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Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disorder. ADPKD is not only associated with progression of renal disease, but also several hepatobiliary manifestations. This report is of a 49-year-old female with recurrent cholelithiasis and cholecystitis following subtotal cholecystectomy in the context of aberrant biliary anatomy and ADPKD. There were significant adhesions obscuring the cystic duct, necessitating the second cholecystectomy be performed open. The right posterior hepatic duct was adhered to the gallbladder wall and was perforated while attempting to remove the gallbladder remnant. The duct was repaired over a T-tube, without any subsequent biliary leak. The cystic duct was hugely dilated and impacted with stones down to the junction with the common bile duct, which were evacuated, and the cystic duct was oversewn along with the remnant of the gallbladder wall. The recovery course was unremarkable.
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Pectus excavatum (PE) is a congenital defect that presents with an anterior depression of the chest wall, which can impact cardiopulmonary function. A 25-year-old hypermobile male presented with a history of PE and chronic dyspnea on exertion, chronic cough, and intermittent chest wall pain. This study explores osteopathic manipulative treatment (OMT) as a possible alternative to improve symptoms associated with PE. Osteopathic structural exam (OSE), volumetric measurements of the thoracic cavity, vitals, and pulmonary function tests were evaluated at baseline and after OMT. The patient was treated with 14 weeks of weekly OMT for his exertional dyspnea, cough, and chest wall pain. Somatic dysfunctions were addressed through OMT, which all improved by the end of the 14-week treatment. Notably, the excursion at the sternal angle increased by threefold after complete treatment. The patient reported subjective improvement in all symptoms, with durable improvement in chest wall pain at 10 months after cessation of treatment. The application of OMT can help alleviate symptoms of pectus excavatum and aid in the management of patients who have not received surgical interventions.
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BACKGROUND AND AIMS: Drugs resolving steatotic liver disease (SLD) could prevent the evolution of metabolic dysfunction associated SLD (MASLD) to more aggressive forms but must show not only efficacy, but also a high safety profile. Repurposing of drugs in clinical use, such as pemafibrate and mirabegron, could facilitate the finding of an effective and safe drug-treatment for SLD. APPROACH AND RESULTS: The SLD High Fat High Fructose (HFHFr) rat model develops steatosis without the influence of other metabolic disturbances, such as obesity, inflammation, or type 2 diabetes. Further, liver fatty acids are provided, as in human pathology, both from dietary origin and de novo lipid synthesis. We used the HFHFr model to evaluate the efficacy of pemafibrate and mirabegron, alone or in combination, in the resolution of SLD, analyzing zoometric, biochemical, histological, transcriptomic, fecal metabolomic and microbiome data. We provide evidence showing that pemafibrate, but not mirabegron, completely reverted liver steatosis, due to a direct effect on liver PPARα-driven fatty acid catabolism, without changes in total energy consumption, subcutaneous, perigonadal and brown fat, blood lipids and body weight. Moreover, pemafibrate treatment showed a neutral effect on whole-body glucose metabolism, but deeply modified fecal bile acid composition and microbiota. CONCLUSIONS: Pemafibrate administration reverts liver steatosis in the HFHFr dietary rat SLD model without altering parameters related to metabolic or organ toxicity. Our results strongly support further clinical research to reposition pemafibrate for the treatment of SLD/MASLD.
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Benzoxazóis , Ácidos e Sais Biliares , Modelos Animais de Doenças , Fezes , Animais , Ácidos e Sais Biliares/metabolismo , Masculino , Ratos , Benzoxazóis/farmacologia , Fezes/microbiologia , Fezes/química , Microbioma Gastrointestinal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Acetanilidas/farmacologia , Butiratos/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Ratos Wistar , Tiazóis/farmacologia , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/patologia , Fígado Gorduroso/metabolismo , Frutose/efeitos adversosRESUMO
BACKGROUND: Spinal muscular atrophy (SMA) is a neuromuscular disease, causing progressive muscle weakness due to loss of lower motoneurons. Since 2017, three therapies, two modifying gene transcription and one adding the defective gene, have been approved with comparable efficacy on motor outcome. Data on cognitive outcomes of treated SMA type 1 patients is limited. The aim of this study was to evaluate cognitive function in symptomatic and presymptomatic SMA type 1 patients with two or three SMN2 copies who received SMN-modifying or gene-addition therapy in the first year of life. METHODS: Cognitive testing was performed in 20 patients, including 19 symptomatic SMA type 1 patients with up to three SMN2 copies and 1 pre-symptomatically treated patient. Children were tested using Bayley Scales of Infant Development (BSID-III) at the age of 2 or 3 years or the Wechsler Preschool and Primary Scale of Intelligence (WPSII-IV) at the of age of 5 years. RESULTS: 11/20 patients showed subnormal cognitive development. Boys had significantly lower cognitive scores. Patients requiring assisted ventilation or feeding support were more likely to have cognitive deficits. Achieving more motor milestones was associated with a better cognitive outcome. CONCLUSION: Treated patients with SMA type 1 have heterogeneous cognitive function with 55 % of patients showing deficits. Risk factors for cognitive impairment in our cohort were male gender and need for assisted ventilation or feeding support. Therefore, cognitive assessment should be included in the standard of care to allow early identification of deficits and potential therapeutic interventions.
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Atrofias Musculares Espinais da Infância , Proteína 2 de Sobrevivência do Neurônio Motor , Humanos , Masculino , Feminino , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Pré-Escolar , Lactente , Atrofias Musculares Espinais da Infância/terapia , Atrofias Musculares Espinais da Infância/genética , Atrofias Musculares Espinais da Infância/psicologia , Terapia Genética/métodos , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/terapia , Cognição/fisiologia , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/terapiaRESUMO
Imine-based vitrimers were prepared from synthesized diimine-dimethacrylate monomer derived from biobased vanillin. First, a methacrylate derivative starting from vanillin was synthesized. The diimine derivative was synthesized by condensation of the aldehyde groups from two vanillin methacrylate units with the amine groups of hexamethylenediamine (HMDA). The synthesized product was used in formulations containing ethylene glycol phenyl ether methacrylate (EGPMA) as a reactive diluent for the customization of final material properties and cured by exposure to ultraviolet (UV)-light using suitable radical photoinitiators or else with temperature using a radical thermal initiator. Materials with glass transition temperatures (Tgs) ranging from 70 to 90 °C were prepared, showing good thermal stability and mechanical and thermomechanical properties. The evaluation of their vitrimeric characteristics revealed that all materials achieved a stress-relaxation factor (σ = 0.37σ0) in less than 130 s at 160 °C, with photocured materials exhibiting faster relaxation rates. The catalytic effect of phosphine oxide groups in imine metathesis has also been evidenced. All prepared materials could be mechanically recycled and completely solubilized in a two-step degradation process, putting evidence of their potential use for carbon fiber-reinforced composites (CFRCs). In addition, they demonstrated promising self-repairing abilities. Finally, as a proof of concept, it was established that these formulations could be effectively processed using a Digital Light Processing three-dimensional (3D) Printer (DLP), resulting in the fabrication of complex shapes with high resolution.
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Prolapso de Órgão Pélvico , Rim Policístico Autossômico Dominante , Humanos , Feminino , Tolvaptan/uso terapêutico , Rim Policístico Autossômico Dominante/complicações , Rim Policístico Autossômico Dominante/tratamento farmacológico , Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Taxa de Filtração GlomerularRESUMO
Autosomal recessive tyrosine kinase 2 (TYK2) deficiency is characterized by susceptibility to mycobacterial and viral infections. Here, we report a 4-year-old female with severe respiratory viral infections, EBV-driven Burkitt-like lymphoma, and infection with the neurotropic Jamestown Canyon virus. A novel, homozygous c.745C > T (p.R249*) variant was found in TYK2. The deleterious effects of the TYK2 lesion were confirmed by immunoblotting; by evaluating functional responses to IFN-α/ß, IL-10, and IL-23; and by assessing its scaffolding effect on the cell surface expression of cytokine receptor subunits. The effects of the mutation could not be pharmacologically circumvented in vitro, suggesting that alternative modalities, such as hematopoietic stem cell transplantation or gene therapy, may be needed. We characterize the first patient from Canada with a novel homozygous mutation in TYK2.
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Encefalite Viral , Linfoma , Viroses , Feminino , Humanos , Pré-Escolar , Herpesvirus Humano 4 , TYK2 Quinase/genética , Mutação/genéticaRESUMO
OBJECTIVE: Implementation fidelity is a key dimension in process evaluation but has been scarcely studied. Reptes is a selective alcohol and cannabis use prevention program performed in vulnerable young people (16-21 years) from different educational and leisure settings. The study aimed to describe the components of this program, its implementation fidelity, and satisfaction among participants and facilitators. METHOD: A descriptive cross-sectional study was conducted. Implementation fidelity was assessed in terms of adherence, dose, participant responsiveness, and quality of the intervention through self-reports completed by 15 facilitators and self-administered questionnaires by 99 youth from the 15 groups completing the program. RESULTS: 70.7% of the groups performed 30 of the 43 planned activities with high use of various teaching methods, except for Information and Communication Technology resources. Fidelity implementation was above 70%. 2/3 groups completed an acceptable intervention and 1/3 completed a qualified intervention. Satisfaction was higher than 7. CONCLUSIONS: Our results show high implementation fidelity and satisfaction compared with those from similar studies.
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Cannabis , Alucinógenos , Adolescente , Humanos , Estudos Transversais , Etanol , EscolaridadeRESUMO
Mucolipidosis type II (MLII), an ultra-rare lysosomal storage disorder, manifests as a fatal multi-systemic disease. Mental inhibition and progressive neurodegeneration are commonly reported disease manifestations. Nevertheless, longitudinal data on neurocognitive testing and neuroimaging lack in current literature. This study aimed to provide details on central nervous system manifestations in MLII. All MLII patients with at least one standardized developmental assessment performed between 2005 and 2022 were included by retrospective chart review. A multiple mixed linear regression model was applied. Eleven patients with a median age of 34.0 months (range 1.6-159.6) underwent 32 neurocognitive and 28 adaptive behaviour assessments as well as 14 brain magnetic resonance imagings. The scales used were mainly BSID-III (42%) and VABS-II (47%). Neurocognitive testing (per patient: mean 2.9, standard deviation (SD) 2.0) performed over 0-52.1 months (median 12.1) revealed profound impairment with a mean developmental quotient of 36.7% (SD 20.4) at last assessment. The patients showed sustained development; on average, they gained 0.28 age-equivalent score points per month (confidence interval 0.17-0.38). Apart from common (63%) cervical spinal stenosis, neuroimaging revealed unspecific, non-progressive abnormalities (i.e., mild brain atrophy, white matter lesions). In summary, MLII is associated with profound developmental impairment, but not with neurodegeneration and neurocognitive decline.
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Hyperventilation (HV) therapy uses vasoconstriction to reduce intracranial pressure (ICP) by reducing cerebral blood volume. However, as HV also lowers cerebral blood flow (CBF), it may provoke misery perfusion (MP), in which the decrease in CBF is coupled with increased oxygen extraction fraction (OEF). MP may rapidly lead to the exhaustion of brain energy metabolites, making the brain vulnerable to ischemia. MP is difficult to detect at the bedside, which is where transcranial hybrid, near-infrared spectroscopies are promising because they non-invasively measure OEF and CBF. We have tested this technology during HV (â¼30 min) with bilateral, frontal lobe monitoring to assess MP in 27 sessions in 18 patients with traumatic brain injury. In this study, HV did not lead to MP at a group level (p > 0.05). However, a statistical approach yielded 89 events with a high probability of MP in 19 sessions. We have characterized each statistically significant event in detail and its possible relationship to clinical and radiological status (decompressive craniectomy and presence of a cerebral lesion), without detecting any statistically significant difference (p > 0.05). However, MP detection stresses the need for personalized, real-time assessment in future clinical trials with HV, in order to provide an optimal evaluation of the risk-benefit balance of HV. Our study provides pilot data demonstrating that bedside transcranial hybrid near-infrared spectroscopies could be utilized to assess potential MP.
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Lesões Encefálicas Traumáticas , Isquemia Encefálica , Humanos , Hiperventilação/terapia , Hiperventilação/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/complicações , Encéfalo , Isquemia Encefálica/metabolismo , Perfusão/efeitos adversos , Circulação Cerebrovascular , Pressão Intracraniana/fisiologiaRESUMO
PURPOSE: To assess maternal mental health during the first weeks after birth including birth experience, postpartum adjustment to early motherhood and the perception of newborn behaviour, and how this may be influenced by the first wave of the COVID-19 pandemic. METHODS: Ninety women who gave birth after the first enforcement of nation-wide disease control restrictions in Germany between 16 March and 10 May 2020 were surveyed and compared with 101 women who had given birth before the pandemic. Information on maternal mental health and maternal perception of early motherhood and neonatal behaviour were assessed at 3-8 weeks postpartum. RESULTS: Mothers who gave birth under the COVID-19-associated disease control restrictions did not show significant differences in depression, anxiety and social support scales compared to mothers before the pandemic. Birth experience was similar, while support during birth was perceived to be higher under the COVID-19 restrictions. Confidence in caretaking of the newborn and perception of neonatal behaviour were comparable between the two groups. Mothers expressed significantly higher dissatisfaction with the maternal role during the pandemic. CONCLUSIONS: Overall, maternal mental health and the perception of the newborn and early caretaking during the first COVID-19 wave did not substantially differ from the perceptions of mothers before the pandemic. A potential influence of the pandemic on higher dissatisfaction with the maternal role may be associated with the pandemic conditions affecting everyday life and should be addressed in postpartum care and in future qualitative and longitudinal studies.
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COVID-19 , Recém-Nascido , Gravidez , Humanos , Feminino , Pandemias , Parto , Alemanha/epidemiologia , MãesRESUMO
Simultaneous pancreas-kidney transplantation (SPKT) leads to increased survival and quality of life, and is an alternative treatment for insulin-dependent diabetes mellitus and end-stage kidney disease. Due to the particularities of this population (often with multiple comorbidities) and of the surgery (only performed in a few centers), a comprehensive analysis of patients' experience along the SPKT process is crucial to improve patient care and add value to this procedure. Therefore, we applied a systematic and iterative methodology with the participation of both patients and professional teams working together to explore and identify unmet needs and value-adding steps along the transplant patient journey at an established pancreas transplant program. Four main steps (to comprehend, to explore, to experiment and to assess) led to several interventions around three major areas: Administration and logistics, information and communication, and perceived quality of assistance. As a result, both displacements to the hospital for diagnostic purposes and the time delay involved in joining the patient waiting list for transplantation were reduced in parallel to the administrative procedures. In conclusion, the methodological implementation of key organizational changes has great impact on overall patient experience. Further quantitative analysis from the patient's perspective will consolidate our program and may add new prototype service design components.
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Transplante de Rim , Transplante de Pâncreas , Humanos , Pâncreas , Avaliação de Resultados da Assistência ao Paciente , Qualidade de VidaRESUMO
BACKGROUND: Several motor learning models have been used to teach highly complex procedural skills in medical education. Two approaches are often employed amongst health care professionals: Halsted's "See one - do one - teach one" concept and Peyton's Four-step approach. Peyton's deconstruction of the learning process into 4 sub-steps was reported to be preferable for learning/acquiring/teaching complex clinical skills. However, a new increasingly popular technique is known as the spaced learning method. In a previous study, we were able to confirm that the spaced learning concept is superior for laparoscopic suturing and knot tying compared to conventional training curricula, this current study aimed to assess the influence of spaced learning in combination with Halsted's and Peyton's tutoring approaches on laparoscopic knot tying of medical students. METHODS: After randomization, 20 medical students were either assigned to Halsted's or Peyton's teaching approach and trained one-on-one (teacher-student). Additionally, all subjects were trained according to the spaced learning concept, containing 40 minutes of content-blocks, followed by a 20-minute break involving coordinated, standardized physical activity. This was repeated three times. Primary endpoints were time, knot quality, precision, knot strength, as well as overall laparoscopic knotting performance and competency. To evaluate the motivation of the subjects, an 18-item questionnaire was utilized to measure four motivational factors (anxiety, probability of success, interest, and challenge). RESULTS: All trainees significantly improved after training in all knot attributes. Trainees assigned to Halsted's method were able to significantly outperform the Peyton group in knot quantity within 30 minutes (pâ¯=â¯0.013), time/knot (pâ¯=â¯0.033), performance score (pâ¯=â¯0.009), and precision (pâ¯=â¯0.032). No significant difference between Halsted and Peyton was found for knot strength and quality. Furthermore, no significant difference was identified comparing motivation pre- and post-training. However, subjects in the Peyton appeared to be significantly more anxious after training. CONCLUSION: Combining spaced learning technique with Halsted's "see one - do one - teach one" appears to be superior to Peyton's Four-step approach in conjunction with spaced learning in surgical naïve students. We recommend further studies evaluating the combination of spaced learning with Halsted and Peyton's instructional methods.
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Educação Médica , Estudantes de Medicina , Competência Clínica , Currículo , Educação Médica/métodos , Humanos , Aprendizagem , Técnicas de Sutura/educaçãoRESUMO
BACKGROUND: Thyroid dysfunction during pregnancy is relatively common and can cause obstetric complications and significantly influence fetal development. AIMS: We aimed to evaluate postnatal clinical and laboratory characteristics in the first days of life in infants born to mothers with a thyroid disorder. STUDY DESIGN AND SUBJECTS: We conducted a retrospective single-center study with neonates born between January 2010 and May 2020. Early laboratory parameters and clinical findings in neonates of mothers with different maternal thyroid disorders were analysed. RESULTS: We included 314 newborns of mothers with Hashimoto's thyroiditis, 171 with non-Hashimoto's hypothyroidism, 42 with Graves' disease, 12 with non-Graves' hyperthyroidism, and 190 neonates born to mothers without thyroid dysfunction. No demographic, clinical, and laboratory differences were observed between neonates from mothers with a thyroid disorder and healthy mothers. FT3 and fT4 correlated positively with gestational age (p < 0.001; p < 0.001) and negatively with maximum postnatal weight loss (p = 0.043; p < 0.001). High fT3 values were associated with lower maximum bilirubin levels (p = 0.020). CONCLUSION: Despite an increased morbidity risk due to the transplacental exposure to maternal antibodies, most neonates born to mothers with thyroid disorders show normal postnatal development and thyroid function tests during the first days of life.
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Complicações na Gravidez , Doenças da Glândula Tireoide , Feminino , Humanos , Lactente , Recém-Nascido , Mães , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos , Doenças da Glândula Tireoide/epidemiologiaRESUMO
BACKGROUND: The use of COVID-19 vaccines has been prioritised to protect the most vulnerable-notably, older people. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been used. However, the effectiveness of these strategies in frail, older people are unknown. We aimed to assess the antigenicity of mRNA-based COVID-19 vaccines in frail, older people in a real-world setting, with a rationed interval dosing of 16 weeks between the prime and boost doses. METHODS: This prospective observational cohort study was done across 12 long-term care facilities of the Montréal Centre-Sud - Integrated University Health and Social Services Centre in Montréal, Québec, Canada. Under a rationing strategy mandated by the provincial government, adults aged 65 years and older residing in long-term care facilities in Québec, Canada, with or without previously documented SARS-CoV-2 infection, were administered homologous or heterologous mRNA vaccines, with an extended 16-week interval between doses. All older residents in participating long-term care facilities who received two vaccine doses were eligible for inclusion in this study. Participants were enrolled from Dec 31, 2020, to Feb 16, 2021, and data were collected up to June 9, 2021. Clinical data and blood samples were serially collected from participants at the following timepoints: at baseline, before the first dose; 4 weeks after the first dose; 6-10 weeks after the first dose; 16 weeks after the first dose, up to 2 days before administration of the second dose; and 4 weeks after the second dose. Sera were tested for SARS-CoV-2-specific IgG antibodies (to the trimeric spike protein, the receptor-binding domain [RBD] of the spike protein, and the nucleocapsid protein) by automated chemiluminescent ELISA. Two cohorts were used in this study: a discovery cohort, for which blood samples were collected before administration of the first vaccine dose and longitudinally thereafter; and a confirmatory cohort, for which blood samples were only collected from 4 weeks after the prime dose. Analyses were done in the discovery cohort, with validation in the confirmatory cohort, when applicable. FINDINGS: The total study sample consisted of 185 participants. 65 participants received two doses of mRNA-1273 (Spikevax; Moderna), 36 received two doses of BNT162b2 (Comirnaty; Pfizer-BioNTech), and 84 received mRNA-1273 followed by BNT162b2. In the discovery cohort, after a significant increase in anti-RBD and anti-spike IgG concentrations 4 weeks after the prime dose (from 4·86 log binding antibody units [BAU]/mL to 8·53 log BAU/mL for anti-RBD IgG and from 5·21 log BAU/mL to 8·05 log BAU/mL for anti-spike IgG), there was a significant decline in anti-RBD and anti-spike IgG concentrations until the boost dose (7·10 log BAU/mL for anti-RBD IgG and 7·60 log BAU/mL for anti-spike IgG), followed by an increase 4 weeks later for both vaccines (9·58 log BAU/mL for anti-RBD IgG and 9·23 log BAU/mL for anti-spike IgG). SARS-CoV-2-naive individuals showed lower antibody responses than previously infected individuals at all timepoints tested up to 16 weeks after the prime dose, but achieved similar antibody responses to previously infected participants by 4 weeks after the second dose. Individuals primed with the BNT162b2 vaccine showed a larger decrease in mean anti-RBD and anti-spike IgG concentrations with a 16-week interval between doses (from 8·12 log BAU/mL to 4·25 log BAU/mL for anti-RBD IgG responses and from 8·18 log BAU/mL to 6·66 log BAU/mL for anti-spike IgG responses) than did those who received the mRNA-1273 vaccine (two doses of mRNA-1273: from 8·06 log BAU/mL to 7·49 log BAU/mL for anti-RBD IgG responses and from 6·82 log BAU/mL to 7·56 log BAU/mL for anti-spike IgG responses; mRNA-1273 followed by BNT162b2: from 8·83 log BAU/mL to 7·95 log BAU/mL for anti-RBD IgG responses and from 8·50 log BAU/mL to 7·97 log BAU/mL for anti-spike IgG responses). No differences in antibody responses 4 weeks after the second dose were noted between the two vaccines, in either homologous or heterologous combinations. INTERPRETATION: Interim results of this ongoing longitudinal study show that among frail, older people, previous SARS-CoV-2 infection and the type of mRNA vaccine influenced antibody responses when used with a 16-week interval between doses. In these cohorts of frail, older individuals with a similar age and comorbidity distribution, we found that serological responses were similar and clinically equivalent between the discovery and confirmatory cohorts. Homologous and heterologous use of mRNA vaccines was not associated with significant differences in antibody responses 4 weeks following the second dose, supporting their interchangeability. FUNDING: Public Health Agency of Canada, Vaccine Surveillance Reference Group; and the COVID-19 Immunity Task Force. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
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Vacinas contra COVID-19 , COVID-19 , Vacina de mRNA-1273 contra 2019-nCoV , Idoso , Vacina BNT162 , Idoso Fragilizado , Humanos , Imunoglobulina G , Estudos Longitudinais , Estudos Prospectivos , RNA Mensageiro , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação , Vacinas Sintéticas , Vacinas de mRNAAssuntos
Infecções por Citomegalovirus , Doenças da Imunodeficiência Primária , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Humanos , Ligante Coestimulador de Linfócitos T Induzíveis , Proteína Coestimuladora de Linfócitos T InduzíveisRESUMO
INTRODUCTION: Monogenic diseases play an important role in critically ill neonates and infants treated in the intensive care unit. This study aimed to determine the diagnostic yield of whole-exome sequencing (WES) for monogenic diseases and identify phenotypes more likely associated with a genetic etiology. METHODS: From March 2017 to 2020, a comprehensive diagnostic workup including WES in a single academic center was performed in 61 unrelated, critically ill neonates and infants with an unknown underlying disease within the first year of life. We conducted 59 trio-WES, 1 duo-WES, and 1 single-WES analyses. Symptoms were classified according to the Human Phenotype Ontology. RESULTS: The overall molecular genetic diagnostic rate within our cohort was 46% (28/61) and 50% (15/30) in the subgroup of preterm neonates. Identifying the genetic cause of disease facilitates individualized management in the majority of patients. A positive or negative predictive power of specific clinical features for a genetic diagnosis could not be observed. CONCLUSION: WES is a powerful noninvasive diagnostic tool in critically ill neonates and infants with a high diagnostic rate. We recommend initiating WES as early as possible due to the impact on management and family counseling. Recommendations regarding the clinical utility of WES in critically ill neonates and infants should not be based on the phenotype alone. Here, we present a clinical workflow for the application of WES for critically ill neonates and infants in an interdisciplinary setting.
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Estado Terminal , Unidades de Terapia Intensiva , Testes Genéticos , Humanos , Lactente , Fenótipo , Sequenciamento do ExomaRESUMO
OBJECTIVES: To explore the health effects of a community health intervention on older people who are isolated at home due to mobility problems or architectural barriers, to identify associated characteristics and to assess participants' satisfaction. DESIGN: Quasi-experimental before-after study. SETTING: Five low-income neighbourhoods of Barcelona during 2010-15. PARTICIPANTS: 147 participants, aged ≥59, living in isolation due to mobility problems or architectural barriers were interviewed before the intervention and after 6 months. INTERVENTION: Primary Health Care teams, public health and social workers, and other community agents carried out a community health intervention, consisting of weekly outings, facilitated by volunteers. MEASUREMENTS: We assessed self-rated health, mental health using the General Health Questionnaire (GHQ-12), and quality of life through the EuroQol scale. Satisfaction with the programme was evaluated using a set of questions. We analysed pre and post data with McNemar tests and fitted lineal and Poisson regression models. RESULTS: At 6 months, participants showed improvements in self-rated health and mental health and a reduction of anxiety. Improvements were greater among women, those who had not left home for ≥4 months, those with lower educational level, and those who had made ≥9 outings. Self-rated health [aRR: 1.29(1.04-1.62)] and mental health improvements [ß: 2.92(1.64-4.2)] remained significant in the multivariate models. Mean satisfaction was 9.3 out of 10. CONCLUSION: This community health intervention appears to improve several health outcomes in isolated elderly people, especially among the most vulnerable groups. Replications of this type of intervention could work in similar contexts.
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Saúde Mental , Saúde Pública , Idoso , Acessibilidade Arquitetônica , Feminino , Humanos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Advances in neonatology now enable increasing numbers of very low birth weight neonates (<1500 g) to survive into early adulthood and beyond. What are the implications for their long-term care? METHODS: Selective literature search on the outcome of very low birth weight neo - nates in adulthood ("adults born preterm"). RESULTS: Robust data are available on the pulmonary, metabolic, cardiovascular, renal, neurocognitive, sensory-visual, social-emotional, mental, reproductive, and musculoskeletal long-term risks. On the somatic level, elevated rates have been documented for asthma (odds Ratio [OR] 2.37), diabetes mellitus (OR 1.54), and chronic renal disease (hazard ratio [HR] 3.01), along with the cardiovascular and cerebrovascular sequelae of a tendency toward arterial hypertension. On the psychosocial level, the main findings are deficits in romantic partnerships (OR 0.72) and a lower reproduction rate (relative risk [RR] male/female 0.24/0.33). The affected women also have an elevated risk of preterm delivery. CONCLUSION: A risk profile with both somatic and psychosocial aspects can be discerned for adults who were born prematurely, even if some of these risks are present in low absolute numbers. As the ability to compensate for latent deficits declines with age, such adults may suffer from "premature aging as the late price of premature birth." A holistic approach to care with personalized prevention strategies- which for most of them was discontinued at discharge from pediatric followup- therefore seems appropriate in adulthood as well.