Vitamin B12: For more than just the treatment of megaloblastic anemia?

Vitamin B12, or cobalamin, belongs to the group of water-soluble vitamins and is ingested through food of animal origin such as eggs, milk, red meat and poultry, fish, and shellfish. Its clinical indication is the treatment of hypovitaminosis B12 administered orally or intramuscularly in the form of hydroxocobalamin. Hypovitaminosis B12 is mainly caused by deficient dietary intake (individuals with malnutrition, vegetarians or vegans, older adults, pregnant people, individuals with alcohol use disorder); when intestinal absorption is reduced (atrophic gastritis, malabsorption syndrome, gastrointestinal surgery); and for causes associated with the intake of drugs (antacids, metformin). Hypervitaminosis B12 has been associated with renal failure; liver diseases such as cirrhosis and acute-phase hepatitis; alcohol use disorder with or without liver involvement; solid tumors of the lung, liver, esophagus, pancreas, and colorectum; and in hematological malignancies such as leukemia and bone marrow dysplasia.

Impact of substrate overloading on archaeal populations in anaerobic digestion of animal waste.

AIMS: To characterize adaptive changes in methanogenic microbial community in response to substrate overloading and identify potential linkages between process performance and microbial community composition. METHODS AND RESULTS: Triplicate continuous anaerobic digesters were developed as model anaerobic digestion processes, which were subsequently disrupted by substrate overloading. The clone library analysis of archaeal communities experiencing substrate overloading showed that populations related to Methanosaeta were the dominant methanogens before and after substrate overloading, suggesting the functional importance of these acetoclastic methanogens in balanced anaerobic digestion processes characterized with low organic acids concentrations. Population redundancy in Methanosaeta increased following substrate overloading with the emergence of additional populations of Methanosaeta. More importantly, the methanogenic community responded to process imbalance with greater functional diversity with increased abundance of functionally distinct hydrogenotrophic and acetoclastic methanogens, which likely enhanced the functional stability of anaerobic digestion during disruptions in the anaerobic food web under process perturbation. Crenarchaeota were identified as persistent constituents of the archaeal communities in anaerobic digestion, warranting further efforts to identifying the functions of these phylogenetically distinct populations in anaerobic digestion. CONCLUSIONS: Substrate overloading in anaerobic digestion resulted in an increased functional diversity of the methanogenic community, which enhanced the capacity to overcome subsequent occurrences of process perturbations without performance disruption, providing a potential strategy to maintain process stability in anaerobic digestion. SIGNIFICANCE AND IMPACT OF THE STUDY: Anaerobic digestion is a sustainable option for waste treatment and renewable energy production. However, process instability resulting from variations in substrate loading has been one of the obstacles to the broader adoption of anaerobic digestion technology. Insight into the linkages between process performance and microbial community gained in this study is valuable for developing strategies for the mitigation of the impact of substrate overloading on anaerobic digestion processes.

Guillain-Barre syndrome in Mexico: clinical features and validation of Brighton Collaboration Group criteria. / Síndrome de Guillain-Barré en México: características clínicas y validación de los criterios de Brighton.

INTRODUCTION: As SARS-CoV-2 vaccination is ongoing in Mexico and Guillain-Barre syndrome (GBS) cases have been reported, validation of Brighton criteria in Mexico is necessary. Moreover, epidemiology of GBS in Mexico differs from European and North American countries. OBJECTIVE: To describe the clinical, cerebrospinal and electrodiagnostic features in Mexican patients diagnosed with GBS and classify them according to the Brighton Collaboration Group diagnostic criteria. Patrients and methods. An ambispective cohort study was conducted. We included patients that fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) diagnostic criteria for Guillain-Barre syndrome. Patients in this study were classified according to Brighton collaboration group levels of certainty for Guillain-Barre syndrome. RESULTS: Sixty eight percent of patients were male. Of the 248 patients included, 58.4% had history of a precedent infection, mean time from symptom onset to admission was 5 (1-30) days. Mean Medical Research Council sum score 30.3 ± 15.5. Almost 98% of patients had a monophasic course. Level 1 of certainty according to Brighton collaboration group criteria was fulfilled by 54.6% of patients, level 2 by 45% and level 4 by 0.6%. Patients meeting level 2 of certainty were mostly because normal cerebrospinal fluid findings or findings in nerve conduction studies not consistent with any GBS variants. CONCLUSION: GBS is a frequent autoimmune neuropathy that has been associated with preceding infections and with vaccination campaigns. For SARS-CoV-2 vaccination campaign in Mexico, validation of Brighton Criteria is necessary. Although Mexico's GBS epidemiology has been changing throughout recent years, this study provides similar data compared to other countries.

TITLE: Síndrome de Guillain-Barré en México: características clínicas y validación de los criterios de Brighton.Introducción. Dado que la vacunación contra el SARS-CoV-2 está en curso en México y se han notificado casos de Guillain-Barré, es necesaria la validación de los criterios de Brighton en México. La epidemiología de Guillain-Barré en México difiere de la de los países europeos y norteamericanos. Objetivo. Describir las características clínicas, cerebroespinales y electrodiagnósticas en pacientes mexicanos con diagnóstico de Guillain-Barré y clasificarlos según los criterios diagnósticos del Brighton Collaboration Group. Pacientes y métodos. Se realizó un estudio de cohorte ambispectivo. Se incluyó a pacientes que cumplen con los criterios del National Institute of Neurological Disorders and Stroke para el síndrome de Guillain-Barré (SGB). Se clasificó a los pacientes según los niveles de certeza del Brighton Collaboration Group para el SGB. Resultados. El 68% de los pacientes eran hombres. De los 248 pacientes incluidos, el 58,4% tenía antecedentes de infección previa. La media desde el inicio de los síntomas hasta el ingreso fue de 5 (1-30) días, y la puntuación media de la suma del Medical Research Council, de 30,3 ± 15,5. El nivel 1 de certeza según los criterios del Brighton Collaboration Group se cumplió en el 54,6% de los pacientes; el nivel 2, en el 45%; y el nivel 4, en el 0,6%. Los pacientes que alcanzaron el nivel 2 de certeza se debieron principalmente a hallazgos normales en el líquido cefalorraquídeo o a hallazgos en estudios de neuroconducción que no cumplen los criterios de ninguna variante de SGB. Conclusión. El SGB es una neuropatía autoinmune frecuente que se ha asociado con infecciones previas y con campañas de vacunación. Para la campaña de vacunación contra el SARS-CoV-2 en México es necesaria la validación de los criterios de Brighton. Aunque la epidemiología del SGB en México ha ido cambiando a lo largo de los últimos años, este estudio proporciona datos similares en comparación con otros países.

[Clinical and neurophysiological patterns of early presenting symptoms in acute onset chronic inflammatory demyelinating polyradiculoneuropathy]. / Patrones clínicos y neurofisiológicos de presentación temprana en la polirradiculoneuropatía inflamatoria desmielinizante crónica de inicio agudo.

INTRODUCTION: The phenotypes of chronic inflammatory demyelinating polyneuropathy (CIDP) include an acute-onset phenotype (A-CIDP) with an evolution time of less than eight weeks from the onset of symptoms. This entity can be confused with Guillain-Barre syndrome of the acute inflammatory demyelinating variety (AIDP), delaying the start of treatment. OBJECTIVE: To analyze the clinical and electrophysiological differences between A-CIDP, classic CIDP and AIDP, in order to identify factors that may help in the early differential diagnosis. PATIENTS AND METHODS: A cross-sectional study was carried out with patients seen at the neuromuscular disease clinic of the National Institute of Neurology and Neurosurgery with a diagnosis of CIDP according to the criteria of the European Federation of Neurological Societies and Peripheral Nerve Society. Patients with CIDP <8 weeks were categorized as A-CIDP and were compared with patients diagnosed with classic CIDP and AIDP. Clinical, paraclinical and electrophysiological variables were obtained and analyzed. RESULTS: Significant differences in history of infection, cranial nerve involvement and dysautonomia were observed between A-CIDP and AIDP. Electrophysiological recordings reported significant differences in motor nerve conduction velocity and sural nerve recordings, being lower in the A-CIDP group. CONCLUSION: A history of infection, cranial nerve involvement and dysautonomia are important parameters to take into account for the differential diagnosis of these entities. Electrophysiological analysis is similar between A-CIDP and CIDP. The differential diagnosis between these types of demyelinating polyneuropathy must be based on clinical assessment.

TITLE: Patrones clínicos y neurofisiológicos de presentación temprana en la polirradiculoneuropatía inflamatoria desmielinizante crónica de inicio agudo.Introducción. Dentro de los fenotipos de polineuropatía desmielinizante inflamatoria crónica (CIDP) existe uno cuyo tiempo de evolución es menor de ocho semanas desde el inicio de los síntomas, denominado de inicio agudo (A-CIDP). Esta entidad puede confundirse con el síndrome de Guillain-Barré, variedad desmielinizante inflamatoria aguda (AIDP), lo que retrasa el inicio del tratamiento. Objetivo. Analizar las diferencias clínicas y electrofisiológicas entre A-CIDP, CIDP clásica y AIDP, con el fin de identificar factores que auxilien al diagnóstico diferencial de forma temprana. Pacientes y métodos. Se realizó un estudio transversal con pacientes atendidos en la clínica de enfermedades neuromusculares del Instituto Nacional de Neurología y Neurocirugía con diagnóstico de CIDP según criterios de la European Federation of Neurological Societies and Peripheral Nerve Society. Los pacientes con CIDP inferior a 8 semanas se catalogaron como A-CIDP y fueron comparados con pacientes diagnosticados con CIDP clásica y AIDP. Se obtuvieron y analizaron variables clínicas, paraclínicas y electrofisiológicas. Resultados. Se observaron diferencias significativas en antecedente de infección, afección de nervios del cráneo y disautonomías entre la A-CIDP y la AIDP. Los registros electrofisiológicos describieron diferencias significativas en velocidad de conducción de los nervios motores y en los registros del nervio sural, que fueron menores en el grupo de A-CIDP. Conclusión. El antecedente de infección, la afección de nervios del cráneo y las disautonomías son parámetros importantes que se debe tener en cuenta para el diagnóstico diferencial de estas entidades. El análisis electrofisiológico es similar entre la A-CIDP y la CIDP. El diagnóstico diferencial entre estos tipos de polineuropatía desmielinizante debe basarse en el juicio clínico.

Efficacy of long-term prednisone therapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP): a retrospective cohort study. / Eficacia del uso de prednisona como terapia a largo plazo en pacientes con polineuropatía desmielinizante inflamatoria crónica (PDIC): una cohorte retrospectiva.

INTRODUCTION: Patients with CIDP respond adequately to steroid therapy and intravenous immunoglobulin (IVIG). However, few patients have access to IVIG in developing countries. Little information exists about the clinical response to steroid therapy in Latin American countries. OBJECTIVE: to describe the long-term functional clinical response (24 months) to prednisone therapy in CIDP patients. MATERIAL AND METHODS: A retrospective cohort was conducted. Selection included patients with definitive CIDP diagnosis according to European criteria from the Neuromuscular Diseases clinic of the National Institute of Neurology and Neurosurgery between January 2016 and December 2020. Good response to steroid therapy was defined as with improvement in at least one point on the GBS disability score. Poor response to steroid therapy was defined as patients who did not show improvement in at least one point on the GBS disability score. Patients were evaluated at 3, 6, 12, 18 and 24 months. RESULTS: Forty-seven patients with CIDP were included. Half of them were male and mean age was 46±15 years. Mean time since symptom onset to diagnosis was 6 (IQR 2-12) months. The most common clinical variant was sensory-motor 57.4%, followed by acute-onset CIDP 21.3% and atypical variants 21.2%. At diagnosis our patients presented: mean GBS disability score of 3 (2.25-4) points, MRC score 39.5 ± 12 points, independent gait in 17%, mean prednisone dose of 50 mg (32.5-50). Twenty-four months after prednisone therapy, a less mean GBS disability score -1(0-2) points-, mean MRC score 56.3 ± 5.1 points, independent gait 93% and prednisone dose 1 (0-5) mg. Patients with poor three-month functional clinical response had a delay in diagnosis > 6 months (64.7% vs 27.5%) and atypical clinical variants (47% vs 6.8%). CONCLUSION: CIDP patients treated with prednisone have good long-term functional clinical response. Delay in diagnosis and atypical variant are common clinical characteristics for poor functional clinical response in treatment with prednisone.

TITLE: Eficacia del uso de prednisona como terapia a largo plazo en pacientes con polineuropatía desmielinizante inflamatoria crónica (PDIC): una cohorte retrospectiva.Introducción. Los pacientes con polineuropatía desmielinizante inflamatoria crónica (PDIC) responden adecuadamente a la terapia con esteroides y a la inmunoglobulina intravenosa (IgIV). Sin embargo, pocos pacientes tienen acceso a la IgIV en los países en desarrollo. Existe poca información sobre la respuesta clínica a la terapia con esteroides en los países de Latinoamérica. Objetivo. Describir la respuesta clínica funcional a largo plazo (24 meses) a la terapia con prednisona en pacientes con PDIC. Material y métodos. Se realizó una cohorte retrospectiva. La selección incluyó a pacientes con diagnóstico definitivo de PDIC según los criterios europeos de la Clínica de Enfermedades Neuromusculares del Instituto Nacional de Neurología y Neurocirugía entre enero de 2016 y diciembre de 2020. La buena respuesta a la terapia con esteroides se definió como una mejoría al menos en un punto de la Guillain-Barre Disability Score (GBS). La mala respuesta a la terapia con esteroides se definió como pacientes que no mostraron mejoría al menos en un punto en la GBS. Los pacientes fueron evaluados a los 3, 6, 12, 18 y 24 meses. Resultados. Se incluyó a 47 pacientes con PDIC. La mitad de ellos eran varones y la edad media fue de 46 ± 15 años. El tiempo medio desde el inicio de los síntomas hasta el diagnóstico fue de 6 (rango intercuartílico: 2-12) meses. La variante clínica más común fue la sensomotora (57,4%), seguida de la PDIC de inicio agudo (21,3%) y de variantes atípicas (21,2%). En el momento del diagnóstico, nuestros pacientes presentaban: GBS media de 3 (2,25-4) puntos, puntuación de la escala del Medical Research Council (MRC) de 39,5 ± 12 puntos, marcha independiente en el 17% y dosis media de prednisona de 50 mg (32,5-50). Veinticuatro meses después de la terapia con prednisona, la GBS media era menor ­1 (0-2) puntos­, la puntuación media del MRC era de 56,3 ± 5,1 puntos, había marcha independiente en el 93% y la dosis de prednisona era de 1 mg (0-5). Los pacientes con mala respuesta clínica funcional a los tres meses tuvieron un retraso en el diagnóstico > 6 meses (64,7% frente a 27,5%) y variantes clínicas atípicas (47% frente a 6,8%). Conclusión. Los pacientes con PDIC tratados con prednisona tienen una buena respuesta clínica funcional a largo plazo. El retraso en el diagnóstico y la variante atípica son características clínicas frecuentes de la respuesta clínica funcional deficiente en el tratamiento con prednisona.

Guillain-Barre syndrome during COVID-19 pandemic: experience from a referral healthcare center in Mexico. / Síndrome de Guillain-Barré durante la pandemia de COVID-19: experiencia de un centro de referencia en México.

INTRODUCTION: To describe clinical characteristics and electrophysiological variants of GBS cases during the pandemic, we carried out a comparative analysis between SARS-CoV2 related GBS and non-SARS-CoV2 patients and then compared to the 2019 cases. PATIENTS AND METHODS: We carried out a cross-sectional study of GBS patients diagnosed according to Asbury and Cornblath criteria. We collected information on clinical and paraclinical variables. We defined a SARS-CoV-2 related GBS case according to the description of Ellul et al. We used Hadden criteria to classify the electrophysiological variants. We performed a comparative analysis between groups. RESULTS: Fourty-two patients were diagnosed with GBS in 2020, men 64.2%, age 46 ± 17.4 years, patients with obesity/overweight 42.8%, previous diarrhea 31%, history of respiratory tract infection 14.2%. Guillain Barre Disability Scale = 3 points 71.4% and, cranial nerve involvement 69%. The most frequent electrophysiological variant was acute inflammatory demyelinating polyradiculoneuropathy (AIDP) 53.5%. Seven (16.6%) cases were SARS-CoV2 related, four men, age 43.4 ± 13.4 years. When comparing patients with GBS in 2020 vs patients in 2019, we observed a decrease in the previous infection history during 2020 (45.2% vs 73.3%, p-value = 0.005) and a decrease in previous respiratory infection (14.2% vs 33.3%, p = 0.045), as well as a higher frequency of cranial nerve involvement, and albuminocytologic dissociation. CONCLUSIONS: SARS-CoV2 virus infection preventive measures may be impacting the presentation of post-infectious diseases such as GBS. We did not observe an increase in GBS cases during 2020. Also, the AIDP variant were more frequent in our population in the COVID-19 pandemic.

TITLE: Síndrome de Guillain-Barré durante la pandemia de COVID-19: experiencia de un centro de referencia en México.Introducción. Se trata de describir las características clínicas y variantes electrofisiológicas de los casos de síndrome de Guillain-Barré (SGB) durante la pandemia. Llevamos a cabo un análisis comparativo entre pacientes con SGB relacionado con el SARS-CoV-2 y sin antecedente del virus, y posteriormente realizamos una comparación con los casos de 2019. Pacientes y métodos. Se llevó a cabo un estudio transversal de los pacientes con diagnóstico de SGB según los criterios de Asbury y Cornblath. Se recolectaron información clínica y variables paraclínicas. Definimos el SGB relacionado con el SARS-CoV-2 conforme a la descripción de Ellul et al. Se utilizaron los criterios de Hadden para la clasificación de las variantes electrofisiológicas. Por último, realizamos un análisis comparativo entre grupos. Resultados. Se diagnosticó a 42 pacientes con SGB en 2020, un 64,2% hombres, con una edad de 46 ± 17,4 años, un 42,8% con obesidad/sobrepeso, un 31% con historia de diarrea previa y un 14,2% con infección respiratoria previa. El 71,4% tuvo una puntuación en la Guillain-Barré Disability Score igual o mayor que 3 puntos y el 69% tenía afectados los nervios del cráneo. La variante electrofisiológica más común fue la polirradiculoneuropatía desmielinizante inflamatoria aguda (PDIA; 53,5%). Siete (16,6%) casos tuvieron relación con el SARS-CoV-2, cuatro hombres, con edad de 43,4 ± 13,4 años. Al realizar la comparación entre pacientes con SGB de 2020 frente a los de 2019, observamos un decremento en el antecedente de infección previa en 2020 (45,2 frente a 73,3%; p = 0,005) y un decremento específico en la historia de infección respiratoria (14,2 frente a 33,3%; p = 0,045), así como una mayor frecuencia de afectación de los nervios del cráneo y de disociación albuminocitológica. Conclusiones. Las maniobras preventivas para la infección por el SARS-CoV-2 impactan directamente en la presentación de enfermedades postinfecciosas como el SGB. No observamos un incremento en los casos de SGB durante 2020. Asimismo, la variante de PDIA fue la más frecuente en nuestra población durante la pandemia de COVID-19.

[Vulpian-Bernhardt syndrome. Its frequency and clinical and electrophysiological features in a tertiary care centre in Mexico]. / Síndrome de Vulpian-Bernhardt. Frecuencia, características clínicas y electrofisiológicas en un centro de atención de tercer nivel en México.

INTRODUCTION: Vulpian-Bernhardt syndrome (VBS) is an atypical rare clinical phenotype of amyotrophic lateral sclerosis (ALS) that causes a significant delay in diagnosis, and thus it is important to recognise its clinical and electrophysiological features. MATERIALS AND METHODS: Retrospective cross-sectional study. We reviewed the clinical records of patients diagnosed with ALS in the period from January to December 2019. Those meeting criteria for VBS were included so as to describe their frequency as well as their clinical and electrophysiological features. RESULTS: Twenty patients (15.8%) met criteria for VBS; 55% were female; age at onset of symptoms was 46.6 ± 12.9 years; 40% were smokers; median delay in diagnosis was 24 (12-96) months; median time to involvement of the second body segment was 24 (12-132) months, which was lumbosacral in 65%; mean Revised Amyotrophic Lateral Sclerosis Functional Rating Scale score was 27 ± 7 points; 45% met the El Escorial criteria for ALS defined at diagnosis and 58.8% met the Awaji criteria. There were 19 nerve conduction studies and 17 electromyograms, and an abductor digiti minimi-abductor pollicis brevis (ADM/APB) ratio < 0.6 was found in 63% (split hand). CONCLUSIONS: There is a significant delay in the diagnosis of motor neuron diseases in general and more particularly in VBS. Calculating the ADM/APB ratio and applying the Awaji criteria in the electrophysiology study can be a valuable aid to increase diagnostic certainty in this clinical entity.

TITLE: Síndrome de Vulpian-Bernhardt. Frecuencia, características clínicas y electrofisiológicas en un centro de atención de tercer nivel en México.Introducción. El síndrome de Vulpian-Bernhardt (SVB) es un fenotipo clínico atípico e infrecuente de la esclerosis lateral amiotrófica (ELA) que condiciona un importante retraso diagnóstico, por lo que reconocer sus características clínicas y electrofisiológicas tiene relevancia. Materiales y métodos. Estudio retrospectivo y transversal. Se revisaron los expedientes clínicos de pacientes con diagnóstico de ELA en el período de enero de 2017 a diciembre de 2019. Se incluyeron los que cumplían criterios para SVB para describir su frecuencia, características clínicas y electrofisiológicas. Resultados. Veinte pacientes (15,8%) cumplieron los criterios para el SVB; el 55% eran mujeres; la edad de inicio de los síntomas era de 46,6 ± 12,9 años; presentaba tabaquismo el 40%; la mediana de retraso del diagnóstico fue de 24 (12-96) meses; la mediana en afectarse un segundo segmento corporal fue de 24 (12-132) meses, que fue el lumbosacro en el 65%; el promedio en la escala Revised Amyotrophic Lateral Sclerosis Functional Rating Scale fue de 27 ± 7 puntos; el 45% cumplía los criterios de El Escorial para ELA definida en el momento del diagnóstico y el 58,8%, los de Awaji. Se contó con 19 estudios de neuroconducción y 17 electromiogramas, y se encontró una razón abductor digiti minimi-abductor pollicis brevis (APB/ADM) menos de 0,6 en el 63% (mano dividida). Conclusiones. Existe un retraso importante en el diagnóstico de enfermedades de la motoneurona en general y de SVB en particular. Calcular la razón APB/ADM y aplicar los criterios de Awaji en el estudio de electrofisiología puede ser de gran ayuda para aumentar la certeza diagnóstica en esta entidad clínica.

Strongyloides stercoralis hyperinfection transmitted by liver allograft in a transplant recipient.

We describe a case of Strongyloides stercoralis hyperinfection in a liver allograft recipient 2.5 months after transplantation. The patient lives in Spain, which is not considered an endemic country for strongyloidiasis, and denied prior residence or travel to any known endemic area. The initial symptoms were fever and vomiting, and he subsequently developed a severe respiratory disease. An endoscopic biopsy of ulcerative lesions of the duodenum revealed massive mucosa infiltration by larvae and adult worms, which were also found in respiratory samples. The patient was successfully treated with combined therapy with albendazole and ivermectin. The strongyloides infection was transmitted by the liver allograft. The donor was from Ecuador and, retrospectively, his serum tested positive for S. stercoralis IgG antibodies. Additionally, the pancreas-left kidney allograft recipient from the same donor later developed an intestinal strongyloidiasis without hyperinfection syndrome. To our knowledge, this is the first confirmed case of S. stercoralis infection transmission from the same donor to two solid allograft recipients.

Prevalence of fatal adverse drug reactions in hospitalized patients.

OBJECTIVE: The aims of the present study were to assess the prevalence of fatal adverse drug reactions (FADRs) in a hospitalized population, identify the drugs involved and investigate reported risk factors for these events. METHODS: The study population of this retrospective, single-centre case study comprised 289 patients dying between 1 January 2004 and 31 December 2004 and registered in the Cause of Death Register of a teaching hospital. All compiled data were recorded by two observers especially trained to identify and report adverse drug reactions (ADRs). The degree of probability that the ADR led directly to death was determined by using WHO criteria and an adapted version of Naranjo's score. RESULTS: Among 289 deceased study subjects, 17 (5.9%) were suspected to have died from an ADR. The most common suspected FADRs were gastrointestinal hemorrhages (52.9%), central nervous system hemorrhages (17.6%), cardiac disorders (17.6%), drug-induced myelosuppression (6%) and antimicrobial-related enterocolitis (6%). The drugs most frequently implicated in a FADR were antithrombotic drugs (65%), nonsteroidal anti-inflammatory drugs (NSAIDs) (47%) and corticosteroids (29%). The only risk factors associated with FADRs in this population were multiple-drug therapy and the presence of platelet antiaggregants and NSAIDs, alone or associated. CONCLUSIONS: FADRs are an important cause of death in hospitalized patients. Hemorrhages were seen in a majority of the fatal reactions, and antithrombotic agents or NSAIDs were implicated in most of these events.

[Drug-related mortality among inpatients admitted in Internal Medicine]. / Mortalidad hospitalaria asociada a medicamentos en un Servicio de Medicina Interna.

BACKGROUND: To analyze the mortality associated with prescriptions, the drugs most frequently involved and the associated risk factors in patients admitted to Internal Medicine. METHODS: A retrospective, observational study. The clinical records of adult patients who died consecutively in the department of Internal Medicine in a Spanish tertiary hospital over twenty-two months were reviewed. The main variable was the prevalence of hospital death suspected of being related to the medications administered during admission. RESULTS: Out of the 455 deaths analyzed, 22.2% were related to the medications received; in 55 cases (12.1%) the drugs were suspected of being the cause of death and in 46 cases (10.1%) of contributing to it. The most frequent diagnoses in cases of death associated with drugs were cardiac arrhythmia (23.7%), severe hemorrhage (19.8%) and aspiration pneumonia (12.8%). The drugs with the highest prevalence in deaths related to pharmacological treatment were an-tithrombotic drugs (23.7%), digoxin (21.7%), antipsychotics (17.8%) and benzodiazepines (14.8%). The only independent risk factor for mortality associated with treatment was the number of medications administered (OR=1.25, 95%CI: 1.14-1.37). No significant association was found with age, sex, number of pathologies or duration of hospital stay. CONCLUSION: A high percentage of deaths of patients admitted to Internal Medicine were considered related to the medications received. Antithrombotic drugs, digoxin and psychotropic drugs were the agents most frequently implicated. This mortality is independently and significantly associated with the number of medications administered.

[Adverse drug reactions in patients visiting a general hospital: a meta-analysis of results]. / Reacciones adversas a medicamentos en pacientes que acudieron a un hospital general: un meta-análisis de resultados.

OBJECTIVES: The aim of this study was to present the results of a meta-analysis on adverse drug reactions (ADR) in spanish patients admitted to hospital and presenting to emergency department over the past 20 years. PATIENTS AND METHODS: An exhaustive review was undertaken of relevant articles in the IME (Spanish Medical Index) and MEDLINE databases and published between 1985 and 2006, rigorously selecting 12 out of 30 publications after applying inclusion and exclusion criteria. Information was required on: symptomatology, prognosis, type, drugs involved, imputability and admissions for ADR; and factors associated with ADR onset, e.g., age, sex, number of drugs, previous history of ADR, method used for ADR detection, and length of study period. A random-effects model (DerSimonian and Laird) and the STATA 9.1 programme were used for the meta-analysis. RESULTS: The combined estimation of the percentage of Spanish patients with ADR was 13% (95% CI); with severe ADR, 12 % (95% CI) and with fatal ADR, 0.1% (95% CI). ADR diagnosis was definite in 36% (95% CI), probable in 49.6% (95% CI), and type A in 71% (95% CI) of cases. Among patients in the Emergency Department for ADR, 5.1% (95% IC) were hospitalized. No association was found with number of prescriptions or previous history. Association was established with advanced age and female sex. Digestive, skin, nervous and cardiovascular systems were those most affected by ADR. The drugs most frequently implicated included NSAIDs, digoxin, IACE, calcium antagonists, furosemide, i.v. metamizol, antidiabetics, benzodiazepines, adrenergic bronchodilators and classic antipsychotics. CONCLUSIONS: ADRs constitute a major medical and economic problem with aspects that have yet to be defined. Greater efforts are warranted to unify criteria for the publication of results in observational studies on ARD and to determine the role played by some factors associated with their onset, e.g., sex, previous history and comorbidities.

Pharmacokinetics of zidovudine in end-stage renal disease: influence of haemodialysis.

OBJECTIVE: To study the pharmacokinetics of zidovudine (ZDV) and its glucoronide metabolite (G-ZDV) in a patient with end-stage renal disease in haemodialysis. DESIGN: Pharmacokinetics study performed during and between haemodialysis sessions. METHODS: The patient was treated with oral ZDV (100 mg every 8 h). Concentrations of ZDV and G-ZDV were measured by radioimmunoassay. A monocompartmental model was used to calculate pharmacokinetic parameters. RESULTS: The peak plasma concentrations of ZDV and G-ZDV after drug administration between haemodialysis sessions were 0.57 and 10.01 micrograms/ml, respectively. The half-lives of ZDV and G-ZDV rose to 3.2 and 14.2 h, respectively. The total body clearance for ZDV in the period between haemodialysis sessions (0.44 l/kg/h) was 66% lower than normal values. The ZDV half-life was normalized by haemodialysis, the total body clearance of ZDV increased (1.12 l/kg/h) and the G-ZDV half-life shortened (5.9-7.9 h). Neither G-ZDV accumulation nor derived ZDV toxicity occurred. CONCLUSIONS: Our data suggest that ZDV is safe and an efficient drug when administered at a dosage of 100 mg three times daily in patients with end-stage renal disease in haemodialysis sessions, and that ZDV and G-ZDV are cleared by haemodialysis.

A study of indomethacin combined with ritodrine in threatened preterm labor.

A prospective and double-blind study was undertaken to compare the effectiveness of two different treatments on two randomized groups of patients with threatened preterm labor. The first treatment consisted of the administration of ritodrine and a placebo; in the second, ritodrine was combined with indomethacin. 22 patients were evaluated in each group. The results obtained for gain in days, number of patients delivered at term, weight of newborns and number of recurrences in each group suggest that treatment with ritodrine and indomethacin is slightly but significantly more effective than treatment with ritodrine and placebo in prolonging pregnancy. No evidence has been found of possible unfavorable vascular effects of indomethacin in the fetus or the newborn.

[Septic abortion. Complications and therapeutic considerations (author's transl)]. / Aborto séptico. Complicaciones y consideraciones terapéuticas.

A study is presented on the incidence and complications of septic abortion in a group of patients admited on the 1st. Obstetric and Gynecologic Clinic of the University of Barcelona during a period of 5 years (1971-1975). Abortion is the cause of admision of 20,2% of patients in the gynecology ward and represents the 12,3% of the overall number of patients during the same period. In 7,8% of the patients admited because of abortion we found the criteria for establishing the diagnosis of septic complication and in 15,2% of those extrapelvic involvement is found, mainly endotoxic shock, acute renal failure and difuse peritonitis. Endocervical cultures were positive in 73% of cases and in 65,7% gram negative germs were isolated, being the most common E. coli. The different clinical patterns are discussed in cases in which anaerobics are implicated and the diagnostic and therapeutic aproaches in the different complications are reviewed particularly in concern to the indications of surgery when this may be the only lifesaving procedure.

[Usefulness of cerebral biopsy in focal cerebral lesions in patients with human immunodeficiency virus infection]. / Utilidad de la biopsia cerebral en las lesiones cerebrales focales en pacientes con infección por el virus de la inmunodeficiencia humana.

Brain mass lesions (BML) occurred in 10% of patients infected by the human immunodeficiency virus (HIV), as expression of severe and sometimes treatable diseases. However, the management of them is not well established. We analyzed, retrospectively, 26 brain biopsies (22 estereotaxic) in patients with HIV infection and BML to know their usefulness and safety. The inclusion criteria were: Failure of the anti-Toxoplasma empirical treatment, atypical scan appearance for toxoplasmosis, or severe neurological picture. Brain biopsy yielded a diagnosis in 19 patients (73.1%): Progressive multifocal leukoencephalopathy (n = 8; 30.8%), primary central nervous system lymphoma (n = 6; 23.1%), mycobacteriosis (n = 2; 7.7%), toxoplasmosis (n = 2; 7.7%), criptococcosis (n = 1), cryptosporidiosis (n = 1) and HIV-encephalitis (n = 1). In one case there was a multiple diagnosis: mycobacteriosis, toxoplasmosis, and lymphoma. Brain biopsy results decided a change in therapy in 65.4%, the resolution or improvement of the neurological process in 30.8%, and the determination of the prognosis in 30.8%. In 8 cases (30.7%) there were biopsy complications, with secondary mortality in one. Brain biopsy of BML in HIV-infected patients is a diagnostic method with a high overall diagnostic rentability and uncommon non reversible complications, offering the possibility to prescribe a specific and potentially curative treatment.

[Pharmacokinetic study of zidovudine in parenteral drug addicts with human immunodeficiency virus infection]. / Estudio farmacocinético de zidovudina en adictos a drogas parenterales con infección por el virus de la inmunodeficiencia humana.

BACKGROUND: The aim of this study was to know the pharmacokinetics of zidovudine (ZDV) in steady state in patients with infection by the human immunodeficiency virus (HIV) in whom the risk factor was intravenous drug use. METHODS: The study was carried out in 8 patients in stage IV of the Centers for Disease Control (CDC) with no acute intercurrent process, with normal liver and renal function, orally receiving 250 mg of ZDV every 6 hours. Blood samples were taken between 30 and 360 minutes from the last doses taken during fasting. Plasma concentrations of ZDV and glucuronide zidovudine (G-ZDV) were determined by radioimmunoassay with the data being adapted to a monocompartmental pharmacokinetic model. RESULTS: The maximum concentration (Cmax) of ZDV was 0.81 +/- 0.38 microgram/ml demonstrating high interindividual variability with values between 0.35 microgram/ml and 1.45 microgram/ml. The mean Cmax of G-ZDV was 1.44 +/- 0.64 microgram/ml. The mean t1/2 of ZDV and G-ZDV was 1.63 +/- 0.75 hours and 1.12 +/- 0.32 hours, respectively, with values oscillating between 0.99 and 3.14 h in the case of ZDV. The area below the curve concentration/time (AUC) of ZDV was 1.43 +/- 0.34 microgram-h/ml and in the case of G-ZDV the AUC was 2.73 +/- 0.91 microgram-h/ml. Total body clearance (Clb) of ZDV was 2.11 +/- 0.64 l/kg/h and the volume of distribution (Vd) of ZDV was 5.6 +/- 1.73 l/kg. CONCLUSIONS: The results of this study demonstrate that there is a marked interindividual variability in the pharmacokinetics of zidovudine suggesting the need for adapting dosage to patients weight and monitoring plasma concentration.

[The study of occupational satisfaction and its determining factors among health professionals working in one of the areas in Madrid]. / Estudio de la satisfacción laboral y sus determinantes en los trabajadores sanitarios de un área de Madrid.

BACKGROUND: It is well known that job satisfaction influences health care services quality. The aim of this study is to evaluate sanitary workers' job satisfaction and to determine its components, in a sanitary district institutions: primary health care centres, speciality centres and district hospital. METHODS: A cross-sectional study was designed. The sample is proportional, stratified and randomized. It is composed of 947 workers, 460 of which are speciality care workers (SCW) (from a total study population of 1579 people), and 486 are primary care workers (PCW) (the whole population of PCW) from the tenth sanitary area of Madrid. We have used two questionnaires: the first one is Font-Roja's questionnaire which consists of 27 items that are evaluated through a Likert 1-5 scale. The second questionnaire consists of independent variables: socio-demographic and job variables. We have made an exploratory factorial analysis of various satisfaction components. We have evaluated the relationship between each dimension and the independent variables. RESULTS: 255 professionals of SCW (55.4% of the whole) and 357 of PCW (73.9% of the whole) answered the questionnaire. The dimensions that reached the lowest score were these factors: stress related with job and professional promotion (this factor was lowest in nurses and administrative worker). There are significant differences with respect to studied factors, professional level, and kind of job. CONCLUSIONS: We have found a half way satisfaction level in this sanitary district health care workers. Our results suggest that modifications in management and working conditions are needed, according to satisfaction dimension scores.

[Inappropriate blood levels of digoxin in a study of 2,849 patients from a teaching hospital: the influence of age and sex]. / Niveles inapropiados de digoxina en sangre relativos a 2.849 pacientes procedentes de un hospital universitario: influencia de la edad y el sexo.

OBJECTIVES: Digoxin is used to treat congestive heart failure and atrial fibrillation. Blood levels need to be monitored to optimize therapeutic performance, detect noncompliance and reduce toxicity. The aim of this study was to evaluate the use of digoxin by measuring blood levels of this drug. The influence of sex and age were also considered. PATIENTS AND METHOD: A retrospective study reviewed determinations of blood digoxin concentration in hospitalized and ambulatory patients with congestive heart failure, atrial fibrillation, or both, seen at the University of Granada Teaching Hospital (Spain) from 1992 to 2002. A chi square test was applied to results. RESULTS: A total of 5,623 laboratory tests for digoxin were done for 2,849 adult patients. Patients whose medical record was incomplete were excluded, and the final sample consisted of 2,629 patients. The 55.4% had inappropriate blood levels of digoxin. Inappropriate concentrations to digoxin were significantly higher in women (p < 0.001). The percentage of patients with high levels of the drug was significantly greater among men (p < 0.001). Very low concentrations (< 0.5 ng/ml) were found in 16% of the patients, with no significant difference between sexes. CONCLUSIONS: We detect a large percentage of older patients with inappropriate levels of digoxin in blood. Women were more likely than men to have high levels to digoxin in blood. There is evidence that therapeutic monitoring of blood levels of digoxin is not done as often as is advisable; this has implications for the care of patients being treated with this drug.