From speculative to real: community attitudes towards government COVID-19 vaccine mandates in Western Australia from May 2021 to April 2022.

Many governments employed mandates for COVID-19 vaccines, imposing consequences upon unvaccinated people. Attitudes towards these policies have generally been positive, but little is known about how discourses around them changed as the characteristics of the disease and the vaccinations evolved. Western Australia (WA) employed sweeping COVID-19 vaccine mandates for employment and public spaces whilst the state was closed off from the rest of the country and world, and mostly with no COVID-19 in the community. This article analyses WA public attitudes during the mandate policy lifecycle from speculative to real. Qualitative interview data from 151 adults were analysed in NVivo 20 via a novel chronological analysis anchored in key policy phases: no vaccine mandates, key worker vaccine mandates, vaccine mandates covering 75% of the workforce and public space mandates. Participants justified mandates as essential for border reopening and, less frequently, for goals such as protecting the health system. However, public discourse focusing on 'getting coverage rates up' may prove counter-productive for building support for vaccination; governments should reinforce end goals in public messaging (reducing suffering and saving lives) because such messaging is likely to be more meaningful to vaccination behaviour in the longer term.

Vaccination Recommendations in Solid Organ Transplant Adult Candidates and Recipients.

Prevention of infections is crucial in solid organ transplant (SOT) candidates and recipients. These patients are exposed to an increased infectious risk due to previous organ insufficiency and to pharmacologic immunosuppression. Besides infectious-related morbidity and mortality, this vulnerable group of patients is also exposed to the risk of acute decompensation and organ rejection or failure in the pre- and post-transplant period, respectively, since antimicrobial treatments are less effective than in the immunocompetent patients. Vaccination represents a major preventive measure against specific infectious risks in this population but as responses to vaccines are reduced, especially in the early post-transplant period or after treatment for rejection, an optimal vaccination status should be obtained prior to transplantation whenever possible. This review reports the currently available data on the indications and protocols of vaccination in SOT adult candidates and recipients.

Increased prevalence of autoimmune thyroid disease after COVID-19: A single-center, prospective study.

Introduction: Thyroid dysfunctions associated with SARS-CoV-2 acute infection have been extensively described since the beginning of COVID-19 pandemics. Conversely, few data are available on the occurrence of thyroid autoimmunity after COVID-19 resolution. We assessed the prevalence of autoimmune thyroid disease (ATD) and thyroid dysfunctions in COVID-19 survivors three months after hospital admission. Design and methods: Single-center, prospective, observational, cohort study performed at ASST Papa Giovanni XXIII Hospital, Bergamo, Italy. 599 COVID-19 survivors were prospectively evaluated for thyroid function and autoimmunity thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb). When a positive antibody concentration was detected, thyroid ultrasound was performed. Multiple logistic regression model was used to estimate the association between autoimmunity and demographic characteristics, respiratory support, and comorbidities. Autoimmunity results were compared to a cohort of 498 controls referred to our Institution for non-thyroid diseases before the pandemic onset. A sensitivity analysis comparing 330 COVID-19 patients with 330 age and sex-matched controls was performed. Results: Univariate and multivariate analysis found that female sex was positively associated (OR 2.01, SE 0.48, p = 0.003), and type 2 diabetes (T2DM) was negatively associated (OR 0.36, SE 0.16, p = 0.025) with thyroid autoimmunity; hospitalization, ICU admission, respiratory support, or COVID-19 treatment were not associated with thyroid autoimmunity (p > 0.05). TPOAb prevalence was greater in COVID-19 survivors than in controls: 15.7% vs 7.7%, p = 0.002. Ultrasonographic features of thyroiditis were present in 94.9% of the evaluated patients with positive antibodies. TSH was within the normal range in 95% of patients. Conclusions: Autoimmune thyroid disease prevalence in COVID-19 survivors was doubled as compared to age and sex-matched controls, suggesting a role of SARS-CoV-2 in eliciting thyroid autoimmunity.

Vascular graft infections caused by Mycobacterium bovis BCG after BCG immunotherapy for non-muscle-invasive bladder cancer: Case report and review of literature.

Bacillus Calmette-Guerin (BCG) immunotherapy (i.e., intravesical instillation of live attenuated strain of Mycobacterium bovis) is a standard of care for non-muscle-invasive bladder cancer (NMIBC). The risk of infective adverse events is generally low as studies have reported an incidence of systemic BCG infections between 3% and 7%. In the majority of cases, BCG infections are disseminated (34.4%), genitourinary (23.4%), osteomuscular (19.9%), or vascular (6.7%). Regarding vascular involvement, mycotic aortic aneurysm, aorto-enteric fistula and vascular bypass graft infections have been described. A 73-year-old man with a prosthetic femoral-popliteal bypass was treated with BCG immunotherapy for a relapsed NMIBC. Two months later, the patient developed fever and hyporexia. PET-CT and CT scans of the abdomen showed an abscess surrounding the superficial femoral artery, while blood cultures yielded M. bovis BCG, and antitubercular therapy (with RMP + EMB + INH) was started. The prosthetic graft was removed and its cultures tested positive for M. bovis as well. A total of 14 cases of vascular prosthesis infections caused by M. bovis BCG following BCG instillation are so far reported. All the cases occurred in adult symptomatic men. Abdominal aorta was involved in the majority of cases. CT scan played a pivotal role in the diagnostic process. Mycobacterium bovis BCG was isolated from several different sources. Treatment required surgery and medical therapy, the latter showing wide variability. Previous BCG immunotherapy must be considered in the differential diagnosis in patients with infected vascular grafts. These infectious complications are rare and, while the infected grafts should be removed, there are no definite recommendations regarding the type of regimen and duration of treatment.

SARS-CoV-2 infection clinical picture and outcomes in adults living with HIV: a cohort analysis.

Existing evidence about HIV and SARS-CoV-2 co-infection has, so far, yield conflicting results. Methods: This is a cohort, single center, clinical study aimed at identifying possible characteristics of PLWH that could correlate with the risk of acquiring SARS-CoV-2 and would influence the outcome. 155 cases of SARS-CoV-2 infection were compared with 307 PLWH who tested negative. No variable was associated with an increased risk of infection. SARS-CoV-2 PLWH were completely asymptomatic in 20.6% of cases. Factors associated with severe COVID-19 were age (P=0.001), diabetes (P=0.009) hypertension (P=0.004), cardiovascular disease (P=0.001) or an increasing number of chronic co-morbidities (P=0.002); only the first two variables retained statistical significance in a multivariable model. Only older age and a lower CD4 count were statistically associated with death in the multivariate model. Sixteen PLWH not included in the analysis were infected by SARS-Cov-2 after vaccination. In 4 cases the infection was completely asymptomatic, while in the remaining 12 cases the infection was mild and resembled a flu-like syndrome. Conclusions: No baseline characteristic defines patients at greater risk of SARS-CoV-2 infection. Older age and the presence of multi-comorbidities are risk factors for a severe clinical course. Lower CD4 counts correlate with a fatal outcome.

One-year mortality in COVID-19 is associated with patients' comorbidities rather than pneumonia severity.

BACKGROUND: In patients with pneumonia or acute respiratory distress syndrome who survived hospitalization, one-year mortality can affect up to one third of discharged patients. Therefore, significant long-term mortality after COVID-19 respiratory failure could be expected. The primary outcome of the present study was one-year all-cause mortality in hospitalized COVID-19 patients. METHODS: Observational study of COVID-19 patients hospitalized at Papa Giovanni XXIII Hospital (Bergamo, Italy), during the first pandemic wave. RESULTS: A total of 1326 COVID-19 patients were hospitalized. Overall one-year mortality was 33.6% (N 446/1326), with the majority of deaths occurring during hospitalization (N=412, 92.4%). Thirty-four patients amongst the 914 discharged (3.7%) subsequentely died within one year. A third of these patients died for advanced cancer, while death without a cause other than COVID-19 was uncommon (8.8% of the overall post-discharge mortality). In-hospital late mortality (i.e. after 28 days of admission) interested a population with a lower age, and fewer comorbidities, more frequentely admitted in ICU. Independent predictors of post-discharge mortality were age over 65 years (HR 3.19; 95% CI 1.28-7.96, p-value=0.013), presence of chronic obstructive pulmonary disease (COPD) (HR 2.52; 95% CI 1.09-5.83, p-value=0.031) or proxy of cardiovascular disease (HR 4.93; 95% CI 1.45-16.75, p-value=0.010), and presence of active cancer (HR 3.64; 95% CI 1.50-8.84, p-value=0.004), but not pneumonia severity. CONCLUSIONS: One-year post-discharge mortality depends on underlying patients' comorbidities rather than COVID-19 pneumonia severity per se. Awareness among physicians of predictors of post-discharge mortality might be helpful in structuring a follow-up program for discharged patients.

Consumers or Patients? Medical Device Recipients under Australian Law Straddle Two Worlds.

This article analyses the status of medical device recipients under Australian law. The 2021 Gill v Ethicon Sàrl litigation in the Federal Court of Australia has brought the issue to the fore. Moving from the Court's findings, the article dissects the specific vulnerability of medical device recipients and explores the under-researched distinction between patients and consumers under Australian law. The analysis spans the regulatory landscape for medical devices prior to marketing approval, the statutory protections and causes of actions available to consumers under the Australian Consumer Law, and the safeguards for patients developed under medical law (particularly medical negligence). In addition to doctrinal clarifications, the article provides a discussion of key policy considerations that frame the various regimes. Patients and consumers share characteristics, but their legal protections differ in terms of focus and objectives. Medical device recipients straddle both worlds, requiring the highest levels of care and disclosure.

Consolidating a research agenda for vaccine mandates.

A workshop on mandatory vaccination was pitched to the World Public Health Congress in 2019 and the resultant special issue was pitched to Vaccine in 2020. During this project, the COVID-19 pandemic pushed vaccine policy to the forefront of global public health policy, and the imposition of vaccine mandates prompted a new wave of scholarship in the field. This introductory article employs the heuristic of Lasswell's (1956) policy cycle to synthesise the findings of the articles in the special issue. It considers the temporal lifetime of mandates and highlights findings regarding: the emergence of mandates as a policy option, public support and policy instrument design, what matters in the implementation of mandates, and what we can learn from evaluating them. The second half of the paper categorizes the included papers in terms of what aspects of mandates they study and the methods they employ to do so, in order to formulate a guide for future researchers of vaccine mandates. Scholars study either speculative or existing mandates - research can address several stages of the policy cycle or just one of them, ranging from attitudinal research to implementation studies and impact studies. Historical and contextual studies that take deep dives into a particular mandate are a much needed resource for studying emerging mandates, too, and scoping and framework- building work will undoubtedly be valuable in understanding and appreciating the wealth of knowledge production in this growing field. This special issue can serve as a roadmap for a consolidation of this interdisciplinary research agenda, and provide a helpful resource for decisionmakers at this historical juncture.

Real World Data on Forgiveness to Uncomplete Adherence to Bictegravir/ Emtricitabine/Tenofovir Alafenamide.

Background: forgiveness is the ability of a given regimen to maintain complete viral suppression despite a documented imperfect adherence. We explored forgiveness of bictegravir/emtricitabine/tenofovir alafenamide. Methods: drug refills were used to calculate the percent day covered (PDC) as a proxy of adherence. Forgiveness was calculated as the achieved rate of a selected HIV-RNA threshold by a given level of imperfect adherence. Results: 281 adult PLWH were followed for 343 patient/years. Adherence was very high with a median of 98% (IQR 95-100%). A PDC as low as 70% was sufficient to obtain 100% and maintain virologic suppression. According to probit analysis adherence was not related to the possibility to maintain an HIV-RNA TND or < 50 copies/ml. Conclusions: Long-term success of ART needs effective regimens that are the least intrusive of the patient's lifestyle, an elevated forgiveness may be considered as an additional feature that can further improve long-term outcomes.

What is the impact of SARS-CoV-2 pandemic on antimicrobial stewardship programs (ASPs)? The results of a survey among a regional network of infectious disease centres.

Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.

Population Pharmacokinetic and Pharmacodynamic Analysis of Dalbavancin for Long-Term Treatment of Subacute and/or Chronic Infectious Diseases: The Major Role of Therapeutic Drug Monitoring.

A population pharmacokinetic analysis of dalbavancin was conducted in patients with different infection sites. Non-linear mixed effect modeling was used for pharmacokinetic analysis and covariate evaluation. Monte Carlo simulations assessed the probability of target attainment (PTA) of total dalbavancin concentration ≥ 8.04 mg/L over time (associated with ≥90% probability of optimal pharmacodynamic target attainment of fAUC24h/MIC > 111.1 against S. aureus) associated with a single or double dosage, one week apart, of 1000 or 1500 mg in patients with different classes of renal function. Sixty-nine patients with 289 concentrations were included. Most of them (53/69, 76.8%) had bone and joint infections. A two-compartment model adequately fitted dalbavancin concentration−time data. Creatinine clearance (CLCR) was the only covariate associated with dalbavancin clearance. Monte Carlo simulations showed that, in patients with severe renal dysfunction, the 1000 mg single or double one week apart dosage may ensure optimal PTAs of 2 and 5 weeks, respectively. In patients with preserved renal function, the 1500 mg single or double one-week apart dosage may ensure optimal PTAs of 2 and 4 to 6 weeks, respectively. Therapeutic drug monitoring should be considered mandatory for managing inter-individual variability and for supporting clinicians in long-term treatments of subacute and chronic infections.

Adherence to and Forgiveness of 3TC/DTG in a Real-World Cohort.

Background: adherence and forgiveness are key factors for virologic success. We evaluated them for 3TC/DTG. Methods: pharmacy refills were used to calculate the proportion of days covered (PDC). Forgiveness was calculated as the achieved rate of HIV-RNA threshold by a given level of imperfect adherence. Results: 240 PLWH were included. The median follow-up was 819 days (IQR 450-1459) for a total of 681 person/years of follow-up. Adherence was very high with a median of 99% (IQR 95%-100%). Consequently, the virologic response was sustained with 83.8% of PLWH never exceeding a HIV RNA of 50 copies/ml and 95.8% of subjects with a steadily HIV-RNA < 200 copies/ml. A PDC lower than 80% was associated with a negative outcome irrespective of the HIV-RNA threshold considered. Conclusions: The extensive virologic efficacy of 3TC/DTG demonstrated both in clinical trials and real-world experiences seems to rely more on its friendliness than on its forgiveness.

Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients.

Introduction: In a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization. Materials and Methods: Intensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed. Results: Patients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding. Conclusion: This study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.

The changing pattern of bacterial and fungal respiratory isolates in patients with and without COVID-19 admitted to intensive care unit.

OBJECTIVES: Severe acute respiratory syndrome 2 (SARS-CoV-2) pandemic has had a heavy impact on national health system, especially in the first wave. That impact hit principally the intensive care units (ICUs). The large number of patients requiring hospitalization in ICUs lead to a complete upheaval of intensive wards. The increase in bed, the fewer number of nurses per patient, the constant use of personal protective equipment, the new antimicrobial surveillance protocols could have had deeply effects on microbiological flora of these wards. Moreover, the overconsumption of antimicrobial therapy in COVID-19 patients, like several studies report, could have impact of this aspect. Aim of this study is to evaluate the changing pattern of microbiological respiratory isolates during and before COVID-19 pandemic in a tertiary hospital ICUs. METHODS: A retrospective, observational study was conducted in ICUs of "ASST Papa Giovanni XXIII", a large tertiary referral hospital in Northern Italy. We have retrospectively collected the microbiological data from bronchoalveolar lavage (BAL) and tracheal aspirate (TA) of patients with COVID-19, hospitalized in ICUs from 22nd February 2020 to 31st May 2020 (Period 1), and without COVID-19, from 22nd February 2019 to 31st May 2019 (Period 2). We compared the prevalence and the antibiotic profile of bacterial and fungal species in the two time periods. RESULTS: The prevalence of Pseudomonas spp. shows a statistically significant increase from patients without COVID-19 compared to COVID-19 positive as well as the prevalence of Enterococcus spp. On the contrary, the prevalence of Gram negative non fermenting bacteria (GN-NFB), Haemophilus influenzae and Streptococcus pneumoniae showed a significant reduction between two periods. There was a statistically significant increase in resistance of Pseudomonas spp. to carbapenems and piperacillin/tazobactam and Enterobacterales spp. for piperacillin/tazobactam, in COVID-19 positive patients compared to patients without COVID-19. We did not observe significant changing in fungal respiratory isolates. CONCLUSIONS: A changing pattern in prevalence and resistance profiles of bacterial and fungal species was observed during COVID-19 pandemic.

Frequency, characteristics, and outcome of patients with COVID-19 pneumonia and "silent hypoxemia" at admission: a severity-matched analysis.

BACKGROUND: An aspect of COVID-19 baffling physicians is the presentation of patients with acute respiratory failure, but normal mental faculties and no perception of dyspnea (i.e. "silent hypoxemia"). The aim of this study was to investigate the frequency, characteristics, and outcome of COVID-19 patients with silent hypoxemic status and comparing them with a symptomatic severity-matched group. METHODS: This is a retrospective monocentric observational study involving all patients with PCR confirmed SARS-CoV-2 pneumonia, admitted at Papa Giovanni XXIII Hospital, Bergamo (Italy) from Emergency Department due to acute respiratory failure, during the first Italian pandemic peak (February-April 2020). RESULTS: Overall 28-day mortality in 1316 patients was 26.9%. Patients who did not report dyspnea at admission (N 469, 35.6%) had a lower 28-day mortality (22.6 vs. 29.3%, P=0.009). The severity matching analysis (i.e. PaO2/FiO2 and imaging) led to the identification of two groups of 254 patients that did not differ for sex prevalence, age, BMI, smoking history, comorbidities, and PaCO2 at admission. The use of CPAP during the first 24 hours, such as the need of endotracheal intubation (ETI) during the overall admission were significantly lower in matched patients with silent hypoxemia, whereas 28-day mortality resulted similar (P=0.21). CONCLUSIONS: Lack of dyspnea is common in patients suffering from severe COVID-19 pneumonia leading to respiratory failure, since up to a third of them could be asymptomatic on admission. Dyspnea per se correlates with pneumonia severity, and prognosis. However, dyspnea loses its predictive relevance once other findings to evaluate pneumonia severity are available such as PaO2/FiO2 and imaging. Silent hypoxemic patients are less likely to receive CPAP during the first 24 hours and ETI during the hospitalization, in spite of a comparable mortality to the dyspneic ones.

COVID-19 vaccine Mandates: An Australian attitudinal study.

BACKGROUND: The rollout of vaccines against COVID-19 is prompting governments and the private sector to adopt mandates. However, there has been little conceptual analysis of the types of mandates available, nor empirical analysis of how the public thinks about different mandates and why. Our conceptual study examines available instruments, how they have been implemented pre-COVID, and their use for COVID-19 globally. Then, our qualitative study reports the acceptability of such measures in Western Australia, which has experienced very limited community transmission, posing an interesting scenario for vaccine acceptance and acceptability of measures to enforce it. METHOD: Our conceptual study developed categories of mandates from extant work, news reports, and legislative interventions globally. Then, our empirical study asked 44 West Australians about their attitudes towards potential mandatory policies, with data analysed using NVivo 12. RESULTS: Our novel studies contribute richness and depth to emerging literature on the types and varying acceptability of vaccine requirements. Participants demonstrated tensions and confusion about whether instruments were incentives or punishments, and many supported strong consequences for non-vaccination even if they ostensibly opposed mandates. Those attached to restrictions for disease prevention were most popular. There were similar degrees of support for mandates imposed by employers or businesses, with participants showing little concern for potential issues of accountability linked to public health decisions delegated to the private sector. Participants mostly supported tightly regulated medical exemptions granted by specialists, with little interest in religious or personal belief exemptions. CONCLUSION: Our participants are used to being governed by vaccine mandates, and now by rigorous lockdown and travel restrictions that have ensured limited local COVID-19 disease and transmission. These factors appear influential in their general openness to COVID-19 vaccine mandates, especially when linked explicitly to the prevention of disease in high-risk settings.

AI, big data, and the future of consent.

In this paper, we discuss several problems with current Big data practices which, we claim, seriously erode the role of informed consent as it pertains to the use of personal information. To illustrate these problems, we consider how the notion of informed consent has been understood and operationalised in the ethical regulation of biomedical research (and medical practices, more broadly) and compare this with current Big data practices. We do so by first discussing three types of problems that can impede informed consent with respect to Big data use. First, we discuss the transparency (or explanation) problem. Second, we discuss the re-repurposed data problem. Third, we discuss the meaningful alternatives problem. In the final section of the paper, we suggest some solutions to these problems. In particular, we propose that the use of personal data for commercial and administrative objectives could be subject to a 'soft governance' ethical regulation, akin to the way that all projects involving human participants (e.g., social science projects, human medical data and tissue use) are regulated in Australia through the Human Research Ethics Committees (HRECs). We also consider alternatives to the standard consent forms, and privacy policies, that could make use of some of the latest research focussed on the usability of pictorial legal contracts.