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Although influenza is primarily considered a respiratory infection and causes significant respiratory mortality, evidence suggests that influenza has an additional burden due to broader consequences of the illness. Some of these broader consequences include cardiovascular events, exacerbations of chronic underlying conditions, increased susceptibility to secondary bacterial infections, functional decline, and poor pregnancy outcomes, all of which may lead to an increased risk for hospitalization and death. Although it is methodologically difficult to measure these impacts, epidemiological and interventional study designs have evolved over recent decades to better take them into account. Recognizing these broader consequences of influenza virus infection is essential to determine the full burden of influenza among different subpopulations and the value of preventive approaches. In this review, we outline the main influenza complications and societal impacts beyond the classical respiratory symptoms of the disease.

Developing a completely effective and safe dengue vaccine has been a complicated process. Dengvaxia®, by Sanofi-Pasteur, and recently TAK003, by Takeda, have strengths and weaknesses, but they seem to complement each other. In this work, we elaborate a rationale that could be applicable in a combined program of these vaccines for the control of dengue.

A recent study reported enterococci that developed alcohol tolerance. We measured minimum inhibitory concentrations (MICs) of isopropyl alcohol against 55 vancomycin-resistant Enterococcus faecium. We did not find an increase in MICs when comparing the periods before and after the use of alcohol for hand hygiene in a hospital, and we did not find a single isolate with a MIC higher than 11.5%. We consider alcohol to still be an effective measure for hand antisepsis.

Objective To evaluate the costs associated with evaluation of β-lactam allergy in children labeled as allergic. Study design We performed a prospective year-long real life observational study designed to evaluate all pediatric patients with suspected β-lactam allergy who consulted for allergy evaluation. Direct and indirect costs were systematically recorded. Direct healthcare costs were calculated by taking into account the number of visits and all complementary and diagnostic tests performed. Direct nonhealthcare costs were calculated by considering the number of visits and the kilometers from their homes to the clinic. Finally, indirect costs were evaluated by considering the absenteeism of parents or other companions who took the children to the clinic. Results A total of 40 children with suspected allergy to β-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct healthcare costs were $5038.03, with an average cost per patient of $125.95. Direct nonhealthcare costs reached $901.87 ($22.55 per patient) and indirect nonhealthcare costs reached $6384.35 ($159.61 per patient). The total cost was $12 324.25, a cost of $308.11 per patient. Conclusions Elective evaluation of β-lactam allergy and delabeling children who are not allergic is not expensive. In addition, it could save future expenses because of an unnecessary lifelong use of alternative antibiotics that are usually more expensive, less effective, and more frequently associated with antimicrobial resistance and different side effects.

Transfer factor (TF), also called "Lawrence transfer factor", or dialyzable leukocyte extract (DLE), has been used since the mid-twentieth century to transfer specific skin hypersensitivity through the injection of leukocytes from immunized donors to animals and humans. The main mechanism of action of TF has been suggested at the level of cell-mediated immunity, as it induces the production of migration inhibitory factor (MIF) and interferon gamma (IFN-γ). Otherwise, TF can inhibit nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), and decrease tumoral necrosis factor α (TNF-α) and IL-4 levels. Given these biological effects, TF has been prescribed for a wide variety of conditions including infections, allergies, autoimmunity, and cancer, with inconsistent results. The exact nature of TF, however, remains unknown, so it has been impossible to accurately define its pharmacokinetics or dosage. This is further complicated because researchers have used TF in a variety of ways across the different studies: antigen-specific or non-antigen-specific, orally or subcutaneously administered, human and non-human origin. In this review we summarize the most important data about what TF is, its mechanism of action, how it is produced, its biological effects, and the available clinical trials using it, in order to establish its role and potential clinical applications in modern medicine.

Background: Being labeled as allergic to penicillin (unverified ß-lactam allergy) can result in patients receiving broader-spectrum antibiotics than necessary that may be more toxic, less effective, and/or more expensive than alternative options. Objective: We aimed to evaluate the real costs of evaluating ß-lactam allergy. Methods: We performed a prospective real-life observational study designed to evaluate all adult patients who consulted for suspected ß-lactam allergy over a 1-year period. Direct and indirect costs were systematically recorded. Direct health costs were calculated based on the number of visits and all additional and diagnostic tests performed, direct nonhealth costs based on the number of visits and the distance from their homes to the Allergy Department, and indirect costs based on absenteeism. Results: A total of 296 patients with suspected allergy to ß-lactams were evaluated in our outpatient clinic from June 1, 2017 to May 31, 2018. Total direct health care costs were €28 176.70, with a mean (SD) cost of €95.19 (37.20). Direct nonhealth costs reached €6551.73, that is, €22.13 (40.44) per patient. Indirect health costs reached €20 769.20, with a mean of €70.17 (127.40). In summary, the total cost was €55 497.63, that is, a cost per patient of €187.49 (148.14). Conclusions: When all possible costs are taken into account, the evaluation of ß-lactam allergy is not expensive and can reduce future expense arising from unnecessary use of more expensive and less effective antibiotics.

Elastosis perforans serpiginosa (EPS) is a rare skin disorder characterized by transepidermal elimination of abnormal elastic fibres. We present a new case of D-penicillamine (DPA)-induced EPS, and describe the clinical, dermoscopic, histopathological and direct immunofluorescence (DIF) findings. A 33-year-old woman receiving treatment with DPA presented with annular skin lesions. Digital dermoscopy of the lesions showed a central area of pink and yellowish discolouration with keratotic papules in the periphery, surrounded by a white halo, disposed in a way that resembled the islands of an archipelago. Other lesions showed a white to yellow central colouration and 'chrysalides' surrounding the keratotic plugs. Linear and granular deposits of IgG attached to the abnormal elastic fibres were seen with DIF. Dermoscopy can be helpful in the diagnosis of EPS. Moreover, DIF findings in skin biopsies of this case support the immune-mediated pathogenesis of EPS.

Background An accurate diagnosis of β-lactam (BL) allergy improves the use of antibiotics, increases patients’ safety, and reduces costs to health systems. Nevertheless, it requires skin and drug provocation tests, which are time-consuming and put the patient at risk. Furthermore, allergy testing is not available in circumstances such as the urgent need for antibiotic therapy. Objective To evaluate the usefulness of an artificial neural network (ANN) in the prediction of hypersensitivity to BLs, and compare it with logistic regression (LR) analysis. Methods In a single-center study, 656 patients evaluated for BL allergy between 1994 and 2000 were retrospectively analyzed, and the data were used to construct an ANN. The ANN predictive capabilities were compared with LR and then prospectively evaluated in 615 patients who underwent BL evaluation between 2011 and 2017. Results A total of 1271 patients were evaluated. All patients had a definite diagnosis as allergic or nonallergic to BL. The prospective sample showed a lower percentage of patients with allergy than the retrospective sample (20.7% vs 25.8%; P = .018). In the retrospective and prospective series, the ANN reached a sensitivity of 89.5% and 81.1%, a specificity of 86.1% and 97.9%, a positive predictive value of 82.1% and 91.1%, and a negative predictive value of 92.1% and 95.2%, respectively. The ANN's performance was far superior to that of the LR, whose best performance reached a sensitivity of 31.9% and a specificity of 98.8%. Conclusions This ANN demonstrated a superior performance than the LR in predicting BL hypersensitivity without misdiagnosing severe allergic reactions. The ANN could be a helpful tool to classify the reaction risk, particularly in the identification of low-risk patients, in which an open challenge could be done to delabel patients.

Dengue remains an unmet public health burden. We determined risk factors for dengue in-hospital mortality in Brazil. Of 326,380 hospitalised dengue cases in 9-45-year-old individuals, there were 971 deaths. Risk of dying was 11-times higher in the presence of underlying common comorbidities (renal, infectious, pulmonary disease and diabetes), similar to the risk of dying from severe dengue and much higher with the combination. Ensuring access to integrated dengue preventative measures in individuals aged ≥ 9 years including those with comorbidities may help achieve the WHO objective of 50% reduction in mortality and 25% reduction in morbidity due to dengue by 2020.

The presence of gram-negative bacteria in the oral cavity is an undesirable occurrence in patients undergoing chemotherapy. Our aim was to investigate the antibacterial effect of 0.12% chlorhexidine mouthwash in chemotherapypatients with a randomized, double-blind, placebo-controlled trial. There were no significant differences between oral colonization rates; there may be local factors that interfere with chlorhexidine activity.

Patients with autoimmune disorders are predisposed to develop a second immunologic disease, frequently with systemic involvement. We present a patient who developed lesions of discoid lupus erythematosus (DLE) limited to the face, and, concurrently, a linear morphoea involving her right axilla. No criteria for systemic lupus erythematosus or systemic scleroderma were present in the patient. To our knowledge, no patients with concomitant DLE and linear morphoea, without systemic involvement, have been previously reported in the literature.

Background False-positive blood cultures can lead to unnecessary risks and misuse of antibiotics; to reduce rates of false-positives, it would be useful to determine whether use of an antiseptic with a prolonged effect is required. Methods Clinical study of efficacy (blinded and randomized) to compare the rate of blood culture contamination when skin antisepsis was performed with 70% isopropyl alcohol or 2% chlorhexidine gluconate in 70% isopropyl alcohol in 2 hospitals. Patients aged 16 years or older with suspected bloodstream infection who were allocated in the emergency room, internal medicine ward, or intensive care unit were included. Results Five of 563 (0.9%) blood cultures from the isopropyl arm and 10 of 539 (1.9%) from the chlorhexidine arm were contaminated. No significant differences were observed among the rate of contamination (χ 2 = 1.27; P = .3) or the relative risk of contamination (relative risk = 2.09; 95% confidence interval, 0.72-6.07; P = .2). Conclusions The rates of blood contamination were not different when isopropyl alcohol and chlorhexidine were compared. Isopropyl alcohol could be used for skin antisepsis before blood collection.

European Network on Drug Allergy (ENDA) has proposed an algorithm for diagnosing immediate beta-lactam (BL) allergy. We evaluated its performance in real life. During 1994-2014, 1779 patients with suspected immediate reactions to BL were evaluated following ENDA's short diagnostic algorithm. Five hundred and nine patients (28.6%) were diagnosed of BL hypersensitivity. Of them, 457 (25.7%) were at first evaluation [403 by skin tests (ST), 12 by positive IgE and 42 by controlled provocation tests (CPT)]. At second evaluation (SE), 52 additional patients (10.2% of allergic patients) were diagnosed, [50 (2.8%) by ST and 2 (0.1%) by CPT]. Time between reaction and study was significantly longer in patients diagnosed at SE (median 5 vs 42 months; IQR 34 vs 170; P < 0.0001). Anaphylaxis was significantly associated with a diagnosis at SE. European Network on Drug Allergy/EAACI protocol was appropriate and safe when evaluating BL immediate reactions. Re-evaluation should be performed, particularly when anaphylaxis and long interval to diagnosis are present.

The 2009–2010 influenza A (H1N1pdm09) pandemic caused substantial morbidity and mortality among young patients; however, mortality estimates have been confounded by regional differences in eligibility criteria and inclusion of selected populations. In 2013–2014, H1N1pdm09 became North America’s dominant seasonal influenza strain. Our objective was to compare the baseline characteristics, resources, and treatments with outcomes among critically ill patients with influenza A (H1N1pdm09) in Mexican and Canadian hospitals in 2014 using consistent eligibility criteria. Observational study and a survey of available healthcare setting resources. Twenty-one hospitals, 13 in Mexico and eight in Canada. Critically ill patients with confirmed H1N1pdm09 during 2013–2014 influenza season. None. The main outcome measures were 90-day mortality and independent predictors of mortality. Among 165 adult patients with H1N1pdm09-related critical illness between September 2013 and March 2014, mean age was 48.3 years, 64% were males, and nearly all influenza was community acquired. Patients were severely hypoxic (median PaO2-to-FIO2 ratio, 83 mm Hg), 97% received mechanical ventilation, with mean positive end-expiratory pressure of 14 cm H2O at the onset of critical illness and 26.7% received rescue oxygenation therapy with prone ventilation, extracorporeal life support, high-frequency oscillatory ventilation, or inhaled nitric oxide. At 90 days, mortality was 34.6% (13.9% in Canada vs 50.5% in Mexico, p < 0.0001). Independent predictors of mortality included lower presenting PaO2-to-FIO2 ratio (odds ratio, 0.89 per 10-point increase [95% CI, 0.80–0.99]), age (odds ratio, 1.49 per 10 yr increment [95% CI, 1.10–2.02]), and requiring critical care in Mexico (odds ratio, 7.76 [95% CI, 2.02–27.35]). ICUs in Canada generally had more beds, ventilators, healthcare personnel, and rescue oxygenation therapies. Influenza A (H1N1pdm09)-related critical illness still predominantly affects relatively young to middle-aged patients and is associated with severe hypoxemic respiratory failure. The local critical care system and available resources may be influential determinants of patient outcome.

Objective To determine differences in the recontamination of stethoscope membranes after cleaning with chlorhexidine, triclosan, or alcohol. Methods Experimental, controlled, blinded trial to determine differences in the bacterial load on stethoscope membranes. Membranes were cultured by direct imprint after disinfection with 70% isopropyl alcohol, 1% triclosan, or 1% chlorhexidine and normal use for 4 hours. As a baseline and an immediate effect control, bacterial load of membranes without disinfection and after 1 minute of disinfection with isopropyl alcohol was determined as well. Results Three hundred seventy cultures of in-use stethoscopes were taken, 74 from each arm. In the baseline arm the median growth was 10 CFU (interquartile range [IQR], 32-42 CFU); meanwhile, in the isopropyl alcohol immediate-effect arm it was 0 CFU (IQR, 0-0 CFU). In the arms cultured after 4 hours, a median growth of 8 CFU (IQR, 1-28 CFU) in the isopropyl alcohol arm, 4 CFU (IQR, 0-17 CFU) in the triclosan arm, and 0 CFU (IQR, 0-1 CFU) in the chlorhexidine arm were seen. No significant differences were observed between the bacterial load of the chlorhexidine arm (after 4 hours of use) and that of the isopropyl alcohol arm (after 1 minute without use) ( Z = 2.41; P > .05). Conclusions Chlorhexidine can inhibit recontamination of stethoscope membranes and its use could help avoid cross-infection.

Background We do not know whether differences exist between the residual effect of 2% chlorhexidine in 70% isopropyl alcohol when compared with 1% triclosan in 70% isopropyl alcohol. Methods Using an analytic, longitudinal, controlled, and comparative experimental trial, with blinded measurements, we recruited healthy, adult volunteers from the University of Guanajuato who completed a stabilization phase of skin microbiota and had no history of skin allergies. Four 25-cm 2 areas of the inner surface of the forearms were designated for study: unscrubbed control for establishing baseline bacterial counts, scrubbed control with tridistilled water, scrubbed with chlorhexidine, and scrubbed with triclosan. Quantitative cultures were taken of all the areas at 0, 3, and 24 hours, using agar plates with neutralizing agents. Results A total of 135 healthy volunteers were tested. At 24 hours, the unscrubbed control counts were 288 CFU/cm 2 , whereas the scrubbed control counts were 96 CFU/cm 2 ; 24 CFU/cm 2 for chlorhexidine and 96 CFU/cm 2 for triclosan (Kruskal-Wallis χ 2 H = 64.27; P .001). Conclusions Chlorhexidine is the best antiseptic option when a prolonged antiseptic effect is needed; for instance, when implanting medical devices or performing surgical procedures.