Search

The COVID-19 pandemic requires a range of healthcare services to meet the needs of society. The objective was to explore what is known about the roles and services performed by frontline pharmacists during the first year of the COVID-19 pandemic. A scoping review was conducted of frontline pharmacists’ roles and services during the first year of the COVID-19 pandemic. A medical librarian conducted comprehensive searches in five bibliographic databases—MEDLINE (via Ovid), Embase (Ovid), CINAHL, Scopus, and Web of Science Core Collection for articles published between December 2019 and December 2020. The initial search retrieved 3269 articles. After removing duplicates, 1196 articles titles and abstracts were screened, 281 full texts were reviewed for eligibility, and 63 articles were included. This scoping review presents a conceptual framework model of the different layers made visible by COVID-19 of pharmacist roles in public health, information, and medication management. It is theorized that there is an invisible layer of change representing evolving professional role identity that may influence permanent role change following the pandemic. Thus, the pharmacy profession needs to build upon the lessons and experiences of this global pandemic and not let the momentum of the visible and invisible changes go to waste.

Background: Traditional open sternotomy coronary artery bypass grafting (CABG) utilizes highly invasive techniques that lead to several serious complications. In response, minimally invasive cardiac surgery CABG (MICS-CABG) was developed. MICS-CABG is safe, reproducible, and with fewer complications, while allowing for better postoperative recovery periods. There is a paucity of data exploring rates of repeat revascularization in patients post MICS-CABG compared to post traditional sternotomy CABG., Methods: This was a retrospective billing database review examining 1468 CABG patients at a large university medical center from January 2005 to December 2017. The primary objective was to compare the rate of repeat revascularization events between MICS-CABG and traditional open sternotomy CABG over an eight-year follow-up period., Results: Our study population consisted of 1468 patients, of whom 513 had MICS-CABG and 955 had traditional CABG. The number of patients undergoing repeat revascularization within the eight-year surveillance was 99 for MICS-CABG and 75 for traditional CABG. The Kaplan-Meier survival probability estimates for eight years were 0.86 for MICS-CABG and 0.91 for traditional CABG. The mean time until a repeat revascularization event was 84.1 months for MICS-CABG and 88.5 months for traditional CABG., Conclusions:  Traditional CABG was found to have a statistically significantly longer time to repeat revascularization than MICS-CABG. Despite the technical challenges associated with MICS-CABG, the time to repeat revascularization was different by only about four months, which may not hold large clinical significance. This suggests that MICS-CABG may have a role to play due to previous findings showing a reduction in complications while allowing for better postoperative recovery periods., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Olson et al.)

Reverse Takotsubo Cardiomyopathy (rTTC) is a rare variant of Takotsubo Cardiomyopathy (TTC) that is characterized by hypokinesis of the base and sparing of the mid to apical wall of the left ventricle best seen on echocardiogram. Intracranial hemorrhage (ICH) has been identified as a risk factor rTTC. Nearly around 10% of the patients with TTC develop cardiogenic shock. We hereby report the successful use of the Impella Ventricular Assist Device (Impella CP®) for management of rTTC in the setting of acute ICH. Our patient is a young female who presented with loss of consciousness after an acute headache and imaging studies revealed left posterior cerebral artery aneurysm with intraventricular hemorrhage. Subsequently the patient developed hypoxia, severe hypotension and cardiac arrest. After resuscitation, an echocardiogram showed that the patient had rTTC and a cardiac angiogram showed patent coronary arteries. The Impella CP® was successfully inserted followed by immediate cerebral angiography and aneurysmal coiling. Systemic anticoagulation was started during coiling. In the next three days, the patient's left ventricular function recovered, and she was discharged home. Up to our knowledge, this is the first case report to mark the successful placement of the Impella CP® with delayed initial anticoagulation for management of rTTC. Our patient was challenging as there are no current guidelines in the management of cardiogenic shock secondary to rTTC in the setting of acute ICH., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Acute electrocardiogram abnormalities are common in patients afflicted with pulmonary embolism (PE). Rarely, a patient with acute pulmonary embolism and electrocardiogram changes may have an underlying conduction abnormality that complicates their course., Case Presentation: We describe a patient with known history of left bundle branch block who presented with acute PE and developed a right bundle branch block, which devolved into complete third degree heart block without ventricular escape rhythm and led to concomitant hemodynamic compromise., Discussion: Given the rarity of this clinical scenario, we call for clinicians to be aware of PE-associated conduction pathology as well as the possibility that malignant cardiac conduction blocks may occur in the setting of PE particularly if the patient is known to have underlying conduction system disease. We emphasize the importance of continuous telemetry monitoring in patients presenting with PE as these types of arrhythmic complications and hemodynamic decompensation has been observed., Competing Interests: Declaration of Competing Interest The author(s) declare(s) that there is no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Bioprosthetic (BP) valves have been increasingly used for aortic valve replacement over the last decade. Due to their limited durability, patients presenting with failed BP valves are rising. Valve in Valve - Transcatheter Aortic Valve Implantation (ViV-TAVI) emerged as an alternative to the gold standard redo-Surgical Aortic Valve Replacement (redo-SAVR). However, the utility of ViV-TAVI is poorly understood., Methods: A systematic electronic search of the scientific literature was done in PubMed, EMBASE, SCOPUS, Google Scholar, and ClinicalTrials.gov. Only studies which compared the safety and efficacy of ViV-TAVI and redo-SAVR head to head in failed BP valves were included., Results: Six observational studies were eligible and included 594 patients, of whom 255 underwent ViV- TAVI and 339 underwent redo-SAVR. There was no significant difference between ViV-TAVI and redo- SAVR for procedural, 30 day and 1 year mortality rates. ViV-TAVI was associated with lower risk of permanent pacemaker implantation (PPI) (OR: 0.43, CI: 0.21-0.89; P = 0.02) and a trend toward increased risk of paravalvular leak (PVL) (OR: 5.45, CI: 0.94-31.58; P = 0.06). There was no significant difference for stroke, major bleeding, vascular complications and postprocedural aortic valvular gradients more than 20 mm-hg., Conclusion: Our results reiterate the safety and feasibility of ViV-TAVI for failed aortic BP valves in patients deemed to be at high risk for surgery. VIV-TAVI was associated with lower risk of permanent pacemaker implantation with a trend toward increased risk of paravalvular leak., (© 2018 Wiley Periodicals, Inc.)

Reverse takotsubo cardiomyopathy is an uncommon cardiomyopathy characterized by reversible regional wall motion abnormalities in the basilar segment of the left ventricle. This happens in the absence of any coronary artery pathology. Although it shares some pathogenic mechanisms with its more common variant, takotsubo cardiomyopathy, differences exist in terms of echocardiographic features, demographics, clinical manifestations, laboratory features, and prognosis. Cases of postoperative reverse takotsubo cardiomyopathy are less described in the literature. Herein, we report a case of reverse takotsubo cardiomyopathy in a 44-year-old woman occurring after exploratory laparotomy., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The treatment of advanced renal cell carcinoma (RCC) has advanced significantly over the last two decades. This multicenter study was designed with the primary objective to evaluate the efficacy and safety of sorafenib as first-line treatment in patients with advanced or metastatic RCC in the Middle East, who were considered to be ineligible for other approved first-line therapies. A total of 75 eligible patients from 8 centers in the Middle East were included in this study. The patients comprised 48 men and 27 women, with a median age of 52 years (range, 19-78 years). A total of 50 patients had clear cell carcinoma, 17 had papillary carcinoma and 8 had other pathological subtypes. At enrollment, 55 of the 75 patients had undergone previous nephrectomy. A total of 67 patients presented with metastatic disease, while 8 patients had regional residual lesions or local recurrence. The patients were treated with 400 mg oral sorafenib twice daily on a continuous basis as a single agent. Treatment was discontinued upon disease progression, prohibitive toxicity, surgical complications, loss to follow-up, or refusal to continue therapy. The median treatment duration was 21 weeks (range, 1-137 weeks). Sorafenib was tolerated by the majority of the patients. Grade 3/4 hand-foot syndrome occurred in 17 patients; diarrhea, elevated liver enzymes and fatigue were observed in 3 patients each; and grade 3/4 vomiting, hypertension and anemia, in 1 patient each. Of the 75 patients included in this study, 60 were evaluable for response. One patient achieved a complete response for 91 weeks and 6 patients exhibited a partial response (median duration of 23 weeks) with an overall response rate of 11.7%. Disease stabilization occurred in 37 patients (61.7%). Thus, disease control was achieved in 44 of the 60 patientrs (73%). At a median follow-up period of 53.5 weeks (range, 8.5-192 weeks), an intention-to-treat analysis demonstrated a median time-to-disease progression of 25.7 weeks, with a median overall survival of 54.8 weeks. In conclusion, sorafenib was found to be tolerable and effective as first-line therapy in patients with advanced RCC.

Objective: This study was conducted to determine long-term predictors of target lesion reintervention (TLR) after subclavian artery stenting (SAS)., Methods: This was a single-center retrospective review of patients with symptomatic atherosclerotic subclavian artery disease who underwent SAS between January 1999 and December 2013. Repeat intervention was only performed in patients with recurrent symptoms and ≥70% in-stent restenosis (ISR). TLR was defined as need for a repeat percutaneous intervention involving a previously stented area. Freedom from events (ISR and TLR) was analyzed using Kaplan-Meier curves. Cox regression analysis was used to determine the significant predictors of TLR and ISR., Results: Index procedures were performed on 139 arteries in 138 patients (69.6% female). Patients were an average age of 64.5 years, with major comorbidities of hypertension (80.4%), hyperlipidemia (72.5%), and tobacco use (60.1%). Also performed during the study period were 24 TLR procedures, resulting 166 SAS interventions attempted for patients with subclavian atherosclerotic disease during a 15-year span. Of 166 procedures, 163 (98.2%) were treated successfully. Stents were placed in all but two index arteries. The main indications for SAS were subclavian steal syndrome (48.9%), arm claudication (21.6%), and coronary steal syndrome (28.8%). The average preprocedure stenosis was 87.2% ± 11.2%. For index procedures (139 arteries), duplex follow-up was available for 134 arteries (96.4%), with an overall ISR rate of 18.7% (25 of 134). Primary patency for the index procedures was 84.7% at 10 years. The overall TLR rate for the index procedures was 12.7% (17 cases). Seven patients required more than one secondary procedure. For all cases, the freedom from ISR was 91%, 77%, and 68% at 1, 5, and 10 years, respectively, and freedom from TLR was 94%, 85%, and 82% at 1, 5, and 10 years, respectively. Multivariate analysis showed the significant predictors of ISR were smoking/chronic obstructive pulmonary disease (hazard ratio [HR], 3.2; P = .001), age by decade (HR, 0.5; P < .001), discharged with statin therapy (HR, 0.3; P = .001), vessel diameter ≤7 mm (HR, 2.3; P = .028), and right-sided intervention (HR, 0.3; P = .040). The sole significant predictor of TLR was age by decade (HR, 0.6; P = .008)., Conclusions: SAS has a high primary success and durability with satisfactory outcomes well beyond 10 years. ISR was more likely to develop in patients who were smokers with chronic obstructive disease or had a baseline vessel size of ≤7 mm. Younger age could be an independent risk factor for secondary intervention., (Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

We present a case series and literature review on the use of rescue human chorionic gonadotropin (hCG) in cases of empty follicle syndrome (EFS) after a gonadotropin-releasing hormone agonist (GnRHa) trigger. EFS was diagnosed after failure to collect any oocytes from one ovary. In such cases, a single dose of hCG was administered and the oocyte retrieval was repeated 36 h later. The main outcome measures were the number of mature oocytes (M2) and embryos (2PN), incidence of hospitalisation for severe ovarian hyperstimulation syndrome (OHSS) and clinical pregnancy when fresh embryo transfers occurred. Our population consisted of 322 patients, who had a GnRH agonist as oocyte maturation trigger (2-mg subcutaneous buserelin). Six patients (1.8%) developed EFS after the use of a GnRHa trigger. Mature oocytes were retrieved in 5 patients after the use of rescue hCG. One patient developed severe OHSS. Two patients had a fresh embryo transfer and one clinical pregnancy was reported. This is the first case series to report fresh embryo transfers and a clinical pregnancy with the use of rescue hCG after failure of the GnRHa trigger.

In response to harsh environmental conditions, ascomycetes produce stress-resistant spores to promote survival. As sporulation requires a diploid DNA content, species with a haploid lifestyle, such as Kluyveromyces lactis, first induce mating in response to stress. In K. lactis, mating and mating-type switching are induced by the DNA-binding protein Mts1. Mts1 expression is known to be upregulated by nutrient limitation, but the mechanism is unknown. We show that a ras2 mutation results in a hyperswitching phenotype. In contrast, strains lacking the phosphodiesterase Pde2 had lower switching rates compared to that of the wild type (WT). As Ras2 promotes cyclic AMP (cAMP) production and Pde2 degrades cAMP, these data suggest that low cAMP levels induce switching. Because the MTS1 regulatory region contains several Msn2 binding sites and Msn2 is a transcription factor that is activated by low cAMP levels, we investigated if Msn2 regulates MTS1 transcription. Consistently with this idea, an msn2 mutant strain displayed lower switching rates than the WT strain. The transcription of MTS1 is highly induced in the ras2 mutant strain. In contrast, an msn2 ras2 double mutant strain displays WT levels of the MTS1 transcript, showing that Msn2 is a critical inducer of MTS1 transcription. Strains lacking Msn2 and Pde2 also exhibit mating defects that can be complemented by the ectopic expression of Mts1. Finally, we show that MTS1 is subjected to negative autoregulation, presumably adding robustness to the mating and switching responses. We suggest a model in which Ras2/cAMP/Msn2 mediates the stress-induced mating and mating-type switching responses in K. lactis.

The Saccharomyces cerevisiae Dun1 protein kinase is a downstream target of the conserved Mec1-Rad53 checkpoint pathway. Dun1 regulates dNTP pools during an unperturbed cell cycle and after DNA damage by modulating the activity of ribonucleotide reductase (RNR) by multiple mechanisms, including phosphorylation of RNR inhibitors Sml1 and Dif1. Dun1 also activates DNA-damage-inducible genes by inhibiting the Crt1 transcriptional repressor. Among the genes repressed by Crt1 are three out of four RNR genes: RNR2, RNR3, and RNR4. The fourth RNR gene, RNR1, is also DNA damage-inducible, but is not controlled by Crt1. It has been shown that the deletion of DUN1 is synthetic lethal with the deletion of IXR1, encoding an HMG-box-containing DNA binding protein, but the reason for this lethality is not known. Here we demonstrate that the dun1 ixr1 synthetic lethality is caused by an inadequate RNR activity. The deletion of IXR1 results in decreased dNTP levels due to a reduced RNR1 expression. The ixr1 single mutants compensate for the reduced Rnr1 levels by the Mec1-Rad53-Dun1-Crt1-dependent elevation of Rnr3 and Rnr4 levels and downregulation of Sml1 levels, explaining why DUN1 is indispensible in ixr1 mutants. The dun1 ixr1 synthetic lethality is rescued by an artificial elevation of the dNTP pools. We show that Ixr1 is phosphorylated at several residues and that Ser366, a residue important for the interaction of HMG boxes with DNA, is required for Ixr1 phosphorylation. Ixr1 interacts with DNA at multiple loci, including the RNR1 promoter. Ixr1 levels are decreased in Rad53-deficient cells, which are known to have excessive histone levels. A reduction of the histone gene dosage in the rad53 mutant restores Ixr1 levels. Our results demonstrate that Ixr1, but not Dun1, is required for the proper RNR1 expression both during an unperturbed cell cycle and after DNA damage., Competing Interests: The authors have declared that no competing interests exist.

To explore the similarities and differences of regulatory circuits among budding yeasts, we characterized the role of the unscheduled meiotic gene expression 6 (UME6) gene in Kluyveromyces lactis. We found that Ume6 was required for transcriptional silencing of the cryptic mating-type loci HMLalpha and HMRa. Chromatin immunoprecipitation (ChIP) suggested that Ume6 acted directly by binding the cis-regulatory silencers of these loci. Unexpectedly, a MATa ume6 strain was mating proficient, whereas a MATalpha ume6 strain was sterile. This observation was explained by the fact that ume6 derepressed HMLalpha2 only weakly, but derepressed HMRa1 strongly. Consistently, two a/alpha-repressed genes (MTS1 and STE4) were repressed in the MATalpha ume6 strain, but were expressed in the MATa ume6 strain. Surprisingly, ume6 partially suppressed the mating defect of a MATa sir2 strain. MTS1 and STE4 were repressed in the MATa sir2 ume6 double-mutant strain, indicating that the suppression acted downstream of the a1/alpha2-repressor. We show that both STE12 and the MATa2/HMRa2 genes were overexpressed in the MATa sir2 ume6 strain. Consistent with the idea that this deregulation suppressed the mating defect, ectopic overexpression of Ste12 and a2 in a MATa sir2 strain resulted in efficient mating. In addition, Ume6 served as a block to polyploidy, since ume6/ume6 diploids mated as pseudo a-strains. Finally, Ume6 was required for repression of three meiotic genes, independently of the Rpd3 and Sin3 corepressors.

Theoretical models predict that selfish DNA elements require host sex to persist in a population. Therefore, a transposon that induces sex would strongly favor its own spread. We demonstrate that a protein homologous to transposases, called alpha3, was essential for mating type switch in Kluyveromyces lactis. Mutational analysis showed that amino acids conserved among transposases were essential for its function. During switching, sequences in the 5' and 3' flanking regions of the alpha3 gene were joined, forming a DNA circle, showing that alpha3 mobilized from the genome. The sequences encompassing the alpha3 gene circle junctions in the mating type alpha (MATalpha) locus were essential for switching from MATalpha to MATa, suggesting that alpha3 mobilization was a coupled event. Switching also required a DNA-binding protein, Mating type switch 1 (Mts1), whose binding sites in MATalpha were important. Expression of Mts1 was repressed in MATa/MATalpha diploids and by nutrients, limiting switching to haploids in low-nutrient conditions. A hairpin-capped DNA double-strand break (DSB) was observed in the MATa locus in mre11 mutant strains, indicating that mating type switch was induced by MAT-specific DSBs. This study provides empirical evidence for selfish DNA promoting host sexual reproduction by mediating mating type switch.

Objective: To ascertain if serum concentrations following injection of human chorionic gonadotropin (hCG) influenced the outcome of in vitro fertilisation (IVF) treatment and correlated to body mass index (BMI)., Study Design: A prospective study conducted with the participation of 149 women undergoing IVF and/or intracytoplasmic sperm injection (ICSI) treatment at the regional IVF Unit in Liverpool, UK. The BMI of each individual was calculated and serum hCG concentrations were measured at 12 and 36 h following a subcutaneously (SC) injection of 5000 IU hCG. The main outcome measures were fertilisation rate and biochemical pregnancy rate., Results: No correlation was found between serum hCG levels at 12 and 36 h with the number of oocytes retrieved or the number of oocytes fertilised. Furthermore, there was no correlation between BMI and hCG levels at 12 and 36 h following administration (Pearson's correlation coefficient: -0.23, -0.24, respectively)., Conclusion: Our results suggest that the serum concentrations of hCG do not influence IVF outcome and that the serum levels of hCG achieved following administration do not correlate with the individual's BMI. Serum hCG concentration also does not correlate with number of oocytes collected or fertilisation rate.

Cdc25 phosphatases are essential for the activation of mitotic cyclin-Cdks, but the precise roles of the three mammalian isoforms (A, B, and C) are unclear. Using RNA interference to reduce the expression of each Cdc25 isoform in HeLa and HEK293 cells, we observed that Cdc25A and -B are both needed for mitotic entry, whereas Cdc25C alone cannot induce mitosis. We found that the G2 delay caused by small interfering RNA to Cdc25A or -B was accompanied by reduced activities of both cyclin B1-Cdk1 and cyclin A-Cdk2 complexes and a delayed accumulation of cyclin B1 protein. Further, three-dimensional time-lapse microscopy and quantification of Cdk1 phosphorylation versus cyclin B1 levels in individual cells revealed that Cdc25A and -B exert specific functions in the initiation of mitosis: Cdc25A may play a role in chromatin condensation, whereas Cdc25B specifically activates cyclin B1-Cdk1 on centrosomes.