Durvalumab-Induced Immune Thrombocytopenia in Patients with Advanced Cholangiocarcinoma Undergoing Yttrium-90 Radioembolization.

Introduction: Immune thrombocytopenia (ITP) secondary to durvalumab, a programmed cell death ligand 1 inhibitor, is a rare but clinically significant immune-related adverse event. Herein, we present 2 patients with cholangiocarcinoma who developed ITP immediately post-yttrium-90 radioembolization (Y90-RE) while on durvalumab-based systemic therapy. We hypothesize that given the timing, the immunotherapy and the radioembolization combination led to this event. It is not uncommon given the approval of immunotherapy and its role in locoregional therapies, that patients are treated with a combination of systemic immunotherapy and radioembolization or other forms of radiation, thus signifying the importance of potential complications. Case Presentation: Two patients, a 67-year-old female and a 60-year-old man, with biopsy-proven advanced unresectable cholangiocarcinoma, received a combination of systemic therapy with durvalumab, gemcitabine, and cisplatin and subsequently Y90-RE. Both patients developed ITP following in the immediate post-Y90-RE period. All other causes of ITP were comprehensively ruled out and treatment for ITP was initiated in the form of high-dose steroid and intravenous immunoglobulins. Durvalumab was discontinued, and only gemcitabine/cisplatin-based chemotherapy was continued thereafter. Due to recurrence, one of the patients required longer courses of steroids as well as thrombopoietin receptor agonists. Conclusion: Immunotherapy in the form of durvalumab and now pembrolizumab alongside chemotherapy is an approved first-line standard of care. Furthermore, it is not uncommon for patients to receive Y90-RE to improve patient outcomes. This report highlights the development of ITP in 2 patients who received durvalumab alongside Y90-RE. Awareness of this as a potential immune-mediated event is important to allow for close monitoring of platelet counts and for early intervention/management when this occurs.

Chemotherapeutic Activity of Imidazolium-Supported Pd(II) o-Vanillylidene Diaminocyclohexane Complexes Immobilized in Nanolipid as Inhibitors for HER2/neu and FGFR2/FGF2 Axis Overexpression in Breast Cancer Cells.

Two bis-(imidazolium-vanillylidene)-(R,R)-diaminocyclohexane ligands (H2(VAN)2dach, H2L1,2) and their Pd(II) complexes (PdL1 and PdL2) were successfully synthesized and structurally characterized using microanalytical and spectral methods. Subsequently, to target the development of new effective and safe anti-breast cancer chemotherapeutic agents, these complexes were encapsulated by lipid nanoparticles (LNPs) to formulate (PdL1LNP and PdL2LNP), which are physicochemically and morphologically characterized. PdL1LNP and PdL2LNP significantly cause DNA fragmentation in MCF-7 cells, while trastuzumab has a 10% damaging activity. Additionally, the encapsulated Pd1,2LNPs complexes activated the apoptotic mechanisms through the upregulated P53 with p < 0.001 and p < 0.05, respectively. The apoptotic activity may be triggered through the activity mechanism of the Pd1,2LNPs in the inhibitory actions against the FGFR2/FGF2 axis on the gene level with p < 0.001 and the Her2/neu with p < 0.05 and p < 0.01. All these aspects have triggered the activity of the PdL1LNP and PdL2LNP to downregulate TGFß1 by p < 0.01 for both complexes. In conclusion, LNP-encapsulated Pd(II) complexes can be employed as anti-cancer drugs with additional benefits in regulating the signal mechanisms of the apoptotic mechanisms among breast cancer cells with chemotherapeutic-safe actions.

Clinical spectrum of sarcoidosis in patients at a tertiary care hospital, Pakistan: Ten-year follow-up study.

OBJECTIVE: To identify the local patterns of manifestations, organ involvement other than lungs, diagnostic tools and treatment regimens related to patients of sarcoidosis. Methods: The retrospective study was conducted from November 1, 2019, to February 28, 2020, at the Aga Khan University Hospital, Karachi, and comprised data of sarcoidosis patients who needed hospitalisation between 2009 and 2019. The entire clinical spectrum was noted based on organ involvement. Data was analysed using SPSS 21. RESULTS: Of the 80 patients, 53(66.3%) were women. The overall mean age at diagnosis was 52.0±13.5 years. Pulmonary sarcoidosis was found in 60(75%) patients, while 13(16.3%) had extrapulmonary manifestations, and 6(8.8%) had both pulmonary and extrapulmonary involvement. None of the patients had hypercalcaemia, while antinuclear antibodies were positive in 2 (18.2%) patients. In terms of treatment, 75(93.8%) patients received corticosteroids. Acute exacerbation of interstitial lung disease was the most common reason of hospitalisation 16(20%). Mortality was the outcome in 11(14.7%) cases. CONCLUSIONS: Sarcoidosis was found to be more prevalent in women aged 50 years and above. A quarter of patients had extrapulmonary manifestation, while interstitial lung disease was the most common complication.

Culture-Specific Observations in a Saudi Arabian Digital Home Health Care Program: Focus Group Discussions With Patients and Their Caregivers.

BACKGROUND: There is growing evidence of the need to consider cultural factors in the design and implementation of digital health interventions. However, there is still inadequate knowledge pertaining to the aspects of the Saudi Arabian culture that need to be considered in the design and implementation of digital health programs, especially in the context of home health care services for patients who are chronically and terminally ill. OBJECTIVE: This study aims to explore the specific cultural factors related to patients and their caregivers from the perspective of physicians, nurses, and trainers that have influenced the pilot implementation of Remotely Accessible Healthcare At Home, a connected health program in the Home Health Care department at King Saud University Medical City, Riyadh, Saudi Arabia. METHODS: A qualitative study design was adopted to conduct a focus group discussion in July 2019 using a semistructured interview guide with 3 female and 4 male participants working as nurses, family physicians, and information technologists. Qualitative data obtained were analyzed using a thematic framework analysis. RESULTS: A total of 2 categories emerged from the focus group discussion that influenced the experiences of digital health program intervention: first, culture-related factors including language and communication, cultural views on using cameras during consultation, nonadherence to web-based consultations, and family role and commitment and second, caregiver characteristics in telemedicine that includes their skills and education and electronic literacy. Participants of this study revealed that indirect contact with patients and their family members may work as a barrier to proper communication through the Remotely Accessible Healthcare At Home program. CONCLUSIONS: We recommend exploring the use of interpreters in digital health, creating awareness among the local population regarding privacy in digital health, and actively involving direct family members with the health care providers.

Willingness to Use Digital Health Tools in Patient Care Among Health Care Professionals and Students at a University Hospital in Saudi Arabia: Quantitative Cross-sectional Survey.

BACKGROUND: The adoption rate of digital health in the health care sector is low in many countries. A facilitating factor for successful implementation and adoption of digital health is acceptance by current and future health care professionals. OBJECTIVE: This study was conducted to identify factors associated with willingness to use digital health tools in patient care among health care professionals and students. METHODS: This was a quantitative cross-sectional survey study conducted among health care professionals and students at a university hospital in Riyadh, Saudi Arabia. A nonprobability convenience sampling procedure was used to recruit participants. Data were collected using a self-completed e-questionnaire that was distributed by email. Chi-square tests, t tests, and logistic regression were used to analyze the data. RESULTS: We found that 181 out of 218 health care professionals (83.0%; 75.6% [59/78] physicians; 87.1% [122/140] nurses) and 115 out of 154 students (74.7%; 80.0% [76/95] medical students and 66.1% [39/59] nursing students) were willing to use digital tools in patient care. Willingness to use digital tools was significantly associated with attitude (Adjusted Odds Ratios [AOR] 1.96; 95% CI 1.14-3.36) and self-efficacy (AOR 1.64; 95% CI 1.17-2.30) among health care professionals, and with current year of study (AOR 2.08; 95% CI 1.18-3.68) and self-efficacy (AOR 1.77; 95% CI 1.17-2.69) among students. No significant difference in willingness to use digital tools was found between physicians and nurses (P=.113), and between medical and nursing students (P=.079). CONCLUSIONS: The findings of this study should encourage policy makers and hospital managers to implement relevant eHealth interventions within routine health care systems in Saudi Arabia. For successful implementation, digital health education programs should be implemented simultaneously, so that current and future health care professionals are able to develop required positive attitudes as well as practical skills and competencies.

The Need for Transgender Healthcare Medical Education in a Developing Country.

PURPOSE: The single most significant barrier to healthcare for people who identify as transgender is poor access to healthcare providers trained in trans-health. Despite this, trans-health education is far from being a routine component of the undergraduate medical curriculum in developing countries like Pakistan. This study aimed to assess knowledge and attitudes regarding people who identify as transgender, as well as the perceived need for trans-health in the curriculum, amongst medical students in Pakistan. MATERIALS AND METHODS: A cross-sectional study using a self-designed questionnaire was carried out amongst undergraduate medical students at the Aga Khan University. Stratified random sampling was used, whereby students were stratified based on their current year of medical education. RESULTS: A total of 249 students were included in this survey. The majority (61%) had poor overall knowledge, with a significantly higher percentage of pre-clinical students (79.6%) having poor knowledge regarding differences in transgender health needs compared to clinical students (60.3%; p = 0.001). Most students acknowledged that individuals who identified as transgender faced a lack of access to healthcare (78.3%), were poorly integrated into society (92.0%) and were treated differently in a clinical setting (58.6%). Many students were unsure of how to address (49.8%) and clinically examine (38.2%) patients identifying as transgender. However, most students demonstrated good (49.4%) or fair (45.0%) attitudes towards individuals who identified as transgender, and the majority reported a high (54.6%) or moderate (42.2%) perceived need for the inclusion of trans-health in the medical curriculum. CONCLUSION: Despite deficiencies in trans-health education in the medical school curriculum, positive attitudes and a high perceived need among students lay the foundation for developing a medical curriculum that gives due priority to trans-health. In developing countries, this can help bridge disparities in healthcare provision to people who identify as transgender.

Implementing a connected health intervention for remote patient monitoring in Saudi Arabia and Pakistan: explaining 'the what' and 'the how'.

BACKGROUND: Recent developments in connected health technology provide an opportunity to remotely monitor and provide health care to the patient needing long-term medical care. However, information about how any connected health interventions should be implemented for remote patient monitoring, and how patients should be educated and enabled for active participation in treatment is still not available to a sufficient degree. DISCUSSION: In this paper, we discussed what the components of a connected health intervention, entitled Remotely Accessible Health Care at Home (RAHAH), are, and how this intervention has been implemented in Saudi Arabia and Pakistan. The aim of this intervention is to remotely monitor, treat and educate patients needing long-term medical care. The description of the intervention is presented based on the Template for Intervention Description and Replication (TIDieR) checklist for the transparent, comprehensive and explicit reporting. CONCLUSION: We believe, successful implementation of RAHAH would be crucial to monitor and manage growing chronic care populations more effectively and efficiently in Saudi Arabia and Pakistan.

Synthesis, physical studies and uptake behavior of: copper(II) and lead(II) by Schiff base chelating resins.

Two new chelating resins possessing multiple functional groups capable of coordinating with several metal ions are reported. The resins were synthesized by condensing Schiff bases derived from 2-aminophenol, 2-hydroxy-5-chloroaniline and terephthaldehyde with formaldehyde in an alkaline medium. The effects of pH and contact time of the Cu(2+) and Pb(2+) in aqueous solutions on the uptake behavior of the resins were studied. The metal ion uptake behavior of the resins was investigated by the batch method. Both the uptake and the selectivity of the resins towards the investigated metal ions were related to the structure of the resins, type of the metal ion and the uptake conditions. The resins showed maximum uptake capacity for Cu(2+) and Pb(2+) at pH 10. Cu(2+) was seen to undergo preferential adsorption in separate and mixture solutions of Cu(2+) and Pb(2+). Kinetic studies for the resins using Langmiur equation were also performed. The Schiff base monomers and their formaldehyde resins were characterized by elemental analyses, FTIR and (1)H NMR spectroscopy. The thermal stability of the resins was studied using TGA/DTG analysis.