Ceftaroline fosamil: clinical experience after 23-month prescription in a tertiary hospital.

OBJECTIVE: To determine the indications, success rate and adverse effects of ceftaroline fosamil treatment in a tertiary hospital. METHODS: In total, 84 cases from February 2018 to December 2019 were retrospectively analysed. No exclusion criteria were applied. RESULTS: Eighty-four patients, with a median age of 70 years, of which, 6.7% (56) were male, were treated with ceftaroline fosamil for a median of 14 days. Most indications were off-label, including 29 endocarditis (34.5%), 14 bacteraemia (16.6%), 5 Central nervous system (CNS) infections (6%) and 19 osteoarticular infections (22.6%). Staphylococcus aureus was the most frequently isolated microorganism, including 28 methicillin-sensitive S. aureus (MSSA; 33.3%) and 14 methicillin-resistant S. aureus (MRSA; 16.7%), followed by coagulase-negative Staphylococcus (23, 27.4%). The main reason for ceftaroline fosamil prescription was the failure of previous treatment (41.7% of cases). Treatment was successful in 60/84 patients (71.4%) and failed clinically or microbiologically in 14 (16.7%). Eight patients died for a reason not related to the infection and two were found to have a non-infectious condition. Twenty-two of thirty-five (62.8%) patients prescribed ceftaroline because of failure of previous treatment improved, including eight endocarditis and seven bacteraemia. Adverse effects were reported in five patients (5.9%) including neutropenia, thrombocytopenia, transaminases elevation and creatinine elevation; all except one were mild and all resolved after discontinuation of treatment. CONCLUSIONS: Ceftaroline fosamil is a well-tolerated cephalosporine, effective against multi- resistant gram-positive and many gram-negative microorganisms. Our experience suggests that it is effective as a rescue or first-line therapy in other indications than those currently approved.

Glycaemic control and hypoglycaemia risk with insulin glargine 300 U/mL versus glargine 100 U/mL: A patient-level meta-analysis examining older and younger adults with type 2 diabetes.

AIM: Older people with type 2 diabetes (T2DM) are at an increased risk of hypoglycaemia and its consequences. However, efficacy and safety data for basal insulin therapy are limited in these individuals. This patient-level meta-analysis assessed the treatment effects of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with T2DM ≥ 65 years old. METHODS: Data were pooled for patients randomised to receive Gla-300 or Gla-100 in the Phase 3a, treat-to-target EDITION 1, 2 and 3 trials. Glycaemic efficacy, hypoglycaemia, changes in body weight and insulin dosage and adverse events were examined over 6 months' treatment with Gla-300 versus Gla-100 for participants aged ≥ 65 and < 65 years. RESULTS: Of 2496 participants randomised, 662 were ≥ 65 years (Gla-300, n = 329; Gla-100, n = 333). Glycaemic control was comparable for Gla-300 and Gla-100 in participants ≥ 65 years (LS mean [95% CI] difference in HbA1c change from baseline to month 6: 0.00 [-0.14 to 0.15] %; 0.00 [-1.53 to 1.64] mmol/mol) and < 65 years (0.00 [-0.09 to 0.08] %; 0.00 [-0.98 to 0.87] mmol/mol). Fewer participants receiving Gla-300 versus Gla-100 experienced nocturnal confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycaemia (relative risk: ≥ 65 years: 0.70 [0.57 to 0.85]; < 65 years: 0.77 [0.68 to 0.87]). Annualised rates of nocturnal confirmed or severe hypoglycaemia were lower with Gla-300 than Gla-100 for both age groups. CONCLUSION: Gla-300 was associated with a reduced risk of nocturnal hypoglycaemia versus Gla-100, accompanied by comparable glycaemic improvement, for people aged ≥ 65 and < 65 years with T2DM.

Analysis of the new code stroke protocol in Asturias after one year. Experience at one hospital. / Análisis del primer año del nuevo protocolo de código ictus en Asturias. Experiencia de un único centro.

INTRODUCTION: Prehospital code stroke (CS) systems have been proved effective for improving access to specialised medical care in acute stroke cases. They also improve the prognosis of this disease, which is one of the leading causes of death and disability in our setting. The aim of this study is to analyse results one year after implementation of the new code stroke protocol at one hospital in Asturias. PATIENTS AND METHODS: We prospectively included patients who were admitted to our tertiary care centre as per the code stroke protocol for the period of one year. RESULTS: We analysed 363 patients. Mean age was 69 years and 54% of the cases were men. During the same period in the previous year, there were 236 non-hospital CS activations. One hundred forty-seven recanalisation treatments were performed (66 fibrinolysis and 81 mechanical thrombectomies or combined treatments), representing a 25% increase with regard to the previous year. CONCLUSIONS: Recent advances in the management of acute stroke call for coordinated code stroke protocols that are adapted to the needs of each specific region. This may result in an increased number of patients receiving early care, as well as revascularisation treatments.

Assessment of hypoglycaemia during basal insulin therapy: Temporal distribution and risk of events using a predefined or an expanded definition of nocturnal events.

AIM: To describe in type 2 diabetes the 24-hour distribution of hypoglycaemia and compare the frequency of nocturnal events based on a predefined nocturnal window or an expanded interval, using illustrative data for two insulin glargine formulations. METHODS: Temporal distribution of hypoglycaemic events was assessed descriptively and by profile using participant-level data from three randomized trials comparing insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100). Risk of hypoglycaemia and annualized event rates were compared for the predefined nocturnal interval (00:00 to 05:59h) and an expanded window (22:00h to the pre-breakfast glucose measurement). RESULTS: Confirmed (≤3.9mmol/L [≤70 mg/dL]) or severe hypoglycaemic events were reported most frequently between 06:00 and 10:00 h with both insulins. Nearly threefold more events were identified using the expanded nocturnal interval. Risk of ≥1 nocturnal event was 25% lower with Gla-300 than Gla-100 with the predefined, and 16% lower with the expanded interval; annualized event rates were 31% and 24% lower with the predefined and expanded window, respectively. The between-insulin difference in number of nocturnal events depended markedly on the chosen nocturnal interval (556 vs. 1145 fewer events with Gla-300 using the predefined vs. expanded interval). CONCLUSIONS: The predefined 00:00-05:59h nocturnal interval excluded many hypoglycaemic events occurring during the actual overnight interval. While Gla-300 reduced hypoglycaemic events versus Gla-100 (regardless of the interval considered), the results obtained using the expanded window better reflect the clinical experience of people treated with basal insulin.

Code stroke in Asturias.

BACKGROUND: Intravenous thrombolysis with alteplase is an effective treatment for ischaemic stroke when applied during the first 4.5 hours, but less than 15% of patients have access to this technique. Mechanical thrombectomy is more frequently able to recanalise proximal occlusions in large vessels, but the infrastructure it requires makes it even less available. METHODS: We describe the implementation of code stroke in Asturias, as well as the process of adapting various existing resources for urgent stroke care in the region. By considering these resources, and the demographic and geographic circumstances of our region, we examine ways of reorganising the code stroke protocol that would optimise treatment times and provide the most appropriate treatment for each patient. RESULTS: We distributed the 8 health districts in Asturias so as to permit referral of candidates for reperfusion therapies to either of the 2 hospitals with 24-hour stroke units and on-call neurologists and providing IV fibrinolysis. Hospitals were assigned according to proximity and stroke severity; the most severe cases were immediately referred to the hospital with on-call interventional neurology care. Patient triage was provided by pre-hospital emergency services according to the NIHSS score. CONCLUSIONS: Modifications to code stroke in Asturias have allowed us to apply reperfusion therapies with good results, while emphasising equitable care and managing the severity-time ratio to offer the best and safest treatment for each patient as soon as possible.

The HUGE formula (hematocrit, urea and gender): association with cardiovascular risk.

OBJECTIVES: To evaluate the relationship between chronic renal failure (CFR) defined through HUGE (hematocrit, urea and gender) formula score and the patient's cardiovascular risk measured through cardiovascular disease antecedents such as ischemic cardiopathy, cerebrovascular disease and peripheral arterial disease. DESIGN AND METHODS: The sample consisted of 2,831 subjects. Mean age was 51.2±14.7 years and 53.5% were female. Serum creatinine, urea, hematocrit and 24h proteinuria were analyzed. HUGE score was calculated from gender, urea and hematocrit. GFR was estimated from uncalibrated serum creatinine using the abbreviated Modification of Diet in Renal Disease equation (MDRD-4). UAE was measured in first morning urine sample. RESULTS: Using HUGE formula 2.2% (n = 61) of subjects had CRF. Of them, 12 (19.7%) had cardiovascular disease history. Among patients without CRF (n = 2770), 194 subjects had history of previous cardiovascular diseases (0.07%; p < 0.001 Square Chi test). Using the MDRD-4 formula 4.0% of subjects (n = 113) had a GFR < 60 ml/min. Of them, 18 (15.9%) had cardiovascular disease history. Among patients without CRF (n = 2718), 188 subjects had history of previous cardiovascular diseases (0.07%; p < 0.001 Square Chi test). Odd's ratio for cardiovascular diseases using HUGE definition of CRF was 3.25 (p = 0.001, Mantel-Haenszel test). CFR was associated to higher pulse pressure (PP) and increased urinary albumin excretion. CONCLUSIONS: A significant cardiovascular risk was associated to the diagnosis of CRF through HUGE formula. This relation was closer than the obtained using MDRD estimated GFR in spite of a bigger sample. HUGE formula seems to be a useful tool for diagnosing CRF and evaluate the cardiovascular risk of these patients.

Prevalence of abnormal urinary albumin excretion in elderly people: a Spanish survey.

OBJECTIVES: HERMEX is a population-based study, which tries to evaluate the prevalence of cardiovascular risk factors in the population of Extremadura, Spain. This report provides the data concerning albuminuria in the elderly people recruited in the survey. DESIGN AND METHODS: 3,402 subjects were randomly selected from the database of the Health Care System of Extremadura. The final sample included 2,813 subjects (mean age 51.2 years, 53.5 % female). Urinary albumin excretion rate (UAER) in the first morning urine sample was analyzed. Albuminuria was diagnosed when UAER (albumin-to-creatinine ratio) was ≥ 22 mg/g in men or ≥ 31 mg/g in women. RESULTS: The prevalence of abnormal UAER in the elderly population was 10.9 % (microalbuminuria: 8.9 %; overt proteinuria: 1.8 %). The younger subjects showed a lower prevalence of microalbuminuria (3.4 %, p < 0.001). Elderly patients showed a higher prevalence of cardiovascular risk factors than the younger ones. The elderly had higher systolic blood pressure and pulse pressure than the younger ones. Furthermore, the elderly subjects had lower plasma levels of HDL cholesterol, but higher triglycerides, glucose, creatinine, and glycosylated hemoglobin; no differences were found for total and LDL cholesterol. When the prevalence of causes of microalbuminuria was compared between age groups, we found a sharp increase in diabetic and, especially, hypertensive patients in the elderly group. The multivariate analysis showed an independent association of microalbuminuria with systolic blood pressure and plasma creatinine. CONCLUSIONS: A high prevalence of abnormal UAER in elderly people was detected in a randomly selected sample of Spanish general population. In most elderly patients, microalbuminuria was associated with high blood pressure and, less frequently, with diabetes mellitus.

Localization and post-Golgi trafficking of tumor necrosis factor-alpha in macrophages.

Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine secreted by activated macrophages. In this study, we examined the intracellular distribution and trafficking of TNF-alpha. Immunofluorescence and immunogold localization demonstrated that in lipopolysaccharide (LPS)-stimulated RAW264 macrophages, the greatest concentration of TNF-alpha is found in the perinuclear Golgi complex. Staining of the Golgi complex appeared 20 min after activation of cells and persisted for 2-12 h, and TNF-alpha appeared on the cell surface only transiently during this time. The rate of disappearance of Golgi staining correlated with the release of the cleaved, mature TNF-alpha into the medium. Pulse chase labeling and subcellular fractionation studies indicated that both 26-kDa and 17-kDa forms of TNF-alpha may be present at the level of the Golgi complex. Post-Golgi trafficking of TNF-alpha was modulated by agents that disrupt the cytoskeleton. Interferon-gamma (IFN-gamma), which primes macrophages for TNF-alpha-dependent cellular cytotoxicity, potentiated the effect of LPS by sustaining enhanced intracellular pools of TNF-alpha and also promoted redistribution of TNF-alpha into post-Golgi vesicular compartments. We propose that the primary pool of biologically active TNF-alpha in activated macrophages is held in the Golgi complex and that the cytokine is recruited directly from this intracellular pool for release in response to tumor cells or pathogens.

Immunohistochemical analysis of sialic acid and fucose composition in human colorectal adenocarcinoma.

The expression of different sialoglycoconjugates and fucoglycoconjugates in normal mucosa and adenocarcinoma samples from 43 colorectal cancer patients was investigated by using specific lectins and applying a semiquantitative analysis. A pronounced decrease in the intracellular binding of the Maackia amurensis lectin, which recognizes alpha(2,3)-linked sialic acid residues, was found in the tumoral tissue. In contrast, a significant increase in the staining with the Sambucus nigra lectin (SNA I), which binds to alpha(2,6)-linked sialic acid residues, was detected in the epithelial cells as well as in the mucins from tumors. No significant differences in the reactivity with the Aleuria aurantia lectin, which recognizes the sequence Fuc(alpha1,6)GlcNAc, between normal and malignant colorectal tissues were detected. Furthermore, the correlation between lectin-binding profiles and the prognosis of colorectal cancer patients was examined. After an average postoperative follow-up period of 31 months, patients with tumors showing a strong SNA I staining presented a greater probability of disease recurrence. This result suggests that the intensity of staining with SNA I could be a valid parameter for predicting recurrence in colorectal cancer.

Application of a nested polymerase chain reaction assay to detect Mycoplasma hyopneumoniae from nasal swabs.

The porcine respiratory disease complex (PRDC) is an increasingly important cause of decreased swine productivity and is characterized by slow growth, decreased feed efficiency, anorexia, cough, and dyspnea. Mycoplasma hyopneumoniae is among the most prevalent and important infectious agents associated with PRDC. Understanding of mycoplasmal pneumonia has been hindered by inadequate diagnostic methods. Many of the currently available tests are relatively insensitive or nonspecific when used in a diagnostic laboratory setting or are too costly or difficult for routine diagnostic use. Several polymerase chain reaction (PCR) assays have been described, but they are not sensitive enough to detect the microorganisms in live pigs, from either nasal or tracheal swabs. A nested PCR using 2 species-specific sets of primers from the 16S ribosomal DNA gave positive results with as little as 80 microorganisms and did not cross-react with other mycoplasma species or with other microorganisms commonly found in the respiratory tract of pigs. This assay was better suited for detection of M. hyopneumoniae from nasal swabs than was conventional PCR. Nasal swab samples were taken at different time periods following experimental challenge of 10 susceptible pigs. Only 2 of the 55 swabs examined gave a positive result with conventional PCR, whereas 30 of the 55 swabs gave a positive result using the nested PCR. Twenty of 40 (50%) nasal swabs from pigs experiencing a respiratory disease outbreak where M. hyopneumoniae had been diagnosed also gave a positive result with the nested PCR. To confirm that the amplified product was specific, 4 nested PCR products were purified, sequences were determined and aligned, and they were confirmed to be from M. hyopneumoniae.

Toxicity of methomyl following intravenous administration in the horse.

Methomyl (S-methyl-N-((methylcarbamoyl)oxy) thioacetimidate) toxicity was studied in horses using i.v. dosages from 0.01 to 3.0 mg/kg. Doses of 1-3 mg methomyl/kg produced increased GI motility and respirations, facial fasiculations, salivation, lacrimation and convulsions. The only effect at 0.5 mg/kg was increased GI sounds in 1/4 horses. This extensively used crop insecticide had been associated with episodes of morbidity and mortality and led to speculation that it was extremely potent to the horse. This was not supported by these clinical studies.