings are considered pivotal for improving patient outcomes. The advances in molecular and genetic knowledge and technique and their integration in treatment options have paved the way for multiple therapeutic options. However, the adoption of personalised treatment choices is associated with a huge financial burden, especially in low and middle-income countries (LMICs). A molecular tumour board can help to identify and suggest the most appropriate plan of management. Key Words: Molecular, Genetics, Personalised, Challenges.

Determinants of Physicians' Job Satisfaction: A national multi-centre study from the Sultanate of Oman.

Objectives: This study aimed to examine and assess job satisfaction of physicians across several factors, such as quality of care, ease of practice, relationship with leadership and inter-professional collaboration. Methods: The data for this descriptive cross-sectional study were collected between July 2019 and January 2020. Participants provided demographic information and completed surveys related to physician job satisfaction and inter-professional collaboration. Multiple linear regressions were used to determine the relationship between overall job satisfaction and demographic features and inter-professional collaboration. Results: Out of the 396 physicians contacted, 354 responded (response rate: 89.4%). Results showed that out of the 354 physicians, 4.3% were not satisfied with their jobs, 36.5% expressed a moderate level of satisfaction and 59.2% were highly satisfied. There was no difference in the mean job satisfaction score among different groups of study participants, except for gender and the working grade (P <0.05). The overall job satisfaction rates were higher for the quality of care (mean = 3.93 ± 0.61) and ease of practice (mean = 3.89 ± 0.55) and lower for relationship with leadership (mean = 3.67 ± 0.86). Having a clinical postgraduate degree together with a PhD, a senior level of responsibility and good inter-professional relationship were associated with higher job satisfaction rates (P = 0.003 and 0.007, respectively). Conclusion: Overall, the job satisfaction rate was high. There was no difference among different groups of study participants, except for the working grade. Having a clinical postgraduate degree, a senior level of responsibility and good inter-professional relationship were associated with higher job satisfaction rates. The overall job satisfaction rates were higher for the quality of care and for ease of practice and lower for relationship with the leadership. Relationship with leadership is a modifiable factor and efforts at enhancing the physician-leadership relationship may lead to even higher satisfaction rates.