To provide a detailed genomic-epidemiological description of a complex multi-ward SARS-CoV-2 outbreak, which originated in the crowded emergency department (ED) in our hospital during the third wave ...of the COVID-19 pandemic, and was elucidated promptly by local whole-genome sequencing (WGS).
SARS-CoV-2 was detected by reverse transcriptase real-time polymerase chain reaction on viral RNA extracted from nasopharyngeal swabs. WGS was performed using an Oxford MinION Mk1C instrument following the ARTIC v3 sequencing protocol. High-quality consensus genomes were assembled with the artic-ncov2019 bioinformatics pipeline and viral phylogenetic trees were built, inferred by maximum-likelihood. Clusters were defined using a threshold of 0–1 single nucleotide polymorphisms (SNPs) between epidemiologically linked sequences.
In April 2021, outbreaks of COVID-19 were declared on two wards at University Hospital Limerick after 4 healthcare-associated SARS-CoV-2 infections were detected by post-admission surveillance testing. Contact tracing identified 12 further connected cases; all with direct or indirect links to the ED ‘COVID Zone’. All sequences were assigned to the Pangolin B.1.1.7 lineage by WGS, and SNP-level analysis revealed two distinct but simultaneous clusters of infections. Repeated transmission in the ED was demonstrated, involving patients accommodated on trolleys in crowded areas, resulting in multiple generations of infections across three inpatient hospital wards and subsequently to the local community. These findings informed mitigation efforts to prevent cross-transmission in the ED.
Cross-transmission of SARS-CoV-2 occurred repeatedly in an overcrowded emergency department. Viral WGS elucidated complex viral transmission networks in our hospital and informed infection, prevention and control practice.
Although benzodiazepines are invaluable in the treatment of anxiety disorders, they have some potential for abuse and may cause dependence or addiction. It is important to distinguish between ...addiction to and normal physical dependence on benzodiazepines. Intentional abusers of benzodiazepines usually have other substance abuse problems. Benzodiazepines are usually a secondary drug of abuse-used mainly to augment the high received from another drug or to offset the adverse effects of other drugs. Few cases of addiction arise from legitimate use of benzodiazepines. Pharmacologic dependence, a predictable and natural adaptation of a body system long accustomed to the presence of a drug, may occur in patients taking therapeutic doses of benzodiazepines. However, this dependence, which generally manifests itself in withdrawal symptoms upon the abrupt discontinuation of the medication, may be controlled and ended through dose tapering, medication switching, and/or medication augmentation. Due to the chronic nature of anxiety, long-term low-dose benzodiazepine treatment may be necessary for some patients; this continuation of treatment should not be considered abuse or addiction.
OBJECTIVE: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during ...cue-induced craving in humans. METHOD: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions. RESULTS: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the nondrug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). CONCLUSIONS: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.
Addictive disorders are partly heritable, chronic, relapsing conditions that account for a tremendous disease burden. Currently available addiction pharmacotherapies are only moderately successful, ...continue to be viewed with considerable scepticism outside the scientific community and have not become widely adopted as treatments. More effective medical treatments are needed to transform addiction treatment and address currently unmet medical needs. Emerging evidence from alcoholism research suggests that no single advance can be expected to fundamentally change treatment outcomes. Rather, studies of opioid, corticotropin-releasing factor, GABA and serotonin systems suggest that incremental advances in treatment outcomes will result from an improved understanding of the genetic heterogeneity among patients with alcohol addiction, and the development of personalized treatments.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Laboratory models, both animal and human, have made enormous contributions to our understanding of addiction. For addictive disorders, animal models have the great advantage of possessing both face ...validity and a significant degree of predictive validity, already demonstrated. Another important advantage to this field is the ability of reciprocal interplay between preclinical and clinical experiments. These models have made important contributions to the development of medications to treat addictive disorders and will likely result in even more advances in the future. Human laboratory models have gone beyond data obtained from patient histories and enabled investigators to make direct observations of human drug self-administration and test the effects of putative medications on this behavior. This review examines in detail some animal and human models that have led not only to important theories of addiction mechanisms but also to medications shown to be effective in the clinic.
Abstract
Background
Acute coronary syndrome (ACS) is one of the leading causes of cardiovascular related deaths for adults in US. The clinical presentation of ACS is broad, which includes ST-segment ...elevation myocardial infarction (STEMI), non-ST-segment elevation MI (NSTEMI), and unstable angina (UA). There are limited data around contemporary real-world treatment landscape, therefore it is critical to understand the treatment pattern of the US ACS patients in the real-world setting.
Purpose
This study evaluated antiplatelet therapy (APT) treatment patterns among US patients without atrial fibrillation or oral anticoagulants (OACs) who experienced their first hospitalized ACS event during observation period.
Methods
The Optum® de-identified Electronic Health Record dataset from January 2018 through December 2020 was used for this study. Adult patients with an inpatient primary diagnosis of ACS during the index period were identified by ICD10 codes. The date of admission for the first ACS hospitalization was the index date. Patients with atrial fibrillation diagnosis or a record for OAC use before index date and during hospitalization were excluded. ACS subgroups and percutaneous coronary intervention (PCI) status were assessed during index hospitalization; patient characteristics and in-hospital antiplatelet treatment type were also evaluated.
Results
Among 63,767 patients included in this study, the mean age was 64.1 and 40.5% were female; 89.2% were treated with APT. For those patients not treated with APT, majority were treated with parental anticoagulants. Among 89.2% APT treated patients, 52.7% were initiated on dual antiplatelet therapy (DAPT), 27.4% were initiated on single antiplatelet therapy (SAPT), and 9.1% switched between different DAPT regimens. The top three used DAPT were aspirin+clopidogrel (30.5%), aspirin+ticagrelor (18.9%) and aspirin+prasugrel (2.6%); the most used SAPT were aspirin (22.6%), clopidogrel (2.6%), and ticagrelor (2.0%). For ACS subtypes, 26.3% were diagnosed as STEMI, 62.9% were NSTEMI, and 10.8% were UA; of them, 45.0% had PCI procedure within 30-days before or after the index date. ACS patients with PCI procedure had the highest APT treatment rate (95.2%) and highest DAPT treatment rate (70.6%). Across ACS subtypes, patients hospitalized for STEMI had the highest usage of aspirin+ticagrelor (34.5%), whereas patients hospitalized for NSTEMI had the highest usage of aspirin+clopidogrel (34.7%).
Conclusion
We observed wide variability in APT treatment across STEMI vs. NSTEMI and +/-PCI. Only 38.1% of non-PCI treated ACS patients received DAPT despite current guidelines. Further analyses are planned to explore the varying APT (and/or anticoagulant) regimens.Figure 1Figure 2
Pharmacotherapeutic options for multiple sclerosis (MS)-related fatigue are limited. Thirty patients were randomly assigned to aspirin (ASA) 1,300 mg/day or placebo in a double-blind crossover study. ...Results favored ASA for the main clinical outcomes: Modified Fatigue Impact Scale scores (p = 0.043) and treatment preference (p = 0.012). There were no significant adverse effects. The results warrant further study and support a role for ASA-influenced mechanisms, perhaps immunologic, in the generation of MS-related chronic fatigue.
There are no established treatments for patients with acute, severe neurological deficits caused by multiple sclerosis or other inflammatory demyelinating diseases of the central nervous system who ...fail to recover after treatment with high‐dose corticosteroids. We conducted a randomized, sham‐controlled, double‐masked study of plasma exchange without concomitant immunosuppressive treatment in patients with recently acquired, severe neurological deficits resulting from attacks of inflammatory demyelinating disease, who failed to recover after treatment with intravenous corticosteroids. Patients who did not achieve moderate or greater improvement after the first treatment phase crossed over to the opposite treatment. Moderate or greater improvement in neurological disability occurred during 8 of 19 (42.1%) courses of active treatment compared with 1 of 17 (5.9%) courses of sham treatment. The primary analysis was positive. Improvement occurred early in the course of treatment, and was sustained on follow‐up. However, 4 of the patients who responded to the active treatment experienced new attacks of demyelinating disease during 6 months of follow‐up. Moderate or greater improvement occurred during follow‐up in only 2 of 13 patients who failed to improve during the treatment phase. Plasma exchange leads to functionally important neurological recovery in an important proportion of severely disabled patients with acute attacks of idiopathic inflammatory demyelinating disease.
Objectives: To determine risk factors for sudden cardiac death and the role of diabetic autonomic neuropathy (DAN) in the Rochester diabetic neuropathy study (RDNS) Methods: Associations between ...diabetic and cardiovascular complications, including DAN, and the risk of sudden cardiac death were studied among 462 diabetic patients (151 type 1) enrolled in the RDNS. Medical records, death certificates, and necropsy reports were assessed for causes of sudden cardiac death. Results: 21 cases of sudden cardiac death were identified over 15 years of follow up. In bivariate analysis of risk covariates, the following were significant: ECG 1 (evolving and previous myocardial infarctions): hazard ratio (HR) = 4.4 (95% confidence interval (CI), 1.6 to 12.1), p = 0.004; ECG 2 (bundle branch block or pacing): HR = 8.6 (2.9 to 25.4), p<0.001; ECG 1 or ECG 2: HR = 4.2 (1.3 to 13.4), p = 0.014; and nephropathy stage: HR = 2.1 (1.3 to 3.4), p = 0.002. Adjusting for ECG 1 or ECG 2, autonomic scores, QTc interval, high density lipoprotein (HDL) cholesterol, 24 hour microalbuminuria, and 24 hour total proteinuria were significant. However, adjusting for nephropathy, none of the autonomic indices, QTc interval, HDL cholesterol, microalbuminuria, or total proteinuria was significant. At necropsy, all patients with sudden cardiac death had coronary artery or myocardial disease. Conclusions: Sudden cardiac death was correlated with atherosclerotic heart disease and nephropathy, and to a lesser degree with DAN and HDL cholesterol. Although DAN is associated with sudden cardiac death, it is unlikely to be its primary cause.
Alcohol and the athlete O'Brien, C P; Lyons, F
Sports medicine (Auckland),
05/2000, Letnik:
29, Številka:
5
Journal Article
Recenzirano
Alcohol and the athlete have been linked together since ancient times. It continues to be the most commonly consumed drug among the athletic population. Alcohol use carries significant potential ...adverse effects for both the health and welfare of the individual. It is suggested that alcohol related problems may be more prevalent in the athletic population due to their risk taking mentality and the age profile of athletes (18- to 24-year-old males). Alcohol consumption also appears to have a causative effect in sports related injury, with an injury incidence of 54.8% in drinkers compared with 23.5% in nondrinkers (p < 0.005). This may be due in part to the hangover effect of alcohol consumption, which has been shown to reduce athletic performance by 11.4%. Alcohol is a potentially lethal drug and is a banned substance for certain Olympic sports. Education is the cornerstone for appropriate social use of this drug. Athletes and coaches need to be aware of the sports related adverse effects of alcohol consumption and its role in sports injury and poor physiological performance. It is recommended that alcohol should be avoided by the serious athlete.
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