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SARS-CoV-2 infection risk during delivery of childhood vaccination campaigns: a modelling study
Get PDFThe COVID-19 pandemic has disrupted the delivery of immunisation services globally. Many countries have postponed vaccination campaigns out of concern about infection risks to the staff delivering vaccination, the children being vaccinated, and their families. The World Health Organization recommends considering both the benefit of preventive campaigns and the risk of SARS-CoV-2 transmission when making decisions about campaigns during COVID-19 outbreaks, but there has been little quantification of the risks.
Methods
We modelled excess SARS-CoV-2 infection risk to vaccinators, vaccinees, and their caregivers resulting from vaccination campaigns delivered during a COVID-19 epidemic. Our model used population age structure and contact patterns from three exemplar countries (Burkina Faso, Ethiopia, and Brazil). It combined an existing compartmental transmission model of an underlying COVID-19 epidemic with a Reed-Frost model of SARS-CoV-2 infection risk to vaccinators and vaccinees. We explored how excess risk depends on key parameters governing SARS-CoV-2 transmissibility, and aspects of campaign delivery such as campaign duration, number of vaccinations, and effectiveness of personal protective equipment (PPE) and symptomatic screening.
Results
Infection risks differ considerably depending on the circumstances in which vaccination campaigns are conducted. A campaign conducted at the peak of a SARS-CoV-2 epidemic with high prevalence and without special infection mitigation measures could increase absolute infection risk by 32 to 45% for vaccinators and 0.3 to 0.5% for vaccinees and caregivers. However, these risks could be reduced to 3.6 to 5.3% and 0.1 to 0.2% respectively by use of PPE that reduces transmission by 90% (as might be achieved with N95 respirators or high-quality surgical masks) and symptomatic screening.
Conclusions
SARS-CoV-2 infection risks to vaccinators, vaccinees, and caregivers during vaccination campaigns can be greatly reduced by adequate PPE, symptomatic screening, and appropriate campaign timing. Our results support the use of adequate risk mitigation measures for vaccination campaigns held during SARS-CoV-2 epidemics, rather than cancelling them entirely
Renal function and lipid metabolism are major predictors of circumpapillary retinal nerve fiber layer thickness—the LIFE-Adult Study
Get PDFCircumpapillary retinal nerve fiber layer thickness (cpRNFLT) as assessed by spectral domain optical coherence tomography (SD-OCT) is a new technique used for the detection and evaluation of glaucoma and other optic neuropathies. Before translating cpRNFLT into clinics, it is crucially important to investigate anthropometric, biochemical, and clinical parameters potentially affecting cpRNFLT in a large population-based dataset.
Methods
The population-based LIFE-Adult Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. All participants underwent standardized systemic assessment of various cardiometabolic risk markers and ocular imaging, including cpRNFLT measurement using SD-OCT (Spectralis, Heidelberg Engineering). After employing strict SD-OCT quality criteria, 8952 individuals were analyzed. Multivariable linear regression analyses were used to evaluate the independent associations of various cardiometabolic risk markers with sector-specific cpRNFLT. For significant markers, the relative strength of the observed associations was compared to each other to identify the most relevant factors influencing cpRNFLT. In all analyses, the false discovery rate method for multiple comparisons was applied.
Results
In the entire cohort, female subjects had significantly thicker global and also sectoral cpRNFLT compared to male subjects (p < 0.05). Multivariable linear regression analyses revealed a significant and independent association between global and sectoral cpRNFLT with biomarkers of renal function and lipid profile. Thus, thinner cpRNFLT was associated with worse renal function as assessed by cystatin C and estimated glomerular filtration rate. Furthermore, an adverse lipid profile (i.e., low high-density lipoprotein (HDL) cholesterol, as well as high total, high non-HDL, high low-density lipoprotein cholesterol, and high apolipoprotein B) was independently and statistically significantly related to thicker cpRNFLT. In contrast, we do not observe a significant association between cpRNFLT and markers of inflammation, glucose homeostasis, liver function, blood pressure, or obesity in our sector-specific analysis and globally.
Conclusions
Markers of renal function and lipid metabolism are predictors of sectoral cpRNFLT in a large and deeply phenotyped population-based study independently of previously established covariates. Future studies on cpRNFLT should include these biomarkers and need to investigate whether incorporation will improve the diagnosis of early eye diseases based on cpRNFLT
Advancing the diagnosis and classification of renal cell carcinomas
Get PDFRenal cancer is of concern due to its rising incidence worldwide, with new cases per year expected to climb by as much as 20% by 2030 [1]. Renal neoplasms encompass a variety of malignant and benign tumours with varying prognoses. Accurate classification and diagnosis currently rely on immunohistochemistry to detect known protein markers, in combination with examination of morphological characteristics. Accurate identifications are not always possible, which in turn hinders the delivery of a diagnosis and process to adapted treatment plans. Advanced-stage renal cell carcinomas carry extremely poor prognoses, so improved methods are urgently needed.
High-resolution mass spectrometry (MS) is the cornerstone of proteomics technologies and rapidly evolving tool that promises to drive such methods forward. In MS-based proteomics, large numbers of proteins can be characterised and their absolute amounts measured in solid and liquid biopsies, termed the “total protein approach” (TPA) [2]. Tumours may then be distinguished by the unique concentration ranges of protein biomarkers. With an unparalleled depth of interrogation of tumour proteomes, the technique enables new protein markers of specific neoplasms to be found among the vast number of overexpressed proteins in tumour cells. TPA does not require labelling of the sample or the addition of specific antibodies to the sample, and neither are calibration standards required. While some studies have applied the technique to cell or animal models, only one has been conducted with tissue biopsies from cancer patients [3], whose aim was to elucidate changes in energy metabolism and plasma membrane transport, rather than improve clinical practice and patient outcomes. No previous study has applied TPA to renal neoplasms
Evaluation of the Use of Blood Products in ICU Hospitalized COVID-19 Patients
Get PDF(1) Background: The COVID-19 pandemic tested the public health system’s readiness for crises and highlighted the importance of knowing the demand for blood products and the maintenance of the blood supply chain. The aim of this study was to evaluate blood product usage in a series of patients that were hospitalized due to COVID-19 and to analyze their demographics and clinical characteristics. (2) Methods: In this retrospective cohort study, we analyzed data from transfused COVID-19 patients that were treated in the University Hospital Medical Center Bezanijska Kosa in Belgrade, Serbia during the second wave of the epidemic. (3) Results: This study included 90 patients. The median age of the patients was 72 (range 23–95) years. The median time of hospitalization was 23 days (range 3–73 days). In intensive care units (ICUs) the median time of hospitalization was 9 days (range 0–73). One or more comorbidities were observed in 86 individuals (95.6%). The total number of transfused red blood cell concetrates (RBC) was 304 (139 in ICU, 165 in other wards), with a mean of 3 units/patient (range 1–14). Comorbidities, severity of illness and hospital duration in the ICU were statistically significant predictors of higher RBC use. (4) Conclusion: Knowledge of the transfusion profile of COVID-19 patients allowed better management of the hospital’s blood stocks during the COVID-19 pandemic
Identifying Consensus and Open Questions around Assessing or Predicting the Quality and Success of Cartilage Repair: A Delphi Study
Get PDFA range of surgical techniques have been developed for the repair or regeneration of lesioned cartilage in the human knee and a corresponding array of scoring systems have been created to assess their outcomes. The published literature displays a wide range of opinions regarding the factors that influence the success of surgical cartilage repair and which parameters are the most useful for measuring the quality of the repair at follow-up. Our objective was to provide some clarity to the field by collating items that were agreed upon by a panel of experts to be important in these areas. A modified, three-round Delphi consensus study was carried out consisting of one idea-generating focus-group and two subsequent, self-completed questionnaire rounds. In each round, items were assessed for their importance and level of consensus against pre-determined threshold levels. In total, 31 items reached consensus, including a hierarchy of tissues in the joint based on their importance in cartilage repair, markers of repair cartilage quality and the implications of environmental and patient-related factors. Items were stratified into those that can be employed for predicting the success of cartilage repair and those that could be used for assessing the structural quality of the resulting repair cartilage. Items that did not reach consensus represent areas where dissent remains and could, therefore, be used to guide future clinical and fundamental scientific research
Circulating vitamin C concentration and risk of cancers: a Mendelian randomization study
Get PDFCirculating vitamin C concentrations have been associated with several cancers in observational studies, but little is known about the causal direction of the associations. This study aims to explore the potential causal relationship between circulating vitamin C and risk of five most common cancers in Europe.
Methods
We used summary-level data for genetic variants associated with plasma vitamin C in a large vitamin C genome-wide association study (GWAS) meta-analysis on 52,018 Europeans, and the corresponding associations with lung, breast, prostate, colon, and rectal cancer from GWAS consortia including up to 870,984 participants of European ancestry. We performed two-sample, bi-directional Mendelian randomization (MR) analyses using inverse-variance-weighted method as the primary approach, while using 6 additional methods (e.g., MR-Egger, weighted median-based, and mode-based methods) as sensitivity analysis to detect and adjust for pleiotropy. We also conducted a meta-analysis of prospective cohort studies and randomized controlled trials to examine the association of vitamin C intakes with cancer outcomes.
Results
The MR analysis showed no evidence of a causal association of circulating vitamin C concentration with any examined cancer. Although the odds ratio (OR) per one standard deviation increase in genetically predicted circulating vitamin C concentration was 1.34 (95% confidence interval 1.14 to 1.57) for breast cancer in the UK Biobank, this association could not be replicated in the Breast Cancer Association Consortium with an OR of 1.05 (0.94 to 1.17). Smoking initiation, as a positive control for our reverse MR analysis, showed a negative association with circulating vitamin C concentration. However, there was no strong evidence of a causal association of any examined cancer with circulating vitamin C. Sensitivity analysis using 6 different analytical approaches yielded similar results. Moreover, our MR results were consistent with the null findings from the meta-analysis exploring prospective associations of dietary or supplemental vitamin C intakes with cancer risk, except that higher dietary vitamin C intake, but not vitamin C supplement, was associated with a lower risk of lung cancer (risk ratio: 0.84, 95% confidence interval 0.71 to 0.99)
Optimal SARS-CoV-2 vaccine allocation using real-time attack-rate estimates in Rhode Island and Massachusetts
Get PDFWhen three SARS-CoV-2 vaccines came to market in Europe and North America in the winter of 2020–2021, distribution networks were in a race against a major epidemiological wave of SARS-CoV-2 that began in autumn 2020. Rapid and optimized vaccine allocation was critical during this time. With 95% efficacy reported for two of the vaccines, near-term public health needs likely require that distribution is prioritized to the elderly, health care workers, teachers, essential workers, and individuals with comorbidities putting them at risk of severe clinical progression.
Methods
We evaluate various age-based vaccine distributions using a validated mathematical model based on current epidemic trends in Rhode Island and Massachusetts. We allow for varying waning efficacy of vaccine-induced immunity, as this has not yet been measured. We account for the fact that known COVID-positive cases may not have been included in the first round of vaccination. And, we account for age-specific immune patterns in both states at the time of the start of the vaccination program. Our analysis assumes that health systems during winter 2020–2021 had equal staffing and capacity to previous phases of the SARS-CoV-2 epidemic; we do not consider the effects of understaffed hospitals or unvaccinated medical staff.
Results
We find that allocating a substantial proportion (>75%) of vaccine supply to individuals over the age of 70 is optimal in terms of reducing total cumulative deaths through mid-2021. This result is robust to different profiles of waning vaccine efficacy and several different assumptions on age mixing during and after lockdown periods. As we do not explicitly model other high-mortality groups, our results on vaccine allocation apply to all groups at high risk of mortality if infected. A median of 327 to 340 deaths can be avoided in Rhode Island (3444 to 3647 in Massachusetts) by optimizing vaccine allocation and vaccinating the elderly first. The vaccination campaigns are expected to save a median of 639 to 664 lives in Rhode Island and 6278 to 6618 lives in Massachusetts in the first half of 2021 when compared to a scenario with no vaccine. A policy of vaccinating only seronegative individuals avoids redundancy in vaccine use on individuals that may already be immune, and would result in 0.5% to 1% reductions in cumulative hospitalizations and deaths by mid-2021.
Conclusions
Assuming high vaccination coverage (>28%) and no major changes in distancing, masking, gathering size, hygiene guidelines, and virus transmissibility between 1 January 2021 and 1 July 2021 a combination of vaccination and population immunity may lead to low or near-zero transmission levels by the second quarter of 2021
Sequelae, persistent symptomatology and outcomes after COVID-19 hospitalization: the ANCOHVID multicentre 6-month follow-up study
Get PDFong-term effects of COVID-19, also called Long COVID, affect more than 10% of patients. The most severe cases (i.e. those requiring hospitalization) present a higher frequency of sequelae, but detailed information on these effects is still lacking. The objective of this study is to identify and quantify the frequency and outcomes associated with the presence of sequelae or persistent symptomatology (SPS) during the 6 months after discharge for COVID-19.
Methods
Retrospective observational 6-month follow-up study conducted in four hospitals of Spain. A cohort of all 969 patients who were hospitalized with PCR-confirmed SARS-CoV-2 from March 1 to April 15, 2020, was included. We collected all the SPS during the 6 months after discharge reported by patients during follow-up from primary care records. Cluster analyses were performed to validate the measures. The main outcome measures were return to the Emergency Services, hospital readmission and post-discharge death. Surviving patients’ outcomes were collected through clinical histories and primary care reports. Multiple logistic regression models were applied.
Results
The 797 (82.2%) patients who survived constituted the sample followed, while the rest died from COVID-19. The mean age was 63.0 years, 53.7% of them were men and 509 (63.9%) reported some sequelae during the first 6 months after discharge. These sequelae were very diverse, but the most frequent were respiratory (42.0%), systemic (36.1%), neurological (20.8%), mental health (12.2%) and infectious (7.9%) SPS, with some differences by sex. Women presented higher frequencies of headache and mental health SPS, among others. A total of 160 (20.1%) patients returned to the Emergency Services, 35 (4.4%) required hospital readmission and 8 (1.0%) died during follow-up. The main factors independently associated with the return to Emergency Services were persistent fever, dermatological SPS, arrythmia or palpitations, thoracic pain and pneumonia.
Conclusion
Scales to Assess Knowledge, Motivation, and Self-Efficacy for HIV PrEP in Colombian MSM: PrEP-COL Study
Get PDFObjective. We evaluated the construct validity Spanish version of knowledge, stigma, norms, and self-efficacy scales regarding PrEP in MSM. Methods. Sample of 287 MSM. Exploratory confirmatory factor analysis and item response theory were used to validate the constructs. Correlations and confidence interval-based estimation of relevance analyses were conducted to correlate the scales with willingness and intention to use PrEP. Results. Attitude, stigma, and descriptive and subjective norms scales showed good construct validity and were related to intention and willingness to use PrEP. However, the knowledge scale and self-efficacy scales require further refinement. Conclusions. The study provides useful information for assessing information, motivation, and self-efficacy related to PrEP use. Our results could be used to test the scales and the theoretical model in other contexts to confirm their usefulness.
1. Introduction
As MSM continue to be disproportionately affected by HIV, a combination of preventive strategies, including preexposure prophylaxis (PrEP), is urgently needed to curtail the rate of new HIV diagnoses worldwide. PrEP acceptance in MSM has been low despite years of availability and demonstrated efficacy [1, 2]. In the United States only one of five PrEP-eligible MSM is taking PrEP [3, 4]. Latino MSM in North America had lower PrEP knowledge, acceptance, and uptake [5, 6]. In Latin American countries, where MSM account for 40% of the new cases of HIV each year, PrEP awareness was reported around to 58%, and nearly 52% were willing to use daily PrEP [6]. PrEP uptake is a complex behaviour [1, 7], and the use of a theoretical model to identify appropriate targets for interventions is needed if PrEP is to be adopted widely.
One explanatory model for reducing HIV risk behaviours that has potential in MSM populations is the information motivational behavioural (IMB) model [8]. The IMB model posits that individuals will likely initiate and sustain a behaviour if they are well informed and motivated and perceive themselves as having the skills to initiate and maintain the behaviour. The IMB model has been used to develop HIV prevention interventions proven to be effective in decreasing condomless sex [9] and increasing adherence to antiretroviral therapy [10, 11]. Barriers related to PrEP uptake in MSM are also consistent with the IMB model, including lack of knowledge, negative attitudes, lack of self-efficacy, and low motivation due to stigma [12]. Hence, it is a relevant framework for the development of behavioural interventions for populations at risk of HIV infection and in need of PrEP [12–14].
Identification of PrEP knowledge, motivation, and skills in MSM requires either new instruments or the adaptation and validation of existing ones in different populations. In a recent publication, Walsh [14] used the IMB model to develop new measures for these constructs and relate them to PrEP uptake. The scales assessing knowledge, descriptive norms, and subjective norms have high levels of reliability with alphas of Cronbach greater than or equal to 0.90. The attitude, stigma, and self-efficacy scales had good alphas from 0.79 to 0.87. Confirmatory factor analyses supported the correlation of the scales and the item loading in each a priori latent construct, with most of the scales related to the intention to use PrEP, thus supporting the IMB model. Since the scales have been recently developed and only used in MSM populations living in the United States and are not yet available in Spanish, in this paper, we present the assessment of their internal coherence and construct validity in a sample of MSM from Colombia. In this work, we explored if the items of the scales represent one construct and a relationship exists between the scales and the intention to uptake PrEP. If the PrEP scales are valid and the relations are supported, the results could be used to gain an understanding of PrEP uptake in other Spanish-speaking MSM populations and delineate interventions
Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting
Get PDFHealthy individuals and patients with cancer who are carriers of germline pathogenic variants in the BRCA1/2 genes face multiple reproductive challenges that require appropriate counseling and specific expertise.
Main body
On December 5th–7th, 2019, patient advocates and physicians with expertise in the field of reproductive medicine, fertility preservation, and oncology were invited to “San Giuseppe Moscati” Hospital in Avellino (Italy) for a workshop on reproductive management of women with germline pathogenic variants in the BRCA1/2 genes. From the discussion regarding the current evidence and future prospective in the field, eight main research questions were formulated and eight recommendations were developed regarding fertility, fertility preservation, preimplantation genetic testing, and pregnancy in healthy carriers and patients with cancer.
Conclusion
Several misconceptions about the topic persist among health care providers and patients often resulting in a discontinuous and suboptimal management. With the aim to offer patient-tailored counseling about reproductive issues, both awareness of current evidences and research should be promoted