Genome-based epidemiology and antimicrobial resistance of Neisseria gonorrhoeae in Spain: A prospective multicentre study.

BACKGROUND: Whole-genome sequencing (WGS) of Neisseria gonorrhoeae isolates combined with epidemiological and phenotypic data provides better understanding of population dynamics. AIM: The objective of this study was to investigate the molecular epidemiology of N. gonorrhoeae isolates from three centres in Spain and determine associations of antimicrobial resistance. METHODS: Genetic characterization was performed in 170 N. gonorrhoeae isolates. WGS was carried out with the HiSeq platform (Illumina). Genome assemblies were submitted to the PubMLST Neisseria database website to determine NG-MAST, MLST and NG-STAR. Antimicrobial resistance genes and point mutations were identified with PubMLST. Phylogenomic comparison was based on whole-genome single nucleotide polymorphism analysis. RESULTS: Twenty-six MLST, 49 NG-MAST and 41 NG-STAR sequence types were detected, the most prevalent being MLST-ST9363 (27.1%), NG-MAST ST569 (12.4%) and NG-STAR ST193 (14.7%). Phylogenetic analysis identified 13 clusters comprising 69% of the isolates, with two of note: one involved cefixime-resistant isolates from Barcelona presenting a mosaic penA X and belonging to MLST-ST7363 and the other involved azithromycin-resistant isolates from Mallorca that possessed the C2611T mutation in the four 23S rRNA alleles belonging to MLST-ST1901. CONCLUSION: The population of N. gonorrhoeae is quite heterogeneous in Spain. Our results agree with previous data published in Europe, albeit with some differences in distribution between regions. This study describes the circulation of two gonococcal populations with a specific resistance profile and sequence type in a specific geographic area. WGS is an effective tool for epidemiological surveillance of gonococcal infection and detection of resistance genes.

Neisseria gonorrhoeae culture growth rates from asymptomatic individuals with a positive nucleic acid amplification test.

Gonorrhoea infections are frequently diagnosed at extragenital locations in asymptomatic individuals and are historically related to poor recovery in culture, which hinders antimicrobial susceptibility testing. The aim of this study was to evaluate recovery rates of Neisseria gonorrhoeae by culture among asymptomatic individuals who tested positive by nucleic acid amplification tests between 2018 and 2019 in Barcelona (Spain). In total, 10 396 individuals were tested for N. gonorrhoeae on first-void urine, rectal, pharyngeal and/or vaginal swabs depending on sexual behaviour. Overall infection prevalence was 5·5% (95% confidence interval [CI] 5·0-5·9). Seven hundred and ten samples were positive corresponding to 567 individuals. The most common site of infection was the pharynx (71·3%), followed by rectum (23·1%) and genitals (4·7%) (P < 0·0001). The N. gonorrhoeae recovery rate in culture, time from positive screening to culture specimen and inoculation delay were calculated. Recovery rate was 21·7% in pharynx, 66·9% in rectum and 37·0% in genitals (25·0% vagina, 71·4% urethra) (P < 0·0001). Median culture collection time was 1 [0; 3] days, and median inoculation delay was 5·01 [4·99-7·99] h, with no impact on N. gonorrhoeae recovery, P = 0·8367 and P = 0·7670, respectively. Despite efforts towards optimizing pre-analytical conditions, the N. gonorrhoeae recovery rate in asymptomatic individuals is unacceptably low (especially for pharynx), representing a problem for monitoring antimicrobial-resistant infections.

Emergence and dissemination of three mild outbreaks of Neisseria gonorrhoeae with high-level resistance to azithromycin in Barcelona, 2016-18.

BACKGROUND: Neisseria gonorrhoeae (NG) isolates with high-level azithromycin resistance (HL-AziR) have emerged worldwide in recent decades, threatening the sustainability of current dual-antimicrobial therapy. OBJECTIVES: This study aimed to characterize the first 16 NG isolates with HL-AziR in Barcelona between 2016 and 2018. METHODS: WGS was used to identify the mechanisms of antimicrobial resistance, to establish the MLST ST, NG multiantigen sequence typing (NG-MAST) ST and NG sequence typing for antimicrobial resistance (NG-STAR) ST and to identify the clonal relatedness of the isolates with other closely related NG previously described in other countries based on a whole-genome SNP analysis approach. The sociodemographic characteristics of the patients included in the study were collected by comprehensive review of their medical records. RESULTS: Twelve out of 16 HL-AziR isolates belonged to the MLST ST7823/NG-MAST ST5309 genotype and 4 to MLST ST9363/NG-MAST ST3935. All presented the A2059G mutation in all four alleles of the 23S rRNA gene. MLST ST7823/NG-MAST ST5309 isolates were only identified in men who have sex with women and MLST ST9363/NG-MAST ST3935 were found in MSM. Phylogenomic analysis revealed the presence of three transmission clusters of three different NG strains independently associated with sexual behaviour. CONCLUSIONS: Our findings support the first appearance of three mild outbreaks of NG with HL-AziR in Spain. These results highlight the continuous capacity of NG to develop antimicrobial resistance and spread among sexual networks. The enhanced resolution of WGS provides valuable information for outbreak investigation, complementing the implementation of public health measures focused on the prevention and dissemination of MDR NG.

[Protocol for the management of patients with chronic obstructive pulmonary disease after exacerbation in the emergency department]. / Protocolo de manejo de pacientes con enfermedad pulmonar obstructiva crónica tras agudización en urgencias.

In chronic obstructive pulmonary disease, an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an episode of clinical instability due to the worsening of expiratory airflow limitation or of the underlying inflammatory process. The severity of AECOPD depends on baseline risk stratification and the intensity of the acute episode. Primary Care is the epicenter of the AECOPD care circuit, but it can be extended to the out-of-hospital emergency department and the hospital itself depending on the clinical situation, the level of severity, the availability of complementary tests, and the therapeutic resources required for each patient. Recording clinical data, history, triggering factors, treatment, and evolution of previous episodes of AECOPD in the electronic medical record is an essential aspect to adjust current treatment and prevent the occurrence of future episodes.

Sexual risk behaviors for HIV infection in Spanish male sex workers: differences according to educational level, country of origin and sexual orientation.

The stigma associated with male sex workers (MSW) hinders the prevention, treatment, and care of HIV infection in this population. These factors make social and public health resources less accessible to MSW. To improve the effectiveness of prevention strategies, this study examines social factors such as educational level, country of origin, and sexual orientation. Semi-structured interviews of 100 MSW in Castellón and Valencia (Spanish cities) indicate that knowledge of HIV transmission is good; nevertheless, MSW significantly overestimate or underestimate some sexual practices. Levels of condom use are high; notably, they are higher during anal sex. Levels of condom use are lower with intimate partners than with clients. MSW do not present differences in terms of the socio-demographic variables analyzed and sexual orientation. Furthermore, regression analyses are not significant. These results offer more accurate profiles of MSW than were previously available, which will ultimately help improve the effectiveness of prevention programs.

[Available resources for the management of chronic obstructive pulmonary disease exacerbations in Spain]. / Recursos disponibles para el manejo de la agudización de la enfermedad pulmonar obstructiva crónica en España.

OBJECTIVE: Chronic obstructive pulmonary disease exacerbations (COPDE) lead to a high use of healthcare resources. This study assesses the healthcare and organisational resources of Spanish health care centres for the management of COPDE at different care levels (Primary Care (PC), Respiratory Diseases, Internal Medicine, and Emergency Departments), and compare with current recommendations. MATERIAL AND METHODS: An observational study was carried out through telephone interviews to General Practitioners, Chest Diseases, Internal Medicine, and Emergency Department doctors. RESULTS: A total of 284 doctors were interviewed. According to their responses, at PC centres there is a high availability of pulse oximetry (98.9%) and electrocardiograph (100%), and a low availability of Chest X-Ray (19.1%), or urgent laboratory tests (17.0%) in sites. In hospital wards, non-invasive mechanical ventilation (NIV) availability was 76.1%, with only a 69.7% of nursing staff properly trained in its use. Respiratory intermediate care units (RICUs) were available in 18.3% of public hospitals versus 41.7% of private hospitals. Specific training for COPDE management was received by 47.9% of Emergency Department doctors in the previous year. Only 31.9% of PC centres had specific protocols for referring patients to specialists. More than 35% of PC centres and hospitals do not have their electronic medical records integrated with other healthcare levels. CONCLUSIONS: In general terms, there are sufficient resources available in Spanish healthcare centres. However, several areas of improvement were identified, such as an insufficient level of electronic medical record integration between healthcare levels, limited implementation of RICUs in public hospitals, and deficiencies related to specific training in NIV management.

[Use of complementary tests in emergencies and their relation with patient safety incidents]. / Uso de pruebas complementarias en urgencias y su relación con incidentes de seguridad.

OBJECTIVE: To analyse the use of complementary tests and their relationship with safety incidents in hospital emergency departments. METHODOLOGY: An analysis was performed on 935 patients seen in the 9 hospital emergency departments. The source of data used for the detection of incidents were: emergency department clinical record and reports, together with face-to-face observation in the department, plus a telephone survey of the patient or family member at one week after the care. Statistical tests used: The Student t test for quantitative variables, Chi squared test for qualitative variables, and the ANOVA test. RESULTS: A peripheral venous catheter was used in 397 patients (42.4% (95% CI; 39.3-45.5%)), with a variability with significant differences between hospitals (P<.01), with a range of use from 37% to 81.8%. It was also observed that in 23.4% (95% CI; 19.2-27.6%) of the cases, the catheter was not used after the first blood draw. Radiological tests were requested for 351 patients, 37.7% (95% CI; 34.6-40.8%), also with significant differences between hospitals (P<.01), ranging from 24.6 to 65, 1%. Incidents were detected in 95 (10.2%) patients (95% CI; 8.3-12.1%) in the all the study centres. A higher proportion of safety incidents have been observed in patients where peripheral venous catheter has been used (12.8%) than in those in whom they had not been used (8.5%) (P=.03), as well as in patients on whom an x-ray was requested (12.8%) compared to those who did not (8.64%) (P=.04). A longer stay was also observed in cases with an incident (mean 248.9minutes) than in those where there were none (mean 164.1minutes) (P<.001). No statistically significant differences were found in the other parameters studied. CONCLUSION: A relationship was observed between the use of a peripheral venous catheter (many of them without use) and radiological tests and the occurrence of safety incidents in the Emergency Departments.

[Delayed diagnosis of phenylketonuria as the cause of mental retardation in an adolescent]. / Diagnóstico tardío de fenilcetonuria como causa de retraso mental en un adolescente.

INTRODUCTION: The hyperphenylalaninemias (HFA) form a diverse group of recessive autosomic disorders. They are caused by defects in the hepatic system for hydroxylation of the amino acid phenylalamine to tyrosine. The estimated incidence is approximately 10 cases per 100,000 live births. Children with this metabolic disorder may present with varied neurological symptoms. Control of plasma levels, so that they are more normal as soon as possible after birth, significantly prevents mental retardation and other neuropsychological dysfunction. For this reason HFA has been included in neonatal screening. However, some patients are not detected on screening. When they are adults, these patients pose problems of diagnosis for neurologists who attend adults. CLINICAL CASE: We describe an adolescent with mental and linguistic retardation, in whom neonatal screening to rule out metabolic defects was normal. At the age of 15, the phenylalanine in blood and urine were found to be raised. On cerebral magnetic resonance changes typical of pheynylketonuria (PKU) were seen. CONCLUSIONS: The HFA should be considered as causes of cerebral dysfunction in adults, since in spite of neonatal screening, false negatives may occur. We describe a clinical case and consider different forms of hyperphenylaleninemias. Their diagnosis and treatment.

[Late onset epileptic crisis and cerebrovascular disease]. / Crisis epilépticas de comienzo tardío y enfermedad vascular cerebral.

INTRODUCTION: Stroke is the most frequent cause of epilepsy in adults, specially in those over 60 years old. Our aim was to analyze the etiologic relevance of stroke among the different etiologies of late onset seizures and to evaluate the clinical characteristics of the subgroup of patients with late onset seizures associated to stroke. PATIENTS AND METHODS: Patients aged over 20 who were admitted to the Neurology or Neurosurgery departments in our hospital for a first-ever seizure over a period of five years were identified retrospectively. The total number of patients included was 248. RESULTS: The most frequent etiologies were stroke (26.2%), tumors (26.2%), unknown (24.6%) and chronic alcohol intake (18.5%). Stroke was the most frequent etiology in patients over 60 (50%). Five of the 65 patients with stroke related seizures had suffered an intracranial hemorrhage and the rest had ischemic lesions. Seven patients had clinically silent infarctions. Seizures were generalized in 60% of the cases. Nearly in all the patients lesions were placed close to the cortex and mainly in carotid artery territory. CONCLUSIONS: Late onset seizures are due to a lesion in the brain in an important number of cases. Stroke is the most prevalent cause and this prevalence increases with age. A complete diagnostic procedures is warranted in this patients.

[Meningiomas of the lateral ventricles: a case report]. / Meningiomas de los ventrículos laterales: a propósito de un caso.

We describe the case of a patient with an intraventricular meningioma, which initially manifested as transient mental impairment. Meningiomas are slowly growing, bening tumours, which usually remain asymptomatic or show only insidious clinical manifestations for long periods. In our case the distinct localization of the tumor gives rise to a peculiar clinical picture, with special reference to the episodic nature of symptoms. In this case we want to remark the role of both the clinical and neuroradiological data in the diagnosis of this pathology.

[Risk factors in recurrent febrile seizures]. / Factores de riesgo en las convulsiones febriles recurrentes.

INTRODUCTION: Febrile convulsions are the most frequent type of seizures in children under 6 years old. They usually have a good prognosis. Only a few of these children will later suffer from non-febrile seizures. The low risk of non-febrile seizures and important side-effects of antiepileptic drugs have limited the use of continuous prophylaxis in children with recurrent febrile seizures. OBJECTIVES: Our aim has been to identify the main factors that imply a higher risk for recurrent febrile convulsions and also to identify the frequency of antiepileptic prophylactic medication in our area. MATERIAL AND METHODS: We have carried out a protocoled study in children which were sent consecutively and with no previous selection to a reference electroencephalography (EEG) outpatient unit in Murcia with the clinical diagnosis of febrile convulsions. Data included have been: sex, actual age and age at the time of the first seizure, total number of seizures, family and personal history of either febrile seizures or epilepsy, EEG findings, treatment and side-effects. Data collection was accomplished between September 1991 and June 1993. A total of 509 patients have been included. RESULTS: A 34% of the children had suffered two or more seizures. Children with recurrent seizures were younger at onset (16.7 vs 21 months) and had more often family history of febrile seizures (40.6% vs 28%) and epilepsy (21.5% vs 12.5%). 60% of the children who had family history of febrile seizures of epilepsy and who suffered the first episode before the age of 16 months had recurrent febrile convulsions. CONCLUSIONS: An age under 16 months at the moment of the first convulsion and the existence of family history of febrile seizures or epilepsy increase the risk of recurrent febrile seizures.

[Cerebrovascular disease in young women]. / Patología vascular cerebral en mujeres jóvenes.

INTRODUCTION: Cerebrovascular disease is an important cause of morbi-mortality. Although its incidence is maximal in older groups, its incidence in young people cannot be forgotten, even more if we consider the socioeconomic and personal consequences derived from it. There are several works on this subject but few of them analyze the specific problem of stroke in women. There is some degree of controversy in this subject, specially about the role of several factors which are more prevalent or either exclusive for women. OBJECTIVES: We wanted to analyze the risk factors and clinical characteristics in a group of women under 45 who suffered a stroke and also to compare these risk factors between women under 35 and those from 35 to 45. MATERIAL AND METHODS: We have carried out a descriptive study, including 61 women under 45 admitted to our centre consecutively between January 1989 and October 1996. RESULTS: Among the most prevalent factors we have found hypertension (27.8%), tobacco consumption (24.5%) and the presence of cardiac abnormalities (22.9%), specially associated to valvular pathology, as well as a higher incidence of contraceptives consumption in women under 35 (80%). CONCLUSIONS: These factors are similar to those found in studies on the general population of young people. Our data indicate that the relevance of the main factors for stroke is common for both sexes and is also significant in young patients.

[Stiff-man syndrome. Presentation of a new case]. / Síndrome de la persona rígida. Presentación de un nuevo caso.

INTRODUCTION: The stiff-man syndrome (SPR) is a rare neurological condition characterized by the presence of marked, involuntary rigidity of the axial muscles and limbs, together with intense painful muscle spasms which characteristically occur following external stimuli such as sudden noises, brusque movements or emotional stimuli. Symptoms are markedly improved by sleep and by diazepam. The aetiology is unknown, although it is associated with certain auto-immune disorders, particularly diabetes mellitus (DM) and others such as thyroid disease, vitiligo, pernicious anaemia, adrenal insufficiency, etc. The presence of high titres of glutamate-decarboxylase (GAD) antibodies seems to indicate an auto-immune aetiology. CLINICAL CASE: We describe a 59 year old woman who complained of an illness starting seven years previously with progressive pain and contractions of the dorso-lumbar muscles, which later spread to the cervical and abdominal muscles and to the upper limbs. From the time of onset, there were exacerbations of the condition following external stimuli. Also there was generalized vitiligo and whilst this progressed, DM developed (which finally required insulin to control it). On EMG there was continuous muscular activity and absence of muscle relaxation. The presence of high titres of anti-nuclear antibodies, gastric parietal cell antibodies and anti-GAD was very marked. There was a spectacular response to treatment with diazepam, with progressive improvement although ever increasing dosage was required. CONCLUSIONS: A new case of the 'stiff-man' syndrome is presented and aspects of aetiopathology and treatment are reviewed.

[Pontine hemorrhage as a cause of peripheral facial paralysis]. / Hemorragia protuberancial como causa de parálisis facial periférica.

Bell's palsy is the most frequent type of peripheral facial nerve paralysis. Nevertheless there are other less frequent causes of peripheral facial palsy, among which, we can find lesions in the brain stem affecting the seventh cranial nerve nucleus or its fibers. These lesions of the pons which paralyze the muscles of the face are often accompanied by lesions to other structures in the vicinity of the nucleus. We present the case of peripheral facial nerve palsy caused by hemorrhage in the pons, seen both on brain CT-scan and MRI, which affected the nucleus of the seventh cranial nerve and was not accompanied by any other clinical manifestations due to lesions of structures placed in the vicinity of this nucleus.

[McArdle disease: report of four brothers with myophosphorylase deficiency]. / Enfermedad de McArdle: descripción de cuatro hermanos con déficit de miofosforilasa.

Myophosphorylase deficiency, or McArdle disease, is an uncommon entity. The gene for human myophosphorylase has been cloned and is located on chromosome 11, in keeping with the autosomal recessive nature of the disease and there is an excess of male patients. The diagnosis is established by documentation of elevated glycogen content and reduced phosphorylase activity in biopsied muscle tissue. We report four cases with McArdle disease which were 16, 15, 11 and 5 years old. They were brothers, and they came to the hospital because of pain, cramps and myoglobinuria after exercise or infection; in the first case, a male patient, myoglobinuria caused acute renal failure. Three of them showed reduced phosphorylase activity in biopsied muscle tissue. We discuss the different therapeutic possibilities.

Protocolo de manejo de pacientes con enfermedad pulmonar obstructiva crónica tras agudización en urgencias / Protocol for the management of patients with chronic obstructive pulmonary disease after exacerbation in the emergency department

En la enfermedad pulmonar obstructiva crónica el síndrome de agudización (SAE) es un episodio de inestabilidad clínica por agravamiento de la limitación espiratoria al flujo aéreo o del proceso inflamatorio subyacente. La gravedad del SAE depende de la estratificación del riesgo basal y la intensidad del episodio agudo. La Atención Primaria es el epicentro del circuito asistencial del SAE, pero puede extenderse al Servicio de Urgencias Extrahospitalarias y al propio hospital dependiendo de la situación clínica, del nivel de gravedad, de la disponibilidad de pruebas complementarias y de los recursos terapéuticos necesarios para cada paciente. El registro de los datos clínicos, antecedentes, factores desencadenantes, tratamiento y evolución de los episodios previos de SAE en la historia clínica electrónica son un aspecto esencial para ajustar el tratamiento actual y prevenir la aparición de futuros episodios (AU)

In chronic obstructive pulmonary disease, an acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an episode of clinical instability due to the worsening of expiratory airflow limitation or of the underlying inflammatory process. The severity of AECOPD depends on baseline risk stratification and the intensity of the acute episode. Primary Care is the epicenter of the AECOPD care circuit, but it can be extended to the out-of-hospital emergency department and the hospital itself depending on the clinical situation, the level of severity, the availability of complementary tests, and the therapeutic resources required for each patient. Recording clinical data, history, triggering factors, treatment, and evolution of previous episodes of AECOPD in the electronic medical record is an essential aspect to adjust current treatment and prevent the occurrence of future episodes (AU)

[Characteristics and epidemiological changes for patients with community-acquired pneumonia in hospital emergency departments]. / Características y cambios epidemiológicos de los pacientes con neumonía adquirida en la comunidad en los servicios de urgencias hospitalarios.

BACKGROUND: The aim of this paper is to determine both the prevalence of community-acquired pneumonia (CAP) in the A & E Department and the most relevant epidemiological changes in the last decade, as well as the profile and management of these patients. METHODS: Descriptive cross-sectional analysis at 49 Spanish A & E Departments during 12 months. All patients with infections, respiratory infection or CAP diagnosis were included. All patients attended to in A & E during the study were recorded as well. RESULTS: CAP has increased its prevalence among patients in the A & E Departments in the past decade (0.85% to 1.35%, p <0.001). Fifty-one per cent were over 70 years old. Sixty-nine point eight per cent had some underlying disease and 17.8% had risk factors. Eleven point seven per cent met sepsis criteria, 4.6% severe sepsis and 3% septic shock. Thirty-seven per cent of patients were directly discharged from the A & E Departments. CONCLUSIONS: The impact and prevalence of CAP in A & E Departments has increased in the last decade. It is the most common cause of sepsis, severe sepsis and septic shock, admission to intensive care units and death due to infectious disease.

De la cabina al quirófano / From the cockpit to the operating room

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