The clinical and Practice Dilemma of Frequent Switching Among Generic Medications: Magnitude and Patient Safety Prospective.

Objective: To assess the magnitude of generic-generic and brand-generic medication switching and its impact on patients' understanding and the potential risk of medication errors. Methods: The study composed of 2 parts. The first part is a retrospective study to measure the frequency of medications switching in King Faisal Specialist Hospital and Research Centre (KFSH&RC), from 1st of January 2015 to the 31st of December, 2020. Brand medications that were switched to generic medications, generic medications that were switched to brand medications and generic medications that were switched to other generic medications were included. Medications that were switched before or after the study period were excluded. The primary outcomes are the total percentage of switching from brand to generic of all medications in KFSH&RC drug formulary, frequency of generic-generic medications switching and percentage of switching back from generic to brand medications. The second part is a cross sectional survey-based study to assess patients' understanding of their medications and the potential for medication errors by assessing their ability to identify the discrepancies and duplications utilizing a validated questionnaire. Results: Over 5 years, the number of generic medications increased from 553 (35.5%) to 640 (41.1%) out of the 1554 formulary items. Percentage of switching from brand to generic over that 5-year period was 15.9%. Percentage of switching back from generic to brand was 12.8%. Total number of generic medications that had been switched to other generic medications was 256 (16.5%). Out of the 218 patients who had been switched from generic to generic medication, only 43 patients (19.7%) knew the indication for the generic medication they were taking. One hundred forty-six patients (67%) knew the indication of generic medications exclusively by their physical "trademark" characteristics, with 11.5% unrecognized duplication. Conclusion: There is a clear tendency to switch brand medications to generics and to switch between generics. We found the percentage of subsequent switching back to branded products is alarming. Frequent switching between medications negatively impacted patient comprehension and resulted in medication duplication. There is a crucial need for appropriate medication counseling and medication use ecosystem redesign.

A substitution mutation in cardiac ubiquitin ligase, FBXO32, is associated with an autosomal recessive form of dilated cardiomyopathy.

BACKGROUND: Familial dilated cardiomyopathy (DCM) is genetically heterogeneous. Mutations in more than 40 genes have been identified in familial cases, mostly inherited in an autosomal dominant pattern. DCM due to recessive mutations is rarely observed. In consanguineous families, homozygosity mapping and whole exome sequencing (WES) can be utilized to identify the genetic defects in recessively inherited DCM. METHODS: In a consanguineous family with four affected siblings with severe DCM, we combined homozygosity mapping, linkage analysis and WES, to uncover the genetic defect. RESULTS: A region of homozygosity (ROH) on chromosome 8q24.13-24.23 was found to be shared by all of the four affected siblings. WES detected ~47,000 variants that were filtered to a homozygous mutation (p.Gly243Arg) in the FBXO32 gene, located within the identified ROH. The mutation segregated with the phenotype, replaced a highly-conserved amino acid, and was not detected in 1986 ethnically-matched chromosomes. FBXO32, which encodes a muscle-specific ubiquitin ligase, has been implicated in the pathogenesis of cardiomyopathy through the ubiquitin proteasome system (UPS). In addition, FBXO32-knockout mice manifest with cardiomyopathy. Screening the index patient for all of the WES variants in 48 genes known to be implicated in hypertrophic and dilated cardiomyopathy was negative. CONCLUSIONS: Our data suggest that FBXO32 is a candidate gene for recessive DCM. Acting as a cardiac ubiquitin ligase, mutated FBXO32 could perturb the degradation of target proteins in the UPS, the impairment of which has been observed in cardiomyopathy. Our work proposes that genes encoding other ubiquitin ligases could also be implicated in familial cardiomyopathy.

Spontaneous Coronary Artery Dissection in a Transplanted Heart.

We report the case of a 37-year-old man who presented with shortness of breath 1 year post heart transplantation. He was receiving tacrolimus, methylprednisolone, and mycophenolate. An angiogram showed spontaneous coronary artery dissection involving the left anterior descending artery. Percutaneous coronary intervention was performed successfully, with stent placement and return of flow. (Level of Difficulty: Advanced.).

Disseminated histoplasmosis in a heart transplant recipient from Saudi Arabia: A case report.

Histoplasma is endemic in North and Central America. We describe a case of disseminated histoplasmosis in a heart transplant recipient outside the known endemic areas. A 68-year-old gentleman known to have dilated cardiomyopathy. He underwent left ventricular assist device (LVAD) implantation in India and 2 years later did heart transplant in King Faisal Specialist and Research Center Hospital. Six weeks post-transplant he presented with headache and fever. All investigations were negative, and he was discharged home. Four days after discharge he presented with headache, fever, blurred vision, and an episode of loss of consciousness. Examination showed an ill looking patient who is highly febrile. Repeated work up showed pancytopenia. A repeat LP was negative. Bone marrow biopsy showed Small intracellular organisms. Extended work up revealed a positive Histoplasma urinary antigen, positive Histoplasma PCR from the bone marrow biopsy. Patient was started on Liposomal Amphotericin followed by Itraconazole with marker clinical improvement. This is the first reported case of disseminated Histoplasmosis in Saudi Arabia. We postulate that the patient had reactivation of a latent infection acquired at the time of LVAD insertion in India rather than donor derived infection by the negative fungal culture and PCR done on the donor's lung granuloma tissue.

Solid organ transplantation following allogeneic haematopoietic cell transplantation: experience from a referral organ transplantation center and systematic review of literature.

Solid organ transplantation (SOT) following haematopoietic cell transplantation (HCT) is a rare event. Uncertainty exists whether such recipients are at higher risk of relapse of underlying haematological disease or at increased risk of developing infectious or immunological complications and malignancies following SOT. The experience at our referral organ transplantation center and the present literature of SOT (n = 198) in recipients following previous HCT was systematically reviewed. Outcome analysis of 206 SOT recipients following HCT challenges the validity of the frequently stated comparable outcome with recipients without prior HCT. SOT recipients after HCT are younger and have a higher mortality and morbidity in comparison with "standard" recipients. Rejection rates for SOT recipients following HCT appear to be lower for all organs, except for liver transplantation. In the setting of liver transplantation following HCT, mortality for recipients of deceased donor grafts appears to be exceptionally high, although experience with grafts of living donors are favourable. Morbidity was mostly associated with infectious and malignant complications. Of note some SOT recipients who received solid organ donation from the same HCT donor were able to achieve successful withdrawal of immune suppression. Despite limited follow-up, recipients with prior HCT show a different course after SOT, necessitating attention and closer follow-up.