Transition of patients with mucopolysaccharidosis from paediatric to adult care.

Mucopolysaccharidoses (MPS) are rare disorders associated with enzyme deficiencies, resulting in glycosaminoglycan (GAG) accumulation in multiple organ systems. As patients increasingly survive to adulthood, the need for a smooth transition into adult care is essential. Using case studies, we outline strategies and highlight the challenges of transition, illustrating practical solutions that may be used to optimise the transition process for patients with MPS disorders. Seven MPS case studies were provided by four European inherited metabolic disease centres; six of these patients transferred to an adult care setting and the final patient remained under paediatric care. Of the patients who transferred, age at the start of transition ranged between 14 and 18 years (age at transfer ranged from 16 to 19 years). While there were some shared features of transition strategies, they varied in duration, the healthcare professionals involved and the management of adult patients with MPS. Challenges included complex symptoms, patients' unwillingness to attend appointments with unfamiliar team members and attachment to paediatricians. Challenges were resolved by starting transition at an early age, educating patients and families, and providing regular communication with and reassurance to the patient and family. Sufficient time should be provided to allow patients to understand their responsibilities in the adult care setting while feeling assured of continued support from healthcare professionals. The involvement of a coordinated multidisciplinary team with expertise in MPS is also key. Overall, transition strategies must be comprehensive and individualised to patients' needs.

Efficacy of Idursulfase therapy in patients with Mucopolysaccharidosis type II who initiated enzyme replacement therapy in adult age. A systematic review of the literature.

BACKGROUND: Enzyme replacement therapy (ERT) has been shown to decrease urine glycosaminoglycans (uGAGs) and liver and spleen volumes, and to improve clinical symptoms in mucopolysaccharidosis type II (MPS-II) patients. METHODS: A systematic search of the literature, from inception to August 2017, was conducted to identify randomized trials or observational studies including ≥1 MPS-II patients with ERT initiated in adult age (≥16 years) and evaluating ERT efficacy. Evidence was rated according to GRADE criteria. Common efficacy outcomes of the clinical studies were analyzed. Case reports were separately evaluated. RESULTS: One randomized clinical trial, 4 observational studies and 5 case reports were selected. ERT decreased uGAG levels and liver and spleen size with moderate evidence level and led to anti-ERT antibody and IRRS development in a significant proportion of patients with moderate evidence level. There were no conclusive results for beneficial effects on 6MWT, respiratory, cardiac and neurological function, joint mobility, sleep disorders of respiratory origin, and quality of life. LIMITATIONS: Excluding one observational study, all others were not conducted specifically in the target population (ERT ≥16 years). Data were from subgroup analyses of selected studies. There was a great heterogeneity between study designs and clinical outcomes evaluated. CONCLUSIONS: ERT improves uGAGs and liver/spleen volume with a moderate evidence level in MPS-II patients initiating therapy as adults, although the putative associated clinical benefit is unclear.

The view of experts on initiatives to be undertaken to promote equity in the access to orphan drugs and specialised care for rare diseases in Spain: A Delphi consensus.

OBJECTIVES: To reach a consensus amongst experts on the most feasible actions to be undertaken to facilitate patient access to specialised care and orphan drugs (OD) in the public health sector in Spain. METHODS: Two Delphi rounds were completed. The questionnaire was based on a literature review and 2 focus groups. Agreement was sought on the desire (D) and prognosis (P) for the implementation within the next 5 years, on a 5-point Likert scale. Consensus was reached when ≥75% participants chose agreement (1-2) or disagreement options (4-5). RESULTS: 82 experts on rare disease (RD) participated. Agreement on the D and P was reached in 66.07% statements: OD pricing review [absence of clinical effectiveness (D:85.37%; P:85.90%), target population increase (D:79.27%; P:91.03%)]; reference team definition of referral protocols and clinical practice guidelines (D: 97.56%; P: 89.74%); and a unified, usable, etiology-based registry (D:97.56%; P:84.62%). D and P assessment diverged in 32.14% items: creation of a specific funding system for OD (D: 97.56%; P: 60.25%); and a network of medical teams to coordinate the care of RD patients (D: 99%; P: 62%). CONCLUSIONS: The results have shown the need to promote dialogue between stakeholders, introduce European recommendation to national and regional Spanish policies and set up priorities and undertake actions to drive relevant changes in current medical practice in managing RD patients.

Transición desde la asistencia pediátrica a la adulta en pacientes con mucopolisacaridosis / Transition from paediatric care to adult care for patients with mucopolysaccharidosis

Las mucopolisacaridosis son enfermedades multisistémicas que requieren para su atención equipos multidisciplinares amplios. Por ello se hacen necesarias recomendaciones específicas para la transición de la edad pediátrica a la adulta en este grupo de pacientes. Para la superación de las barreras que pudieran surgir durante la transición, los autores consideran esencial realizar un plan flexible con un coordinador de todo el proceso, sistematizar la información a través de un informe de alta pediátrico estandarizado, formar al paciente y su familia sobre la enfermedad y mostrar las características del sistema sanitario en esta nueva etapa. El objetivo final es que al concluir la transición a la edad adulta se haya maximizado la autonomía y el potencial de desarrollo del paciente y este reciba una atención sanitaria adecuada durante dicho periodo de transición (AU)

Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition (AU)

Transition from paediatric care to adult care for patients with mucopolysaccharidosis. / Transición desde la asistencia pediátrica a la adulta en pacientes con mucopolisacaridosis.

Mucopolysaccharidosis are multisystem diseases that require large multidisciplinary teams for their care. Specific recommendations are therefore needed for the transition from childhood to adulthood in this patient group. To overcome the barriers that might arise during the transition, the authors consider it essential to implement a flexible plan with a coordinator for the entire process, systematising the information through a standardised paediatric discharge report and educating the patient and their family about the disease, showing the characteristics of the healthcare system in this new stage. The final objective is that, once the transition to adulthood has been completed, the patient's autonomy and potential development are maximised and that the patient receives appropriate healthcare during this transition.

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.

Neutrophils extracellular traps damage Naegleria fowleri trophozoites opsonized with human IgG.

Naegleria fowleri infects humans through the nasal mucosa causing a disease in the central nervous system known as primary amoebic meningoencephalitis (PAM). Polymorphonuclear cells (PMNs) play a critical role in the early phase of N. fowleri infection. Recently, a new biological defence mechanism called neutrophil extracellular traps (NETs) has been attracting attention. NETs are composed of nuclear DNA combined with histones and antibacterial proteins, and these structures are released from the cell to direct its antimicrobial attack. In this work, we evaluate the capacity of N. fowleri to induce the liberation of NETs by human PMN cells. Neutrophils were cocultured with unopsonized or IgG-opsonized N. fowleri trophozoites. DNA, histone, myeloperoxidase (MPO) and neutrophil elastase (NE) were stained, and the formation of NETs was evaluated by confocal microscopy and by quantifying the levels of extracellular DNA. Our results showed N. fowleri induce the liberation of NETs including release of MPO and NE by human PMN cells as exposure interaction time is increased, but N. fowleri trophozoites evaded killing. However, when trophozoites were opsonized, they were susceptible to the neutrophils activity. Therefore, our study suggests that antibody-mediated PMNs activation through NET formation may be crucial for antimicrobial responses against N. fowleri.

Revisión de cavidad uterina instrumentada gentil frente a la revisión manual y su relación con la hemorragia posparto / Gentle instrumented uterine cavity assessment in comparison to manual assessment and its association to post-partum hemorrhage

Objetivo: Demostrar que la revisión de la cavidad uterina instrumental gentil previene mayormente, la hemorragia posparto en comparación con la revisión manual de la cavidad uterina. Métodos: Estudio observacional, transversal, descriptivo y asociativo. Se llevó a cabo en las pacientes que ingresaron a las unidades toco-quirúrgicas de 2 hospitales públicos en el Estado de México. Muestreo por conveniencia (aquellas pacientes a quienes se les realizó revisión de cavidad uterina, durante la atención del parto). Muestra integrada por 236 pacientes. Resultados: Hubo 76 casos de hemorragia posparto, que se analizaron por grupos de edad, distinguiendo entre adolescentes, en edad reproductiva óptima y en edad materna avanzada, encontrándose mayor incidencia en el primer y tercer grupo, con el 34.4% y 48.3% de los casos, respectivamente. La relación entre hemorragia posparto y tipo de técnica de revisión de cavidad uterina, mostró mayor incidencia en la revisión manual. Los casos analizados según la instrucción del personal que brindó la atención, mostraron mayor número de casos de hemorragias, en quienes fueron atendidos por personal en formación. Los especialistas de Enfermería Perinatal, llevaron a cabo 97 procedimientos de atención de parto, 25 presentaron hemorragia posparto, frente a 72 que no presentaron la patología. Conclusiones: La revisión manual de cavidad uterina se asocia estrechamente con la aparición de hemorragia posparto, en contraste con la revisión instrumentada gentil, en la que se registró menor incidencia de esta complicación. La revisión de cavidad uterina debe practicarse bajo indicaciones precisas, hecho que contribuye a la disminución de complicaciones en el posparto.

Objective: to demonstrate that the gentle instrumental uterine cavity assessment largely prevents postpartum hemorrhage in comparison to the manual assessment. Methods: cross-sectional, observational, descriptive, and associative study on patients admitted to the labor-surgical units of two public hospitals in the State of México, using a convenience sample (patients to whom a uterine cavity assessment was performed during their labor process) of 236. Results: There were 76 total cases of post-partum hemorrhage. Patients were classified in three age groups: adolescents, optimal reproductive age, and advanced maternal age. Post-partum hemorrhage cases were prevalent in the first and third groups with 34.4% and 48.3% respectively. The manual uterine cavity assessment technique resulted in a higher prevalence of post-partum hemorrhage. More post-partum hemorrhage cases were also found in those patients attended by inexpert staff. Perinatal Nursing Specialists, conducted 97 childbirth care procedures, 25 had Postpartum Hemorrhage, compared to 72 who did not have the pathology. Conclusions: The manual uterine cavity assessment technique, is closely associated with the onset of Postpartum Hemorrhage, Gentle instrumented uterine cavity assessment resulted in a lower incidence of post-partum hemorrhage. In order to decrease post-partum complications, the uterine cavity assessment must be performed through precise procedures.

Clinical guidelines for late-onset Pompe disease.

Before 2006, Pompe disease or glycogenosis storage disease type II was an incurable disease whose treatment was merely palliative. The development of a recombinant human alpha-glucosidase enzymatic replacement therapy has become the first specific treatment for this illness. The aim of this guide is to serve as reference for the management of the late-onset Pompe disease, the type of Pompe disease that develops after one year of age. In the guide a group of Spanish experts make specific recommendations about diagnosis, follow-up and treatment of this illness. With regard to diagnosis, the dried blood spots method is essential as the first step for the diagnosis of Pompe disease. The confirmation of the diagnosis of Pompe disease must be made by means of an study of enzymatic activity in isolated lymphocytes or a mutation analysis of the alpha-glucosidase gene. With regard to treatment with enzymatic replacement therapy, the experts say that is effective improving or stabilizating the motor function and the respiratory function and it must be introduced when the first symptoms attributable to Pompe disease appear.

Association of ACACB polymorphisms with obesity and diabetes.

Acetyl-CoA carboxylase beta, encoded by the ACAB gene, plays an important role in the oxidation of fatty acids. The aim of this study was to check the hypothesis that allelic variants of ACACB influence the risk of obesity and type 2 diabetes mellitus. Twenty five tagging single nucleotide polymorphisms (SNPs) capturing common variants of the ACACB gene were selected and analyzed in two cohorts including 1695 postmenopausal women of the general population and in 161 women with severe obesity (BMI>35). In vitro binding of transcription factors was explored by electrophoretic mobility shift assays (EMSA). T alleles at the rs2268388 locus were overrepresented in women with severe obesity (18% vs. 10% in controls; OR 1.74 [95% confidence interval 1.30-2.47]), which was statistically significant after multiple-test adjustment (p=0.0004). Likewise, T alleles at the rs2268388 locus and C alleles at the rs2239607 locus were associated with diabetes, in the discovery as well as in the replication cohorts, even after women with severe obesity were excluded (OR 3.6 and 2.8, for TT and CC homozygotes, respectively). Allelic differences in the binding affinity for nuclear proteins were revealed in vitro by EMSA and competition experiments were consistent with the binding of glucorticoid receptor and serum response factor. In conclusion, common polymorphisms of ACACB gene are associated with obesity and, independently, with type 2 diabetes in postmenopausal women, suggesting that the activity of acetyl-CoA carboxylase beta plays an important role in these disorders related to energy metabolism.

Update of the Atlanta Classification of severity of acute pancreatitis: should a moderate category be included?

BACKGROUND: Persistent and multiple organ failure (POF and MOF) are predictive of death in acute pancreatitis (AP). Local complications without organ failure are associated with morbidity but a low risk of mortality. AIM: To design a three-category classification of AP severity and to compare it with the Atlanta Classification (AC) in terms of morbidity and mortality. METHOD: Severe AP was defined as death, POF (>48 h) or MOF. Moderate AP was defined as the presence of acute collections and/or pancreatic necrosis. Mild AP was defined by exclusion. We compared this classification with AC in 144 episodes of AP. RESULTS: In the three-category classification, severe AP was associated with significantly more frequent intensive care unit admission, invasive treatment and mortality than moderate and mild AP (p < 0.01). Severe AP patients required longer hospital stay and more nutritional support than mild AP patients (p < 0.01). Patients with moderate AP had significantly longer hospital stay and more need for nutritional support than patients with mild AP (p < 0.01). Five patients died, all of them with MOF and/or POF. CONCLUSIONS: A three-category classification distinguishes three homogeneous groups of severity.

Epidemiology and clinical features of community-acquired, healthcare-associated and nosocomial bloodstream infections in tertiary-care and community hospitals.

Classification of bloodstream infections (BSIs) as community-acquired (CA), healthcare-associated (HCA) and hospital-acquired (HA) has been proposed. The epidemiology and clinical features of BSI according to that classification in tertiary-care (TH) and community (CH) hospitals were investigated in a prospective cohort of 821 BSI episodes from 15 hospitals (ten TH and five CH hospitals) in Andalucía, Spain. Eighteen percent were CA, 24% were HCA and 58% were HA. The incidence of CA and HCA BSI was higher in CH than in TH (CA: 3.9 episodes per 1000 admissions vs. 2.2, p <0.01; HCA: 5.0 vs. 2.9, p <0.01), whereas the incidence of HA BSI was lower (7.7 vs. 8.7, p <0.01). In CA and HCA BSI, the respiratory tract was more frequently the source in CH than in TH (CA: 30% vs. 15%; HCA: 20% vs. 9%, p ≤0.03). In HCA BSI, chronic renal insufficiency and tunnelled catheters were less frequent in CH than in TH (11% vs. 26% and 7% vs. 19%, p ≤0.03), although chronic ulcers were more frequent (22% vs. 8%, p 0.008). BSIs as a result of methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa were very rare in CA episodes, although extended-spectrum b-lactamase-producing Escherichia coli (ESBLEC) caused a similar proportion of all BSIs in CA, HCA and HA episodes. Multivariate analysis revealed no significant difference in mortality rates in CH and TH. HCA infections should be considered as a separate class of BSI in both TH and CH, although differences between hospitals must be considered. CA BSIs were not caused by multidrug-resistant pathogens, except for ESBLEC.

Detection of new mutations conferring resistance to linezolid in glycopeptide-intermediate susceptibility Staphylococcus hominis subspecies hominis circulating in an intensive care unit.

Glycopeptides and linezolid are the most widely used antibiotics to treat infections by methicillin-resistant Staphylococcus spp. We report the presence of various isolates of methicillin-resistant S. hominis subsp. hominis with resistance to linezolid and reduced susceptibility to glycopeptides. We studied ten blood culture isolates of S. hominis subsp. hominis from nine patients admitted to our hospital. Etest was used to study susceptibility to antibiotics commonly prescribed against staphylococci. Domain V region of the 23S rRNA gene was amplified and sequenced to detect possible mutations that confer resistance to linezolid. Pulsed-field gel electrophoresis (PFGE) was used for the clonality study of isolates. All isolates were resistant to oxacillin, gentamicin, levofloxacin, cotrimoxazole, and linezolid, and susceptible to tigecycline and daptomycin. Nine of the isolates were resistant to erythromycin and clindamycin, and showed heterogeneous resistance to glycopeptides. C2190T, G2603T, and G2474T mutations were detected in domain V of the 23S rRNA gene. PFGE showed the presence of two different clones. This report alerts to the possible appearance of clinical strains of methicillin-resistant staphylococci with intermediate resistance to glycopeptides, resistance to linezolid, and multiple resistance to other second-line antibiotics.

Colour-duplex ultrasonography of the temporal and ophthalmic arteries in the diagnosis and follow-up of giant cell arteritis.

OBJECTIVE: To evaluate the diagnostic value of colour-duplex ultrasonography (CDU) of the temporal and ophthalmic arteries in the diagnosis of giant cell arteritis (GCA) and its usefulness in the follow-up of the disease. Furthermore, to examine the relationship between CDU abnormalities in ophthalmic arteries and blindness. METHODS: This is a prospective study of all patients with clinical suspicion of GCA or polymyalgia rheumatica (PMR) seen consecutively at the Internal Medicine Department at Vall d'Hebron University Hospital, Spain, between March 2003 and July 2006. Patients were evaluated with regard to the sensitivity and specificity of the dark halo sign in the temporal artery for the diagnosis of GCA, as well as the sensitivity and specificity of the presence of stenosis in temporal and/or ophthalmic arteries. Additionally, the usefulness of the dark halo sign in the follow-up of GCA was addressed. RESULTS: Forty-seven patients (30 with GCA, 17 with PMR) and 13 controls were included in the study. The sensitivity and specificity for the diagnosis of biopsy-proven GCA were higher for the temporal halo (72% in both cases) than for temporal artery stenosis (41% and 89%, respectively), or for ophthalmic artery stenosis (58% and 89%, respectively). Disappearance of the halo was observed in 50% of patients six months after diagnosis, although all patients were in clinical remission, and laboratory parameters were within normal values. CONCLUSION: CDU of the temporal arteries may be a valid tool in the diagnosis of GCA. However, its role in the follow up of the disease deserves re-evaluation. CDU of the ophthalmic arteries is less useful for CGA diagnosis and no relationship with blindness is suspected.

Rheology of the Pluronic P103/water system in a semidilute regime: evidence of nonequilibrium critical behavior.

The linear and nonlinear rheological behaviors of semidilute aqueous solutions of the amphiphile triblock polymer Pluronics P103 in water are reported here. For C(surf) < or = 20 wt%, micelles are spherical at temperatures lower than ca. 27 degrees C and grow with increasing temperature to form long polymer-like micelles. These polymer-like micelles exhibit strong viscoelasticity and a shear-banding region that shrinks as the cloud point is approached. Master time-temperature-concentration curves were obtained for the dynamic moduli using traditional shifting factors. In the nonlinear regime, P103 polymer-like micellar solutions follow the master dynamic phase diagram proposed by Berret and colleagues, in which the flow curves overlap in the low-shear-rate homogeneous flow region. Within the nonhomogeneous flow region (confirmed by flow birefringence and small-angle light-scattering measurements), oscillations and overshoots are detected at the inception of shear flow, and two main relaxation mechanisms are apparent after cessation of steady shear flow. Evidence for nonequilibrium critical behavior is presented, in which the order parameter is the difference of critical shear rates that limit the span of the plateau stress. Most of the steady-state and transient features of the nonlinear rheology of the P103 polymer-like micelles are reproduced with the Bautista-Manero-Puig (BMP) model, including the predictions of nonequilibrium critical behavior under flow.

First Detection of Virulence in Puccinia triticina to Resistance Genes Lr27 + Lr31 Present in Durum Wheat in Mexico.

Leaf rust caused by Puccinia triticina Eriks. was observed during the 2007-2008 crop season in the state of Sonora, Mexico on previously resistant durum wheat (Triticum turgidum L.) cvs. Jupare C2001 (Lr27 + 31) and Banamichi C2004. Single uredinial isolates were made from disease samples collected in the field and tested mostly on 'Thatcher' differentials at seedling or adult-plant stages (1). The isolates were identified as a new race, BBG/BP, resembling race BBG/BN predominant on durum wheat (2), but with additional virulences to resistance genes Lr27 + Lr31 in Gatcher and adult-plant resistance gene Lr12. The new race was also identified in samples collected from durum wheat in the State of Nuevo Leon during the same season. The avirulence/virulence formula of race BBG/BP is Lr1, 2a, 2b, 2c, 3, 3ka, 3bg, 9, 13, 14a, 15, 16, 17, 18, 19, 21, 22a, 24, 25, 26, 28, 29, 30, 32, 35, 37/Lr10, 11, 12, 14b, 20, 23, 27 + 31, 33. Although virulences to Lr27 + Lr31 and Lr12 is known to occur in P. triticina races predominant on bread wheat (T. aestivum L.) (1), to our knowledge, this is the first report of such virulences in the pathogen population on durum wheat. Pure isolates of race BBG/BP are stored in the CIMMYT leaf rust collection. References: (1) R. P. Singh. Plant Dis. 75:790, 1991. (2) R. P. Singh et al. Plant Dis. 88:703, 2004.

[Specialized home care of medical diseases in an urban tertiary university hospital. Coordination between the medical services of the hospital and the primary health care]. / Atención especializada domiciliaria de patologías médicas desde un hospital universitario terciario urbano. Coordinación entre los servicios médicos del hospital y la Atención Primaria de salud del territorio.

INTRODUCTION: The experience of an urban Tertiary University Hospital in the design and implementation of Hospital at Home Program (HaHP) integrated in a Department of Internal Medicine and highly coordinated with Medical Services of the Hospital and the Primary Health Care, that contemplates the like main objectives of the promotion of specialized home care medical diseases and the improvement of the coordination with the primary health care. PATIENTS AND METHOD: Systematic collection in all the patients admitted between April 2006 and March 2007 in the HaHP of the following variables: age, gender, service of origin, main diagnosis, Barthel and Charlson index, number of visits per day to doctors and nurses, destination on discharge and medical team. The descriptive statistical analysis was made in April 2007. The results are presented globally and differentiated by teams (internal medicine, respiratory and nutritional support teams). RESULTS: 506 admissions in 390 patients with a mean age of 66.5 (18) years, 53% being women. The Charlson index was 2 (2.2) and the Barthel index 63.5 (40,4). Average stay was 7.9 (8.2) days. The main reasons for admission were the infections and domiciliary intravenous antibiotic therapy in 153 (30.5%) cases, followed by patients with chronic obstructive pulmonary disease or cardiac failure in 107 (21%) cases, and home enteral and parenteral nutrition in 102 (20%) cases. Two hundred (39.5) patients were subsequently controlled by their primary care team after discharger, 241 (47.5) patients were followed-up in the hospital consultations, and 45 (9%) of the patients had to return directly to the hospital. CONCLUSIONS: The creation of a HaHP, for medical diseases, in internal medicine department that is highly coordinated with medical services of the hospital, especially with emergency, respiratory, and nutritional support teams, and with the primary health care, facilitates specialized home care of medical diseases and improves coordination with the primary health care.