Efficacy of generic sofosbuvir with daclatasvir compared to sofosbuvir/ledipasvir in genotype 4 hepatitis C virus: A prospective comparison with historical control.

Background and Aim: Management of genotype 4 hepatitis C virus (HCV) has shifted to interferon-free regimens with a high sustained virological response (SVR-12), especially with NS5B/NS5A inhibitor combinations such as sofosbuvir and ledipasvir (Sof-Led). The guidelines have recommended the combination of sofosbuvir and another NS5A inhibitor, daclatasvir, to manage HCV genotypes 1-3. However, its use was extended to genotype 4 HCV based on extrapolating evidence. Our aim is to assess the efficacy of generic sofosbuvir + branded daclatasvir (Sof-Dac) compared to the Sof-Led combination in treating genotype 4 HCV. Methods: This study is an open-label, 2-period, noninferiority study that compared patients receiving a combination of generic sofosbuvir 400 mg and daclatasvir 60 mg orally daily (Group 2) prospectively to a historical control (Group 1) that included patients who received a combination of sofosbuvir/ledipasvir 400/90 mg orally daily. The primary endpoint is the proportion of patients who achieved SVR-12. Results: The study included 111 patients in the (Sof-Led) Group 1 and 109 patients (Sof-Dac) Group 2. For the primary outcome, SVR-12 was achieved in 106 (95.5%) of the patients in Group 1 versus 108 (99.1%) in Group 2 (p = 0.2). In addition, all patients who achieved SVR-12 also achieved SVR-24. Conclusion: Generic sofosbuvir combined with branded daclatasvir was safe and effective for treating genotype 4 HCV compared to Sof-Led. This combination may significantly reduce the cost burden, enabling a larger pool of treated patients. Office of research affairs at KFSHRC RAC# 2171 036.

Tacrolimus-Induced Neurotoxicity in Early Post-Liver Transplant Saudi Patients: Incidence and Risk Factors.

BACKGROUND Tacrolimus is a calcineurin inhibitor (CNI) commonly used as an immunosuppressant to prevent the rejection of organ transplants. After liver transplantation, it can cause early neurological complications, known as early calcineurin inhibitor-induced neurotoxicity (ECIIN). Its management requires CNI withdrawal, a measure that can affect post-transplant outcomes, primarily allograft rejection. In addition, it can negatively impact the quality of life. The incidence and risk factor of ECIIN has not been reported in the Saudi population. We investigated the incidence and risk factors of ECIIN after liver transplant in Saudi patients. We also looked at the length of stay in the Intensive Care Unit, hospital, and 30-day mortality as secondary endpoints. MATERIAL AND METHODS This was a retrospective cohort study of adult patients on tacrolimus with mild, moderate, or severe neurological events within the first month after liver transplantation at a single center of patients who meet the inclusion criteria and were over age 14 years. A total of 338 patients were included in the analysis, and the sample size was calculated based on a pilot study. RESULTS Among 338 liver transplantation patients, 63 patients (19%) developed ECIIN. Forty-eight percent of patients had seizures, 23% had agitation, 21% had psychosis, 10% had severe tremors, 13% had confusion, and 6% developed coma. The median time of the incident to develop ECIIN was 9 (IQR: 5-13.5) days after transplant. Thirty-eight patients were managed by switching to cyclosporine, 12 required a reduction in the dose, and 3 were managed temporarily by discontinuing therapy. Autoimmune hepatitis as an underlying liver disease was one of the statistically significant risk factors (P=0.0311). The median length of hospital stay was 31 (IQR: 21-75.5) days, ICU length of stay was 10 (IQR: 5-20.5) days, and 8 patients died within 30 days after transplant. CONCLUSIONS The incidence of ECIIN in Saud Arabia was similar to that reported in other populations with similar risk factors. Electrolyte imbalance, mainly hyponatremia, was significantly associated with developing ECIIN. Therefore, ECIIN may potentially increase hospital and ICU length of stay.

Pharmacy service accreditation: Raising the bar of practice standards.

PURPOSE: To summarize the journey of a tertiary and quaternary care hospital outside the United States in receiving American Society of Health-System Pharmacists (ASHP) accreditation for its pharmacy services. SUMMARY: Tertiary and quaternary care hospitals have gained their reputation owing to the high quality and advanced services that they provide. Our organization, King Faisal Hospital & Research Center (KFSH&RC), Riyadh, Saudi Arabia, is a 1300-bed capacity hospital that serves as a center of excellence in solid organ transplant, genetic and metabolic diseases, hematology and oncology, and cardiology, in addition to a diversity of medical services. Accreditation of the pharmacy services by ASHP represents an important recognition of the quality and breadth of the services performed at KFSH&RC. The process of accreditation and the accreditation standards have also continued to serve as a guide for the hospital to maintain pharmacy service standards as they evolve. CONCLUSION: As the first internationally accredited pharmacy services, KFSH&RC now demonstrates the path forward for other international hospitals seeking to reach the same standards of practice defined by ASHP.

Developing a multidisciplinary HCV direct-acting antivirals utilization management and assessment program.

BACKGROUND: The introduction of direct-acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) infections has revolutionized outcomes for patients with HCV. Cost-effective use of these antivirals in addition to ensuring patient adherence is of paramount importance. OBJECTIVES: The goal of this article is to describe the processes by which a tertiary care, multisite institution managed the complexities involved in administering DAA treatment and managing the increased cost of therapy. Specifically, the objectives of this article are to describe the development of a multidisciplinary HCV management program and the role of pharmacists in this program, including formulary management strategies and monitoring of DAAs use in our institution, development of guidelines, electronic prescribing protocols and order sets, and specific outcomes based on a concurrent medication use evaluation. PRACTICE DESCRIPTION: King Faisal Specialist Hospital and Research Centre is a tertiary care referral hospital. As a tertiary referral hospital, it offers primary and highly specialized inpatient and outpatient medical care. The process of selecting and developing institutional HCV management program is described. PRACTICE INNOVATION: This article provides key details regarding how a multidisciplinary HCV program using DAAs can be implemented successfully at a tertiary care facility. Key facets of our innovation include establishing formulary guidelines, setting up eligibility criteria for patients, and establishing an HCV taskforce and multidisciplinary HCV program clinic. EVALUATION: Medication use evaluations were regularly conducted to monitor sustained virologic response rates, adherence to guidelines, adverse reactions, and drug interactions. METHODS: Formulary guidelines, setting up an eligibility criterion for patients, and an HCV taskforce and multidisciplinary HCV program clinic were established. RESULTS: The involvement of pharmacists in a multidisciplinary HCV program in outpatient settings resulted in improved formulary decision making, reduction of costs, and improvement of adherence to institutional guidelines. PRACTICE IMPLICATIONS: The role of a pharmacist in the management of patients with HCV with DAAs is important. Pharmacists play an integral part in medication management and overall reduction in health care expenditure. Many disease management programs can be complemented with pharmacists to improve patient care and reduce cost. CONCLUSION: HCV treatment is challenging, and a multidisciplinary approach to treat HCV is critical. It is a rapidly evolving field; therefore, it requires dynamic formulary management and collaborative practice approaches to monitor pharmacotherapy carefully and efficiently. Clinical pharmacists play a pivotal role within the multidisciplinary team by providing support to both patients and health care providers with regard to the treatment of HCV.

Efficacy and safety of three times daily dosing of tacrolimus in pediatric kidney transplantation patients: A single-center comparative study.

BACKGROUND/AIM: Several PK studies have shown that most pediatric patients may require higher doses on a mg/kg basis compared to adults to attain similar therapeutic trough concentrations. The aim of this study was to compare the efficacy and safety of three times daily to twice a day dosing of tacrolimus in pediatric kidney transplant recipients at a major tertiary care transplant center. METHODS AND MATERIALS: Retrospective, single-center, and comparative cohort study. All pediatric kidney transplant recipients received either tacrolimus BID (group 1) or tacrolimus TID (group 2). RESULTS: A total of 87 patients were included in this study; 48 patients received BID tacrolimus (group 1), and 39 patients received TID tacrolimus (group 2). The percentage of patients who achieved therapeutic trough concentrations in group 2 did not significantly differ from those in group 1 at day 7 (84.62% TID vs 83.33% BID; P = .42). The median time to reach therapeutic trough concentrations was three days in group 1 compared to four days in group 2. CONCLUSION: No significant difference was observed between tacrolimus BID and TID dosing in the time to reach therapeutic trough concentration or in the proportion of patients achieving therapeutic trough concentrations at day 7.

Cost analysis of kidney transplantation in highly sensitized recipients compared to intermittent maintenance hemodialysis.

BACKGROUND: Kidney transplantation in allosensitized recipients has recently increased. Studies performing cost analysis of desensitization protocols are scarce. MATERIAL/METHODS: We performed an actual cost comparison between kidney transplantation following desensitization and maintenance hemodialysis. Group A (n=35) consisted of allosensitized recipients who underwent desensitization using immunoadsorption and/or plasmapheresis, intravenous immunoglobulin and anti-CD20 antibody who were followed for ≥ 2 years. Group B (n=49) consisted of matched patients who remained on hemodialysis throughout the study period. Actual costs of donor care, surgical procedures, out-patient visits, in-hospital admissions, medications, hemodialysis, immunoadsorption, plasmapheresis, and laboratory and radiology investigations were calculated. Health care services were provided by a single institution. RESULTS: Mortality rate was similar between both groups. The average 4-year actual total cost was $210,779 in group A and $317,186.3 in group B; respectively (p=0.017). Average total cost per patient in group A was $186,608; $14,233; $5,536; $4,402 in the first, second, third and fourth years after transplantation respectively while the average total annual cost per patient in group B was $79,296. The total cost in both groups became equal by month 31. The predicted annual cost savings in group A after 31 months was $33,943. CONCLUSIONS: Despite using costly desensitization protocols, kidney transplantation in sensitized patients provides long-term cost savings compared to maintenance hemodialysis.

Exploring the role of cyclosporine in reducing homograft degeneration post-Ross.

The Ross procedure is safe and effective for children with aortic valve disease. Pulmonary homograft degeneration, proposed to be immune-mediated, is a major cause of reoperation. Cyclosporine increased homograft valve survival in animals, but has not been studied in humans. To investigate the efficacy of low-dose cyclosporine in preventing homograft degeneration and complications, a retrospective historical-controlled study was performed on data of all children who underwent Ross procedure and received cyclosporine. The primary endpoint was homograft function at the last follow-up; secondary endpoints were readmission, reoperation, death, and safety. Seventeen patients were matched with 16 controls. At the end of the follow-up period (cyclosporine, 6.7 years; controls, 8 years), homograft stenosis and/or regurgitation were present in half of all patients. Three (18%) patients in the cyclosporine group and 5 (29%) in the control group were readmitted. Surgical intervention due to homograft failure was needed in 1 (6%) cyclosporine patient and 3 (19%) of the controls. Although cyclosporine failed to show a significant difference in signs of homograft degeneration, it might decrease the need for reoperation following the Ross procedure. Larger prospective well-designed studies are required to confirm these findings.