Long-term health effects of COVID-19 among patients in Croatian primary care settings

COVID-19 and smoking: Considerations after two years

Metabolic biomarkers measured from single blood test can identify apparently healthy people at high susceptibility for developing severe pneumonia, and may also be useful for preventive COVID-19 screening.

Immunization Update 2021

The integration and long-term success of dental implants exploit the unique biology of the oral cavity, which allows for osseous incorporation of a biomaterial and its long-term health within a bacteria-laden oral milieu.1 The delicate balance of defense and repair mechanisms underlying this unique environment may be challenged by various factors that can act both locally and/or systemically, thereby increasing the risk of implant loss and jeopardizing the long-term success of inserted implants. Local risk factors that are present in the oral cavity and systemic risk factors that have the potential to affect oral health on a systemic level can compromise implant treatment at all stages of treatment delivery by: (a) complicating surgical procedures and other invasive measures required during treatment; (b) compromising the process of tissue healing following implant insertion/increasing the risk of wound infection; and (c) contributing to the deterioration of long-term peri-implant health and tissue stability (Table 1). Reduced bone healing Reduced implant stability Reduced bone remodeling Reduced angiogenesis Reduced bone regeneration Acquired immunosuppression Hypovascularity Iatrogenic immunosuppression Reduced tissue regeneration Hypovascularity hypoxia Leukocyte dysfunction Conditions that interfere with invasive procedures, which include poor general health status (https://www.asahq.org/resources/clinical-information/asa-physical-status-classification-system) as a result of severe systemic disease, may impact upon implant surgery, healing, and maintenance. These are mostly cardiovascular conditions that can place the patient at high risk during surgery, irrespective of the nature of the intervention. Bleeding disorders, which may be innate or acquired, as well as attributable to the use of anticoagulants, may also complicate invasive measures. While the former are considered to be relatively rare, the latter may have a significant impact on daily implant treatment in an aging population. All these conditions can also have a negative impact on long-term peri-implant health and maintenance of peri-implant tissues as a result of compromised vascularity, as well as alterations in the immune defense or repair capacity of peri-implant tissues. The increasing patient demand for implant-based treatments in conjunction with a demographic shift of the patient population has resulted in a growing body of literature dealing with an increasing number of patients presenting with medical conditions. A recent cross-sectional analysis indicated that almost 90% of patients aged > 65 years were taking medication for underlying systemic diseases, which could jeopardize implant success.2 The advent of new treatment modalities, such as antiresorptive drugs or monoclonal antibody therapies, adds to the number of potential risk factors,3 leading to an increasing challenge for the provision of implant-based treatments in the future. The aim of this narrative review was therefore to analyze the importance of systemic and local conditions as risk factors for implant loss by critically evaluating the available evidence. During evaluation of the available literature, it was obvious that the term "implant loss" was used to a much lesser degree than "implant failure." Very few reports clearly defined implant failure as implant loss, but the context in which this term has historically been used indicates that implant failure was synonymous for implant loss. It is only in the last decade or so that definitions of implant failure have been published, and not until the 2017 World Workshop on Periodontal and Peri-Implant Disease Classification was an international definition agreed upon.4 One of the major reasons for implant loss is the progressive loss of peri-implant bone support. Therefore, marginal bone loss was also included in the analysis. As progressive crestal bone loss around implants in the absence of clinical signs of soft tissue inflammation is rare,5 reported radiographic bone loss was considered in conjunction with clinical peri-implant parameters (where provided) in the individual reports in order to assess the prognostic relevance of the findings. The effect of cardiovascular conditions on implant treatment has been mostly analyzed in cross-sectional cohort studies. In these reports, 15.6%-37%6-8 of patients were affected by cardiovascular diseases. Two recent multivariate analyses of large cohorts consisting of > 6300 and > 22 000 patients did not identify cardiovascular conditions as significant risk factors for implant loss6 or peri-implant pathology.9 This is in line with other cross-sectional studies of smaller cohorts.10-13 Cardiovascular conditions may, however, be associated with the maintenance of long-term peri-implant tissue health. Patients with diseased implants have shown a higher likelihood of cardiovascular comorbidity,8 and a recent prospective study of 44 patients with fixed mandibular prostheses demonstrated an association between cardiovascular disease and increased radiographic peri-implant bone loss.14 The available evidence currently suggests that cardiovascular conditions are not a major risk factor for implant loss. Although the radiographic bone loss reported had not been classified as progressive, cardiovascular disease should be taken into account in maintenance protocols as a potential comorbidity15 that may affect long-term peri-implant tissue health. Bleeding disorders can be innate, such as hemophilia A/B and von Willebrand–Jürgens Syndrome, or acquired during end stage liver disease, with subsequent deterioration of coagulation factors and platelet counts. The placement of implants in patients with hemophilia is rarely documented in case reports.16, 17 In contrast to this, patients with iatrogenic bleeding disorders as a result of anticoagulation therapy have been studied more frequently. Depending on the underlying disease, anticoagulation therapy may encompass antiplatelet drugs, vitamin K antagonists, or direct oral anticoagulants. There is widespread agreement that anticoagulation therapy with antiplatelet drugs or vitamin K antagonists should not be discontinued for dental surgical procedures, as long as a single drug is used and the level of activity is within the therapeutic range (international normalized ratio 2.5-3.0).18, 19 Some uncertainty exists about the management of patients using direct oral anticoagulants, but it is assumed that no interruption of therapy is required; consulting with the hematologist responsible for the patient's care is always advisable.20 Implant surgery in patients undergoing anticoagulation therapy has been reported in a number of controlled clinical studies, albeit consisting of rather small cohorts.21-24 Follow-up included an immediate postoperative period of 8-10 days. All the authors agreed that implants could be safely placed in patients with anticoagulation therapy without interruption of medication of vitamin K antagonists or direct oral anticoagulants. An exception to this may be dual anticoagulation therapy using two antiplatelet drugs (acetylsalicylic acid and clopidogrel), as is commonly employed following stenting of the coronary arteries. In these cases, postoperative morbidity may occur as a result of the increased risk of postoperative bleeding (Figure 1). Implant surgery should therefore be postponed until dual antiplatelet therapy has returned to single antiplatelet drug use. Depending on the type of stent used, this period may vary from 6 weeks to 6 months. To date, no information is available on implant complications arising in anticoagulated patients beyond the immediate period of surgical wound healing. The management of secondary interventions for soft tissue management or peri-implant diseases has not yet been reported on, but may have an impact on the long-term prognosis of implants, and should be taken into consideration when implants are planned for patients with anticoagulation management. Moreover, it should be noted that the necessity for anticoagulation therapy is commonly an underlying cardiovascular condition that needs to be explored and may require additional action. If anticoagulation therapy is used because of a cardiac condition associated with an increased risk for infective endocarditis, antibiotic prophylaxis is required.25 The necessity for antibiotic prophylaxis has been questioned based on a low risk of bacteremia during implant insertion,26 but adherence to current updates of national guidelines is strongly recommended.27, 28 Osteoporosis is characterized by a loss of structural quality of cancellous bone and a reduction in cortical bone thickness resulting in an overall deterioration of bone density. Approximately 48% of women and 15% of men aged ≥ 75 years are known to be affected.29 Primary osteoporosis can arise because of the loss of osteoanabolic effects of sex hormones (type I) in postmenopausal women (and some 10 years later in men), or because of age-related changes in general metabolism (type II). Osteoporosis may also arise secondary to endocrine diseases (eg, Cushing Syndrome, parathyroid hormone excess) or as a result of medication (eg, corticosteroids). Commonly, the diagnosis is derived from dual energy X-ray absorptiometry of the spine and/or the proximal femur. Dual energy X-ray absorptiometry scans provide a T-score that expresses the deviation of bone mineral density of the patient in standard deviations from the average value of healthy young adults. A T-score of < –2.5 is considered to be indicative of osteoporosis. Osteoporosis has been a concern in implant dentistry from an early stage in the development of the field.30-32 A number of papers have addressed the question of whether reduced skeletal bone density is associated with inferior bone quality in the maxilla or mandible. Subjectively, perceived jaw bone quality did not correlate with documented dual energy X-ray absorptiometry scores.33 Moreover, bone next to implants retrieved from osteoporotic patients did not exhibit a reduced number of bone cells or bone-to-implant contact.34 To identify individuals with reduced skeletal bone density, panoramic indices such as the mandibular cortex width,35 panoramic mandibular index,36 and the Klemetti index37 have been developed. A recent review reported these indices as useful in intercepting patients with reduced bone mineral density (T-score < 1), but did not recommend them to intercept patients with osteopenia/osteoporosis.38 Moreover, a systematic review examining the association between objective measures of jaw bone quality and skeletal bone mineral density was unable to clarify whether skeletal osteoporosis is associated with osteoporosis in the jaw bones.39 The role of osteoporosis in the success of implant treatment and the stability of marginal bone has been evaluated in a number of studies. Recent systematic reviews have found no difference in implant survival rates between patients with and without osteoporosis (risk ratio 1.9, 95% confidence interval 0.93-2.08, P = .11),40 or identified a direct but insignificant effect of osteoporosis on dental implant loss (risk ratio 1.09, 95% confidence interval 0.79-1.52).41 Similarly, earlier reviews and case control studies42-45 did not find evidence for an association between skeletal bone mineral density/osteoporosis and increased implant loss. With regard to peri-implant bone loss, the majority of recent studies (two cross-sectional,46, 47 one prospective,48 and one case control study49) reported no difference in radiographic peri-implant bone loss between patients with and without osteoporosis. Only one cross-sectional study reported significantly increased radiographic loss of marginal bone in osteoporotic patients after 1 year.50 All the patients in this study were part of a maintenance program with low periodontal indices and healthy periodontal conditions. Differences in radiographic bone level changes have been attributed to differences in bone remodeling in osteoporotic patients. The relevance of these findings with regard to long-term implant prognosis remains to be determined. While osteoporosis as such may not play a role in implant failure or loss of peri-implant bone, medications used for osteoporosis therapy may interfere with osseointegration and long-term maintenance of peri-implant health. The drugs prescribed are mostly either bisphosphonates51 or denosumab, a monoclonal antibody against the signaling molecule RANKL that is involved in the recruitment of osteoclasts. Bisphosphonates reduce both the resorptive activity of osteoclasts, as well as the activity of osteoblasts in a dose-dependent manner,52, 53 while denosumab directly reduces osteoclast activity.54 The net effect of the antiresorptive therapy is a decrease in bone turnover and remodeling activity of bone tissues. As remodeling is an essential part of bone regeneration and osseointegration, there has been some concern expressed regarding the capacity of peri-implant bone to incorporate implants inserted under bisphosphonate therapy. Controlled clinical trials have reported implant survival rates of 85.7%-100% in patients taking oral bisphosphonates55, 56 and of 100% for those receiving intravenous bisphosphonates.57 Recent meta-analyses of studies assessing the impact of bisphosphonates on implant treatment concluded that there is insufficient evidence for a negative effect of bisphosphonates on implant survival.58, 59 Besides the effect on implant survival, another aspect of the long-term use of antiresorptive agents is the risk of developing a medication-related necrosis of the jaw.60, 61 Medication-related necrosis of the jaw can be triggered by intra-oral surgical interventions and by bacterial invasion from odontogenic infectious lesions,62 as well as through pressure ulcers resulting from poorly fitting removable dentures.63 Triggering of the onset of medication-related necrosis of the jaw during the insertion of dental implants or through the occurrence of peri-implant infections during follow-up under antiresorptive medication is therefore a significant concern,64-66 and most often requires rather invasive measures for management (Figure 2A-G). The prevalence of medication-related necrosis of the jaw has been considered to depend in part on the route and frequency of bisphosphonate administration, with oral bisphosphonates presenting a lower risk for medication-related necrosis of the jaw than intravenous bisphosphonates. More recent reviews suggest that it is not the route of administration but the dosage of antiresorptive medication that affects the prevalence of medication-related necrosis of the jaw.59 The evidence reported for the occurrence of implant-related medication-related necrosis of the jaw under therapy with either bisphosphonates or denosumab is largely based on case reports64, 67-75 or retrospective case series.63, 76-84 In these reports, the number of cases reported for implant-related medication-related necrosis of the jaw in patients taking oral bisphosphonates is almost as high (n = 74) as in patients receiving intravenous bisphosphonates or denosumab (n = 84), suggesting that it is not the route of administration that is critical for the occurrence of implant-related medication-related necrosis of the jaw. Conversely, a number of case reports and case series reporting on implant treatment with concurrent oral bisphosphonate therapy did not find any cases of medication-related necrosis of the jaw in the patients studied.55, 65, 85-95 The existing level of evidence for an association between implant treatment and the occurrence of medication-related necrosis of the jaw under antiresorptive therapy remains low and needs to be substantiated by appropriately designed randomized controlled trials. Nevertheless, the overall number of reported cases of implant-associated medication-related necrosis of the jaw suggests that antiresorptive drugs need to be considered as a risk factor96 and explained to patients97 prior to the start of the treatment, as part of collecting informed consent. Despite the potential hazards of implant-associated medication-related necrosis of the jaw, implants can help to reduce the occurrence of medication-related necrosis of the jaw, for example, in edentulous patients under antiresorptive drugs by avoiding pressure ulcers resulting from poorly fitting dentures. Therefore, multiple factors need to be considered to inform a balanced decision on whether a patient with antiresorptive drugs is eligible for implant therapy (Table 2). If the majority of these factors indicate a low to moderate risk, implant therapy may also be a valid option in patients with antiresorptive medication. When oral surgical procedures are planned in patients with antiresorptive medication, antibiotic prophylaxis is recommended.98, 99 The ideal protocol for administration of antibiotics has not yet been defined. A clear recommendation is given for preoperative antibiotic coverage,100 however, the dosage and duration of postoperative continuation of antibiotic therapy remain to be determined. Adherence to national guidelines (if available) for the perioperative management of patients with antiresorptive medication is strongly advised. Diabetes mellitus is characterized by a lack of insulin secretion as a result of the loss of insulin-producing beta cells in the Langerhans islands of the pancreas (type 1) or by impaired insulin function because of the failure of insulin receptors to appropriately respond to the stimulation by insulin in the periphery (type 2). This results in constantly elevated blood glucose levels in people with diabetes, which leads to nonenzymatic glycation of numerous proteins to produce advanced glycation end products. An elevated level of advanced glycation end products leads to increased expression and activation of receptors for advanced glycation end products. These receptors are present on many cells (eg, endothelial cells, smooth muscle cells, fibroblasts, and mesanglial cells). Their activation mediates inflammatory reactions, which are considered to be responsible for alterations in the microvasculature and thereby can account for diabetic angiopathy.101 Interaction of advanced glycation end products with receptors for advanced glycation end products on macrophages is considered to be associated with macrophage dysfunction, leading to impaired wound healing in patients with diabetes.102 Moreover, bone regeneration is directly impaired on a molecular level in people with diabetes.103 Clinically, poor glycemic control has been shown to negatively affect the balance of bone growth factors in the peri-implant fluid during implant healing.104 Deterioration of vascularity in conjunction with a less efficient immunologic defense and a decreased regenerative capacity of peri-implant bone may compromise the success of implant treatment in patients with diabetes considerably. The effect of diabetes on implant success and the maintenance of peri-implant tissues has therefore been subject to research for more than 20 years. Numerous reviews have analyzed this relationship.105-115 A recent meta-analysis of 14 controlled clinical trials demonstrated that the risk ratio for implant loss between patients with and without diabetes was 1.07 (95% confidence interval 0.08-1.44), without a significant difference between the groups (P = .65).109 Failure to show an association between the existence of diabetes and an increased loss of dental implants is in line with previous reviews.20, 108, 113, 114, 116 The level of glycemic control as assessed by HbA1c appears to have no effect on implant survival rates, although patients with diabetes have demonstrated a compromised process of implant integration.104, 113, 117-119 Moreover, a recent consensus paper reported only inconclusive evidence for diabetes as a risk factor for peri-implantitis.5 While implant loss and peri-implant tissue health are obviously not affected by the presence of diabetes as such, management of the disease may play a role in the maintenance of peri-implant tissue health. A number of reports and systematic reviews have shown that patients with diabetes and poor glycemic control have an increased risk of peri-implantitis and associated peri-implant bone loss.76, 112, 120 This has been reported to become obvious at 2 years of follow-up compared with healthy individuals.107 However, when HbA1c is within the physiological range and oral hygiene is appropriate, the levels of inflammation have been shown to be reduced to those of healthy patients.121 The prophylactic use of antibiotics in oral surgical procedures in patients with diabetes is still controversial. Data from the scarcely available clinical studies favor the use of antibiotics but the evidence for their benefit is still low.122 The immune system is an indispensable part of tissue healing and repair. This holds true also for bone tissue, where pro-inflammatory cytokines are critical, not only for triggering regeneration but also for orchestrating subsequent bone remodeling.123 Moreover, both nonspecific and specific immune responses are crucial for the defense against bacterial invasion following surgery, as well as during the period of restoration and long-term usage. Immune deficiency can thus be critical for integration of dental implants and for the maintenance of peri-implant tissue health. Immune deficiency can result from a large number of conditions. With the exception of very rare innate immune defects, immune deficiencies are mostly acquired in nature. The nonspecific immune response can be affected by medications (immunosuppression/chemotherapy) and metabolic diseases (eg, diabetes mellitus), or because of chronic malnutrition. Specific immunity can also be reduced by immunosuppressive medication, as well as by hematological diseases and lymphotropic viruses (eg, HIV). Iatrogenic immunosuppression as a result of medications is probably the most frequent cause of immune deficiency in dental implant patients. A major indication for deliberate suppression of the immune response is organ transplantation. Organ transplant patients are treated with a combination of drugs that aim to reduce the proliferation of T-cells and to decrease the number of antigen-presenting cells to avoid rejection of the transplanted organ. Commonly, a combination of monoclonal antibody therapy, inhibitors of that and drugs with of is During the drug are high to immune after which are reduced for maintenance of interventions should not be planned during the of immune The effect of immunosuppression on the success of implant treatment in organ transplant patients has rarely been indicate that the peri-implant bone in a clinical information from a case series on patients with liver reported 100% success after Moreover, two prospective controlled studies found no significant difference in implant survival rates between organ transplant patients and after 1 and years of results without significant differences between groups have also been reported for clinical peri-implant soft tissue and for the of peri-implant The available evidence remains but suggests that the clinical results of implant treatment are and not significantly affected by immunosuppressive drugs used by organ transplant patients. of diseases in which immunosuppressive medication is used is the of diseases. The most for daily clinical are diseases, Syndrome, and disease, as well as conditions of oral and such as oral and systemic with oral or conditions that may largely cause local while such as or disease, may be of concern because of the systemic immunosuppressive medications immunosuppression in and in disease is by a combination of drugs, such as monoclonal against necrosis and drugs are a of agents that include and which are also used for immunosuppression in organ transplant diseases are characterized by and of clinical leading to a level of treatment during their This should be in when treatment for these patients. many patients have medication, the negative of this with regard to bone such as osteoporosis and decreased bone also be taken into osteoporosis is considered to be present at of ≥ These patients should be explored for receiving antiresorptive medication to avoid the There is very information available regarding patients with receiving dental implants. A retrospective evaluation of patients with an implant success of after The success rates but between patients with only and those with tissue diseases The stability of marginal bone by the medication drugs drugs and corticosteroids). The existence of tissue diseases was associated with a significant in peri-implant bone loss and higher bleeding indices compared with patients with an increased of peri-implant tissues to The of authors when examining a smaller cohort of patients with Moreover, a retrospective analysis of a cohort of patients did not identify as a significant risk factor for implant However, an of and systemic may these patients more to marginal peri-implant thus a maintenance The results available for patients with disease are Two cross-sectional analyses and one evaluation of cohorts of were by the examining early and implant loss and the role of implant the study one of the cross-sectional analyses identified a significant association between disease and implant the other cross-sectional study However, the of this is to as the number of patients in this cohort with disease was not diseases with oral Syndrome, systemic and oral in conjunction with dental implants, have largely been reported at an level for almost In and systemic were subject to early case reports years is considered to be critical for implant survival and not only as a result of medication, but more so because of leading to increased and bleeding as well as a higher frequency of As a result of the oral and patients with are often unable to removable and can benefit significantly from implant The level of evidence for the effect of on the success of implant treatment is Two case series and case reports provide into 17 patients with a of 99 implants, with 10 implants after years of Two recent retrospective cohort studies reported success rates of and soft tissues a higher but insignificant in the of patients with compared with healthy The existing thus suggests that implants in patients with are not significantly compromised by either the underlying disease or medication. The for peri-implant in these patients the elevated around in patients with Syndrome, and needs during is a disease associated with general of tissues resulting in reduced with subsequent with and dental has been reported in conjunction with dental implants on an level in individual and for two cases as

Introduction For COVID-19 and Long COVID, determining the highest-risk subgroups, particularly in the context of compound pressures such as influenza and cardiovascular disease (CVD), may identify effective interventions to prevent adverse health outcomes, and inform public health and policy decisions. Methods Using national, linked electronic health records for England (NHS England Secure Data Environment: via CVD-COVID-UK/COVID-IMPACT Consortium), we studied individuals with COVID-19 and Long COVID from January 2020 to February 2023. We compared all-cause hospitalisation and mortality in unmatched and matched cohort analyses, by prior CVD, high CVD risk (by QRISK2), COVID-19 and influenza vaccination status, and prescription of CVD preventive therapies. We investigated potential impact of targeted vaccination and CVD prevention strategies on mortality and hospitalisations by calculating population preventable fractions. Results We identified 17,373,850 individuals with COVID-19 [54.4% female; mean age 38.8 years; COVID-19 vaccination ≥2 doses:50.0%, influenza vaccination (≥1 dose):27.8%; mean follow-up 1.28 years] and 301,115 with Long Covid [61.8% female; mean age 46.0 years; COVID-19 vaccination ≥2 doses:66.4%, influenza vaccination:33.1%; mean follow-up 1.1 years]. Hospitalisation and mortality rates were 15.3% and 2.0% in COVID-19 (Long COVID rate 1.3%) and 16.8% and 1.4% in Long COVID, respectively. Adjusted risk of mortality and hospitalisation were reduced with COVID-19 vaccination ≥2 doses (COVID-19:HR 0.36, 95% CI 0.34-0.38 and 0.69, 0.68-0.69; Long COVID:0.44, 0.42-0.47 and 0.90, 0.89-0.91). With influenza vaccination, mortality was reduced, but not hospitalisation (COVID-19: 0.86, 0.85-0.86 and HR 1.01, 1.01-1.01, and Long COVID: 0.72, 0.67-0.76, and 1.05, 1.03-1.07), with greatest effect in those with prior CVD and high CVD risk. Mortality and hospitalisation were also reduced by CVD prevention in those with CVD, e.g. anticoagulants- COVID-19: 0.69, 0.69-0.70 and 0.92, 0.91-0.93; Long Covid: 0.59, 0.54-0.64, and 0.88, 0.84-0.92. COVID-19 vaccination, influenza vaccination and CVD drugs (Anticoagulants) averted 101117 of 193598, 2138 of 4017 and 16573 of 36847 preventable deaths among individuals after COVID-19, and 875 of 1189, 65 of 127 and 507 of 1007 preventable deaths among those with Long COVID, particularly in people with CVD. Conclusions Prior CVD and high CVD risk are associated with increased hospitalisation and mortality risk in people with COVID-19 and Long COVID. Targeted improvement in COVID-19 vaccination and CVD prevention, especially in those with CVD are priority interventions in pandemics to avoid excess hospitalisation and mortality.Baseline Characteristics and OutcomesHospitalisation/mortality by COVID vaccn

Seminal epidemiological studies led by Barker, Hales and collaborators identifying links between low birth weight and subsequent risk of traditionally adult-onset diseases such as cardiovascular disease and type 2 diabetes led to the concept of what is now termed the Developmental Origins of Health and Disease (DOHaD). This suggests that suboptimal exposures in early life (including the in utero period) permanently influence the structure, physiology, biochemistry and molecular biology of our organ systems and therefore our long-term health. Although the initial epidemiological observations almost 40 years ago focussed on the consequences of nutrient restriction during early life on long-term cardiometabolic health, the DOHaD field has now established a much broader spectrum of suboptimal exposures (including chemicals and environmental toxins) that affect a wide range of health outcomes (including certain forms of cancer and mental health). Epigenetic processes are thought to play an important mechanistic role in mediating the effects of a suboptimal in utero environment on long-term health. This includes changes in DNA methylation and histone modifications that regulate gene expression without affecting the DNA sequence. This special issue focuses on current knowledge on the impact of chemical exposures, such as heavy metals and endocrine disruptors, on the epigenome and long-term health outcomes, including mental health disorders, cardiovascular and neurodegenerative diseases.

COVID-19 severity, rather than sex or age, predicts SARS-CoV-2 kinetics, and SARS-CoV-2 viral load from lower respiratory tract specimens may predict severe disease days before clinical deterioration for COVID-19 patients.

The triumph of vaccination programs requires the modification of human behavior, which in turn, needs an understanding of knowledge, attitudes, and practices (KAPs) regarding vaccine and vaccination. This paper aimed to investigate the COVID-19 vaccine and vaccination KAPs of the teachers. Following a quantitative correlation research design, 2272 K to 12 teachers from Mindanao, Philippines were surveyed using an adapted instrument. The data collected were treated using descriptive statistics, Chi-square, t-test for independent samples, ANOVA, Point Biserial Correlation, and Pearson r. The result shows that most teachers perceive themselves as knowledgeable, possess desirable attitudes, and demonstrate favorable practices toward COVID-19 vaccine and vaccination. It was further found that COVID-19 vaccine and vaccination knowledge significantly differed across gender while both attitudes and practices significantly differed across age, gender, monthly income, and teaching experience. Hence, future policies and measures to improve knowledge, attitudes, and practices should be developed targeting samples with these characteristics. Lastly, the result reveals that COVID-19 vaccine and vaccination knowledge influence attitudes and practices. Thus, to increase desirable attitudes and favorable practices, government officials and concerned groups must promote COVID-19 vaccine and vaccination knowledge.

Targeting the Gut Microbiota in Coronavirus Disease 2019: Hype or Hope?

The initial observations of David Barker, popularly known as the “Barker hypothesis” or “developmental origins of health and disease,” show that being born with low birth weight, as a result of intrauterine growth restriction produced by maternal undernutrition, is associated with a number of chronic diseases later in life [1]. Subsequently, studies show that it is not just intrauterine growth restriction, but also exposure to any other adverse factor during fetal and/or early postnatal development that can increase susceptibility to a number of chronic diseases later in life including cardiovascular and renal disease, hypertension, type 2 diabetes, certain forms of cancer, osteoporosis, Parkinson's disease, dementia, and polycystic ovary syndrome [2–4]. Over 346 million people worldwide have diabetes, and according to the estimates of the World Health Organization, the prevalence of type 2 diabetes will double by the year 2030 [5]. Similarly, the prevalence of obesity has reached alarming levels. There are 1.5 billion adults, 20 years of age and older, who are overweight. Of those, 200 million men and nearly 300 million women are obese [6]. As a result of this growing prevalence of type 2 diabetes and obesity, more and more women of child-bearing age are either obese and/or diabetic during pregnancy. Given that maternal health has a significant impact on the long-term health of the offspring, it is clear that both type 2 diabetes and obesity are not only a health concern for the mother, but also a growing concern for the generations to come. Thus, the importance of examining the impact of maternal overnutrition and diabetes on the long-term health of the offspring is paramount. Several experimental studies report a relationship between maternal overnutrition and health of the offspring in adulthood. Specifically, maternal body weight, overnutrition, or a high fat consumption during pregnancy is linked to the development of elements of the metabolic syndrome, cardiovascular and renal disease, hypertension, and cerebral dysfunction as well as type 2 diabetes and obesity themselves later in the life of the offspring [7–12]. However, the mechanisms by which type 2 diabetes and obesity lead to the development of chronic disease later in life remain unknown. The purpose of this issue is to compile and provide a forum for the discussion of the latest data on the impact of maternal overnutrition and diabetes on the long-term (metabolic) health of the offspring. The current issue presents 5 clinical research papers as well as 7 review articles. The following is a summary of major points and findings presented in these papers. In overweight/obese mothers, greater % kcal from sweets early in pregnancy is the strongest, independent predictor of higher weight for gestational age at birth as well as after 6 months and higher odds of fetal macrosomia, suggesting that mothers' eating behaviors during pregnancy may have a lasting effect on child weight. In nondiabetic women, maternal glucose levels correlate with the extent and distribution of fetal adiposity and birth weight. In the Jerusalem perinatal study (a cohort of over 92,000 births), offspring of mothers with gestational diabetes have higher body mass index and systolic and diastolic blood pressure at 17 years of age compared with offspring of mothers with no gestational diabetes. These data suggest an association between maternal glycemia and cardiometabolic outcomes in the offspring. Interestingly, no association between cardiac function in offspring of type 1 diabetic mothers at 7-8 years of age and maternal glycemic control was found. Whether the cardiac phenotype takes longer to develop in this cohort may need to be examined. At the age of 3 years, offspring of type 1 diabetic mothers were characterized by a delay in cortical evoked responses in both visual and somatosensory systems, suggesting a potential association between maternal glycemia and brain maturation in the offspring. The 7 review articles all provide a comprehensive summary of some of the mechanisms underlying the developmental programming of metabolic syndrome, cardiovascular disease, and obesity later in the life of the offspring. Interestingly, similar mechanisms seem to contribute to different phenotypic outcomes regardless of what the insult was during early development. Specific emphasis is given to the importance of epigenetic changes induced by the maternal environment in predicting later adversity. In summary, this special issue highlights the fact that maternal health plays a significant role in determining as well as predicating the health of the offspring later in their life. Future studies are warranted to specifically examine the mechanisms by which the perturbation of the in utero environment may translate into a health risk in the offspring. Christine Maric-Bilkan Michael Symonds Susan Ozanne Barbara T. Alexander

Exploration of potential risk factors for COVID-19 severity in patients participating in oncology clinical trials

IntroductionCOVID-19 vaccination is crucial for vulnerable people with underlying chronic conditions such as Alzheimer’s disease and related dementias (ADRD) and mild cognitive impairment (MCI). These individuals face unique challenges, including...

Should women undergoing in vitro fertilization treatment or who are in the first trimester of pregnancy be vaccinated immediately against COVID-19

<h3>Context:</h3> Mass vaccination serves as a potential solution to combat the Coronavirus disease 2019 (COVID-19) pandemic, with vaccine hesitancy being a recognized impediment. Collection of data defining the characteristics of healthcare worker (HCW) attitudes towards the vaccine can provide insight into vaccine hesitancy. <h3>Objective:</h3> To determine HCWs’ attitudes regarding the COVID-19 vaccination and reasons for vaccine hesitancy. <h3>Study Design and Analysis:</h3> This cross-sectional study surveyed the attitudes of HCWs in Michigan using three-point agree/disagree scale questions. t-test and analysis of variance were used to measure HCWs’ attitudes towards the COVID-19 virus and vaccines. <h3>Population studied:</h3> 120 HCWs from Isabella, Saginaw, Sanilac, and Wayne counties in Michigan. <h3>Results:</h3> Most HCWs received (95.9%) and recommended (98.3%) the COVID-19 vaccine. The top three factors that HCWs cited for recommending a COVID-19 vaccine to a patient are: 1) Efficacy of the vaccine, 2) Current exposure to patients with active COVID-19 infection and risk of virus spread, and 3) Safety of vaccine and long-term follow-up. Being a female HCW (P=0.01) or being a HCW outside of the 55–64 years age range (P=0.036) was associated with increased concern of contracting COVID-19. Regarding the COVID-19 vaccines, our data demonstrated that: 1) HCWs who specialized in family medicine (P=0.028) were more likely to agree that there was adequate testing compared to those who did not specialize in family medicine; 2) White HCWs (P=0.024) were less concerned with the speed of development compared to non-white HCWs; 3) Of all age groups, HCWs aged 55-64 years (P=0.02) were the least concerned about side effects 4) Of all provider types, physicians (P=0.017) were the least concerned about long-term effects. <h3>Conclusion:</h3> Gender, age, ethnicity, provider type, and medical specialty showed statistically significant differences among attitudes towards the COVID-19 virus and vaccines. Vaccine hesitancy among HCWs can have negative effects on their patients. Focusing educational efforts on HCW demographics who are more likely to have negative attitudes can potentially decrease vaccine hesitancy.

Association Between Collagenous and Lymphocytic Colitis and Risk of Severe Coronavirus Disease 2019