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Theoretical arguments and empirical investigations indicate that a high proportion of published findings do not replicate and are likely false. The current position paper provides a broad perspective on scientific error, which may lead to replication failures. This broad perspective focuses on reform history and on opportunities for future reform. We organize our perspective along four main themes: institutional reform, methodological reform, statistical reform and publishing reform. For each theme, we illustrate potential errors by narrating the story of a fictional researcher during the research cycle. We discuss future opportunities for reform. The resulting agenda provides a resource to usher in an era that is marked by a research culture that is less error-prone and a scientific publication landscape with fewer spurious findings.
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BACKGROUND: Patients on oral anticoagulants (OACs) undergoing percutaneous coronary intervention (PCI) also require aspirin and a P2Y12 inhibitor (triple therapy). However, triple therapy increases bleeding. The use of non-vitamin K antagonist oral anticoagulants (NOACs) and stronger P2Y12 inhibitors has increased. The aim of our study was to gain insight into antithrombotic management over time. METHODS: A prospective cohort study of patients on OACs for atrial fibrillation or a mechanical heart valve undergoing PCI was performed. Thrombotic outcomes were myocardial infarction, stroke, target-vessel revascularisation and all-cause mortality. Bleeding outcome was any bleeding. We report the 30-day outcome. RESULTS: The mean age of the 758 patients was 73.5⯱ 8.2 years. The CHA2DS2-VASc score was ≥â¯3 in 82% and the HAS-BLED score ≥â¯3 in 44%. At discharge, 47% were on vitamin K antagonists (VKAs), 52% on NOACs, 43% on triple therapy and 54% on dual therapy. Treatment with a NOAC plus clopidogrel increased from 14% in 2014 to 67% in 2019. The rate of thrombotic (4.5% vs 2.0%, pâ¯= 0.06) and bleeding (17% vs. 14%, pâ¯= 0.42) events was not significantly different in patients on VKAs versus NOACs. Also, the rate of thrombotic (2.9% vs 3.4%, pâ¯= 0.83) and bleeding (18% vs 14%, pâ¯= 0.26) events did not differ significantly between patients on triple versus dual therapy. CONCLUSIONS: Patients on combined oral anticoagulation and antiplatelet therapy undergoing PCI are elderly and have both a high bleeding and ischaemic risk. Over time, a NOAC plus clopidogrel became the preferred treatment. The rate of thrombotic and bleeding events was not significantly different between patients on triple or dual therapy or between those on VKAs versus NOACs.
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BACKGROUND: Management of pectoralis major (PM) injuries is largely determined by the anatomic location of the injury, with tendon avulsions from the humerus requiring surgery while myotendinous (MT) injuries are typically managed non-operatively. Because physical examination cannot reliably make this distinction, MRI is often used for staging. However, correct classification can also be difficult with MRI where there is extensive soft tissue edema and distorted anatomy. OBJECTIVE: To determine the diagnostic performance of primary and secondary MRI signs of PM injury for distinguishing tendon avulsions from MT injuries in a selected sample of patients that underwent surgical repair using a practical interpretation algorithm. METHODS: In this retrospective study, 3 blinded observers independently assessed the MRI findings of 17 patients with PM injury (including 12 acute injuries, 4 chronic, and 1 of uncertain age) where subsequent surgery documented tendon avulsion (11) and MT injuries (6) by applying the primary MRI criteria of absent tendon at the humerus, retracted tendon stump, epicenter of edema, and the secondary finding of soft tissue edema contacting the anterior humeral cortex. Operative findings were used as the reference standard. Sensitivity, specificity, and positive and negative predictive value were recorded for each finding. RESULTS: The primary MRI finding of lack of a visible tendon at the insertion (sensitivity 82-100%, specificity 100%) and the secondary finding of edema contacting the anterior humeral cortex (sensitivity 64-91%, specificity 67-100%) were both useful for the distinction of tendon avulsion from MT injury, particularly in acute injuries. The presence of a retracted tendon stump and the epicenter of edema were not reliable findings. The use of a decision tree including the secondary finding of humeral edema increased the sensitivity and specificity for 2 of the 3 observers. CONCLUSION: MRI assessment of PM injury focused on the humeral insertion of the PM tendon allows accurate distinction of tendon avulsion from MT injury. CLINICAL IMPACT: This study describes a practical approach to classifying PM injuries with MRI to distinguish injuries that require surgery from those that can potentially be managed conservatively.
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Músculos Pectorales , Traumatismos de los Tendones , Humanos , Imagen por Resonancia Magnética , Estudios Retrospectivos , Traumatismos de los Tendones/diagnóstico por imagen , TendonesRESUMEN
BACKGROUND: Studies on the use of non-vitamin K antagonist oral anticoagulants in unselected patients with atrial fibrillation (AF) show that clinical characteristics and dosing practices differ per region, but lack data on edoxaban. METHODS: With data from Edoxaban Treatment in routiNe clinical prActice for patients with AF in Europe (ETNA-AF-Europe), a large prospective observational study, we compared clinical characteristics (including the dose reduction criteria for edoxaban: creatinine clearance 15-50â¯ml/min, weight ≤60â¯kg, and/or use of strong pglycoprotein inhibitors) of patients from Belgium and the Netherlands (BeNe) with those from other European countries (OEC). RESULTS: Of all 13,639 patients in ETNA-AF-Europe, 2579 were from BeNe. BeNe patients were younger than OEC patients (mean age: 72.3 vs 73.9 years), and had lower CHA2DS2-VASc (mean: 2.8 vs 3.2) and HAS-BLED scores (mean: 2.4 vs 2.6). Patients from BeNe less often had hypertension (61.6% vs 80.4%), and/or diabetes mellitus (17.3% vs 23.1%) than patients from OEC. Moreover, relatively fewer patients in BeNe were prescribed the reduced dose of 30â¯mg edoxaban (14.8%) than in OEC (25.4%). Overall, edoxaban was dosed according to label in 83.1% of patients. Yet, 30â¯mg edoxaban was prescribed in the absence of any dose reduction criteria in 36.9% of 30â¯mg users (5.5% of all patients) in BeNe compared with 35.5% (9.0% of all patients) in OEC. CONCLUSION: There were several notable differences between BeNe and OEC regarding clinical characteristics and dosing practices in patients prescribed edoxaban, which are relevant for the local implementation of dose evaluation and optimisation. TRIAL REGISTRATION: NCT02944019; Date of registration 24 October 2016.
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BACKGROUND: Antithrombotic treatment choices are complicated when patients have both atrial fibrillation (AF) and acute coronary syndrome and/or undergo percutaneous coronary intervention (PCI). In this study, we aimed to gain insight into antithrombotic management strategies in daily clinical practice. METHODS: We invited interventional cardiologists to complete the WOEST (What is the Optimal antiplatElet & Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary StenTing) survey 2018. In this questionnaire, we presented a patient with a non-ST-elevation myocardial infarction (NSTEMI) and an elective PCI case. RESULTS: The results were based on 118 completed questionnaires (response rate 69.4%). In the case of the AF patient with NSTEMI, most cardiologists indicated they would initiate dual antiplatelet therapy (acetylsalicylic acid and clopidogrel) and continue non-vitamin K antagonist oral anticoagulant (NOAC) therapy at admission and during coronary angiography/PCI. At discharge, 70.3% would prescribe triple antithrombotic therapy (oral anticoagulation, acetylsalicylic acid and clopidogrel), mostly for 1 month. One year after NSTEMI, 83.1% would cancel the antiplatelet therapy and prescribe NOAC monotherapy. For the AF patient undergoing elective PCI, 51.7% would start dual antiplatelet therapy prior to the procedure and 52.5% would discontinue NOAC therapy prior to the PCI. At discharge, 55.1% would start triple antithrombotic therapy. Furthermore, 25.4% responded they routinely prescribe a reduced dose of NOAC after discharge. One year after PCI, 89.0% would continue NOAC monotherapy. CONCLUSION: The WOEST survey demonstrated heterogeneity in antithrombotic management strategies among interventional cardiologists. This observed variety mirrors the heterogeneity of the many guidelines and consensus documents. Further research is needed to guide patient-tailored medicine for AF patients undergoing PCI.
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BACKGROUND: Current guidelines recommend non-vitaminK oral anticoagulants (NOACs) as the first-choice therapy for stroke prevention in patients with atrial fibrillation (AF). The use of drugs in a clinical trial setting differs from that in real-world populations. Real-world data are important to accrue more heterogeneous patient populations with respect to co-morbidities and co-medication use. The aim of this study was to evaluate the use of NOACs in daily practice in a large tertiary hospital in the Netherlands. METHODS: A single-centre prospective study was conducted among all patients with AF using a NOAC in the St. Antonius Hospital between 2013 and June 2017. The outcomes were the rates of any bleeding, stroke/transient ischaemic attack, mortality, discontinuation rate and adverse drug reactions. RESULTS: In total, 799 patients were enrolled with a mean follow-up of 1.7 years. Mean age was 69.8 (SD⯱ 11) and 61.2% were male. Mean CHA2DS2-VASc score was 2.8 (SD⯱ 1.6) and mean HAS-BLED score was 1.4 (SD⯱ 0.9). Bleeding occurred in 6.0, major bleeding in 1.8, stroke in 1.2 patients per 100 patient-years, and 87 patients (10.9%) died during the follow-up period. Adverse drug reactions were reported by 59 patients (7.4%). Finally, 249 patients (31.2%) reported a temporary interruption and 132 (16.5%) permanent discontinuation of NOAC treatment, of whom 33 (25%) patients switched to a vitaminK antagonist. CONCLUSIONS: We observed low rates of bleeding and adverse drug reactions. However, rates of mortality and discontinuation were relatively high. These results could possibly be explained by the real-world nature of the data including higher-risk patients.
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BACKGROUND: Non-vitaminK oral anticoagulants (NOACs) are recommended as the first-choice therapy for stroke prevention in patients with non-valvular atrial fibrillation (AF). However, the lack of monitoring may impact patients' adherence, and non-adherence to medication is a potential hazard to safe and efficacious use. This is the first report with a 'comparative patient-oriented perspective' regarding the use of anticoagulant medication in the NOACs era. Our aim was to compare patients' self-reported practical problems, adverse events and non-adherence to anticoagulation therapy. METHODS: A survey was conducted among patients with AF on either NOACs or vitaminK antagonists (VKAs). The outcomes were self-reported non-adherence to anticoagulant medication, and patients' experiences, adverse events and practical problems correlated with the intake of the drug itself. RESULTS: A total of 765 patients filled out the questionnaire, of which 389 (50.9%) were on VKAs and 376 (49.1%) on NOACs. Age (70.6⯱ 8.8 vs 70.3⯱ 9.1 years) and male gender (70.4% vs 64.6%) were similar in the two groups. A significantly higher proportion of VKA users than NOAC users reported having frequent (16.2% vs 3.7%, pâ¯> 0.001) or occasional (4.1% vs 1.3%, pâ¯> 0.001) practical issues with medication intake. Self-reported non-adherence was significantly higher (24.4% vs 18.1%, pâ¯= 0.03) among VKA users. The incidence of self-reported adverse events was similar. CONCLUSION: Patient experiences support the current guideline recommendations for NOACs as the first-choice therapy: NOAC therapy resulted in a higher practical feasibility and better adherence when compared with VKA therapy, with a similar incidence of adverse events in both groups.
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BACKGROUND: Advance care planning (ACP) is a process in which professionals, patients and their relatives discuss wishes and options for future care. ACP in the palliative phase reduces the chance that decisions have to be taken suddenly and can therefore improve the quality of life and death. The primary aim of this study is to explore how ACP takes place in cases of people with intellectual disabilities (ID). METHOD: Medical files were analysed, and interviews were held in six care organisations for people with mild to severe ID. The data concerned people with ID (n = 30), 15 in the palliative phase, identified using the 'surprise question', and 15 who had died after an identifiable period of illness. Additional pre-structured telephone interviews were conducted with their relatives (n = 30) and professionals (n = 33). RESULTS: For half of the people with ID who had died, the first report in their file about palliative care (needs) was less than 1 month before their death. Professionals stated that ACP was started in response to the person's deteriorating health situation. A do-not-attempt-resuscitation order was recorded for nearly all people with ID (93%). A smaller group also had other agreements between professionals and relatives documented in their files, mainly about potentially life-sustaining treatments (43%) and/or hospitalisation admissions (47%). Relatives and professionals are satisfied with the mutual cooperation in ACP in the palliative phase. Cognitive and communication disabilities were most frequently mentioned by relatives and professionals as reasons for not involving people with ID in ACP. CONCLUSIONS: Advance care planning in the palliative phase of people with ID focuses mainly on medical issues at the end of life. Specific challenges concern a proactive identification of changing needs, fear to initiate ACP discussions, documentation of ACP in medical files and the involvement of people with ID in ACP. It is recommended that relatives and professionals should be informed about the content of ACP and professionals should be trained in communicating in advance about wishes for future care.
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Planificación Anticipada de Atención , Discapacidad Intelectual/terapia , Cuidados Paliativos , Órdenes de Resucitación , Adulto , Planificación Anticipada de Atención/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Registros Médicos , Persona de Mediana Edad , Países Bajos , Cuidados Paliativos/estadística & datos numéricos , Investigación CualitativaRESUMEN
In the present work, the synthesis of ternary chitosan/zinc oxide/titanium dioxide (CTS-ZnO-TiO2) nanocomposite was carried out with the use of mechanical stirring (conventional) and ultrasound assisted method. The characterization of prepared CTS-ZnO-TiO2 adsorbent was carried out using XRD, TEM, FTIR and the results of these analysis methods proved the successful preparation of ternary nanocomposite. Crystal violet (CV) dye was used as a pollutant to observe the adsorption ability of the prepared nanocomposite and the nanocomposite prepared by ultrasonic-assisted method proved to be a better adsorbent. The CV dye adsorption was significant for CTS-ZnO-TiO2 nanocomposite synthesized with the use of ultrasound assisted method compared to that prepared by conventional method. It is due to the physical effects of the ultrasonic irradiations due to which formation of finely dispersed nanocomposite takes place than that by conventional method. For batch adsorption the effect of various operating parameters such as initial dye concentration, time, temperature and adsorbent dose has been evaluated. The obtained data were processed using isotherm models, adsorption kinetics and the thermodynamic behavior of the cationic dye adsorption was also studied. The isotherm data was correlated reasonably well by the Temkin adsorption isotherm. Pseudo-second-order kinetic model provided a better correlation for the experimental data compared to pseudo first order, Elovich model and power function kinetics model. Thermodynamic parameters for adsorption indicated that the dye adsorption was spontaneous and endothermic in nature.
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Chronic hepatitis C virus (HCV) infection is a major cause of chronic liver disease and liver-related death. Recently, multiple regimens of different direct-acting antiviral agents (DAAs) have been registered. Although treatment with sofosbuvir (SOF) and simeprevir (SMV) is registered for the treatment of genotype 4 patients in some countries, data on efficacy of this combination are lacking. We aimed to assess the efficacy of SOF and SMV with or without RBV during 12 weeks in a real-life cohort of genotype 4 HCV patients. A retrospective multicentre observational study was conducted in 4 hospitals in Amsterdam, the Netherlands, including patients with advanced liver fibrosis or liver cirrhosis treated with SOF plus SMV with or without RBV during 12 weeks for a genotype 4 chronic HCV infection from 1 January 2015 to 1 August 2015. Sustained viral response (SVR) was established at week 12 after end of treatment. A total of 53 patients with genotype 4 HCV infection, treatment naïve and experienced, were included. SVR was achieved in 49 of 53 patients (92%). The four failures all had a virological relapse and did not receive ribavirin. Three were nonresponder to earlier interferon-based treatment, and one was treatment naive. In this real-life cohort of patients with HCV genotype 4 infection and advanced liver fibrosis/cirrhosis, we show that treatment with SOF and SMV is effective. The addition of RBV could be considered in treatment-experienced patients as recommended in guidelines.
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Antivirales/uso terapéutico , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/tratamiento farmacológico , Cirrosis Hepática/patología , Simeprevir/uso terapéutico , Sofosbuvir/uso terapéutico , Adulto , Anciano , Femenino , Hepacivirus/clasificación , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Cirrosis Hepática/virología , Masculino , Persona de Mediana Edad , Países Bajos , Inhibidores de Proteasas , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Empirical knowledge around palliative care provision and needs of people with intellectual disabilities is extremely limited, as is the availability of research resources, including expertise and funding. This paper describes a consultation process that sought to develop an agenda for research priorities for palliative care of people with intellectual disabilities in Europe. METHODS: A two-day workshop was convened, attended by 16 academics and clinicians in the field of palliative care and intellectual disability from six European countries. The first day consisted of round-table presentations and discussions about the current state of the art, research challenges and knowledge gaps. The second day was focused on developing consensus research priorities with 12 of the workshop participants using nominal group technique, a structured method which involved generating a list of research priorities and ranking them in order of importance. RESULTS: A total of 40 research priorities were proposed and collapsed into eleven research themes. The four most important research themes were: investigating issues around end of life decision making; mapping the scale and scope of the issue; investigating the quality of palliative care for people with intellectual disabilities, including the challenges in achieving best practice; and developing outcome measures and instruments for palliative care of people with intellectual disabilities. CONCLUSIONS: The proposal of four major priority areas and a range of minor themes for future research in intellectual disability, death, dying and palliative care will help researchers to focus limited resources and research expertise on areas where it is most needed and support the building of collaborations. The next steps are to cross-validate these research priorities with people with intellectual disabilities, carers, clinicians, researchers and other stakeholders across Europe; to validate them with local and national policy makers to determine how they could best be incorporated in policy and programmes; and to translate them into actual research studies by setting up European collaborations for specific studies that require such collaboration, develop research proposals and attract research funding.
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Consenso , Discapacidad Intelectual/terapia , Cuidados Paliativos/métodos , Investigación , Europa (Continente) , Investigación sobre Servicios de Salud , HumanosRESUMEN
BACKGROUND: The increasing utilization of balloon guide catheters (BGCs) in thrombectomy therapy for ischemic stroke has led to concerns about large-bore sheaths causing vascular groin complications.Objective To retrospectively assess the impact of large large-bore sheaths and vascular closure devices on groin complication rates at a comprehensive stroke center over a 10-year period. METHODS: Radiological and clinical records of patients with acute ischemic stroke who underwent mechanical endovascular therapy with an 8Fr or larger sheaths were reviewed. A groin complication was defined as the formation of a groin hematoma, retroperitoneal hematoma, femoral artery pseudoaneurysm, or the need for surgical repair. Information collected included size of sheath, type of hemostatic device, and anticoagulation status of the patient. Blood bank records were also analyzed to identify patients who may have had an undocumented blood transfusion for a groin hematoma. RESULTS: A total of 472 patients with acute ischemic stroke who underwent mechanical thrombectomy with a sheath and BGC sized 8Fr or larger were identified. 260 patients (55.1%) had tissue Plasminogen Activator (tPA) administered as part of stroke treatment. Vascular closure devices were used in 97.9% of cases (n=462). Two patients were identified who had definite groin complications and a further two were included as having possible complications. There was a very low rate of clinically significant groin complications (0.4-0.8%) associated with the use of large-bore sheaths. CONCLUSIONS: These findings suggest that concerns for groin complications should not preclude the use of BGCs and large-bore sheaths in mechanical thrombectomy for acute ischemic stroke.
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Isquemia Encefálica/cirugía , Procedimientos Endovasculares/efectos adversos , Arteria Femoral/cirugía , Accidente Cerebrovascular/cirugía , Trombectomía/efectos adversos , Anciano , Aneurisma Falso/etiología , Aneurisma Falso/terapia , Embolectomía con Balón , Catéteres/efectos adversos , Procedimientos Endovasculares/instrumentación , Femenino , Ingle/cirugía , Hematoma/etiología , Hematoma/terapia , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trombectomía/instrumentación , Dispositivos de Cierre Vascular/efectos adversosRESUMEN
The inguinal lymph nodes are an unusual site of metastases for prostate adenocarcinoma. We present a case in which a 61-y-old man with biochemically recurrent prostate cancer underwent attenuation-corrected (11)C-acetate PET/CT, which demonstrated multiple foci of increased activity in the left inguinal, left iliac chain, and right inguinal regions. The attenuation-corrected CT portion of the scan also showed anterior wall thickening of the rectum. The imaging findings were suggestive of metastatic involvement of the rectum below the dentate line with subsequent spread to the inguinal lymph nodes.
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Acetatos , Carbono , Procesamiento de Imagen Asistido por Computador , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Humanos , Metástasis Linfática , Masculino , Persona de Mediana EdadRESUMEN
Deletions in IKZF1 are found in ~15% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). There is strong evidence for the poor prognosis of IKZF1 deletions affecting exons 4-7 and exons 1-8, but evidence for the remaining 33% of cases harboring other variants of IKZF1 deletions is lacking. In an international multicenter study we analyzed the prognostic value of these rare variants in a case-control design. Each IKZF1-deleted case was matched to three IKZF1 wild-type controls based on cytogenetic subtype, treatment protocol, risk stratification arm, white blood cell count and age. Hazard ratios for the prognostic impact of rare IKZF1 deletions on event-free survival were calculated by matched pair Cox regression. Matched pair analysis for all 134 cases with rare IKZF1 deletions together revealed a poor prognosis (P<0.001) that was evident in each risk stratification arm. Rare variant types with the most unfavorable event-free survival were DEL 2-7 (P=0.03), DEL 2-8 (P=0.002) and DEL-Other (P<0.001). The prognosis of each type of rare variant was equal or worse compared with the well-known major DEL 4-7 and DEL 1-8 IKZF1 deletion variants. We therefore conclude that all variants of rare IKZF1 deletions are associated with an unfavorable prognosis in pediatric BCP-ALL.
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Eliminación de Gen , Factor de Transcripción Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Adolescente , Adulto , Niño , Preescolar , Subunidad alfa 2 del Factor de Unión al Sitio Principal/análisis , Humanos , Lactante , Cooperación Internacional , Proteínas de Fusión Oncogénica/análisis , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
A 49-year-old woman was admitted with Hunt and Hess grade 1 subarachnoid haemorrhage. A cerebral aneurysm of the intracranial left vertebral artery (VA) distal to the left posterior inferior cerebellar artery (PICA) was found and treated using parent vessel occlusion with coils. The PICA was preserved. Angiography at three time points during her hospitalisation showed a normal right VA. Eight months later, angiography demonstrated a new 14 mm right VA dissecting aneurysm with 90% outflow stenosis and recurrence of the left VA aneurysm distal to the coils. A Marksman microcatheter would not traverse the stenosis despite the use of two intraluminal wires. Following Gateway balloon (1.5 mm × 9 mm) angioplasty, the Marksman passed easily. The pipeline embolisation device (PED) was successfully deployed across the aneurysm and 11 coils placed through a trapped microcatheter. The patient was discharged home 2 days later. Eighteen-month follow-up has revealed complete resolution of both aneurysms.
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Angioplastia/instrumentación , Angioplastia/métodos , Embolización Terapéutica/métodos , Aneurisma Intracraneal/complicaciones , Disección de la Arteria Vertebral/terapia , Arteria Vertebral/patología , Angiografía Cerebral/métodos , Femenino , Humanos , Persona de Mediana Edad , Recurrencia , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/etiología , Hemorragia Subaracnoidea/terapia , Resultado del Tratamiento , Arteria Vertebral/diagnóstico por imagen , Disección de la Arteria Vertebral/complicaciones , Disección de la Arteria Vertebral/diagnóstico por imagen , Disección de la Arteria Vertebral/etiologíaRESUMEN
Depression has been associated with poor performance following errors, but the clinical implications, response to treatment and neurobiological mechanisms of this post-error behavioral adjustment abnormality remain unclear. To fill this gap in knowledge, we tested depressed patients in a partial hospital setting before and after treatment (cognitive behavior therapy combined with medication) using a flanker task. To evaluate the translational relevance of this metric in rodents, we performed a secondary analysis on existing data from rats tested in the 5-choice serial reaction time task after treatment with corticotropin-releasing factor (CRF), a stress peptide that produces depressive-like signs in rodent models relevant to depression. In addition, to examine the effect of treatment on post-error behavior in rodents, we examined a second cohort of rodents treated with JDTic, a kappa-opioid receptor antagonist that produces antidepressant-like effects in laboratory animals. In depressed patients, baseline post-error accuracy was lower than post-correct accuracy, and, as expected, post-error accuracy improved with treatment. Moreover, baseline post-error accuracy predicted attentional control and rumination (but not depressive symptoms) after treatment. In rats, CRF significantly degraded post-error accuracy, but not post-correct accuracy, and this effect was attenuated by JDTic. Our findings demonstrate deficits in post-error accuracy in depressed patients, as well as a rodent model relevant to depression. These deficits respond to intervention in both species. Although post-error behavior predicted treatment-related changes in attentional control and rumination, a relationship to depressive symptoms remains to be demonstrated.
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Atención , Depresión/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Desempeño Psicomotor , Adolescente , Adulto , Animales , Antidepresivos/uso terapéutico , Terapia Cognitivo-Conductual , Hormona Liberadora de Corticotropina/toxicidad , Depresión/inducido químicamente , Depresión/psicología , Trastorno Depresivo Mayor/psicología , Trastorno Depresivo Mayor/terapia , Modelos Animales de Enfermedad , Femenino , Hormonas/toxicidad , Humanos , Masculino , Ratas , Tiempo de Reacción , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The aim of this article was to investigate the beliefs and considerations of professionals concerning an appropriate environment for end-of-life care for people with intellectual disabilities (ID). METHOD: A survey questionnaire was composed based on a scan of relevant literature and the results of group interviews with professionals, family members and people with ID. The questionnaire focused on the respondents' general beliefs about an appropriate environment for end-of-life care and their specific considerations regarding the place of care of the last client for whom the respondent provided end-of-life care. The questionnaire was sent to 294 care staff members recruited from a nationally representative panel of nurses and social workers, 273 ID physicians recruited from the members list of the Dutch professional association of ID physicians, and 1000 general practitioners (GPs) recruited from a nationally representative sample from a national registration of GPs. RESULTS: The overall response was 46%. Professionals predominantly believe that all efforts should be made to ensure that a person with ID receives end-of-life care in their own home environment, and that 24/7 care is available. Respondents indicated that most of the clients (79%) who had last received end-of-life care from an ID care service were able to stay in their own home environment. Decisions to keep the client in their own home environment were primarily based on the familiarity of the environment and the expertise of the team in end-of-life care. Insufficient expertise and a lack of adequate equipment were the main considerations in decisions to move a client. Despite the belief of care staff in particular that the wishes of the person with ID should always be leading when deciding on the place of end-of-life care, only 8% of the care staff and ID physicians explicitly mentioned that the client's wishes were taken into account in actual decision-making. CONCLUSIONS: Professionals agree that end-of-life care for people with ID should preferably take place in the client's home environment, even when nursing expertise, experience and adequate equipment are not (yet) in place. Nonetheless, a lack of expertise in end-of-life care is the foremost consideration in decisions to move a client. If ID care services want to promote end-of-life care in the client's own home, we recommend formulating a policy on how to realise end-of-life care in the client's own home environment and provide sufficient training and support for staff. To involve people with ID as much as possible, we recommend that professionals integrate more collaborative principles in decision-making about the place of end-of-life care.
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Actitud del Personal de Salud , Encuestas de Atención de la Salud/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Discapacidad Intelectual/enfermería , Cuidado Terminal/métodos , Adulto , Humanos , Persona de Mediana Edad , Países Bajos , Enfermeras y Enfermeros/estadística & datos numéricos , Médicos/estadística & datos numéricos , Servicio Social/estadística & datos numéricos , Cuidado Terminal/estadística & datos numéricosRESUMEN
BACKGROUND: Cow's milk allergy is a common food allergy in childhood and no effective preventive or curative treatment is available. This study aimed at comparing single short-chain galacto- (scGOS), long-chain fructo- (lcFOS) or pectin-derived acidic oligosaccharides (pAOS) and/or mixtures of scGOS/lcFOS (GF) or scGOS/lcFOS/pAOS (GFA) to prevent or treat food allergy. METHODS: In the preventive protocol, C3H/HeOuJ mice were fed diets containing single oligosaccharides or mixtures GF or GFA throughout the study protocol. In the treatment protocol, GF or GFA was provided for 4 wk starting after the last sensitization. The allergic skin response and anaphylaxis scores were determined, after oral challenge whey-specific immunoglobulins were measured, and qPCR for T-cell markers and Foxp3 counts using immunohistochemistry were performed on the small intestine and colon. RESULTS: Only in the preventive setting, the GF or GFA mixture, but not the single oligosaccharides, reduced the allergic skin response and whey-IgG(1) levels in whey-sensitized mice, compared to the control diet. Both GF and GFA increased the number of Foxp3+ cells in the proximal small intestine of whey - compared to sham-sensitized mice. Expression of Th2 and Th17 mRNA markers increased in the middle part of the small intestine of whey-sensitized mice, which was prevented by GF. By contrast, GFA enhanced Tbet (Th1), IL-10 and TGF-ß mRNA expression compared to GF which was maintained in the distal small intestine and/or colon. CONCLUSIONS: Dietary supplementation with scGOS/lcFOS or scGOS/lcFOS/pAOS during sensitization, both effectively reduce allergic symptoms but differentially affect mucosal immune activation in whey-sensitized mice.
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Alérgenos/metabolismo , Mezclas Complejas/metabolismo , Hipersensibilidad a la Leche/inmunología , Oligosacáridos/metabolismo , Subgrupos de Linfocitos T/inmunología , Alérgenos/inmunología , Animales , Bovinos , Mezclas Complejas/inmunología , Suplementos Dietéticos , Digestión , Factores de Transcripción Forkhead/metabolismo , Humanos , Inmunidad Innata , Inmunización , Inmunomodulación , Interleucina-10/metabolismo , Mucosa Intestinal/inmunología , Ratones , Ratones Endogámicos C3H , Leche/inmunología , Oligosacáridos/inmunología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
For the care of the elderly, specific geriatric care facilities in hospitals and specialized rehabilitation centers have been established in the last 20 years throughout Germany. In addition, trauma surgery departments in hospitals and clinics also provide comprehensive care for trauma patients. The present requirements catalog was developed with the aim to ensure the standardization and quality assurance of these care facilities. Thus, the structural basics and, in particular, the structured cooperation between geriatrics and trauma surgery are described and defined in terms of structure, process, and outcome quality. The Bundesverband Geriatrie, the Deutsche Gesellschaft für Geriatrie, and the Deutsche Gesellschaft für Gerontologie und Geriatrie offer documentation for external and internal use and evaluation of the structures and processes for certification of geriatric trauma centers. Prerequisite for certification is to meet the technical requirements defined in the requirements catalogue or documents derived from it, and proof of a quality management system according to ISO 9001.