Economic burden of skin and skin structure infections due to Gram-positive bacteria in patients on hospital at home-based outpatient parenteral antibiotic therapy (OPAT).

OBJECTIVE: To describe and quantify resource use and direct health costs associated with skin and skin structure infections (SSSIs) caused by Gram-positive bacteria in adults receiving outpatient parenteral antimicrobial therapy (OPAT), administered by Hospital at Home units (HaH) in Spain. METHODS: Observational, multicenter, retrospective study. We included patients of both sexes included in the HaH-based OPAT Registry during 2011 to 2017 who were hospitalized due to SSSIs caused by Gram-positive bacteria. Resource use included home visits (nurses and physician), emergency room visits, conventional hospitalization stay, HaH stay and antibiotic treatment. Costs were quantified by multiplying the natural units of the resources by the corresponding unit cost. All costs were updated to 2019 euros. RESULTS: We included 194 episodes in 189 patients from 24 Spanish hospitals. The most frequent main diagnoses were cellulitis (26.8%) and surgical wound infection (24.2%), and 94% of episodes resulted in clinical improvement or cure after treatment. The median HaH stay was 13 days (interquartile range [IR]:8-22.7), and the conventional hospitalization stay was 5 days (IR: 1-10.7). The mean total cost attributable to the complete infectious process was €7,326 (95% confidence interval: €6,316-€8,416). CONCLUSIONS: Our results suggest that OPAT administered by HaH is a safe and efficient alternative for the management of these infections and could lead to lower costs compared with hospital admission.

A genome-wide association study identifies novel gene associations with facial skin wrinkling and mole count in Latin Americans.

BACKGROUND: Genome-wide association studies (GWASs) have identified genes influencing skin ageing and mole count in Europeans, but little is known about the relevance of these (or other genes) in non-Europeans. OBJECTIVES: To conduct a GWAS for facial skin ageing and mole count in adults < 40 years old, of mixed European, Native American and African ancestry, recruited in Latin America. METHODS: Skin ageing and mole count scores were obtained from facial photographs of over 6000 individuals. After quality control checks, three wrinkling traits and mole count were retained for genetic analyses. DNA samples were genotyped with Illumina's HumanOmniExpress chip. Association testing was performed on around 8 703 729 single-nucleotide polymorphisms (SNPs) across the autosomal genome. RESULTS: Genome-wide significant association was observed at four genome regions: two were associated with wrinkling (in 1p13·3 and 21q21·2), one with mole count (in 1q32·3) and one with both wrinkling and mole count (in 5p13·2). Associated SNPs in 5p13·2 and in 1p13·3 are intronic within SLC45A2 and VAV3, respectively, while SNPs in 1q32·3 are near the SLC30A1 gene, and those in 21q21·2 occur in a gene desert. Analyses of SNPs in IRF4 and MC1R are consistent with a role of these genes in skin ageing. CONCLUSIONS: We replicate the association of wrinkling with variants in SLC45A2, IRF4 and MC1R reported in Europeans. We identify VAV3 and SLC30A1 as two novel candidate genes impacting on wrinkling and mole count, respectively. We provide the first evidence that SLC45A2 influences mole count, in addition to variants in this gene affecting melanoma risk in Europeans.

Nasal airflow simulations suggest convergent adaptation in Neanderthals and modern humans.

Both modern humans (MHs) and Neanderthals successfully settled across western Eurasian cold-climate landscapes. Among the many adaptations considered as essential to survival in such landscapes, changes in the nasal morphology and/or function aimed to humidify and warm the air before it reaches the lungs are of key importance. Unfortunately, the lack of soft-tissue evidence in the fossil record turns difficult any comparative study of respiratory performance. Here, we reconstruct the internal nasal cavity of a Neanderthal plus two representatives of climatically divergent MH populations (southwestern Europeans and northeastern Asians). The reconstruction includes mucosa distribution enabling a realistic simulation of the breathing cycle in different climatic conditions via computational fluid dynamics. Striking across-specimens differences in fluid residence times affecting humidification and warming performance at the anterior tract were found under cold/dry climate simulations. Specifically, the Asian model achieves a rapid air conditioning, followed by the Neanderthals, whereas the European model attains a proper conditioning only around the medium-posterior tract. In addition, quantitative-genetic evolutionary analyses of nasal morphology provided signals of stabilizing selection for MH populations, with the removal of Arctic populations turning covariation patterns compatible with evolution by genetic drift. Both results indicate that, departing from important craniofacial differences existing among Neanderthals and MHs, an advantageous species-specific respiratory performance in cold climates may have occurred in both species. Fluid dynamics and evolutionary biology independently provided evidence of nasal evolution, suggesting that adaptive explanations regarding complex functional phenotypes require interdisciplinary approaches aimed to quantify both performance and evolutionary signals on covariation patterns.

Usefulness of Hospital at Home in nosocomial infections: advantages and limitations.

Hospital at Home units allows ambulatory treatment and monitoring of complex and serious infections. Nosocomial infections produce an extension of the stay in hospital often specifying long intravenous treatments without any effective oral alternatives. Daily dosing of antimicrobial are easier to administer at home. The use of portable programmable pump infusion and elastomeric devices allow efficient and safe infu-sions for most antimicrobials at home. Some antibiotics against multidrug-resistant organisms of recent introduction have a suitable profile for outpatient intravenous treatment.

Costs of outpatient parenteral antimicrobial therapy (OPAT) administered by Hospital at Home units in Spain.

The aim of this study was to assess the direct healthcare costs of outpatient parenteral antimicrobial therapy (OPAT) administered by Hospital at Home (HaH) units in Spain. An observational, multicentre, economic evaluation of retrospective cohorts was conducted. Patients were treated at home by the HaH units of three Spanish hospitals between January 2012 and December 2013. From the cost accounting of HaH OPAT (staff, pharmacy, transportation, diagnostic tests and structural), the cost of each outpatient course was obtained following a top-down strategy based on the use of resources. Costs associated with inpatient stay, if any, were estimated based on length of stay and ICD-9-CM diagnosis. There were 1324 HaH episodes in 1190 patients (median age 70 years). The median (interquartile range) stay at home was 10 days (7-15 days). Of the OPAT episodes, 91.5% resulted in cure or improvement on completion of intravenous therapy. The mean total cost of each infectious episode was €6707 [95% confidence interval (CI) €6189-7406]. The mean cost per OPAT episode was €1356 (95% CI €1247-1560), mainly distributed between healthcare staff costs (46%) and pharmacy costs (39%). The mean cost of inpatient hospitalisation of an infectious episode was €4357 (95% CI €3947-4977). The cost per day of inpatient hospitalisation was €519, whilst the cost per day of OPAT was €98, meaning a saving of 81%. This study shows that OPAT administered by HaH units resulted in lower costs compared with inpatient care in Spain.

NAT2 gene diversity and its evolutionary trajectory in the Americas.

N-acetyltransferase 2 (NAT2) is responsible for metabolizing xenobiotics; NAT2 polymorphisms lead to three phenotypes: rapid, intermediate and slow acetylators. We aimed to investigate NAT2 diversity in Native Americans. NAT2 exon 2 was sequenced for 286 individuals from 21 populations (Native American and American Mestizos). Excluding the basal/rapid haplotype NAT2*4, the most frequent haplotypes are NAT2*5B (35.95%) in hunter-gatherers and NAT2*7B (20.61%) and NAT2*5B (19.08%) in agriculturalists that were related to the slow phenotype. A new haplotype was identified in two Amerindians. Data from the ~44 kb region surrounding NAT2 in 819 individuals from Africa, East-Asia, Europe and America were used in additional analyses. No significant differences in the acetylator NAT2 haplotype and phenotype distributions were found between Native American populations practicing farming and/or herding and those practicing hunting and gathering, probably because of the absence or weakness of selection pressures and presence of demographic and random processes preventing detection of any selection signal.

Left-sided infective endocarditis in patients with liver cirrhosis.

OBJECTIVE: To evaluate the course of left-sided infective endocarditis (LsIE) in patients with liver cirrhosis (LC) analyzing its influence on mortality and the impact of surgery. METHODS: Prospective cohort study, conducted from 1984 to 2013 in 26 Spanish hospitals. RESULTS: A total of 3.136 patients with LsIE were enrolled and 308 had LC: 151 Child-Pugh A, 103 B, 34 C and 20 were excluded because of unknown stage. Mortality was significantly higher in the patients with LsIE and LC (42.5% vs. 28.4%; p < 0.01) and this condition was in general an independent worse factor for outcome (HR 1.51, 95% CI: 1.23-1.85; p < 0.001). However, patients in stage A had similar mortality to patients without cirrhosis (31.8% vs. 28.4% p = NS) and in this stage heart surgery had a protective effect (28% in operated patients vs. 60% in non-operated when it was indicated). Mortality was significantly higher in stages B (52.4%) and C (52.9%) and the prognosis was better for patients in stage B who underwent surgery immediately (mortality 50%) compared to those where surgery was delayed (58%) or not performed (74%). Only one patient in stage C underwent surgery. CONCLUSIONS: Patients with liver cirrhosis and infective endocarditis have a poorer prognosis only in stages B and C. Early surgery must be performed in stages A and although in selected patients in stage B when indicated.

Ocular and craniofacial phenotypes in a large Brazilian family with congenital aniridia.

Congenital aniridia is a rare genetic disorder characterized by varying degrees of iris hypoplasia that are associated with additional ocular abnormalities. More than 90% of the causal mutations identified are found in the PAX6 gene, a transcription factor of critical importance in the process of neurogenesis and ocular development. Here, we investigate clinical, molecular, and craniofacial features of a large Brazilian family with congenital aniridia. Among the 56 eyes evaluated, phenotype variation encompassed bilateral total aniridia to mild iris defects with extensive variation between eyes of the same individual. PAX6 molecular screening indicated a heterozygous splice mutation (c.141 + 1G>A). Thus, we hypothesize that this splicing event may cause variation in the expression of the wild-type transcript, which may lead to the observed variation in phenotype. Affected individuals were more brachycephalic, even though their face height and cephalic circumference were not significantly different when compared to those of non-affected relatives. From this, we infer that the head shape of affected subjects may also be a result of the PAX6 splice-site mutation. Our data summarize the clinical variability associated with the ocular phenotype in a large family with aniridia, and help shed light on the role of PAX6 in neurocranial development.

High twinning rate in Cândido Godói: a new role for p53 in human fertility.

BACKGROUND: Cândido Godói (CG) is a small town in South Brazil, which has the highest prevalence of twin births in Brazil. Recently, a number of studies have shown that p53 plays an important role in reproduction through blastocyst implantation and intra utero embryo survival. Thus, gene polymorphisms in the p53 pathway were investigated in this population. METHODS: Single nucleotide polymorphisms from five genes in the p53 pathway were investigated, as well as background characteristics of 42 mothers of twins (cases) and 101 mothers of singletons (controls), all residents from CG. RESULTS: Mothers of twins have higher number of pregnancies and higher frequencies of P72 allele at TP53 and T allele at MDM4 genes compared with controls. Logistic regression shows that both TP53 and number of pregnancies maintained their association with twinning (P =0.004 and P =0.002, respectively), with TP53 having a higher odds ratio than number of pregnancies (2.73 versus 1.70, respectively). No interactive effect between TP53 and MDM4 (P =0.966) is observed. As expected, mothers of twins have three times more cases of cancer in their first-degree relatives than control mothers (P =0.011). CONCLUSIONS: Our results suggest that the P72 allele of TP53 is a strong risk factor for twinning in CG, while the number of pregnancies and the T allele at MDM4 may represent weaker risk factors. These two alleles are associated with infertility, but the anti-apoptotic effect of low levels of p53 in general, and of the P72 allele in particular, may play a role after implantation, enhancing the chance for a double pregnancy to succeed to term.

Linezolid therapy for infective endocarditis.

Linezolid is not yet recognised as a standard therapy for infective endocarditis. This report describes nine patients with endocarditis treated with linezolid and 33 similar cases from the medical literature. The majority of cases involved multiresistant strains, and the reasons for administering linezolid were refractory disease (60%), intolerance (28%), sequential therapy (12%) and a resistant pathogen (1%). Linezolid was administered for a mean of 37 days, with a successful outcome in 79% of cases. Reversible adverse effects were described in ten cases. The mean follow-up period was 8.5 months. Further data from randomised controlled clinical trials are needed to determine the efficacy and safety of linezolid for treating endocarditis.

[Cocaine-induced neurological complications]. / Complicaciones neurológicas por cocaína.

Cocaine intake growth is a well-known fact, and that involves the appearance of unknown or forgotten complications. We have wanted to make a checking of neurologic complications due to the intake of this drug, make a special point of the physiopathological mechanisms and stopping at those related to treatment. We also want to contribute with our experience with regard to these processes.

[Pericardial tamponade and carcinomatous lymphangitis as primary manifestation of lung neoplasm]. / Taponamiento pericárdico y linfangitis carcinomatosa como primera manifestación de neoplasia pulmonar.

Cardiac tamponade (CT) and Carcinomatous lymphangitis (CL) association as an initial clinical presentation of a neoplasm is very uncommon, creating diagnosis difficulties in the patient first evaluation. This paper reports one case of a male who was admitted in Emergency Department with clinical and radiological findings of heart failure. Following studies showed CT and CL secondary to a bronchial adenocarcinoma. Differential diagnosis is really important for its associated therapeutic implications because of the CT hemodynamic worsening situation due to the diuretic and vasodilators used in the treatment of heart failure. An echocardiography should be done because it is very useful for the initial evaluation of a heart failure of obscure origin.

[Community-acquired pneumonia in the aged: prognostic factors]. / Neumonía comunitaria en el anciano: factores pronósticos.

We studied the clinical characteristics and the initial supplementary test available in the emergency service, in aged patients with community-acquired pneumonia, as well as their mortality prognosis value. We assessed 190 patients attended consecutively during one year. Clinical, analytical and radiological data were registered. The parameters associated to a higher mortality were: age, absence of thoracic pain, reduction in the level of consciousness, leukocytosis, increased urea levels, aminotransferases, lactate dehydrogenase and reduction in prothrombin activity and pH. The data associated to a greater relative risk were: age above 80 years, absence of thoracic pain, prothrombin activity lower than 70% and ALT < 40 U/l. The presence of three to four of these variables had a sensitivity of 62% and a specificity of 94% in the prediction of mortality. In the multivariable analysis, the following variables remained significative: age, obnubilation and decrease of prothrombin. We stress the relevance of a high clinical suspicion, given the frequency of these cases with little symptomatology, in order to allow for an early treatment and the identification of right risk patients at the initial assessment.

[Rhabdomyolysis in acute intoxications]. / Rabdomiolisis en intoxicaciones agudas.

The development of rhabdomyolysis is a complications of acute intoxications, although its actual incidences is unknown. We had studied the frequency and differential characteristics of the patients with such complications. A prospective study was conducted with 200 patients admitted to a General Hospital from an urban area due to acute intoxication, recording the etiology of the intoxication, motivation and analytical characteristics of the patients with rhabdomyolysis compared to their patients without rhabdomyolysis. The incidence of rhabdomyolysis was 7.7%. Among the patients with rhabdomyolysis, ludic motivation (59%) and etiology associated to drug abuse (heroin 30%, cocaine 24%) were more frequent compared to the patients without rhabdomyolysis. Twenty per cent of the patients consuming cocaine and 17% of the patients consuming heroin developed rhabdomyolysis. Acute rhabdomyolysis was, thus, a significant complication of acute intoxications, associated to the consumption of illegal drugs and, at least in our cases, with a good evolution regarding the renal function.

[Impact of arterial hypertension on the central nervous system]. / Repercusión de la hipertensión arterial sobre el sistema nervioso central.

Cerebrovascular diseases (CVD) entail high costs associated to therapies, hospitalizations and disabilities. Arterial hypertension (AHT) is the major modifiable risk factor for the development of all types of CVDs (cerebrovascular accidents, vascular dementias, etc.). The increase of arterial pressure causes functional and anatomical changes in the cerebral circulation which facilitate the development of CVDs. The time of evolution and the severity of the AHT, as well as the associated vascular risk factors, will determine its impact on the central nervous system.