Clinical characteristics of adult patients with inborn errors of metabolism in Spain: A review of 500 cases from university hospitals.

Patients with inborn errors of metabolism (IEMs) have become an emerging and challenging group in the adult healthcare system whose needs should be known in order to implement appropriate policies and to adapt adult clinical departments. We aimed to analyze the clinical characteristics of adult patients with IEMs who attend the most important Spanish hospitals caring for these conditions. A cohort study was conducted in 500 patients, categorized by metabolic subtype according to pathophysiological classification. The most prevalent group of IEMs was amino acid disorders, with 108 (21.6%) patients diagnosed with phenylketonuria. Lysosomal storage disorders were the second group, in which 32 (6.4%) and 25 (5%) patients had Fabry disease and Gaucher disease respectively. The great clinical heterogeneity, the significant delay in diagnosis after symptom onset, the existence of some degree of physical dependence in a great number of patients, the need for a multidisciplinary and coordinated approach, and the lack of specific drug treatment are common features in this group of conditions.

[Diagnosis and treatment of imported eosinophilia in travellers and immigrants: Recommendations of the Spanish Society of Tropical Medicine and International Health (SEMTSI)]. / Diagnóstico y tratamiento de la eosinofilia importada en viajeros e inmigrantes: recomendaciones de la Sociedad Española de Medicina Tropical y Salud Internacional (SEMTSI).

According to published data, prevalence of imported eosinophilia among travellers and immigrants is set between 8% and 28.5%. Etiological diagnosis is often troublesome, and depending on the depth of the study and on the population analyzed, a parasitic cause is identified in 17% to 75.9% of the individuals. Among the difficulties encountered to compare studies are the heterogeneity of the studied populations, the type of data collection (prospective/retrospective) and different diagnostic protocols. In this document the recommendations of the expert group of the Spanish Society of Tropical Medicine and International Health (SEMTSI) for the diagnosis and treatment of imported eosinophilia are detailed.

Statin-associated autoimmune myopathy: A distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories.

BACKGROUND AND OBJECTIVE: Statin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has recently been described. Several specific immunoassays are in use to detect HMGCR antibodies. In the course of systematic autoantibody screening we recognized a new distinct IFL staining pattern on rat liver sections that regularly coincided with anti-HMGCR antibodies. In this study we investigated whether this new IFL pattern is specifically associated to statin-associated autoimmune myopathy and corresponds to anti-HMGCR antibodies. PATIENTS AND METHODS: Twenty-three patients positive for anti-HMGCR antibodies (14 diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays and confirmed by immmunoblot. HMGCR associated liver IFL pattern (HALIP) was detected by indirect IFL and the reactivity against HMGCR was confirmed by immunoabsorption using purified human HMGCR antigen. 90 patients with other autoimmune diseases and 45 non-autoimmune statin treated patients were studied as controls. RESULTS: 21 out of 23 (91%) anti-HMGCR positive patients were HALIP positive. The staining was completely and specifically removed by immunoabsorption with human purified HMGCR. None of the control sera from autoimmune patients or non-autoimmune statin treated subjects was positive for HALIP. Statistical concordance between HALIP and anti-HMGCR antibody specific tests was 98.7%, kappa 0.95. CONCLUSIONS: A new and distinct IFL staining pattern (HALIP) is associated to HMGCR associated myopathy. Absorption and concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR or a closely related protein. Awareness of this new pattern can help to detect HMGCR autoantibodies in statin treated patients tested for autoimmune serology.

The changing epidemiology of bacteraemic osteoarticular infections in the early 21st century.

Osteoarticular infections (OAI), which are often associated with bacteraemia, seem to be increasing. We studied all patients with bacteraemia and concomitant OAI: septic arthritis (SA), vertebral osteomyelitis (VOM) or peripheral osteomyelitis (POM), which were seen at our institution (1985-2011). Data were extracted from a prospective protocol of bacteraemia cases recorded. Trends in main findings were considered in five periods. Major antibiotic resistance patterns were studied. A total of 601 cases of bacteraemic OAI, accounting for 1.8% of total bactaeremias, were studied: SA (48%), VOM (40%) and POM (17%). When comparing the 1985-91 and 2007-11 periods, the incidence of bacteraemic OAI increased from 2.34 to 5.78 episodes/100 000 inhabitants per year (p <0.001); and nosocomial and healthcare-related cases increased from 18% to 30% (p <0.001) and from 10% to 25% (p <0.001), respectively. Also, there was an increase of age (median, from 49 to 65 years, p <0.001), patients with comorbidities (23% to 59%, p <0.001), and device-related OAI (7% to 28%, p <0.001). Patterns of OAI were changing over time. Compared with younger patients, older adults (≥ 65 years) had more VOM, prosthetic-joint infections and enterococcal OAI. The percentage of OAI caused by methicillin-susceptible Staphylococcus aureus decreased, while those caused by methicillin-resistant S. aureus, streptococci, enterococci, and Gram-negative bacilli increased. There was a link between certain microorganisms with specific OAI and age of patients. Over the past three decades, bacteraemic OAI increased in association with aging and use of orthopaedic devices. Nosocomial and healthcare-related OAI increased, with a rise in multidrug-resistant bacteria. These trends should be considered when planning diagnostic and therapeutic guidelines for OAI.

Non-specific immunoglobulin titres against cytomegalovirus: an alternative to hyperimmune presentation.

OBJECTIVE: Specific immunoglobulin against cytomegalovirus has demonstrated its effectiveness in preventing and treating infections in solid organ transplantation. Several studies indicate that non-specific immunoglobulin is just as effective. This study aims to determine anti-cytomegalovirus immunoglobulin titres from one of the non-specific immunoglobulin presentations authorised in Spain. METHOD: This was an observational study, in which we analysed the anti-cytomegalovirus antibody titres from different batches of Flebogamma(®) 5% 5g used at the Hospital Universitari Vall d'Hebron during 2008 and 2009. RESULTS: We analysed 27 batches, which included 18,944 vials of Flebogamma(®) 5%. Depending on the origin, the median concentration of anti-cytomegalovirus immunoglobulin was 28PEI-U/ml and 22PEI-U/ml per vial of North American and Spanish origin, respectively (CI 95% for the difference of the medians 5 to 6PEI-U/ml; p<0.001). CONCLUSIONS: The anti-cytomegalovirus antibody concentration of the non-specific immunoglobulin batches analysed was slightly lower than in the specific immunoglobulin preparations. These differences can be compensated by adjusting the dosage.

Electrophysiological study of ephaptic axono-axonal responses in hemifacial spasm.

One of the classic features of hemifacial spasm (HFS) is spread of the blink reflex responses to muscles other than the orbicularis oculi. The pathophysiological mechanisms underlying the generation of such abnormal responses include lateral spread of activity between neighboring fibers of the facial nerve and hyperexcitability of facial motoneurons. In this report we present evidence for another mechanism that can contribute to the generation of responses in lower facial muscles resembling the R1 response of the blink reflex. In 13 HFS patients, we studied the responses induced in orbicularis oris by electrical stimuli applied at various sites between the supraorbital and zygomatic areas. We identified responses with two different components: an early and very stable component, with an onset latency ranging from 10.5 to 14.8 ms, and a more irregular longer-latency component. Displacement of the stimulation site away from the supraorbital nerve and towards the extracranial origin of the facial nerve caused a progressive shortening of response latency. These features indicate that, in our patients, the shortest latency component of the orbicularis oris response was likely generated by antidromic conduction in facial nerve motor axons followed by axono-axonal activation of the fibers innervating the lower facial muscles. Our results suggest that motor axono-axonal responses are generated by stimulation of facial nerve terminals in HFS.

[Drug information management through the intranet of a hospital center]. / Original Breve Gestión de la información de medicamentos mediante la intranet de un centro hospitalario.

OBJECTIVE: This paper describes the methodology used for the implementation and validation of a network resource incorporated to the intranet of the Hospital, in order to retain and disseminate information from the Drug Information Center (DIC) of a pharmacy service in a hospital center. METHOD: A working group designed the structure, contents, memory needs, priority of access for users and a quality assessment questionnaire. RESULTS: The resource developed by the working group had a capacity of 70 Gb and its structure was based on HTML documents, including files with different format and 12 theme areas. Two levels of priority of access were established depending on the user and two persons were in charge of the resource. The questionnaire was delivered after three months of use. Sixty nine per cent of the users regarded the resource as very useful and 31%, as useful. The final structure, according to the results of the survey, had 11 theme areas. CONCLUSIONS: The use of the hospital Intranet in order to include and organize DIC information can be very simple and economic. Furthermore, the involvement of all the users in its design and structure can facilitate the practical use of this tool and improve its quality.

[Clinical and pharmacological databases for personal digital assistants]. / Bases de datos clínicas y farmacológicas para asistentes personales digitales.

Personal digital assistants (PDAs) are part of the new technologies applied to medicine, which could improve both access to and storage of distinct databases. The present article reviews some general technical features, as well as the utility of these devices for consulting specific pediatric, clinical and pharmacological databases. A search was performed in Medline (1999 to 2004) and of web pages that described the use of PDAs and a total of 46 useful applications were identified, including pediatric diagnostic and treatment guidelines, databases of diagnostic procedures, guidelines for antibiotic therapy in the pediatric and adult populations, databases to establish the diagnosis and treatment of patients in emergency and intensive care medicine, catalogues of general drugs with complete pharmacological data (indications, doses, adverse effects, interactions, toxicology, pregnancy, lactation), specific databases of neonatology, otorhinolaryngology and pediatric surgery, and medical calculator software. Each reference details the contents, source of the reference information, memory requirements, operating system, cost, web page for downloads and whether there is a test version. There is a wide variety of pediatrics software for PDAs. Once the quality of these databases has been assessed, each user should evaluate which application will be most useful depending on his or her needs.

[Assesing the GRDOSIS Software program as a tool to analyse drug usase by DRGs]. / Evaluación del programa informático GRDOSIS como herramienta de análisis de la utilización de medicamentos por GRD.

OBJECTIVE: To validate the GRDOSIS software program as a tool to calculate Spanish drug weights within diagnosis-related groups (DRGs), and to analyse information used in this calculation. MATERIAL AND METHODS: Information corresponding to a 7-hospital sample is analysed after exchanging data between the minimum basic data set processed by the DRG-grouping program Estación Clínica -3M and unit-dose drug consumption. Data are purged by eliminating cases with an unusual (either long or short) length of stay in each DRG, and both weights and pondered weights are calculated. Data from the 5 most prevalent DRGs are analysed by using the different options provided by the software program, with the aim of detecting intervention points in order to improve results. RESULTS: Extreme case elimination noticeably reduces mean cost per DRG. A reduced group of DRGs represents a high percentage of total cost. Similarly, a reduced number of drugs may represent a high percentage of cost within a given DRG. The use of specific therapeutic groups for specific DRGs is demonstrated, as is the correct use of first-choice drugs versus other therapeutic options within therapeutic groups. An unwarranted variability regarding drug administration dosing and frequency is, however, observed. CONCLUSIONS: The GRDOSIS software program proves itself a powerful tool for both the qualitative (drug usage profiles, dosage) and quantitative (costs) analysis of information originating in a Pharmacy Department

Alcoholic myopathies.

Ethanol consumption may produce acute or chronic changes in striated skeletal muscle in a dose-dependent manner. The physiopathological mechanisms for such changes are probably related to alterations in membrane fluidity, channels, pumps and ionic transients, depression of muscle contractility, protein synthesis and genetic problems. In patients with alcoholic myopathies, multiorgan involvement is frequent and reversibility is only partially achieved by abstinence.

[Inclusion-body myositis: a familial report of 3 cases]. / Miositis con cuerpos de inclusión: presentación familiar de tres casos.

Inclusion body myositis (IBM) is a myopathy classified until now within the group of idiopathic inflammatory myopathies (IIM). Nevertheless, its clinical and histological features are specific and different from the other IIM. It is refractory to corticosteroid therapy. Recently, a few cases of IBM with familial transmission have been described, which is the first report in our country; previous reported cases in literature are reviewed. The similarities of some forms of IBM with muscle dystrophies, rather than with inflammatory myopathies are discussed.

[Myopathy and polyneuropathy caused by colchicine]. / Miopatía y polineuropatía por colquicina.

A forty-six year old man with chronic renal failure and a toxic chronic liver disease developed progressive muscle weakness after a long trial with colchicine. Physical exam revealed muscle weakness and proximal muscle atrophy with hyporeflexia. Serum levels of creatine kinase were high and signs of myopathy and axonal and demyelinating polyneuropathy was evidenced in electrophysiological studies. Muscle biopsy disclosed a vacuolar myopathy, disruption of myofibers and dilatation of sarcoplasmic reticulum. The clinical pictures was attributed to a toxic myopathy and polyneuropathy due to colchicine, thus this treatment was discontinued. Four week later, the patient was symptom free, the levels of seric creatine kinase were normal and a new muscle biopsy was normal, with disappearance of previous histological findings.