Usefulness of the PARIS Score to Evaluate the Ischemic-hemorrhagic Net Benefit With Ticagrelor and Prasugrel After an Acute Coronary Syndrome

Introduction and objectives

The PARIS score allows combined stratification of ischemic and hemorrhagic risk in patients with ischemic heart disease treated with coronary stenting and dual antiplatelet therapy (DAPT). Its usefulness in patients with acute coronary syndrome (ACS) treated with ticagrelor or prasugrel is unknown. We investigated this issue in an international registry.

Real world experience with teriflunomide in multiple sclerosis: the TER-Italy study

Journal of Neurology - To identify baseline factors associated with disease activity in patients with relapsing–remitting multiple sclerosis (RRMS) under teriflunomide treatment. This was an...     

The Love Addiction Inventory: Preliminary Findings of the Development Process and Psychometric Characteristics

International Journal of Mental Health and Addiction - Although the existence of dysfunctional love relationships is well known and the term “love addiction” dates back to the 1970s,...     

Methodological quality of studies evaluating the burden of drug-resistant infections in humans due to the WHO Global Antimicrobial Resistance Surveillance System target bacteria

BackgroundThe health impact of antimicrobial resistance (AMR) has not been included in the Global Burden of Disease (GBD) report, as reliable data have been lacking. AMR burden estimates have been derived from models combining incidence and/or prevalence data from national and/or international surveillance systems and mortality estimates from clinical studies. Depending on utilized empirical data, statistical methodology and applied endpoints, the validity and reliability of results can differ substantially.ObjectivesWe assessed comprehensiveness, and internal and external validity of studies estimating the clinical impact of infections caused by the priority antibiotic resistant pathogens monitored by the WHO Global Antimicrobial Resistance Surveillance System.Data sourcesOvid MEDLINE, January 1950 to March 2019, In-Process and other non-indexed citations were searched.Study eligibility criteriaStudies reporting mortality, length of hospital stay, duration of the disease until remission and/or death, complications, hospital re-admissions, and follow-up beyond hospital discharge were eligible.MethodsThe literature was searched according to the Cochrane recommendations and reported according to Preferred Reporting Items for Systematic Reviews.ResultsTwo-hundred and eighty-six studies out of 3529 were eligible. Studies derived mainly from high-income countries (215, 75%) and relied on data from retrospective (226, 79%), single-centre (201, 70%), cohort studies (243, 85%). The health impact was mostly limited to all-cause mortality (128, 45%) with heterogeneity in timing of assessment; attributable length of hospital stay was seldom adjusted for pre-infection admission time and a few studies had enough follow-up for assessing long-term sequelae. Overall, adjustment for confounding has shown a substantial improvement. Data on health state definitions and duration of diseases are generally lacking, precluding calculation of disability-adjusted life years, critical for application of the GBD study methodology.ConclusionEfforts to improve harmonization, representativeness, quality of AMR surveillance data and cohort studies to determine AMR attributable mortality and morbidity are urgently required. Policy makers need accurate and detailed burden estimates to inform prioritization of resource allocation, and to select the most effective intervention strategies to halt the AMR crisis.     

Kohlschütter–Tönz Syndrome: Mutations in ROGDI and Evidence of Genetic Heterogeneity

Kohlschütter–Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by amelogenesis imperfecta, psychomotor delay or regression and seizures starting early in childhood. KTS was established as a distinct clinical entity after the first report by Kohlschütter in 1974, and to date, only a total of 20 pedigrees have been reported. The genetic etiology of KTS remained elusive until recently when mutations in ROGDI were independently identified in three unrelated families and in five likely related Druze families. Herein, we report a clinical and genetic study of 10 KTS families. By using a combination of whole exome sequencing, linkage analysis, and Sanger sequencing, we identify novel homozygous or compound heterozygous ROGDI mutations in five families, all presenting with a typical KTS phenotype. The other families, mostly presenting with additional atypical features, were negative for ROGDI mutations, suggesting genetic heterogeneity of atypical forms of the disease.     

Hemorheologic and hemostatic changes in long-standing insulin-dependent (type I) diabetic patients with peripheral and autonomic cardiovascular neuropathy

Summary Diabetic microangiopathy may be associated with the pathogenesis and progression of autonomic and peripheral neuropathy. In 17 long-standing type I diabetic patients with peripheral and autonomic cardiovascular neuropathy, several hemorheological and hemostatic alterations were found compared to 13 matched type I patients without neuropathy. In particular, increased plasma von Willebrand factor antigen (p<0.001), fibronectin (p<0.001) and fibrinogen (p<0.001) levels were demonstrated in neuropathic in comparison with non-neuropathic diabetic patients. Moreover negative correlations between these parameters and both motor and sensitive conduction velocity of median, sural and peroneal nerves were observed in diabetic patients with neuropathy. Higher blood viscosity (p<0.05 at shear-rate of 450 and 225 s⁻¹; p<0.01 at 90 s⁻¹; p<0.001 at 4.5 and 2.25 s⁻¹), plasma viscosity (p<0.001) and lower erythrocyte filtrability (p<0.001) were also found in neuropathic compared to non-neuropathic diabetics. Increased prevalence of retinopathy (p<0.01) and nephropathy (p<0.001) was finally reported in patients with autonomic and peripheral neuropathy. Microvascular disease may be involved in the development of neuropathy in long-term type I diabetes mellitus. This study was presented in part at the 23rd Annual Meeting of the European Association for the Study of Diabetes, Leipzig (GDR), 15–19 September 1987.     

Changing nutrient cycling in Lake Baikal,the world’s oldest lake

Lake Baikal, lying in a rift zone in southeastern Siberia, is the world''s oldest, deepest, and most voluminous lake that began to form over 30 million years ago. Cited as the “most outstanding example of a freshwater ecosystem” and designated a World Heritage Site in 1996 due to its high level of endemicity, the lake and its ecosystem have become increasingly threatened by both climate change and anthropogenic disturbance. Here, we present a record of nutrient cycling in the lake, derived from the silicon isotope composition of diatoms, which dominate aquatic primary productivity. Using historical records from the region, we assess the extent to which natural and anthropogenic factors have altered biogeochemical cycling in the lake over the last 2,000 y. We show that rates of nutrient supply from deep waters to the photic zone have dramatically increased since the mid-19th century in response to changing wind dynamics, reduced ice cover, and their associated impact on limnological processes in the lake. With stressors linked to untreated sewage and catchment development also now impacting the near-shore region of Lake Baikal, the resilience of the lake’s highly endemic ecosystem to ongoing and future disturbance is increasingly uncertain.

Ancient lakes have long been associated with both high levels of biodiversity and endemicity. However, they are also being threatened by anthropogenic forcings that have led to impacts ranging from the warming of lake waters (1), hydrological modifications (2), increases in aquatic toxicity (3), and declining endemic populations due to introductions of nonnative species (4). With global populations increasingly reliant on large and ancient lakes for ecosystem services, the biodiversity (5) and value of aquatic systems to society (6), particularly in ancient lake systems (7), are at risk. Lake Baikal (Russia) is an exceptional example of an ancient lake (Fig. 1). In addition to containing ∼20% of global surface freshwater, the lake is characterized by its high degree of biodiversity with over 2,500 flora and fauna, the majority of which are endemic (8). This has been attributed to the lake’s age and fully oxygenated water column, driven by seasonal overturning and deep water renewal (9, 10) that sustains an almost completely endemic deep water fauna (8).Open in a separate windowFig. 1.Location of Lake Baikal and its catchment (gray) together with the location of World Meteorological Organization station in Irkutsk, major catchment rivers (brown), coring sites (BAIK13-1, BAIK13-4), and sites providing additional data used in this study (BAIK13-7).Concerns exist over the future health of this unique ecosystem, amid evidence of extensive shoreline eutrophication (11, 12) and climate-induced shifts in primary productivity (13, 14). Together, these changes have impacted organisms ranging from sponges and gastropods to ciliates, flagellates, and algal communities (15). Given the likelihood of future anthropogenic disturbance on Lake Baikal, further disrupting productivity exchanges through the lake’s food web, there is a need to place these contemporary observations into their historical setting. In Lake Baikal, we have evidence that algal communities have undergone rapid multidecadal to multicentennial timescale changes over the last 2,000 y (16). However, there is a need to also gain a clearer insight into how biogeochemical and nutrient cycling has altered over the same timescale, both to contextualize natural and anthropogenic drivers of change and to understand the susceptibility of the lake’s ecosystem to further alteration under different climate states (17). Annual primary productivity in Lake Baikal is ultimately regulated by photic zone nutrient availability, in addition to ice/snow cover, which regulates light availability for photosynthesis (10, 18). Here, by analyzing the silicon isotope composition of diatom silica (δ³⁰Si_diatom), we show that nutrient supply to the surface waters of Lake Baikal has rapidly increased through the 20th and 21st centuries coincident with increased wind-driven Ekman transport and reduced ice cover. These changes in photic zone nutrient availability have the potential to alter resource competition and prey–predator interactions across the lake (15, 19).