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BACKGROUND AND AIMS: A hierarchical micro-topography of ridges and steps renders the trap rim of carnivorous Nepenthes pitcher plants unusually wettable, and slippery for insects when wet. This complex three-dimensional epidermis structure forms, hidden from plain sight, inside the still-closed developing pitcher bud. Here, we reveal the sequence of epidermal patterning events that shape the trap rim. By linking this sequence to externally visible markers of bud development, we provide a framework for targeting individual stages of surface development in future studies. METHODS: We used cryo-scanning electron microscopy to investigate the detailed morphogenesis and epidermal patterning of the Nepenthes x hookeriana pitcher rim. In addition, we collected morphometric and qualitative data from developing pitcher traps including those sampled for microscopy. KEY RESULTS: We identified three consecutive patterning events. First, strictly oriented cell divisions resulted in radially aligned rows of cells and established a macroscopic ridge-and-groove pattern. Next, conical papillate cells formed, and papillae elongated towards the trap interior, increasingly overlapping adjacent cells and eventually forming continuous microscopic ridges. In between these ridges, the flattened papillae formed acutely angled arched steps. Finally, the cells elongated radially, thereby establishing the convex collar shape of the rim. This general sequence of surface development also showed a spatial progression from the outer to the inner trap rim edge, with several consecutive developmental stages co-occurring at any given time. CONCLUSIONS: We demonstrate that the complex surface microtopography of the Nepenthes pitcher rim develops by sequentially combining widespread, evolutionarily conserved epidermal patterning processes in a new way. This makes the Nepenthes trap rim an excellent model for studying epidermal patterning mechanisms in leaves.
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BACKGROUND: The German Registry for Cardiac Operations and Interventions in Patients with Congenital Heart Disease is a voluntary registry initiated by the German Society for Thoracic and Cardiovascular Surgery and the German Society for Pediatric Cardiology and Congenital Heart Defects. Since 2012, the registry collects data for the assessment of treatment and outcomes of surgical and interventional procedures in patients with congenital heart disease (CHD) of all age groups. METHODS: This real-world, prospective all-comers registry collects clinical and procedural characteristics, adverse events (AEs), mortality, and medium-term outcomes (up to 90 days) of patients undergoing surgical and interventional. A unique pseudonymous personal identifier (PID) allows longitudinal data acquisition in case of further invasive treatment in any participating German heart center. Prior to evaluation, all data sets are monitored for data completeness and integrity. Evaluation includes risk stratification of interventional and surgical procedures and classification of AEs. Each year's data are summarized in annual reports containing detailed information on the entire cohort, all subgroups, and 15 index procedures. In addition, each participating center receives an institutional benchmark report for comparison with the national results. This paper presents a comprehensive summary of the annual report 2021. RESULTS: In 2021, a total of 5,439 patients were included by 22 participating centers. In total, 3,721 surgical, 3,413 interventional, and 34 hybrid procedures were performed during 6,122 hospital stays. 2,220 cases (36.3%) could be allocated to the 15 index procedures. The mean unadjusted in-hospital mortality ranged from 0.4% among interventional and 2% among surgical cases up to 6.2 % in cases with multiple procedures. In-hospital mortality among index procedures accounted for 2.3% in total cavopulmonary connection, 20.3% in Norwood procedures, and 0.4% following interventional closure of patent ductus arteriosus. For the remaining seven surgical and five interventional index procedures, no in-hospital deaths were recorded. The 10-year longitudinal evaluation of 1,795 patients after tetralogy of Fallot repair revealed repeat interventional or surgical procedures in 21% of the patients. Over the same period, 31.1% of 2,037 patients, following initial treatment of native coarctation, required at least one additional hospital admission, 39.4% after initial interventional, and 21.3% after initial surgical therapy. CONCLUSION: The annual report 2021 of the German Registry for Cardiac Operations and Interventions in CHD shows continuously good results in accordance with previous data of the registry. Compared to international registries on CHD, it can be ascertained that in Germany invasive treatment of CHD is offered on a high medical level with excellent quality. The proven fact that patients with various malformations like tetralogy of Fallot and coarctation of the aorta require repeat procedures during follow-up confirms the urgent requirement for longitudinal assessment of all patients presenting with complex lesions.
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Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Complicações Pós-Operatórias , Sistema de Registros , Humanos , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/mortalidade , Alemanha , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Resultado do Tratamento , Lactente , Fatores de Tempo , Pré-Escolar , Criança , Fatores de Risco , Recém-Nascido , Adolescente , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Masculino , Estudos Prospectivos , Feminino , Benchmarking , Adulto Jovem , Medição de Risco , Indicadores de Qualidade em Assistência à Saúde , Relatórios Anuais como Assunto , Mortalidade Hospitalar , Avaliação de Processos e Resultados em Cuidados de Saúde , AdultoRESUMO
[This corrects the article DOI: 10.1371/journal.pgen.1009679.].
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Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed variation rate testing for DNVs identified in 2,489 parent-offspring trios. Our analysis revealed 21 genes which were significantly affected by rare CNVs and/or DNVs in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in small cases series or show new associations with CHD. In addition, a systems level analysis revealed affected protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes and pathways.
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Variações do Número de Cópias de DNA/genética , Haploinsuficiência/genética , Cardiopatias Congênitas/genética , Bases de Dados Genéticas , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença/genética , Genômica/métodos , Humanos , Canais Iônicos/genética , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único/genética , Transcriptoma/genéticaRESUMO
AIMS: To provide population-based data on the prevalence and clinical significance of immune deficiency syndromes (IDS) associated with congenital heart disease (CHD). METHODS AND RESULTS: Utilizing administrative German Health System data the prevalence of increased susceptibility to infection (ISI) or confirmed IDS was assessed in CHD patients and compared with an age-matched non-congenital control group. Furthermore, the prognostic significance of IDS was assessed using all-cause mortality and freedom from emergency hospital admission. A total of 54 449 CHD patients were included. Of these 14 998 (27.5%) had ISI and 3034 (5.6%) had a documented IDS (compared with 2.9% of the age-matched general population). During an observation period of 394 289 patient-years, 3824 CHD patients died, and 31 017 patients experienced a combined event of all-cause mortality or emergency admission. On multivariable Cox proportional-hazard analysis, the presence of ISI [hazard ratio (HR): 2.14, P < 0.001] or documented IDS (HR: 1.77, P = 0.035) emerged as independent predictors of all-cause mortality. In addition, ISI and confirmed IDS were associated with a significantly higher risk of emergency hospital admission (P = 0.01 for both on competing risk analysis) during follow-up. CONCLUSION: Limited immune competence is common in CHD patients and associated with an increased risk of morbidity and mortality. This highlights the need for structured IDS screening and collaboration with immunology specialists as immunodeficiency may be amenable to specific therapy. Furthermore, studies are required to assess whether IDS patients might benefit from intensified antibiotic shielding or tailored prophylaxis.
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Cardiopatias Congênitas , Hospitalização , Humanos , Fatores de Risco , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Medição de Risco , Modelos de Riscos ProporcionaisRESUMO
Background and Objectives: Patients with congenital heart disease (CHD), especially as a concomitant syndromal disease of trisomy 21 (T21), are at risk for impaired neurodevelopment. This can also affect these patients' education. However, there continues to be a research gap in the educational development of CHD patients and T21 CHD patients. Materials and Methods: In total, data from 2873 patients from the German National Register for Congenital Heart Defects were analyzed. The data are based on two online education surveys conducted among patients registered in the National Register for Congenital Heart Defects (2017, 2020). Results: Of 2873 patients included (mean age: 14.1 ± 4.7 years, 50.5% female), 109 (3.8%) were identified with T21 (mean age: 12.9 ± 4.4 years, 49.5% female). T21 CHD participants had a high demand for early specific interventions (overall cohort 49.1%; T21 cohort 100%). T21 CHD children more frequently attended special schools and, compared to non-trisomy 21 (nT21) CHD patients, the probability of attending a grammar school was reduced. In total, 87.1% of nT21 CHD patients but 11% of T21 CHD patients were enrolled in a regular elementary school, and 12.8% of T21 CHD patients could transfer to a secondary school in contrast to 35.5% of nT21 CHD patients. Most of the T21 CHD patients were diagnosed with psychiatric disorders, e.g., learning, emotional, or behavioral disorders (T21 CHD patients: 82.6%; nT21 CHD patients: 31.4%; p < 0.001). Conclusions: CHD patients are at risk for impaired academic development, and the presence of T21 is an aggravating factor. Routine follow-up examinations should be established to identify developmental deficits and to provide targeted interventions.
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Síndrome de Down , Cardiopatias Congênitas , Humanos , Criança , Feminino , Adolescente , Masculino , Síndrome de Down/complicações , Síndrome de Down/diagnóstico , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Escolaridade , Instituições Acadêmicas , EmoçõesRESUMO
Water shedding from leaves is a complex process depending on multiple leaf traits interacting with rain, wind, and air humidity, and with the entire plant and surrounding vegetation. Here, we synthesize current knowledge of the physics of water shedding with implications for plant physiology and ecology. We argue that the drop retention angle is a more meaningful parameter to characterize the water-shedding capacity of leaves than the commonly measured static contact angle. The understanding of the mechanics of water shedding is largely derived from laboratory experiments on artificial rather than natural surfaces, often on individual aspects such as surface wettability or drop impacts. In contrast, field studies attempting to identify the adaptive value of leaf traits linked to water shedding are largely correlative in nature, with inconclusive results. We make a strong case for taking the hypothesis-driven experimental approach of biomechanical laboratory studies into a real-world field setting to gain a comprehensive understanding of leaf water shedding in a whole-plant ecological and evolutionary context.
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Folhas de Planta , Água , Folhas de Planta/fisiologia , Chuva , MolhabilidadeRESUMO
Carnivorous pitcher plants capture insects in cup-shaped leaves that function as motionless pitfall traps. Nepenthes gracilis evolved a unique 'springboard' trapping mechanism that exploits the impact energy of falling raindrops to actuate a fast pivoting motion of the canopy-like pitcher lid. We superimposed multiple computed micro-tomography images of the same pitcher to reveal distinct deformation patterns in lid-trapping N. gracilis and closely related pitfall-trapping N. rafflesiana. We found prominent differences between downward and upward lid displacement in N. gracilis only. Downward displacement was characterized by bending in two distinct deformation zones whist upward displacement was accomplished by evenly distributed straightening of the entire upper rear section of the pitcher. This suggests an anisotropic impact response, which may help to maximize initial jerk forces for prey capture, as well as the subsequent damping of the oscillation. Our results point to a key role of pitcher geometry for effective 'springboard' trapping in N. gracilis.
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Planta Carnívora , Insetos , Animais , Planta Carnívora/anatomia & histologia , Planta Carnívora/fisiologia , Insetos/fisiologia , Folhas de Planta/fisiologiaRESUMO
BACKGROUND: The annual report of the German Quality Assurance of Congenital Heart Disease displays a broad overview on outcome of interventional and surgical treatment with respect to patient's age and risk categorization. Particular features of the German all-comers registry are the inclusion of all interventional and surgical procedures, the possibility to record repeated treatments with distinct individual patient assignment, and to record various procedures within one case. METHODS: International Pediatric and Congenital Cardiac Code terminology for diagnoses and procedures as well as classified adverse events, also recording of demographic data, key procedural performance indicators, and key quality indicators (mortality, adverse event rates). Surgical and interventional adverse events were classified according to the Society of Thoracic Surgeons and to the Congenital Heart Disease Adjustment for Risk Method of the congenital cardiac catheterization project on outcomes. Annual analysis of all cases and additional long-term evaluation of patients after repair of Fallot and primary treatment of native coarctation of the aorta were performed. RESULTS: In 2020, 5,532 patients with 6,051 cases (hospital stays) with 6,986 procedures were treated in 23 German institutions. Cases dispense on 618 newborns (10.2%), 1,532 infants (25.3%), 3,077 children (50.9%), and 824 adults (13.6%). Freedom from adverse events was 94.5% in 2,795 interventional cases, 67.9% in 2,887 surgical cases, and 42.9% in 336 cases with multiple procedures (without considering the 33 hybrid interventions). In-hospital mortality was 0.5% in interventional, 1.6% in surgical, and 5.7% in cases with multiple treatments. Long-term observation of 1,632 patient after repair of Fallot depicts the impact of previous palliation in 18% of the patients on the rate of 20.8% redo cases. Differentiated analysis of 1,864 patients with native coarctation picture clear differences of patient, age, and procedure selection and outcome. The overall redo procedure rate in this patient population is high with 30.8%. CONCLUSION: Improvement in quality of care requires detailed analysis of risks, performance indicators, and outcomes. The high necessity of redo procedures in patients with complex congenital heart disease underlines the imperative need of long-term observations.
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Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas , Adulto , Coartação Aórtica/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Alemanha , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Recém-Nascido , Sistema de Registros , Resultado do TratamentoRESUMO
AIMS: The aim of this study was to provide population-based data on maternal and neonatal complications and outcome in the pregnancies of women with congenital heart disease (CHD). METHODS AND RESULTS: Based on administrative data from one of the largest German Health Insurance Companies (BARMER GEK, â¼9 million members representative for Germany), all pregnancies in women with CHD between 2005 and 2018 were analysed. In addition, an age-matched non-CHD control group was included for comparison and the association between adult CHD (ACHD) and maternal or neonatal outcomes investigated. Overall, 7512 pregnancies occurred in 4015 women with CHD. The matched non-CHD control group included 6502 women with 11 225 pregnancies. Caesarean deliveries were more common in CHD patients (40.5% vs. 31.5% in the control group; P < 0.001). There was no excess mortality. Although the maternal complication rate was low in absolute terms, women with CHD had a significantly higher rate of stroke, heart failure and cardiac arrhythmias during pregnancy (P < 0.001 for all). Neonatal mortality was low but also significantly higher in the ACHD group (0.83% vs. 0.22%; P = 0.001) and neonates to CHD mothers had low/extremely low birth weight or extreme immaturity (<0.001) or required resuscitation and mechanical ventilation more often compared to non-CHD offspring (P < 0.001 for both). On multivariate logistic regression maternal defect complexity, arterial hypertension, heart failure, prior fertility treatment, and anticoagulation with vitamin K antagonists emerged as significant predictors of adverse neonatal outcome (P < 0.05 for all). Recurrence of CHD was 6.1 times higher in infants to ACHD mothers compared to controls (P < 0.0001). CONCLUSIONS: This population-based study illustrates a reassuringly low maternal mortality rate in a highly developed healthcare system. Nevertheless, maternal morbidity and neonatal morbidity/mortality were significantly increased in women with ACHD and their offspring compared to non-ACHD controls highlighting the need of specialized care and pre-pregnancy counselling.
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Cardiopatias Congênitas , Complicações Cardiovasculares na Gravidez , Cesárea , Feminino , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/epidemiologia , Humanos , Gravidez , Complicações Cardiovasculares na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Estudos RetrospectivosRESUMO
AIMS: The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population. METHODS AND RESULTS: Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients (<70 years of age) were included. Patients were stratified into those followed exclusively by primary care physicians (PCPs) and those with additional cardiology follow-up between 2014 and 2016. Associations between level of care and outcome were assessed by multivariable/propensity score Cox analyses. Overall, 24 139 patients (median age 43 years, 54.8% female) were included. Of these, only 49.7% had cardiology follow-up during the 3-year period, with 49.2% of patients only being cared for by PCPs and 1.1% having no contact with either. After comprehensive multivariable and propensity score adjustment, ACHD patients under cardiology follow-up had a significantly lower risk of death [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.67-0.98; P = 0.03) or major events (HR 0.85, 95% CI 0.78-0.92; P < 0.001) compared to those only followed by PCPs. At 3-year follow-up, the absolute risk difference for mortality was 0.9% higher in ACHD patients with moderate/severe complexity lesions cared by PCPs compared to those under cardiology follow-up. CONCLUSION: Cardiology care compared with primary care is associated with superior survival and lower rates of major complications in ACHD. It is alarming that even in a high resource setting with well-established specialist ACHD care approximately 50% of contemporary ACHD patients are still not linked to regular cardiac care. Almost all patients had at least one contact with a PCP during the study period, suggesting that opportunities to refer patients to cardiac specialists were missed at PCP level. More efforts are required to alert PCPs and patients to appropriate ACHD care.
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Cardiologia , Cardiopatias Congênitas , Adulto , Atenção à Saúde , Feminino , Cardiopatias Congênitas/terapia , Humanos , Masculino , Morbidade , Modelos de Riscos ProporcionaisRESUMO
BACKGROUND: Adults with systemic right ventricle have a significant risk for long-term complications such as arrhythmias or heart failure. METHODS: A nationwide retrospective study based on the German National Register for Congenital Heart Disease was performed. Patients with transposition of the great arteries after atrial switch operation or congenitally corrected TGA were included. RESULTS: Two hundred and eight-five patients with transposition of the great arteries after atrial switch operation and 95 patients with congenitally corrected transposition of the great arteries were included (mean age 33 years). Systolic function of the systemic ventricle was moderately or severely reduced in 25.5 % after atrial switch operation and in 35.1% in patients with congenitally corrected transposition. Regurgitation of the systemic atrioventricular valve was present in 39.5% and 43.2% of the cases, respectively. A significant percentage of patients also had a history for supraventricular or ventricular arrhythmias. However, polypharmacy of cardiovascular drugs was rare (4.5%) and 38.5 % of the patients did not take any cardiovascular medication. The amount of cardiovascular drugs taken was associated with NYHA class as well as systemic right ventricular dysfunction. Patients with congenitally corrected transposition were more likely to receive pharmacological treatment than patients after atrial switch operation. CONCLUSION: A significant portion of patients with systemic right ventricle suffer from a relevant systemic ventricular dysfunction, systemic atrioventricular valve regurgitation, and arrhythmias. Despite this, medication for heart failure treatment is not universally used in this cohort. This emphasises the need for randomised trials in patient with systemic right ventricle.
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Fármacos Cardiovasculares , Cardiopatias Congênitas , Insuficiência Cardíaca , Transposição dos Grandes Vasos , Adulto , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/terapia , Transposição das Grandes Artérias Corrigida Congenitamente , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/cirurgia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/etiologia , Ventrículos do Coração , Humanos , Estudos Retrospectivos , Transposição dos Grandes Vasos/complicações , Função Ventricular , Função Ventricular DireitaRESUMO
BACKGROUND: The number of adults with congenital heart disease (ACHD) is steadily increasing. The present cross-sectional study was conceived to investigate ACHD care from the perspective of patients and family practitioners (specialists for general medicine and internal medicine, general practitioners). METHODS: Questionnaire-based cross-sectional study to analyze the real care situation of ACHD in Germany from the perspective of patients and primary care physicians (PCP). RESULTS: The questionnaire was completed by 4493 ACHD (53.7% female; 41.3⯱ 16.9 years) and 1055 PCP. The majority of ACHD (79.8%) visited their PCP for noncardiac health problems but also for cardiac problems. Almost all ACHD had substantial needs for medical consultation (performance, employment etc.). Of the patients 2014 (44.8%) did not know of any certified ACHD specialists or specialized centers and 2816 (62.7%) respondents were not aware of any ACHD patient organization. Of the PCPs 87.5% had cared for ACHD of all severities due to defect-typical residual and resulting symptoms. Many were not aware of any certified ACHD specialists. Only 28.5% consulted an ACHD specialist. Only 23.5% were aware of ACHD patient organizations. CONCLUSION: General practitioners are a mainstay of ACHD care in Germany. The present study shows that ACHD and their general practitioners are largely uninformed about the specialized care structures available nationwide, despite the high level of need for specialist care. In order to keep the morbidity and mortality of affected patients low, solutions must be elaborated in future to involve and integrate primary care physicians more intensively into the already existing dedicated ACHD care structures, in cooperation with specialized pediatric cardiologists, cardiologists and centers.
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Clínicos Gerais , Cardiopatias Congênitas , Adulto , Criança , Estudos Transversais , Feminino , Alemanha/epidemiologia , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/terapia , Humanos , Medicina Interna , MasculinoRESUMO
Similar to animals, plants have evolved mechanisms for elastic energy storage and release to power and control rapid motion, yet both groups have been largely studied in isolation. This is exacerbated by the lack of consistent terminology and conceptual frameworks describing elastically powered motion in both groups. Iconic examples of fast movements can be found in carnivorous plants, which have become important models to study biomechanics, developmental processes, evolution and ecology. Trapping structures and processes vary considerably between different carnivorous plant groups. Using snap traps, suction traps and springboard-pitfall traps as examples, we illustrate how traps mix and match various mechanisms to power, trigger and actuate motions that contribute to prey capture, retention and digestion. We highlight a fundamental trade-off between energetic investment and movement control and discuss it in a functional-ecological context.
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Planta Carnívora , Movimento , Animais , Fenômenos Biomecânicos , Movimento (Física) , PlantasRESUMO
[This corrects the article DOI: 10.1371/journal.pbio.1000281.].
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AIMS: Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation. METHODS: In a randomized, double-blinded, 2 × 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine-naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine-naloxone 200:1]). Acute naloxone-induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale-German [SOWS-G]) and observer-rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated. RESULTS: Intravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 100:1 > morphine-naloxone 200:1) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone. CONCLUSION: Morphine-naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.
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Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides , Síndrome de Abstinência a Substâncias , Analgésicos Opioides/efeitos adversos , Animais , Feminino , Humanos , Masculino , Morfina/efeitos adversos , Naloxona/administração & dosagem , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , SuínosRESUMO
BACKGROUND: Deep learning algorithms are increasingly used for automatic medical imaging analysis and cardiac chamber segmentation. Especially in congenital heart disease, obtaining a sufficient number of training images and data anonymity issues remain of concern. METHODS: Progressive generative adversarial networks (PG-GAN) were trained on cardiac magnetic resonance imaging (MRI) frames from a nationwide prospective study to generate synthetic MRI frames. These synthetic frames were subsequently used to train segmentation networks (U-Net) and the quality of the synthetic training images, as well as the performance of the segmentation network was compared to U-Net-based solutions trained entirely on patient data. RESULTS: Cardiac MRI data from 303 patients with Tetralogy of Fallot were used for PG-GAN training. Using this model, we generated 100,000 synthetic images with a resolution of 256 × 256 pixels in 4-chamber and 2-chamber views. All synthetic samples were classified as anatomically plausible by human observers. The segmentation performance of the U-Net trained on data from 42 separate patients was statistically significantly better compared to the PG-GAN based training in an external dataset of 50 patients, however, the actual difference in segmentation quality was negligible (< 1% in absolute terms for all models). CONCLUSION: We demonstrate the utility of PG-GANs for generating large amounts of realistically looking cardiac MRI images even in rare cardiac conditions. The generated images are not subject to data anonymity and privacy concerns and can be shared freely between institutions. Training supervised deep learning segmentation networks on this synthetic data yielded similar results compared to direct training on original patient data.
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Imagem Cinética por Ressonância Magnética/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Tetralogia de Fallot/diagnóstico por imagem , Adolescente , Algoritmos , Aprendizado Profundo , Feminino , Humanos , Masculino , Estudos Prospectivos , Aprendizado de Máquina Supervisionado , Adulto JovemRESUMO
BACKGROUND: Uncoordinated interprofessional communication in nursing homes increases the risk of polypharmacy and inappropriate medication use. This may lead to augmented frequency of adverse drug events, hospitalizations and mortality. The aims of this study were (1) to improve interprofessional communication and medication safety using a combined intervention and thus, (2) to improve medication appropriateness and health-related outcomes of the included residents. METHODS: The single-arm interventional study (2014-2017) was conducted in Muenster, Germany and involved healthcare professionals and residents of nursing homes. The intervention consisted of systematic education of participating healthcare professionals and of a structured interprofessional medication review which was performed via an online communication platform. The primary endpoint was assessed using the Medication Appropriateness Index MAI. Secondary endpoints were: cognitive performance, delirium, agitation, mobility, number of drugs, number of severe drug-drug interactions and appropriateness of analgesics. Outcomes were measured before, during and after the intervention. Data were analyzed using descriptive and inference-statistical methods. RESULTS: Fourteen general practitioners, 11 pharmacists, 9 nursing homes and 120 residents (n = 83 at all testing times) participated. Overall MAI sum-score decreased significantly over time (mean reduction: -7.1, CI95% -11.4 - - 2.8; median = - 3.0; dCohen = 0.39), especially in cases with baseline sum-score ≥ 24 points (mean reduction: -17.4, CI95% -27.6 - - 7.2; median = - 15.0; dCohen = 0.86). MAI sum-score of analgesics also decreased (dCohen = 0.45). Mean number of severe drug-drug interactions rose slightly over time (dCohen = 0.17). The proportion of residents showing agitated behavior diminished from 83.9 to 67.8%. Remaining secondary outcomes were without substantial change. CONCLUSION: Medication appropriateness increased particularly in residents with high baseline MAI sum-scores. Cognitive decline of participating residents was seemingly decelerated when compared with epidemiologic studies. A controlled trial is required to confirm these effects. Interprofessional interaction was structured and performance of medication reviews was facilitated as the online communication platform provided unlimited and consistent access to all relevant and updated information. TRIAL REGISTRATION: DRKS Data Management, ID: DRKS00007900 , date of registration: 2015-09-02 (retrospectively registered i.e. 6 weeks after commencement of the first data collection).
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Reconciliação de Medicamentos/normas , Casas de Saúde/normas , Medidas de Resultados Relatados pelo Paciente , Lista de Medicamentos Potencialmente Inapropriados/normas , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Interações Medicamentosas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Clínicos Gerais/normas , Alemanha/epidemiologia , Humanos , Masculino , Informática Médica/métodos , Informática Médica/normas , Reconciliação de Medicamentos/métodos , Farmacêuticos/normas , PolimedicaçãoRESUMO
OBJECTIVES: Somatic development is impaired in children with congenital heart defects (CHDs), and head circumference seems to be a strong predictor of neurodevelopmental prognosis. The aim of this study was to generate up-to-date reference values for the somatic development (head circumference, body weight, and length/height) of children with CHDs. STUDY DESIGN: Our study population consisted of all patients included in the PAN study (Prävalenz angeborener Herzfehler bei Neugeborenen in Deutschland), which was conducted prospectively over a 3-year study period by the Competence Network for Congenital Heart Defects. All children with mild, moderate, and severe CHDs born in 2006-2009 in Germany were enrolled. For computing of z-scores, only children with the following characteristics were included: appropriate for gestational age, nonsyndromic disease, term or post-term delivery, and no cardiac surgery. RESULTS: There were 2818 patients included. New z-scores for the described somatic measures of children with mild, moderate, and severe CHDs were computed. Comparisons with the KiGGS study (Gesundheit von Kindern und Jugendlichen in Deutschland) and the Berlin Longitudinal Study revealed significantly lower measurements for all measures-most notably in children with severe CHDs and/or cardiac surgery. In our cohort, no catch-up growth was seen after cardiac surgery. CONCLUSION: Children with severe CHDs demonstrated the most abnormal pattern in growth, including head circumference before and after cardiac surgery, which is indicative of accompanying brain pathology unrelated to operative injury.
Assuntos
Estatura/fisiologia , Peso Corporal/fisiologia , Desenvolvimento Infantil/fisiologia , Cabeça/crescimento & desenvolvimento , Cardiopatias Congênitas/fisiopatologia , Cefalometria , Pré-Escolar , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Estudos Longitudinais , Masculino , Estudos Prospectivos , Valores de ReferênciaRESUMO
Contents Summary 1035 I. Introduction 1035 II. Evolution of the pitcher 1036 III. Convergent evolution 1036 IV. Divergent evolution 1038 V. Adaptive radiation and speciation 1040 VI. Conclusions and perspectives 1040 Acknowledgements 1040 References 1040 SUMMARY: The pitcher trap is a striking example of convergent evolution across unrelated carnivorous plant lineages. Convergent traits that have evolved across pitcher plant lineages are essential for trap function, suggesting that key selective pressures are in action. Recent studies have also revealed patterns of divergent evolution in functional pitcher morphology within genera. Adaptations to differences in local prey assemblages may drive such divergence and, ultimately, speciation. Here, we review recent research on convergent and divergent evolution in pitcher plant traps, with a focus on the genus Nepenthes, which we propose as a new model for research into adaptive radiation and speciation.