Feline infectious peritonitis (FIP) continues to be one of the most researched infectious diseases of cats. The relatively high mortality of FIP, especially for younger cats from catteries and ...shelters, should be reason enough to stimulate such intense interest. However, it is the complexity of the disease and the grudging manner in which it yields its secrets that most fascinate researchers. Feline leukemia virus infection was conquered in less than two decades and the mysteries of feline immunodeficiency virus were largely unraveled in several years. After a half century, FIP remains one of the last important infections of cats for which we have no single diagnostic test, no vaccine and no definitive explanations for how virus and host interact to cause disease. How can a ubiquitous and largely non-pathogenic enteric coronavirus transform into a highly lethal pathogen? What are the interactions between host and virus that determine both disease form (wet or dry) and outcome (death or resistance)? Why is it so difficult, and perhaps impossible, to develop a vaccine for FIP? What role do genetics play in disease susceptibility? This review will explore research conducted over the last 5 years that attempts to answer these and other questions. Although much has been learned about FIP in the last 5 years, the ultimate answers remain for yet more studies.
This review is concerned with what has been learned about feline infectious peritonitis (FIP) diagnostics and therapeutics since the publication of an extensive overview of literature covering the ...period 1963–2009. Although progress has been made in both areas, obtaining a definitive diagnosis of FIP remains a problem for those veterinarians and/or cat owners who require absolute certainty. This review will cover both indirect and direct diagnostic tests for the disease and will emphasize their limitations, as well as their specificity and sensitivity. There is still no effective treatment for FIP, although there are both claims that such therapies exist and glimmers of hope coming from new therapies that are under research. FIP has also been identified in wild felids and FIP-like disease is now a growing problem among pet ferrets.
Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates ...during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro) with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for further development for important coronaviruses in animals and humans.
The bulk-filling of deep, wide dental cavities is faster and easier than traditional incremental restoration. However, the extent of cure at the bottom of the restoration should be carefully examined ...in combination with the polymerization contraction and gap formation that occur during the restorative procedure. The aim of this study, therefore, was to compare the depth of cure, polymerization contraction, and gap formation in bulk-fill resin composites with those of a conventional resin composite. To achieve this, the depth of cure was assessed in accordance with the International Organization for Standardization 4049 standard, and the polymerization contraction was determined using the bonded-disc method. The gap formation was measured at the dentin margin of Class II cavities. Five bulk-fill resin composites were investigated: two high-viscosity (Tetric EvoCeram Bulk Fill, SonicFill) and three low-viscosity (x-tra base, Venus Bulk Fill, SDR) materials. Compared with the conventional resin composite, the high-viscosity bulk-fill materials exhibited only a small increase (but significant for Tetric EvoCeram Bulk Fill) in depth of cure and polymerization contraction, whereas the low-viscosity bulk-fill materials produced a significantly larger depth of cure and polymerization contraction. Although most of the bulk-fill materials exhibited a gap formation similar to that of the conventional resin composite, two of the low-viscosity bulk-fill resin composites, x-tra base and Venus Bulk Fill, produced larger gaps.
Background
Use of proton pump inhibitors (PPIs) has been associated with cardiovascular disease amongst patients not on antiplatelet therapy. The associations of PPI use, duration and dose, with risk ...of first‐time ischemic stroke and myocardial infarction (MI) are poorly understood.
Methods
All Danish individuals with no prior history of MI or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI use and its dose and used multiple cause‐specific Cox regression and g‐formula methods to analyze long‐term use.
Results
Amongst 214 998 individuals, during a median follow‐up of 5.8 years, there were 7916 ischemic strokes and 5608 MIs. Current PPI exposure was associated with significantly higher rates of both ischemic stroke (Hazard ratio (HR) 1.13; 95% confidence interval (CI) 1.08–1.19) and MI (HR 1.31, CI 1.23–1.39) after adjusting for age, sex, comorbidities and concomitant medication. High‐dose PPI was associated with increased rates of ischemic stroke (HR 1.31, CI 1.21–1.42) and MI (HR 1.43, CI 1.30–1.57). Histamine H2 receptor antagonists (H2RAs) use was not significantly associated with ischemic stroke (HR 1.02, CI 0.84–1.24) or MI (HR 1.15, CI 0.92–1.43). Long‐term users of PPIs, compared with nonusers, had a 29% (CI 5%‐59%) greater absolute risk of ischemic stroke and a 36% (CI 7%‐73%) greater risk of MI within a 6‐month period.
Conclusion
Use of PPIs was associated with increased risks of first‐time ischemic stroke and MI, particularly amongst long‐term users and at high doses.
A family history of schizophrenia is the strongest single indicator of individual schizophrenia risk. Bipolar affective disorder and schizo-affective disorders have been documented to occur more ...frequently in parents and siblings of schizophrenia patients, but the familial occurrence of the broader range of mental illnesses and their role as confounders have not been studied in large population-based samples.
All people born in Denmark between 1955 and 1991 (1.74 million) were followed for the development of schizophrenia (9324 cases) during 28 million person-years at risk. Information of schizophrenia in cohort members and psychiatric history in parents and siblings was established through linkage with the Danish Psychiatric Central Register. Data were analysed using log-linear Poisson regression.
Schizophrenia was, as expected, strongly associated with schizophrenia and related disorders among first-degree relatives. However, almost any other psychiatric disorder among first-degree relatives increased the individual's risk of schizophrenia. The population attributable risk associated with psychiatric family history in general was 27.1% whereas family histories including schizophrenia only accounted for 6.0%. The general psychiatric family history was a confounder of the association between schizophrenia and urbanization of place of birth.
Clinically diagnosed schizophrenia is associated with a much broader range of mental disorders in first-degree relatives than previously reported. This may suggest risk haplotypes shared across many disorders and/or shared environmental factors clustering in families. Failure to take the broad range of psychiatric family history into account may bias results of all risk-factor studies of schizophrenia.
Background
The significance of chronic kidney disease on susceptibility to COVID‐19 and subsequent outcomes remains unaddressed.
Objective
To investigate the association of estimated glomerular ...filtration rate (eGFR) on risk of contracting COVID‐19 and subsequent adverse outcomes.
Methods
Rates of hospital‐diagnosed COVID‐19 were compared across strata of eGFR based on conditional logistic regression using a nested case–control framework with 1:4 matching of patients diagnosed with COVID‐19 with controls from the Danish general population on age, gender, diabetes and hypertension. Risk of subsequent severe COVID‐19 or death was assessed in a cohort study with comparisons across strata of eGFR based on adjusted Cox regression models with G‐computation of results to determine 60‐day risk standardized to the distribution of risk factors in the sample.
Results
Estimated glomerular filtration rate was inversely associated with rate of hospital‐diagnosed COVID‐19: eGFR 61–90 mL/min/1.73m2 HR 1.13 (95% CI 1.03–1.25), P = 0.011; eGFR 46–60 mL/min/1.73m2 HR 1.26 (95% CI 1.06–1.50), P = 0.008; eGFR 31–45 mL/min/1.73m2 HR 1.68 (95% CI 1.34–2.11), P < 0.001; and eGFR ≤ 30 mL/min/1.73m2 3.33 (95% CI 2.50–4.42), P < 0.001 (eGFR > 90 mL/min/1.73m2 as reference), and renal impairment was associated with progressive increase in standardized 60‐day risk of death or severe COVID‐19; eGFR > 90 mL/min/1.73m2 13.9% (95% CI 9.7–15.0); eGFR 90–61 mL/min/1.73m2 16.1% (95% CI 14.5–17.7); eGFR 46–60 mL/min/1.73m2 17.8% (95% CI 14.7–21.2); eGFR 31–45 mL/min/1.73m2 22.6% (95% CI 18.2–26.2); and eGFR ≤ 30 mL/min/1.73m2 23.6% (95% CI 18.1–29.1).
Conclusions
Renal insufficiency was associated with progressive increase in both rate of hospital‐diagnosed COVID‐19 and subsequent risk of adverse outcomes. Results underscore a possible vulnerability associated with impaired renal function in relation to COVID‐19.
Summary
Biopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, ...including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium Anti‐Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).
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