Infective endocarditis

The term ‘predisposing heart condition’ is used as an indication of antimicrobial prophylaxis to prevent infective endocarditis (IE) and as a criterion for diagnosing IE according to the modified Duke criteria. Whereas the use of the term for antimicrobial prophylaxis is well defined, the criterion for diagnosing IE is not. The general objective of this thesis is to narrow the definition of a predisposing heart condition in ‘native’ valves for the diagnosis of IE. Therefore, we reviewed the literature and the evidence about specific heart conditions reported to be a risk factor for IE. In parallel, we reviewed the imaging technique available at the time these studies were published and compared the results with imaging from today’s perspectives and current definitions of a specific heart condition (i.e. valvular disease). Finally, we evaluated the knowledge and opinion of clinicians about the term predisposing heart condition. Our literature review included 207 studies, the vast majority of which were descriptive. Only a few studies investigated valve pathology as a risk factor for IE via analytical statistics. In addition, three-quarters of all included studies involved patients who presented with IE prior to the publication of the modified Duke criteria. Studies focussing on mitral valve prolapse (MVP, 116 publications), prior IE (96 publications), and bicuspid aortic valve (BAV, 78 publications) provided the most data. The odds ratio of developing IE for a patient who had previously experienced an episode of it was approximately 2.5. The mean proportion of patients with IE plus a history of previous IE was 8.3% (median 7.1%, interquartile range [IQR] 4.9%–10.2%). One study associated BAV with a higher risk of IE (hazard ratio 6.3). In 77 descriptive studies, a median of approximately 6% of patients with IE had BAV as an underlying condition. Our literature review on the evolution of imaging methods indicated, however, a considerable influence of medical progress on the diagnosis of MVP. Six analytical studies and 90 of the 110 descriptive studies included patients prior to the publication of the modified Duke criteria in 2000. For many years, MVP was diagnosed via auscultation only, and echocardiographic means for diagnosis were used in the late 90s. Therefore, both the risk of developing IE and the proportion of patients with IE and MVP as a predisposing factor could not be quantified. The literature review on mitral valve stenosis (MS, 23 publications) and pathologies involving the pulmonary valve (18 publications) and the tricuspid valve (nine publications) provided little data. These publications had inconsistent results and low proportions of patients with IE had these valve pathologies. The significance of aortic valve stenosis (AS, 46 publications), mitral valve insufficiency (MI, 41 publications), and aortic valve insufficiency (AI, 39 publications) as a predisposing heart condition was difficult to assess from today’s perspective because of the progress made in imaging methods; of these studies, 75.6%, 78.6%, and 79.5%, respectively, included patients prior to the publication of the modified Duke criteria in the year 2000. In addition, except for AS (1989), the categorisation of mild, moderate, and severe valve pathology was established in 1998 or 2006. The publications had considerable heterogeneity with a wide distribution of results. An observational study indicated that with an increased incidence of AS, the risk of developing IE rises. Only one of these 126 publications for these three valve pathologies used analytical statistics. Congenital AS was associated with a higher risk of IE (hazard ratio of 4.9). The results from the literature review parallel those from a survey that we performed to evaluate the knowledge and opinion of clinicians on the term predisposing heart condition. The survey indicated that there is significant uncertainty among clinicians regarding what is considered to be a Duke minor criterion for a predisposing heart condition in a native valve. The results from 318 questionnaires with responses from specialists in the fields of internal medicine, infectious diseases, and cardiology provided a wide range of answers. Their answers also showed that what the participants believed to be a current Duke minor criterion and what they thought should be a minor criterion had a median accordance of 33%. Taken together, these findings demonstrate that there is uncertainty about what is considered a predisposing heart condition for the diagnosis of IE. This uncertainty is demonstrated in our extensive literature review and reflected in our survey among clinicians. The vast majority of studies used only descriptive statistics and included patients prior to the publication of the modified Duke criteria (2000). The tremendous progress in imaging methods and categorisation of valve pathologies since then makes it difficult to interpret the literature review analyses from today’s perspective. Nonetheless, studies on MVP, a prior episode of IE, and BAV had the highest representation in the literature. Among these three pathologies, MVP is most likely to be affected by the evolution of imaging methods, and therefore its risk cannot be quantified. Sensitivity analyses and mathematical models performed on the data obtained in this systematic review may help to further narrow the definition of a predisposing heart condition

Infective endocarditis: What are predisposing conditions in native valves?

The term ‘predisposing heart condition’ is used as an indication of antimicrobial prophylaxis to prevent infective endocarditis (IE) and as a criterion for diagnosing IE according to the modified Duke criteria. Whereas the use of the term for antimicrobial prophylaxis is well defined, the criterion for diagnosing IE is not. The general objective of this thesis is to narrow the definition of a predisposing heart condition in ‘native’ valves for the diagnosis of IE. Therefore, we reviewed the literature and the evidence about specific heart conditions reported to be a risk factor for IE. In parallel, we reviewed the imaging technique available at the time these studies were published and compared the results with imaging from today’s perspectives and current definitions of a specific heart condition (i.e. valvular disease). Finally, we evaluated the knowledge and opinion of clinicians about the term predisposing heart condition. Our literature review included 207 studies, the vast majority of which were descriptive. Only a few studies investigated valve pathology as a risk factor for IE via analytical statistics. In addition, three-quarters of all included studies involved patients who presented with IE prior to the publication of the modified Duke criteria. Studies focussing on mitral valve prolapse (MVP, 116 publications), prior IE (96 publications), and bicuspid aortic valve (BAV, 78 publications) provided the most data. The odds ratio of developing IE for a patient who had previously experienced an episode of it was approximately 2.5. The mean proportion of patients with IE plus a history of previous IE was 8.3% (median 7.1%, interquartile range [IQR] 4.9%–10.2%). One study associated BAV with a higher risk of IE (hazard ratio 6.3). In 77 descriptive studies, a median of approximately 6% of patients with IE had BAV as an underlying condition. Our literature review on the evolution of imaging methods indicated, however, a considerable influence of medical progress on the diagnosis of MVP. Six analytical studies and 90 of the 110 descriptive studies included patients prior to the publication of the modified Duke criteria in 2000. For many years, MVP was diagnosed via auscultation only, and echocardiographic means for diagnosis were used in the late 90s. Therefore, both the risk of developing IE and the proportion of patients with IE and MVP as a predisposing factor could not be quantified. The literature review on mitral valve stenosis (MS, 23 publications) and pathologies involving the pulmonary valve (18 publications) and the tricuspid valve (nine publications) provided little data. These publications had inconsistent results and low proportions of patients with IE had these valve pathologies. The significance of aortic valve stenosis (AS, 46 publications), mitral valve insufficiency (MI, 41 publications), and aortic valve insufficiency (AI, 39 publications) as a predisposing heart condition was difficult to assess from today’s perspective because of the progress made in imaging methods; of these studies, 75.6%, 78.6%, and 79.5%, respectively, included patients prior to the publication of the modified Duke criteria in the year 2000. In addition, except for AS (1989), the categorisation of mild, moderate, and severe valve pathology was established in 1998 or 2006. The publications had considerable heterogeneity with a wide distribution of results. An observational study indicated that with an increased incidence of AS, the risk of developing IE rises. Only one of these 126 publications for these three valve pathologies used analytical statistics. Congenital AS was associated with a higher risk of IE (hazard ratio of 4.9). The results from the literature review parallel those from a survey that we performed to evaluate the knowledge and opinion of clinicians on the term predisposing heart condition. The survey indicated that there is significant uncertainty among clinicians regarding what is considered to be a Duke minor criterion for a predisposing heart condition in a native valve. The results from 318 questionnaires with responses from specialists in the fields of internal medicine, infectious diseases, and cardiology provided a wide range of answers. Their answers also showed that what the participants believed to be a current Duke minor criterion and what they thought should be a minor criterion had a median accordance of 33%. Taken together, these findings demonstrate that there is uncertainty about what is considered a predisposing heart condition for the diagnosis of IE. This uncertainty is demonstrated in our extensive literature review and reflected in our survey among clinicians. The vast majority of studies used only descriptive statistics and included patients prior to the publication of the modified Duke criteria (2000). The tremendous progress in imaging methods and categorisation of valve pathologies since then makes it difficult to interpret the literature review analyses from today’s perspective. Nonetheless, studies on MVP, a prior episode of IE, and BAV had the highest representation in the literature. Among these three pathologies, MVP is most likely to be affected by the evolution of imaging methods, and therefore its risk cannot be quantified. Sensitivity analyses and mathematical models performed on the data obtained in this systematic review may help to further narrow the definition of a predisposing heart condition

Do quantitative levels of antispike-IgG antibodies aid in predicting protection from SARS-CoV-2 infection? Results from a longitudinal study in a police cohort.

In a COVID-19 sero-surveillance cohort study with predominantly healthy and vaccinated individuals, the objectives were (i) to investigate longitudinally the factors associated with the quantitative dynamics of antispike (anti-S1) IgG antibody levels, (ii) to evaluate whether the levels were associated with protection from SARS-CoV-2 infection, and (iii) to assess whether the association was different in the pre-Omicron compared with the Omicron period. The QuantiVac Euroimmun ELISA test was used to quantify anti-S1 IgG levels. The entire study period (16 months), the 11-month pre-Omicron period and the cross-sectional analysis before the Omicron surge included 3219, 2310, and 895 reactive serum samples from 949, 919, and 895 individuals, respectively. Mixed-effect linear, mixed-effect time-to-event, and logistic regression models were used to achieve the objectives. Age and time since infection or vaccination were the only factors associated with a decline of anti-S1 IgG levels. Higher antibody levels were significantly associated with protection from SARS-CoV-2 infection (0.89, 95% confidence interval [CI] 0.82-0.97), and the association was higher during the time period when Omicron was predominantly circulating compared with the ones when Alpha and Delta variants were predominant (adjusted hazard ratio for interaction 0.66, 95% CI 0.53-0.84). In a prediction model, it was estimated that >8000 BAU/mL anti-S1 IgG was required to reduce the risk of infection with Omicron variants by approximately 20%-30% for 90 days. Though, such high levels were only found in 1.9% of the samples before the Omicron surge, and they were not durable for 3 months. Anti-S1 IgG antibody levels are statistically associated with protection from SARS-CoV-2 infection. However, the prediction impact of the antibody level findings on infection protection is limited

Serosurveillance after a COVID-19 Vaccine Campaign in a Swiss Police Cohort

Introduction: To assess the risk for COVID-19 of police officers, we are studying the seroprevalence in a cohort. The baseline cross-sectional investigation was performed prior to a vaccination campaign in January/February 2021, and demonstrated a seroprevalence of 12.9%. Here, we demonstrate serosurveillance results after a vaccination campaign. Methods: The cohort consists of 1022 study participants. The 3-month and 6-month follow-up visits were performed in April/May and September 2021. Data on infection and vaccination rates were obtained via measuring antibodies to the nucleocapsid protein and spike protein and online questionnaires. Results: The mean age of the population was 41 (SD 8.8) years, 72% were male and 76% had no comorbidity. Seroconversion was identified in 1.05% of the study population at the 3-month visit and in 0.73% at the 6-month visit, resulting in an infection rate of 1.8% over a time period of 6 months. In comparison, the infection rate in the general population over the same time period was higher (3.18%, P=0.018). At the 6-month visit, 77.8% of participants reported being vaccinated once and 70.5% twice; 81% had an anti-S antibody titer of >250 U/mL and 87.1% of ≥2 U/mL. No significant association between infection and job role within the department, working region, or years of experience in the job was found. Anti-spike antibody titers of vaccinated study participants showed a calculated decreasing trend 150 to 200 days after the second vaccine dose. Conclusion: These data confirm the value of the vaccination campaign in an exposed group other than healthcare professionals

Early Switch from Intravenous to Oral Antibiotics in Skin- and Soft-tissue Infections: An Algorithm-based Prospective Multicentre Pilot Trial.

BACKGROUND: In hospitalized patients with skin and soft tissue infections (SSTIs), intravenous (IV) empiric antibiotic treatment is initiated. The best time point for switching from IV to oral treatment is unknown. We used an algorithm-based decision tree for the switch from IV to oral antibiotics within 48 hours and aimed to investigate the treatment outcome of this concept. METHODS: In a nonrandomized trial, we prospectively enrolled 128 patients hospitalized with SSTI from July 2019 to May 2021 at 3 institutions. Clinical and biochemical response data during the first week and at follow-up after 30 days were analyzed. Patients fulfilling criteria for the switch from IV to oral antibiotics were assigned to the intervention group. The primary outcome was a composite definition consisting of the proportion of patients with clinical failure or death of any cause. RESULTS: Ninety-seven (75.8%) patients were assigned to the intervention group. All of them showed signs of clinical improvement (ie, absence of fever or reduction of pain) within 48 hours of IV treatment, irrespective of erythema finding or biochemical response. The median total antibiotic treatment duration was 11 (interquartile range [IQR], 9–13) days in the invention group and 15 (IQR, 11–24) days in the nonintervention group (P < .001). The median duration of hospitalization was 5 (IQR, 4–6) days in the intervention group and 8 (IQR, 6–12) days in the nonintervention group (P < .001). There were 5 (5.2%) failures in the intervention group and 1 (3.2%) in the nonintervention group after a median follow-up of 37 days. CONCLUSIONS: In this pilot trial, the proposed decision algorithm for early switch from IV to oral antibiotics for SSTI treatment was successful in 95% of cases. Clinical Trials Registration. ISRCTN1524549

Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy: a nested study within a randomized placebo controlled trial

The effect of levothyroxine (LT4) therapy for subclinical hypothyroidism (SHypo) on appendicular bone geometry and volumetric density has so far not been studied. In a nested study within the randomized, placebo-controlled Thyroid Hormone Replacement for Subclinical Hypothyroidism (TRUST) trial, we assessed the effect of LT4 therapy on bone geometry as measured by peripheral quantitative computed tomography (pQCT). In the TRUST trial, community-dwelling adults aged ≥65 years with SHypo were randomized to LT4 with dose titration vs. placebo with mock titration. We analyzed data from participants enrolled at the TRUST site in Bern, Switzerland who had bone pQCT measured at baseline and at 1 to 2 years follow-up. The primary outcomes were the annual percentage changes of radius and tibia epi- and diaphysis bone geometry (total and cortical cross-sectional area (CSA) and cortical thickness), and of volumetric bone mineral density (bone mineral content (BMC) and total, trabecular and cortical volumetric bone mineral density (vBMD)). We performed linear regression of the annual percentage changes adjusted for sex, LT4 dose at randomization and muscle cross-sectional area. The 98 included participants had a mean age of 73.9 (±SD 5.4) years, 45.9% were women, and 12% had osteoporosis. They were randomized to placebo (n = 48) or LT4 (n = 50). Annual changes in BMC and vBMD were similar between placebo and LT4-treated groups, without significant difference in bone geometry or volumetric bone mineral density changes, neither at the diaphysis, nor at the epiphysis. For example, in the placebo group, epiphyseal BMC (radius) decreased by a mean 0.2% per year, with a similar decrease of 0.5% per year in the LT4 group (between-group difference in %ΔBMC 0.3, 95% CI -0.70 to 1.21, p = 0.91). Compared to placebo, LT4 therapy for an average 14 months had no significant effect on bone mass, bone geometry and volumetric density in older adults with subclinical hypothyroidism. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov numbers NCT01660126 (TRUST Thyroid trial) and NCT02491008 (Skeletal outcomes)

Infective Endocarditis: How Do We Currently Interpret the Duke Minor Criterion “Predisposing Heart Condition” in Native Valves?

INTRODUCTION The term "predisposing heart condition" is used as an indication of antimicrobial prophylaxis to prevent infective endocarditis (IE) and as a criterion for diagnosing IE according to modified Duke criteria. The purpose of this survey was to elaborate clinician's knowledge and opinion on relevant heart conditions as a Duke minor criterion for the diagnosis of IE. METHODS A questionnaire was created that consisted of two knowledge and two opinion questions on the term predisposing heart condition. The survey included results from 318 questionnaires with responses from specialists in the field of internal medicine, infectious diseases, and cardiology. RESULTS The answers of what participants believed to be currently a Duke minor criterion and what they thought should be minor criterion were very distributed with a median accordance of 33%. CONCLUSION The survey indicates that there is significant uncertainty regarding what is encountered as a Duke minor criterion predisposing heart condition in a native valve

A multidimensional cross-sectional analysis of COVID-19 seroprevalence among a police officer cohort: The PoliCOV-19 study

Background Protests and police fieldwork provides a high exposure environment for SARS-CoV-2 infections. In this cross-sectional analysis, we investigated the seroprevalence among a police cohort, and sociodemographic, work and health-related factors associated with seropositivity. Methods Study participants were invited for serological testing of SARS-CoV-2 and to complete online questionnaires. Serum neutralization titres towards the wild-type SARS-CoV-2 spike protein (expressing D614G) and the alpha and beta variants were measured in seropositive study participants. Results 978 police personnel representing 35% of the entire staff participated from February to March 2021. The seroprevalence was 12.9%. It varied by geographic region within the canton; ranged from 9% to 13.5% in three regions, including the city; and was 22% in Bernese Seeland/Jura with higher odds for seropositivity (OR 2.38, 95% CI 1.28–4.44, P=0.006). Job roles with mainly office activity were associated with a lower risk of seropositivity (0.33, 0.14–0.77, P=0.010). Most seropositive employees (67.5%) reported having had COVID-19 three months or longer prior to serological testing. Selfreported compliance with mask wearing during working hours was 100%; 45% of all seropositive versus 5% of all seronegative participants (P<0.001) reported having had contact with a proven COVID-19 case living in the same household prior to serological testing. The level of serum antibody titres correlated with neutralization capacity. Antibodies derived from natural SARS-CoV-2 infection effectively neutralized the SARS-CoV-2 spike protein, but were less effective against the alpha and beta variants. Conclusions The seroprevalence of anti-SARS-CoV-2 antibodies of police officers was comparable to that reported in the general population, suggesting that the personal protective equipment of the police is effective, and that household contacts are the leading transmission venues. The level of serum antibody titres, in particular that of anti-spike antibodies, correlated well with neutralization capacity. Low antibody titres acquired from natural infection were not effective against variants

Documenting Social Media Engagement as Scholarship: A New Model for Assessing Academic Accomplishment for the Health Professions.

BACKGROUND The traditional model of promotion and tenure in the health professions relies heavily on formal scholarship through teaching, research, and service. Institutions consider how much weight to give activities in each of these areas and determine a threshold for advancement. With the emergence of social media, scholars can engage wider audiences in creative ways and have a broader impact. Conventional metrics like the h-index do not account for social media impact. Social media engagement is poorly represented in most curricula vitae (CV) and therefore is undervalued in promotion and tenure reviews. OBJECTIVE The objective was to develop crowdsourced guidelines for documenting social media scholarship. These guidelines aimed to provide a structure for documenting a scholar's general impact on social media, as well as methods of documenting individual social media contributions exemplifying innovation, education, mentorship, advocacy, and dissemination. METHODS To create unifying guidelines, we created a crowdsourced process that capitalized on the strengths of social media and generated a case example of successful use of the medium for academic collaboration. The primary author created a draft of the guidelines and then sought input from users on Twitter via a publicly accessible Google Document. There was no limitation on who could provide input and the work was done in a democratic, collaborative fashion. Contributors edited the draft over a period of 1 week (September 12-18, 2020). The primary and secondary authors then revised the draft to make it more concise. The guidelines and manuscript were then distributed to the contributors for edits and adopted by the group. All contributors were given the opportunity to serve as coauthors on the publication and were told upfront that authorship would depend on whether they were able to document the ways in which they met the 4 International Committee of Medical Journal Editors authorship criteria. RESULTS We developed 2 sets of guidelines: Guidelines for Listing All Social Media Scholarship Under Public Scholarship (in Research/Scholarship Section of CV) and Guidelines for Listing Social Media Scholarship Under Research, Teaching, and Service Sections of CV. Institutions can choose which set fits their existing CV format. CONCLUSIONS With more uniformity, scholars can better represent the full scope and impact of their work. These guidelines are not intended to dictate how individual institutions should weigh social media contributions within promotion and tenure cases. Instead, by providing an initial set of guidelines, we hope to provide scholars and their institutions with a common format and language to document social media scholarship