Kidney transplantation in patients with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is a disorder of the mammalian target of the rapamycin (mTOR) pathway associated with the development of multisystem tumors, including renal angiomyolipoma (AML). These renal tumors are benign by nature but locally invasive and carry a risk for the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). The frequency of subsequent renal transplantation in this population is largely uncharacterized, although single-center data suggests that 5%-15% of adult TSC patients are kidney transplant recipients. METHODS: This retrospective cohort study utilized United Network for Organ Sharing (UNOS) data. We included candidates waitlisted between 1987 and 2020 for a first kidney transplant with TSC-associated kidney failure. We utilized descriptive statistics to characterize the frequency of first-time kidney transplant waitlisting and transplantation among persons with TSC and the Fine-Gray subdistribution hazard model to evaluate characteristics associated with progression from waitlist. RESULTS: We identified 200 TSC-associated kidney failure patients within the waitlist cohort. Of these, 12 were pediatric patients. Two-thirds (N = 134) of waitlisted persons were female. One hundred forty patients received a transplant with a median waitlist time of 2 years. Younger age at waitlisting was associated with a greater probability of progressing to transplant (HR 0.98 [95% CI: 0.96-0.99]). 91.8% of kidney transplant recipients survived 1-year post-transplant with a functioning allograft. CONCLUSIONS: The majority of patients with TSC who are waitlisted for a kidney transplant progress onto transplantation with excellent 1-year post transplant patient and allograft survival.

The association between cost sharing, prior authorization, and specialty drug utilization: A systematic review.

BACKGROUND: Specialty drugs are identified by high monthly costs and complexity of administration. Payers use utilization management strategies, including prior authorization and separate tiers with higher cost sharing, to control spending. These strategies can negatively impact patients' health outcomes through treatment initiation delays, medication abandonment, and nonadherence. OBJECTIVE: To examine the effect of patient cost sharing on specialty drug utilization and the effect of prior authorization on treatment delay and specialty drug utilization. METHODS: We conducted a literature search in the period between February 2021 and April 2022 using PubMed for articles published in English without restriction on date of publication. We included research papers with prior authorization and cost sharing for specialty drugs as exposure variables and specialty drug utilization as the outcome variable. Studies were reviewed by 2 independent reviewers and relevant information from eligible studies was extracted using a standardized form and approved by 2 reviewers. Review papers, opinion pieces, and projects without data were excluded. RESULTS: Forty-four studies were included in this review after screening and exclusions, 9 on prior authorization and 35 on cost sharing. Patients with lower cost sharing via patient support programs experienced higher adherence, fewer days to fill prescriptions, and lower discontinuation rates. Similar outcomes were noted for patients on low-income subsidy programs. Increasing cost sharing above $100 was associated with up to 75% abandonment rate for certain specialty drugs. This increased level of cost sharing was also associated with higher discontinuation rates and odds. At the same time, decreasing out-of-pocket costs increased initiation of specialty drugs. However, inconsistent results on impact of cost sharing on medication possession ratio (MPR) and proportion of days covered (PDC) were reported. Some studies reported a negative association between higher costs and MPR and PDC; however, MPR and PDC of cancer specialty drugs did not decrease with higher costs. Significant delays in prescription initiation were reported when prior authorization was needed. CONCLUSIONS: Higher levels of patient cost sharing reduce specialty drug use by increasing medication abandonment while generally decreasing initiation and persistence. Similarly, programs that reduce patient cost sharing increase initiation and persistence. In contrast, cost sharing had an inconsistent and bidirectional effect on MPR and PDC. Prior authorization caused treatment delays, but its effects on specialty drug use varied. More research is needed to examine the effect of cost sharing and prior authorization on long-term health outcomes.

Effect of metformin on irinotecan-induced cell cycle arrest in colorectal cancer cell lines HCT116 and SW480.

OBJECTIVES: Metformin is widely used for the treatment of type 2 diabetes mellitus and found to have a crucial rule in the induction of apoptosis in several cancer types including pancreatic cell carcinoma, epithelial ovarian cancer, breast cancer, and renal cell carcinoma. In this study, we propose to explore the potential role of metformin as an adjuvant of irinotecan to target colorectal cancer (CRC) cell lines, exploring the effects underlying the anticancer properties of metformin on CRC cell lines. METHODS: HCT116 and SW480 cell lines were treated with metformin, irinotecan and their combination. The effect of metformin on cell viability was evaluated using MTT assay. Flow cytometry technique was used to analyze apoptosis and cell cycle progression. While, detection of protein expression was analyzed by Western blot. RESULTS: Metformin was found to inhibit growth in both HCT1116 and SW480 cell lines. On combination with irinotecan, it has been revealed that metformin sensitized CRC cells to irinotecan-induced cytotoxicity. Flow cytometry analysis showed that metformin did not induce apoptosis, but blocked cell cycle in G1 and S phases. This blockage was accompanied by decreased cyclin E and Cdk2 levels and increased p21 level. CONCLUSION: Combination of metformin with irinotecan may be an effective treatment strategy for targeting colorectal cancer that are resistant to irinotecan monotherapy.

Knowledge and Awareness of Authorship Practices Among Health Science Students: A Cross-Sectional Study.

BACKGROUND: The International Committee of Medical Journal Editors has published clear guidelines on the authorship of scientific papers. It is the research team's responsibility to review and ensure those guidelines are met. Authorship ethics and practices have been examined among healthcare professionals or among particular health science students such as medical students. However, there is limited evidence to assess the knowledge of authorship roles and practices among health science students. METHODS: We conducted a cross-sectional study to assess the knowledge of authorship guidelines practices among health science students at King Saud bin Abdulaziz University for Health Sciences in Riyadh, Saudi Arabia. A survey was developed and distributed. It covered several domains, including demographic characteristics, participant's knowledge and attitude of authorship practices, knowledge and experience with ghost and guest authorships, and knowledge of institutional authorship policies. Moreover, a score was computed to reflect the respondents' knowledge about authorship practices. RESULTS: Among the 321 participants who agreed to take the survey, two-thirds agreed with and supported that multi-authored articles' credit allocation should be based on the most significant contribution and contributions to the manuscript writing. Almost 47% agreed that team relationships would influence authorship allocation. The majority of the participants were not aware of their institutional research and publication policies. Also, around 50% of participants were not aware of guest or ghost authorships. Finally, the knowledge score about authorship credits, allocation, contribution, order, and guidelines was higher among students who were assigned as corresponding authors and those who were aware of their institutional authorship guidelines and policies. CONCLUSION: In conclusion, our findings suggest that health science students may have limited knowledge about authorship guidelines and unethical behaviors involved in a scientific publication. Universities and research centers should make more efforts to raise the awareness of health science students regarding authorship guidelines while ensuring that they comply with those guidelines.

Real-World Analysis of Potential Pharmacokinetic and Pharmacodynamic Drug Interactions with Apixaban in Patients with Non-Valvular Atrial Fibrillation.

PURPOSE: We conducted this study to assess the real-world prevalence, nature, predictors, and clinical necessity of apixaban pharmacokinetic (PK) and pharmacodynamic (PD) drug interactions in patients with non-valvular atrial fibrillation (NVAF) at a tertiary medical institution in Saudi Arabia. PATIENTS AND METHODS: An observational retrospective cohort analysis was conducted in adult patients diagnosed with NVAF receiving apixaban for stroke prevention from the period of June 2015 to May 2019. RESULTS: Of the 1271 patients included in the analysis, 611 (48.1%) patients had potential PD- or PK-drug interactions with apixaban. Of those, 490 (38.6%) patients had potential PD drug-drug interactions (DDIs) and 121 (9.5%) patients had potential PK-DDIs. PD-DDIs with apixaban were mainly with antiplatelet therapy followed by non-steroidal anti-inflammatory drugs and antidepressants. PK-DDIs with apixaban were mainly with combined P-gp/CYP3A4 inhibitors or inducers. History of minor bleeding was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.455 (OR 1.58; 95% CI 1.01-2.45); p<0.05. History of acute coronary syndrome was positively correlated with PD-DDIs with apixaban, ß coefficient = 0.515 (OR 1.60; 95% CI 1.36-1.99); p<0.05. History of heart failure was positively correlated with PK-DDIs with apixaban, ß coefficient = 0.459 (OR 1.58; 95% CI 1.07-2.35); p<0.05. Almost 15% of the included patients had no clinical indication to receive the potential interacting drug with apixaban and about 20% of them were assuming an inappropriate apixaban dose according to the product package insert. CONCLUSION: Pharmacodynamics and pharmacokinetics interactions are common in more than half of the patients with NVAF receiving apixaban for stroke prevention in this real-world analysis. Some of these interacting medications are not indicated. Drug-drug interactions should always be considered and monitored with apixaban with a regular assessment of the need for any interacting medication.

Adherence and treatment satisfaction in liver transplant recipients.

BACKGROUND/AIMS: Liver transplantation (LT) is a life-saving intervention for patients with liver failure. LT recipients' adherence to their therapeutic regimen is an essential element for graft survival. According to WHO, the impact of medication non-adherence in solid organ transplantation has shown to cost $15-100 million annually. The aim of the present study was to identify the factors that best predict medication adherence and to explore the relationship between treatment satisfaction and medication adherence in liver transplant recipients. PATIENTS AND METHODS: Adult liver transplant patients at King Abdulaziz Medical City were included in the study. Patients completed the 8-item Morisky Medication Adherence Scale (MMAS-8) and the Treatment Satisfaction Questionnaire for Medication (TSQM 1.4) in addition to several socio-demographic and transplant-related data. RESULTS: A total of 154 patients were included in the study and of these 59.7% were adherent. Older age was a significant predictor of adherence (P < 0.05). The mean treatment satisfaction score was 91.9 ± 12.7 in Effectiveness, 80.0 ± 25.9 in Side Effects, 83.5 ± 15.7 in Convenience, and 94.6 ± 8.6 in Global Satisfaction. Further analysis indicated that patients in the adherent group had reported significantly higher satisfaction scores than those in the non-adherent group (P < 0.05) in all treatment satisfaction domains: Effectiveness (94.4 ± 10.4 vs. 88.6 ± 14.8), Side Effects (83.9 ± 22.0 vs. 74.2 ± 30.1), Convenience (87.0 ± 13.9 vs. 77.2 ± 16.1), and Global Satisfaction (96.9 ± 6.6 vs. 91.2 ± 8.6). CONCLUSION: Older patients and those who were more satisfied with their treatment tend to have better adherence to the prescribed medications. Therefore, increasing patients' satisfaction with their treatment should be an integral element of future care plans designed to improve treatment outcomes in liver transplant recipients.