Change-points in antibiotic consumption in the community, European Union/European Economic Area, 1997-2017.

OBJECTIVES: Surveillance of antibiotic consumption in the community is of utmost importance to inform and evaluate control strategies. Data on two decades of antibiotic consumption in the community were collected from 30 EU/European Economic Area (EEA) countries. This article reviews temporal trends and the presence of abrupt changes in subgroups of relevance in antimicrobial stewardship. METHODS: For the period 1997-2017, data on yearly antibiotic consumption in the community, aggregated at the level of the active substance, were collected using the WHO ATC classification and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. We applied a range of non-linear mixed models to assess the presence of changes in the consumption of antibacterials for systemic use (ATC group J01) and eight antibiotic subgroups. RESULTS: For the majority of the studied groups, a country-specific change-point model provided the best fit. Depending on the antibiotic group/subgroup and on the country, change-points were spread out between 2000 and 2013. CONCLUSIONS: Due to the heterogeneity in antibiotic consumption in the community across EU/EEA countries, a country-specific change-point model provided the better fit. Given the limitations of this model, our recommendation for the included countries is to carefully interpret the country-specific results presented in this article and to use the tutorial included in this series to conduct their own change-point analysis when evaluating the impact of changes in regulations, public awareness campaigns, and other national interventions to improve antibiotic consumption in the community.

Safety and tolerability of ubrogepant following intermittent, high-frequency dosing: Randomized, placebo-controlled trial in healthy adults.

BACKGROUND: Ubrogepant is a novel, oral calcitonin gene-related peptide (CGRP) receptor antagonist in development for the acute treatment of migraine. This trial evaluated the safety and tolerability of ubrogepant, focusing on hepatic safety, when administered intermittently with high-frequency dosing to healthy participants. METHODS: In this phase 1, multicenter, double-blind, parallel-group trial, healthy adults (age 18-50 years) were randomized 1:1 to placebo or ubrogepant. Ubrogepant was dosed at 100 mg (2 × 50 mg tablets) on 2 consecutive days followed by 2 consecutive days of placebo, alternating for 8 weeks. Primary outcome measures were safety and tolerability. RESULTS: Of participants randomized (n = 518), 516 were included in the safety population (n = 260 placebo; n = 256 ubrogepant). Treatment-emergent adverse events were reported in 45% of placebo and 44% of ubrogepant participants. The most common was headache (10% placebo; 11% ubrogepant). Overall, seven cases of alanine aminotransferase and/or aspartate aminotransferase levels ≥ 3 × the upper limit of normal (five placebo, two ubrogepant) were reported and adjudicated by a panel of independent liver experts blinded to treatment. Four cases were judged unlikely related to treatment. Two cases (one placebo, one ubrogepant) were judged possibly related, and one (ubrogepant) probably related. Alanine aminotransferase increases to ≥ 3 × the upper limit of normal in the two ubrogepant cases (possibly or probably related) were transient and resolved with continued dosing; both cases were asymptomatic, with no concurrent bilirubin elevation. CONCLUSION: Ubrogepant was well tolerated following intermittent, high-frequency dosing in healthy participants, with no clinically relevant signal of hepatotoxicity. TRIAL REGISTRATION: NA.

Early clinical and echocardiographic outcomes after SAPIEN 3 transcatheter aortic valve replacement in inoperable, high-risk and intermediate-risk patients with aortic stenosis.

AIMS: Based on randomized trials using first-generation devices, transcatheter aortic valve replacement (TAVR) is well established in the treatment of high-risk (HR) patients with severe aortic stenosis (AS). To date, there is a paucity of adjudicated, prospective data evaluating outcomes with newer generation devices and in lower risk patients. We report early outcomes of a large, multicentre registry of inoperable, HR, and intermediate-risk (IR) patients undergoing treatment with the next-generation SAPIEN 3 transcatheter heart valve (THV). METHODS AND RESULTS: Patients with severe, symptomatic AS (583 high surgical risk or inoperable and 1078 IR) were enrolled in a multicentre, non-randomized registry at 57 sites in the USA and Canada. All patients received TAVR with the SAPIEN 3 system via transfemoral (n = 1443, 86.9%) and transapical or transaortic (n = 218, 13.1%) access routes. The rate of 30-day all-cause mortality was 2.2% in HR/inoperable patients [mean Society of Thoracic Surgeons (STS) score 8.7%] and 1.1% in IR patients (mean STS score 5.3%); cardiovascular mortality was 1.4 and 0.9%, respectively. In HR/inoperable patients, the 30-day rate of major/disabling stroke was 0.9%, major bleeding 14.0%, major vascular complications 5.1%, and requirement for permanent pacemaker 13.3%. In IR patients, the 30-day rate of major/disabling stroke was 1.0%, major bleeding 10.6%, major vascular complications 6.1%, and requirement for permanent pacemaker 10.1%. Mean overall Kansas City Cardiomyopathy Questionnaire score increased from 47.8 to 67.8 (HR/inoperable, P < 0.0001) and 54.7 to 74.0 (IR, P < 0.0001). Overall, paravalvular regurgitation at 30 days was none/trace in 55.9% of patients, mild in 40.7%, moderate in 3.4%, and severe in 0.0%. Mean gradients among patients with paired baseline and 30-day or discharge echocardiograms decreased from 45.8 mmHg at baseline to 11.4 mmHg at 30 days, while aortic valve area increased from 0.69 to 1.67 cm(2). CONCLUSIONS: The SAPIEN 3 THV system was associated with low rates of 30-day mortality and major/disabling stroke as well as low rates of moderate or severe paravalvular regurgitation. TRIAL REGISTRATION: ClinicalTrials.gov #NCT01314313.

Outcomes of a dedicated stent in coronary bifurcations with large side branches: A subanalysis of the randomized TRYTON bifurcation study.

OBJECTIVES: To examine the benefit of the Tryton dedicated side branch (SB) stent compared with provisional stenting in the treatment of complex bifurcation lesions involving large SBs. BACKGROUND: The TRYTON Trial was designed to evaluate the utility of a dedicated SB stent to treat true bifurcation lesions involving large (≥2.5 mm by visual estimation) SBs. Patient enrolled in the trial had smaller SB diameters than intended (59% SB ≤2.25 mm by Core Lab QCA). The TRYTON Trial did not meet its primary endpoint due to an increased rate of peri-procedural myocardial infarctions (MIs). METHODS: The TRYTON Trial randomized 704 patients to the Tryton SB stent with main vessel DES versus provisional SB treatment with main vessel DES. The rates of the primary end point of target vessel failure and the secondary powered end point of angiographic percent diameter stenosis in the SB at 9 months were assessed and compared between the two treatment strategies among patients with a SB ≥2.25 mm diameter at baseline determined by Core Lab QCA. RESULTS: Among the 704 patients enrolled in the TRYTON Trial, 289 patients (143 provisional and 146 Tryton stent; 41% of entire cohort) had a SB ≥2.25 mm. The primary end point of TVF was numerically lower in the Tryton group compared with the provisional group (11.3% vs. 15.6%, P = 0.38), and was within the non-inferiority margin. No difference among the rates of clinically driven target vessel revascularization (3.5% vs. 4.3% P = 0.77) or cardiac death (0% both groups) were seen. In-segment percent diameter stenosis of the SB was significantly lower in the Tryton group compared with the provisional group (30.4% vs. 40.6%, P = 0.004). CONCLUSIONS: Analysis of the TRYTON Trial cohort of SB ≥2.25 mm supports the safety and efficacy of the Tryton SB stent compared with a provisional stenting strategy in the treatment of bifurcation lesions involving large SBs. © 2015 Wiley Periodicals, Inc.

Right Upper Quadrant Pain: A Rare Presentation of Diverticulitis.

Acute diverticulitis is a prevalent medical condition with increasing incidence rates. While the sigmoid colon is the most commonly affected part of the large intestine, there have been occurrences of right-sided diverticulitis although uncommon. We present a case report highlighting the atypical presentation of diverticulitis in a 27-year-old female patient. The patient experienced right upper and epigastric pain and was ultimately diagnosed with right-sided diverticulitis, supported by her CT imaging findings. This uncommon presentation underscores the importance of considering diverse clinical manifestations when diagnosing and managing diverticulitis.

A Case of Infective Endocarditis in a Middle-Aged Patient With Trisomy 21 and an Incidentally Discovered Patent Foramen Ovale (PFO).

Trisomy 21 often leads to cardiac complications, usually associated with congenital heart disease, such as atrial septal defects, ventricular septal defects, and patent ductus arteriosus. This case describes an unexpected instance of infective endocarditis (IE) in a middle-aged patient with an incidentally discovered patent foramen ovale (PFO). The common risk factors for IE include previous valve surgery, artificial heart valves, pacemakers, prior IE, congenital defects like bicuspid aortic valve, IV drug use, and the congenital defects mentioned earlier.

Pyruvate Kinase Deficiency Causing Priapism.

Pyruvate kinase deficiency (PKD) is an autosomal recessive defect of the enzyme pyruvate kinase (PK) which is involved in catalyzing a reaction that produces ATP in the glycolytic pathway. It is the most common defect of the glycolytic pathway associated with congenital anemia. Patients usually present with signs of chronic hemolytic anemia such as hyperbilirubinemia, splenomegaly, reticulocytosis, and gallstones; the presentation can vary by age. Diagnosis is usually made by demonstration of decreased PK enzymatic activity in a spectrophotometric assay and on the detection of mutations in the PK-LR gene. Management strategies vary from full splenectomies to hematopoietic stem cell transplants with gene therapies with transfusions and administration of PK-activators coming in between. Thromboembolic complications do occur in patients with splenectomy, but there are not much data regarding this for patients with PKD. We present a case of a patient with PKD who demonstrated priapism to be a thromboembolic complication. This differs greatly as priapism has been frequently reported in patients with other chronic hemoglobinopathies such as sickle cell disease, thalassemia, and G6PD with and without splenectomy. While it is still unclear how splenectomies can result in thrombotic events in PKD, there does appear to be a correlation between splenectomies with resultant thrombocytosis with increased platelet adhesion.

Encephalopathy of Autoimmune Origin: Steroid-Responsive Encephalopathy With Associated Thyroiditis.

Background/Objective: Our objective is to highlight the importance of identifying symptoms of steroid-responsive encephalopathy with associated thyroiditis (SREAT), especially in the setting of intermittent cognitive dysfunction, and to inform that SREAT can develop even in patients with a history of partial thyroidectomies. Case Report: We present a case of a 51-year-old woman with a long-standing history of hypothyroidism presenting with acute onset myoclonus, involuntary tremors, fatigue, malaise, and palpitations for two weeks, with intermittent lapses in cognitive function. The patient's workup is completely within normal limits, including her cognition, except for elevated thyroid stimulating hormone levels and markedly elevated levels of antithyroid peroxidase antibodies, despite the fact that she previously had a partial thyroidectomy. Discussion: SREAT is an autoimmune condition characterized by cognitive dysfunction, elevated thyroid autoantibodies, and therapeutic response to corticosteroids. SREAT is primarily considered a diagnosis of exclusion. A crucial feature is the hallmark of significant improvement in symptoms when glucocorticoids are administered. There is a significant correlation between patients with elevated antithyroid peroxidase antibodies and new-onset SREAT. Although total thyroidectomy has been reported as a definitive treatment of SREAT, response to corticosteroids is the "sine qua non" in diagnosing this condition. Conclusion: Hashimoto's thyroiditis can lead to a rare complication called SREAT, presenting with various neurologic symptoms. Prompt glucocorticoid treatment is vital, and a positive response confirms the diagnosis. Total thyroidectomy may be necessary for definitive SREAT treatment. More research is needed for alternate treatments and an understanding of the pathophysiology of SREAT.

Is Losing Weight Worth Losing Your Kidney: Keto Diet Resulting in Renal Failure.

Keto diet is defined as a high-fat, adequate-protein, and low-carbohydrate nutrition which forces the body to burn fats and use an alternative metabolic fuel resource by stimulating endogenous ketone production. The standard range of ketones in ketosis is up to 3.00mmol/L, and anything beyond this level can result in serious medical conditions. This diet's most common and easily reversible consequences are constipation, low-grade acidosis, hypoglycemia, kidney stones, and increased lipid in the blood. We present a case of a 36-year-old female who presented with pre-renal azotemia after starting a keto diet regimen.

Secondary Immune Thrombocytopenic Purpura Due to Primary Epstein- Barr Virus Infection.

A rare complication of infectious mononucleosis is immune thrombocytopenic purpura (ITP). The majority of people affected by Epstein-Barr Virus (EBV) are below the age of 30, while ITP is usually seen with peaks of incidence in the elderly and children. The unique case of an otherwise healthy 22-year-old female will be discussed, with an initial presentation of ecchymosis, rash, and epistaxis, and was subsequently found to have severe thrombocytopenia. The diagnosis of primary EBV infection due to EBV was eventually made, responsive to intravenous (IV) Methylprednisolone. It is important to consider primary EBV infection in the differential diagnosis of a patient who presents with acute thrombocytopenia.

Nocardia in an Immunocompetent Host Masquerading As Lung Cancer: A Case Report.

Nocardiosis is generally regarded as an opportunistic infection that can present as a cutaneous, pulmonary, or disseminated disease based on host immunity status. Pulmonary nocardiosis is typically seen in immunocompromised patients; however, it can rarely be present in immunocompetent patients. We present a rare case of an immunocompetent patient who was thought to have a lung malignancy but was found to have pulmonary nocardiosis upon further investigation.

Epstein-Barr Virus-Positive Not Otherwise Specified (EBV+ NOS) Lymphoma Presentation of Primary Bone Tumor Underlying a Pathological Fracture.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin's lymphoma (NHL) and accounts for approximately 25% of all NHLs in developed countries. The patients usually present with constitutional symptoms and rapidly enlarging lymphadenopathy and symptomatic mass typically located in the neck or abdomen, along with an aggressive disease course. Most of the patients present with advanced disease with 60% presenting with stage 3 or 4, and those who present with extranodal involvement are usually seen at an earlier stage. Different conditions are associated with non-Hodgkin's lymphoma ranging from hereditary immunodeficiency disorders, autoimmune disorders, infections such as HIV, Epstein-Barr virus (EBV), hepatitis C virus (HCV), Helicobacter pylori, and drugs such as immunosuppressants and chemotherapeutic agents. Epstein-Barr virus (EBV) is the main etiology of DLBCLs with an identified cause and it accounts for 10% of all DLBCLs.  We report a case of a 51-year-old woman who came with a non-traumatic left femur fracture and was subsequently found to have EBV-positive DLBCL. Lymphoma commonly presents as a lymph node swelling and it's uncommon to present as primary bone disease.

The Need to Anticoagulate Patients With Splenic Vein Thrombosis.

Splenic vein thrombosis (SVT) is a well-recognized complication of acute and chronic pancreatitis. It is associated with complications of significant gastrointestinal bleeding and high morbidity if the thrombus propagates. There is a need to consider several factors in choosing whether to anticoagulate the patient. We report a case of SVT in a patient with a previous history of pancreatitis who presented with abdominal pain, nausea, and vomiting to the hospital. At the hospital, a CT scan revealed SVT. This case highlights the importance of undergoing further studies regarding anticoagulation for treating SVT in patients at risk for gastrointestinal bleeding.

Dysphagia Lusoria Causing Aspiration Pneumonitis in a Patient With Recurrent Pancreatitis.

Dysphagia lusoria (DL) occurs due to an aberrant right subclavian artery (ARSA) compressing the esophagus resulting in dysphagia, odynophagia, and/or reflux symptoms. It is diagnosed by barium esophagram followed by a CT scan or MRI. In this case report, there is a 44-year-old male with a chronic history of reflux and a cough that presents after a meal. The case was complicated due to the history of the patient's alcoholism with recurrent pancreatitis. A CT scan was obtained during his admission, which showed pleural effusion, atelectasis, aspiration pneumonia, and an incidental aberrant RCA. Although DL is a rare pathology, 60%-80% of patients remain asymptomatic, and patients with symptoms can be managed conservatively or surgically, depending on their severity.

What Works for One May Not Work for Another: A New Warning for Modafinil.

Narcolepsy is a clinical syndrome of hypothalamic disorder characterized by several sleep-wake disorders. The most common features include daytime sleepiness associated with hallucinations (hypnagogic and hypnopompic hallucinations) at the transition time of sleep-wake time, cataplexy or sudden loss of muscle tone, and sleep paralysis. We present a case of a patient affected with both narcolepsy and postural orthostatic tachycardia syndrome (POTS). POTS is a rare disorder characterized by orthostatic intolerance and abnormal autonomic response while sustaining an upright posture. In this case report, we highlight the impact of POTS on the choice of pharmacotherapy for narcolepsy.

Correction: What Works for One May Not Work for Another: A New Warning for Modafinil.

[This corrects the article DOI: 10.7759/cureus.27287.].

Estimating the impact of school closure on social mixing behaviour and the transmission of close contact infections in eight European countries.

BACKGROUND: Mathematical modelling of infectious disease is increasingly used to help guide public health policy. As directly transmitted infections, such as influenza and tuberculosis, require contact between individuals, knowledge about contact patterns is a necessary pre-requisite of accurate model predictions. Of particular interest is the potential impact of school closure as a means of controlling pandemic influenza (and potentially other pathogens). METHODS: This paper uses a population-based prospective survey of mixing patterns in eight European countries to study the relative change in the basic reproduction number (R0--the average number of secondary cases from a typical primary case in a fully susceptible population) on weekdays versus weekends and during regular versus holiday periods. The relative change in R0 during holiday periods and weekends gives an indication of the impact collective school closures (and prophylactic absenteeism) may have during a pandemic. RESULTS: Social contact patterns differ substantially when comparing weekdays to the weekend and regular to holiday periods mainly due to the reduction in work and/or school contacts. For most countries the basic reproduction number decreases from the week to weekends and regular to holiday periods by about 21% and 17%, respectively. However for other countries no significant decrease was observed. CONCLUSION: We use a large-scale social contact survey in eight different European countries to gain insights in the relative change in the basic reproduction number on weekdays versus weekends and during regular versus holiday periods. The resulting estimates indicate that school closure can have a substantial impact on the spread of a newly emerging infectious disease that is transmitted via close (non sexual) contacts.

The SYNTAX Score Does Not Predict Risk of Adverse Events in Patients With Non-ST Elevation Acute Coronary Syndrome Who Undergo Coronary Artery Bypass Graft Surgery.

OBJECTIVES: We tested the ability of the SYNTAX score (SS) to predict 1-year adverse outcomes for patients with non-ST segment elevation acute coronary syndromes (NSTE-ACS) who undergo coronary artery bypass graft (CABG) surgery. BACKGROUND: The SS effectively risk stratifies patients who undergo percutaneous coronary intervention, but not patients with stable coronary disease who undergo CABG. METHODS: We calculated the SS for 457 patients with NSTE-ACS in the angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) trial who underwent CABG. We stratified and compared patients according to SS tertiles. We tested the ability of the SS, as a linear covariate, to predict adverse events by univariate analyses and by univariate and multivariable Cox proportional hazards model. We also tested the predictive abilities of the Age, Creatinine Clearance, and Ejection Fraction (ACEF) score, the clinical SS, and the logistic clinical SS. RESULTS: The median SS was 23 (interquartile range, 15-30). Baseline clinical characteristics were similar among the groups. One-year mortality and major adverse cardiovascular events (all-cause death, myocardial infarction, any stroke, or urgent revascularization) were similar between the groups (P=.13 and P=.62, respectively). Receiver operating characteristic curves, net reclassification indices, and integrated discrimination indices did not improve with SS, clinical SS, or logistic clinical SS compared with the ACEF score. CONCLUSIONS: The anatomical SS does not appear to be useful in risk stratifying patients with NSTE-ACS who undergo CABG. Clinical variables may better risk stratify patients with complex coronary artery disease considered for CABG.

Impact of Chronic Total Occlusions on Revascularization Scores and Outcome Prediction.

OBJECTIVES: To evaluate the contribution of chronic total occlusion (CTO)-related SYNTAX score (SS) to the overall SS for patients with CTO and compare the traditional SS to a simplified variant. The SS algorithm assigns CTO lesions a greater weight (5× points) than non-CTO lesions (50% to <100% diameter stenosis; 2× points). METHODS: We calculated the SS and the simplified SS (2× points also to CTO lesions) for 4356 patients from the angiographic substudy of the Acute Catheterization and Urgent Intervention Triage StrategY (ACUITY) trial. We compared the association between SS and 1-year mortality and major adverse cardiac events for patients with and without a CTO. We also compared the simplified SS with the traditional SS. RESULTS: The median SS was 20 (interquartile range, 13-27.5) for patients with a CTO and 8 (interquartile range, 2-16) for patients without a CTO. For patients with a CTO, the CTO lesion(s) contributed 67 ± 26% of the total SS. The simplified SS reclassified 187/603 (31.0%) of patients with a SS >22 to a SS ≤22. The traditional SS did not improve discrimination indices for predicting outcomes compared with the simplified SS. CONCLUSIONS: CTO lesions contribute considerably to the total SS in patients with a CTO. A simplified SS that does not differentiate between CTO and non-CTO lesions appeared equivalent to the traditional SS for risk prediction, but reclassified a substantial proportion of patients to a SS ≤22 and may impact choice of revascularization strategy for patients with complex coronary artery disease involving a CTO lesion.