Validation of orthopedic allograft preparation process: a new application of media fill test.

Musculoskeletal allografts represent an important practice in orthopedic surgeries and the demand for them has been growing. For this reason, in order to reduce clinical risk and to more efficiently manage the increase of allograft usage and also to optimize timing of the surgeries, the thawing and washing processes with aseptic technique were centralized in the department of Hospital Pharmacy. This study describe the design and execution of an adapted Media Fill Test (MFT) to demonstrate aseptic thawing and washing of allografts. For this specific and innovative setting, to better simulate the actual processing steps, a surrogate system was developed to simulate the tendon allograft. The aseptic technique of four operators was assessed and an initial performance validation and the first revalidation were described. All MFT were completed successfully, with no observation of turbidity. The readapted MFT shown in this study can provide insight into this innovative and growing field to other health professionals who want to implement this service.

A retrospective hospital benefit and cost analysis of the management of human tissues for orthopaedic allografts.

OBJECTIVES: The transplantation of human tissues is a greatly expanding field of medicine with unquestionable benefits that raise questions about safety, quality and ethics. Since 1 October 2019, the Fondazione Banca dei Tessuti del Veneto (FBTV) stopped sending thawed and ready to be transplanted cadaveric human tissues to hospitals. A retrospective analysis of the period 2016-2019 found a significant number of unused tissues. For this reason, the hospital pharmacy has developed a new centralised service characterised by thawing and washing human tissues for orthopaedic allografts. This study aims to analyse the hospital cost and benefit derived from this new service. METHODS: Aggregate data relating to tissue flows were obtained retrospectively for the period 2016-2022 through the hospital data warehouse. All tissues arriving from FBTV for each year were analysed, dividing them according to the outcome (if used or wasted). The percentage of wasted tissues as well as the economic loss due to wasted allografts were analysed per year and trimester. RESULTS: We identified 2484 allografts requested for the period 2016-2022. In the last 3 years of the analysis, characterised by the new tissue management of the pharmacy department, we found a statistically significant reduction in wasted tissues (p<0.0001) from 16.33% (216/1323) with a cost to the hospital of 176 866€ during the period 2016-2019 to 6.72% (78/1161) with a cost to the hospital of 79 423€ during the period 2020-2022. CONCLUSION: This study shows how the centralised processing of human tissues in the hospital pharmacy makes the procedure safer and more efficient, demonstrating how the synergy between different hospital departments, high professional skills and ethics can lead to a clinical advantage for patients and a better economic impact for the hospital.

Comparison of medium-term adverse reactions induced by the first and second dose of mRNA BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine: a post-marketing Italian study conducted between 1 January and 28 February 2021.

OBJECTIVES: On 21 December 2020 the European Commission granted conditional marketing authorisation in the European Union for the anti-COVID-19 mRNA vaccine Bnt162b2 (Comirnaty, Pfizer/BioNTech). The main endpoint of this epidemiological, observational, prospective and monocentric study was to identify the number, types, and severity of adverse events following immunisation that occurred in subjects who had been previously infected with COVID-19, and in those who had not, after vaccination with Comirnaty, and to compare the two groups of subjects looking at events that occurred within a month after the first and the second dose. METHODS: Data were gathered by a questionnaire. The results included the responses of all healthcare workers (2030) of the IRCCS Sacro Cuore Don Calabria Hospital (Italy) vaccinated between 1st January and 28th February 2021. Adverse effects of the vaccine were reported after the first and the second doses. RESULTS: There was a statistically significant increase (p<0.001, χ2=35.60) in participants who experienced some side-effects after receiving the first dose of the vaccine and who had previously been infected with the coronavirus, compared with participants who had not previously been infected. 46.76% (136) of the participants who had previously been infected experienced some side-effects after the first dose of vaccine, and 63.23% (184) experienced some side-effects after the second dose, compared with 29.15% (507) after the first dose and 70.79% (1231) after the second dose in those who had not been previously infected. The number of participants who experienced side-effects after the second dose and had previously been infected was significantly lower compared with participants who had not previously been infected (p=0.0094, χ2=6.743). CONCLUSIONS: Most of the side-effects identified in this trial were also reported by the manufacturer and the US Food and Drug Administration. Active surveillance should always continue to constantly check the vaccine's risk/benefit ratio over time.

Dabigatran-Induced Nephropathy and Gastrointestinal Bleeding and Its Successful Treatment with Idarucizumab: A Case Report.

Recently, the atrial fibrillation treatment guidelines have been updated to now recommend Non-vitamin K antagonist oral anticoagulants (NOACs) as the preferred alternative to warfarin for systemic embolism and stroke prevention in patients with non-valvular atrial fibrillation. NOACs have major pharmacologic advantages over warfarin, although the most common complications are gastrointestinal bleeding and NOAC-induced nephropathy within 6 weeks after starting therapy, as several recent case-reports stated. We are reporting for the first time a chronic delayed adverse reaction (regularly reported to Authorities) observed in an 82-year-old woman 27 months after starting dabigatran (110 mg twice a day), characterized by concomitant gastrointestinal bleeding and nephropathy. Idarucizumab administration immediately improved both bleeding and renal parameters. Moreover, we are going to highlight the importance of the compliance, the adherence to the therapeutic plan and the supervision of the Hospital Pharmacy on drug prescriptions. In fact in our case, dabigatran was firstly prescribed by the neurologist and delivered by the hospital pharmacy, but the patient continued the treatment for 27 months, prescribed by general practitioner without any laboratory control. This lack of supervision certainly contributed to the onset of the adverse reaction reported.

High-dose ivermectin for early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial.

High concentrations of ivermectin demonstrated antiviral activity against SARS-CoV-2 in vitro. The aim of this study was to assess the safety and efficacy of high-dose ivermectin in reducing viral load in individuals with early SARS-CoV-2 infection. This was a randomised, double-blind, multicentre, phase II, dose-finding, proof-of-concept clinical trial. Participants were adults recently diagnosed with asymptomatic/oligosymptomatic SARS-CoV-2 infection. Exclusion criteria were: pregnant or lactating women; CNS disease; dialysis; severe medical condition with prognosis <6 months; warfarin treatment; and antiviral/chloroquine phosphate/hydroxychloroquine treatment. Participants were assigned (ratio 1:1:1) according to a randomised permuted block procedure to one of the following arms: placebo (arm A); single-dose ivermectin 600 µg/kg plus placebo for 5 days (arm B); and single-dose ivermectin 1200 µg/kg for 5 days (arm C). Primary outcomes were serious adverse drug reactions (SADRs) and change in viral load at Day 7. From 31 July 2020 to 26 May 2021, 32 participants were randomised to arm A, 29 to arm B and 32 to arm C. Recruitment was stopped on 10 June because of a dramatic drop in cases. The safety analysis included 89 participants and the change in viral load was calculated in 87 participants. No SADRs were registered. Mean (S.D.) log10 viral load reduction was 2.9 (1.6) in arm C, 2.5 (2.2) in arm B and 2.0 (2.1) in arm A, with no significant differences (P = 0.099 and 0.122 for C vs. A and B vs. A, respectively). High-dose ivermectin was safe but did not show efficacy to reduce viral load.

Ibrutinib: from bench side to clinical implications.

The activation of the B cell receptor (BCR) is nowadays known to play a primary role in the etiopathogenesis of a multitude of B cell malignancies, being one of the main factors responsible for the enhanced proliferation and survival of transformed cells. Thanks to the characterization and continuous discovery of the pathways driving B cell proliferation in consequence to BCR activation, it has been possible to develop a small molecule inhibitor specifically antagonizing the Bruton's tyrosine kinase (BTK), an enzyme located in an early strategic position within the whole pathway. Ibrutinib, formerly PCI-32765, is a first in class, potent, specific, irreversible and relatively safe BTK inhibitor, demonstrating so far an impressive efficacy in the treatment of chronic lymphocytic leukemia, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma (MCL), Waldenström macroglobulinemia and multiple myeloma. This review will summarize the most important pharmacological evidences available as of today and will take in consideration the latest findings regarding the mechanism of action of ibrutinib.

Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients.

OBJECTIVE: To determine the prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic population and to compare the prevalence of cardiovascular disease (CVD) and its risk factors between people with and without NAFLD. RESEARCH DESIGN AND METHODS: The entire sample of type 2 diabetic outpatients (n = 2,839) who regularly attended our clinic was screened. Main outcome measures were NAFLD (by patient history and liver ultrasound) and manifest CVD (by patient history, review of patient records, electrocardiogram, and echo-Doppler scanning of carotid and lower limb arteries). RESULTS: The unadjusted prevalence of NAFLD was 69.5% among participants, and NAFLD was the most common cause (81.5%) of hepatic steatosis on ultrasound examination. The prevalence of NAFLD increased with age (65.4% among participants aged 40-59 years and 74.6% among those aged > or = 60 years; P < 0.001) and the age-adjusted prevalence of NAFLD was 71.1% in men and 68% in women. NAFLD patients had remarkably (P < 0.001) higher age and sex-adjusted prevalences of coronary (26.6 vs. 18.3%), cerebrovascular (20.0 vs. 13.3%), and peripheral (15.4 vs. 10.0%) vascular disease than their counterparts without NAFLD. In logistic regression analysis, NAFLD was associated with prevalent CVD independent of classical risk factors, glycemic control, medications, and metabolic syndrome features. CONCLUSIONS: NAFLD is extremely common in people with type 2 diabetes and is associated with a higher prevalence of CVD. Follow-up studies are needed to determine whether NAFLD predicts the development and progression of CVD.

Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients.

Nonalcoholic fatty liver disease (NAFLD) is closely correlated to several metabolic syndrome features. We assessed prospectively whether NAFLD predicts future cardiovascular disease (CVD) events among type 2 diabetic individuals, independent of metabolic syndrome features and other classical risk factors. We carried out a prospective nested case-control study in 2,103 type 2 diabetic patients who were free of diagnosed CVD at baseline. During 5 years of follow-up, 248 participants (case subjects) subsequently developed nonfatal coronary heart disease (myocardial infarction and coronary revascularization procedures), ischemic stroke, or cardiovascular death. Using risk-set sampling, 496 patients (control subjects) among those who remained free of diagnosed CVD during follow-up were randomly selected in a 2:1 ratio, matched for age and sex to the case subjects. After adjustment for age, sex, smoking history, diabetes duration, HbA1c, LDL cholesterol, liver enzymes, and use of medications, the presence of NAFLD was significantly associated with an increased CVD risk (odds ratio 1.84, 95% CI 1.4-2.1, P < 0.001). Additional adjustment for the metabolic syndrome (as defined by National Cholesterol Education Program Adult Treatment Panel III criteria) appreciably attenuated, but did not abolish, this association (1.53, 1.1-1.7, P = 0.02). In conclusion, NAFLD is significantly associated with a moderately increased CVD risk among type 2 diabetic individuals. This relationship is independent of classical risk factors and is only partly explained by occurrence of metabolic syndrome.