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Amino acids form peptides and proteins and are therefore considered the main building blocks of life. The kidney has an important but under-appreciated role in the synthesis, degradation, filtration, reabsorption and excretion of amino acids, acting to retain useful metabolites while excreting potentially harmful and waste products from amino acid metabolism. A complex network of kidney transporters and enzymes guides these processes and moderates the competing concentrations of various metabolites and amino acid products. Kidney amino acid metabolism contributes to gluconeogenesis, nitrogen clearance, acid-base metabolism and provision of fuel for tricarboxylic acid cycle and urea cycle intermediates, and is thus a central hub for homeostasis. Conversely, kidney disease affects the levels and metabolism of a variety of amino acids. Here, we review the metabolic role of the kidney in amino acid metabolism and describe how different diseases of the kidney lead to aberrations in amino acid metabolism. Improved understanding of the metabolic and communication routes that are affected by disease could provide new mechanistic insights into the pathogenesis of kidney diseases and potentially enable targeted dietary or pharmacological interventions.
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An 18-year-old woman presented to the emergency department. She had ingested 43 extended-release tablets of carbamazepine 400 mg. Although the patient had high carbamazepine plasma levels and classified as severe intoxication, her clinical symptoms were less severe than expected. With the combination of hemodialysis and continuous venovenous hemodialysis in addition to usual care, including multiple-dose activated charcoal, a fast decrease (within 3 days) in carbamazepine plasma levels to levels in the therapeutic range was achieved. Only one session of hemodialysis was performed because the clinical status of the patient stabilized. In retrospect, the patient did not suffer severe toxicological symptoms from carbamazepine. Therefore, continuous venovenous hemodialysis could have been discontinued earlier. On the other hand, the fast decrease in carbamazepine plasma levels during extracorporeal treatment may have prevented the development of severe or rebound toxicological symptoms. This case report adds evidence to the successful management of carbamazepine intoxication using hemodialysis followed by continuous venovenous hemodialysis.
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BACKGROUND: The Mayo Imaging Classification was developed to predict the rate of disease progression in patients with autosomal dominant polycystic kidney disease. This study aimed to validate its ability to predict kidney outcomes in a large multicenter autosomal dominant polycystic kidney disease cohort. METHODS: Included were patients with ≥1 height-adjusted total kidney volume (HtTKV) measurement and ≥3 eGFR values during ≥1-year follow-up. Mayo HtTKV class stability, kidney growth rates, and eGFR decline rates were calculated. The observed eGFR decline was compared with predictions from the Mayo Clinic future eGFR equation. The future eGFR prediction equation was also tested for nonlinear eGFR decline. Kaplan-Meier survival analysis and Cox regression models were used to assess time to kidney failure using Mayo HtTKV class as a predictor variable. RESULTS: We analyzed 618 patients with a mean age of 47±11 years and mean eGFR of 64±25 ml/min per 1.73 m 2 at baseline. Most patients (82%) remained in their baseline Mayo HtTKV class. During a mean follow-up of 5.1±2.2 years, the mean total kidney volume growth rates and eGFR decline were 5.33%±3.90%/yr and -3.31±2.53 ml/min per 1.73 m 2 per year, respectively. Kidney growth and eGFR decline showed considerable overlap between the classes. The observed annual eGFR decline was not significantly different from the predicted values for classes 1A, 1B, 1C, and 1D but significantly slower for class 1E. This was also observed in patients aged younger than 40 years and older than 60 years and those with PKD2 mutations. A polynomial model allowing nonlinear eGFR decline provided more accurate slope predictions. Ninety-seven patients (16%) developed kidney failure during follow-up. The classification predicted the development of kidney failure, although the sensitivity and positive predictive values were limited. CONCLUSIONS: The Mayo Imaging Classification demonstrated acceptable stability and generally predicted kidney failure and eGFR decline rate. However, there was marked interindividual variability in the rate of disease progression within each class.
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Progresión de la Enfermedad , Tasa de Filtración Glomerular , Riñón , Riñón Poliquístico Autosómico Dominante , Humanos , Riñón Poliquístico Autosómico Dominante/fisiopatología , Riñón Poliquístico Autosómico Dominante/diagnóstico por imagen , Riñón Poliquístico Autosómico Dominante/clasificación , Riñón Poliquístico Autosómico Dominante/patología , Persona de Mediana Edad , Femenino , Masculino , Adulto , Riñón/fisiopatología , Riñón/diagnóstico por imagen , Riñón/patología , Valor Predictivo de las Pruebas , Tamaño de los Órganos , Factores de Tiempo , PronósticoRESUMEN
BACKGROUND AND HYPOTHESIS: Dysregulated energy metabolism is a recently discovered key feature of Autosomal Dominant Polycystic Kidney Disease (ADPKD). Cystic cells depend on glucose and are poorly able to use other energy sources such as ketone bodies. Raising ketone body concentration reduced disease progression in animal models of polycystic kidney diseases. Therefore, we hypothesized that higher endogenous plasma beta-hydroxybutyrate concentrations are associated with reduced disease progression in patients with ADPKD. METHODS: We analyzed data from 670 patients with ADPKD participating in the DIPAK cohort, a multi-center prospective observational cohort study. Beta-hydroxybutyrate was measured at baseline using nuclear magnetic resonance spectroscopy. Participants were excluded if they had type 2 diabetes, were using disease-modifying drugs (e.g. tolvaptan, somatostatin analogs), were not fasting, or had missing beta-hydroxybutyrate levels, leaving 521 participants for the analyses. Linear regression analyses were used to study cross-sectional associations and linear mixed-effect modeling for longitudinal associations. RESULTS: Of the participants, 61% were female, with an age of 47.3 ± 11.8 years, a height-adjusted total kidney volume (htTKV) of 834 (IQR 495-1327) ml/m, and an estimated glomerular filtration rate (eGFR) of 63.3 ± 28.9 mL/min/1.73m2. The median concentration of beta-hydroxybutyrate was 94 (IQR 68-147) µmol/L. Cross-sectionally, beta-hydroxybutyrate was neither associated with eGFR nor with htTKV. Longitudinally, beta-hydroxybutyrate was positively associated with eGFR slope (B = 0.35 ml/min/1.73m2 (95% CI 0.09 to 0.61), p = 0.007), but not with kidney growth. After adjustment for potential confounders, every doubling in beta-hydroxybutyrate concentration was associated with an improvement in the annual rate of eGFR by 0.33 ml/min/1.73m2 (95% CI 0.09 to 0.57, p = 0.008). CONCLUSION: These observational analyses support the hypothesis that interventions that raise beta-hydroxybutyrate concentration could reduce the rate of kidney function decline in patients with ADPKD.
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BACKGROUND: Important elements of programs that train and support infection control link nurses (ICLN) are the engagement of stakeholders, support from hospital and ward management and a structure for iterative improvement. The effects of programs, that combine all these elements, are unknown. We evaluated such a comprehensive program to explore its impact on link nurses and infection prevention practices and routines. METHODS: We used the RE-AIM framework, a robust, evidence-based framework within the field of Implementation Science, to evaluate the impact of our ICLN training and support program. We used a mixed methods approach and organized the outcomes along its five dimensions: Reach, Effectiveness, Adoption, Implementation and Maintenance. RESULTS: Between 2014 and 2018, on average 91% of the inpatient wards and 58% of the outpatient clinics participated in the program (Reach) and impacted guideline adherence in inpatient wards. Link nurses felt engaged and empowered, and perceived their contribution to these results as pivotal. Ward managers confirmed the value of ICLN to help with implementing IPC practices (Effectiveness). The program was adopted both at the hospital and at the ward level (Adoption). Based on ongoing evaluations, the program was adapted by refining education, training and support strategies with emphasis on ward specific aspects (Implementation). The ICLN program was described as a key component of the infection prevention policy to sustain its effects (Maintenance). CONCLUSIONS: Our infection control link nurse program helped ICLN to improve infection prevention practices, especially in inpatient wards. The key to these improvements lay within the adaptability of our link nurse program. The adjustments to the program led to a shift of focus from hospital goals to goals tailored to the ward level. It allowed us to tailor activities to align them with the needs specific to each ward.
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Hospitales , Control de Infecciones , Enfermeras Clínicas , Humanos , Emociones , Adhesión a Directriz , Evaluación de Programas y Proyectos de SaludRESUMEN
BACKGROUND: Neurologic complications from recreational use of nitrous oxide (N2O), which are attributed to vitamin B12 deficiency, have been well documented. With increasing dosages and frequency of N2O use, an additional association with thromboembolisms is becoming apparent. OBJECTIVES: To assess thrombotic complications of recreational N2O use. METHODS: All medical charts at the largest hospital in Amsterdam were searched for N2O use and subsequent neurologic and/or thrombotic events. For patients with thrombotic events, we extracted data on the risk factors for arterial and venous thrombosis as well as serum vitamin B12 and homocysteine concentrations. RESULTS: Between January 2015 and May 2021, 326 patients who reported recreational use of N2O were identified; of these, 17 (5%) patients presented with severe thrombotic events associated with N2O (71% men; median age, 26 years [range, 18-53 years]), 5 patients presented with arterial thrombosis (3 with acute coronary syndrome, 1 with femoral artery thrombosis, and 1 with middle cerebral artery thrombus), and 12 patients presented with venous thromboembolisms (10 with pulmonary embolisms, 1 with portal vein thrombosis and 1 with cerebral vein thrombosis). Additionally, homocysteine were concentrations severely increased (median, 125 µmol/L [range, 22-253 µmol/L]; reference, <15 µmol/L). Patients reported use of 400 to 6000 g (ie, 50-750 balloons) of N2O in 1 day. Fifty percent of these patients had experienced neurologic symptoms before the thrombotic event. CONCLUSION: We describe an alarming incidence of serious thrombotic events among young adults after excessive recreational use of N2O, accompanied by extremely high homocysteine concentrations. The upward trend in the recreational use of N2O warrants more awareness of its dangers among both users and medical professionals. Furthermore, these findings could reopen the discussion on possible associations between hyperhomocysteinemia and thrombosis mediated through N2O.
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Tromboembolia , Trombosis , Trombosis de la Vena , Deficiencia de Vitamina B 12 , Masculino , Humanos , Adulto Joven , Adulto , Femenino , Óxido Nitroso/efectos adversos , Trombosis/inducido químicamente , Trombosis/complicaciones , Deficiencia de Vitamina B 12/inducido químicamente , Deficiencia de Vitamina B 12/complicaciones , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Tromboembolia/complicacionesRESUMEN
INTRODUCTION: Fasting plasma ketone bodies (KB) are elevated in individuals with type 2 diabetes (T2D) and could affect glycemic control and disease progression. Prolonged KB exposure may result in adaptive beneficial responses, counteracting glycemic dysregulation. In the current proof-of-concept study in adults with T2D, we hypothesized that fasting plasma KB are cross-sectionally associated with poorer glycemic control but prospectively with better glycemic control. MATERIALS AND METHODS: Fasting plasma KB were measured via nuclear magnetic resonance spectroscopy in patients with T2D treated in primary care (Zodiac cohort; The Netherlands). We analyzed the associations between KB and HbA1c at baseline using linear regression analyses and HbA1c changes over time using linear mixed models. We adjusted for potential confounders, including risk factors for poor glycemic control. Individuals with T2D participating in the general population-based PREVEND study were used as a replication cohort. RESULTS: We included 271 individuals with T2D with a total of 859 HbA1c measurements during a follow-up period of 3.0 (2.0-3.2) years. At baseline, the total amount of fasting plasma KB was independently and positively associated with HbA1c levels (regression coefficient in the fully adjusted analysis = 0.31; 95% CI 0.06-0.57, per doubling of KB; p = 0.02). In contrast, in the longitudinal analyses, fasting plasma KB were associated with a yearly HbA1c (%) decrease of -0.10 (95% CI -0.19 to -0.00 per doubling baseline KB; p = 0.05). Results were replicated in 387 individuals with T2D from a general population cohort with a total of 1115 glucose measurements during a follow-up period of 7.5 (7.2-8.0) years. A yearly decrease in fasting plasma glucose (mmol/L) of 0.09 was found per doubling of baseline KB. CONCLUSIONS: This study is the first to suggest a paradoxical role of circulating KB on glycemic control in T2D: elevated KB are associated with cross-sectionally poorer glycemic control but longitudinally with better long-term glycemic control.
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Diabetes Mellitus Tipo 2 , Hiperglucemia , Adulto , Glucemia/análisis , Hemoglobina Glucada/análisis , Control Glucémico , Humanos , Hiperglucemia/complicaciones , Cuerpos CetónicosRESUMEN
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors and ketogenesis have been shown to ameliorate disease progression in experimental autosomal dominant polycystic kidney disease (ADPKD). Glucagon is known to lower mTOR activity and stimulate ketogenesis. We hypothesized that in ADPKD patients, higher endogenous glucagon is associated with less disease severity and progression. METHODS: Data were analysed from 664 Dutch ADPKD patients participating in the Developing Intervention Strategies to Halt Progression of ADPKD observational cohort, including patients >18 years of age with an estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 and excluding patients with concomitant diseases or medication use that may impact the natural course of ADPKD. The association between glucagon and disease severity and progression was tested using multivariate linear regression and mixed modelling, respectively. RESULTS: The median glucagon concentration was 5.0 pmol/L [interquartile range (IQR) 3.4-7.2) and differed significantly between females and males [4.3 pmol/L (IQR 2.9-6.0) and 6.6 (4.5-9.5), P < 0.001, respectively]. Intrasubject stability of glucagon in 30 patients showed a strong correlation (Pearson's correlation coefficient 0.893; P < 0.001). Moreover, glucagon showed significant associations with known determinants (sex, body mass index and copeptin; all P < 0.01) and known downstream effects (glucose, haemoglobin A1c and cholesterol; all P < 0.05), suggesting that glucagon was measured reliably. Cross-sectionally, glucagon was associated with eGFR and height-adjusted total kidney volume, but in the opposite direction of our hypothesis, and these lost significance after adjustment for confounders. Glucagon was not associated with an annual decline in kidney function or growth in kidney volume. CONCLUSIONS: These data do not provide evidence for a role of endogenous glucagon as a protective hormone in ADPKD. Intervention studies are needed to determine the relation between glucagon and ADPKD.
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Objectives: E-learning is increasingly used in education on antimicrobial stewardship, but participation rates are often low. Insight into factors that affect participation is therefore needed. Autonomous motivation is associated with higher achievements in medical education and could also play a role in e-learning participation. We therefore aimed to investigate the role of residents' autonomous motivation in their participation in e-learning on antibiotic prescribing. Methods: We performed a multicentre cohort study in two academic and two teaching hospitals. Residents who filled out questionnaires on antibiotic knowledge, the perceived importance of antibiotics and motivation [Self-Regulation Questionnaire - Academic (SRQ-a)] received e-learning access. We used the SRQ-a to calculate relative autonomous motivation (RAM), an index that estimates the amount of autonomous motivation compared with the amount of controlled motivation. We then analysed associations between RAM and participation in e-learning with logistic regression. Results: Eighty-six residents participated (74% female, mean age 30 years). Overall e-learning participation was 58% (n = 50). Participation was 41% in residents with negative RAM (i.e. more controlled motivation) and 62% in residents with positive RAM (i.e. more autonomous motivation). RAM was positively associated with participation, adjusted for residency in an academic hospital (adjusted OR 2.6, 95% CI 1.5-4.6). Conclusions: Participation in non-obligatory e-learning on antibiotic prescribing is higher in residents with more autonomous motivation. Interventions to increase autonomous motivation could improve participation. Preceding e-learning on antibiotic prescribing with face-to-face education, to explain the importance of the subject, could enhance autonomous motivation and thus optimize e-learning efficiency.
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Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Infecciones Bacterianas/tratamiento farmacológico , Instrucción por Computador/métodos , Utilización de Medicamentos/normas , Educación Médica/métodos , Motivación , Adulto , Femenino , Hospitales de Enseñanza , Humanos , Masculino , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
Background: Antimicrobial prescribing behaviour is first established during medical study, but teachers often cite lack of time as an important problem in the implementation of antimicrobial stewardship in the medical curriculum. The use of electronic learning (e-learning) is a potentially time-efficient solution, but its effectiveness in changing long-term prescribing behaviour in medical students is as yet unknown. Methods: We performed a prospective controlled intervention study of the long-term effects of a short interactive e-learning course among fourth year medical students in a Dutch university. The e-learning was temporarily implemented as a non-compulsory course during a 6 week period. Six months later, all students underwent an infectious disease-based objective structured clinical examination (OSCE) aimed at simulating postgraduate prescribing. If they passed, each student did the OSCE only once. We created a control group of students from a period when the e-learning was not implemented. Main outcomes were the OSCE pass percentage and knowledge, drug choice and overall scores. We used propensity scores to create equal comparisons. Results: We included 71 students in the intervention group and 285 students in the control group. E-learning participation in the intervention group was 81%. The OSCE pass percentage was 86% in the control group versus 97% in the intervention group (+11%, OR 5.9, 95% CI 1.7-20.0). OSCE overall, knowledge and drug choice grades (1-10) were also significantly higher in the intervention group (differences +0.31, +0.31 and +0.51, respectively). Conclusions: E-learning during a limited period can significantly improve medical students' performance of an antimicrobial therapeutic consultation in a situation simulating clinical practice 6 months later.
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Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos/métodos , Infecciones Bacterianas/tratamiento farmacológico , Utilización de Medicamentos/normas , Educación Médica/métodos , Pautas de la Práctica en Medicina/normas , Estudiantes de Medicina , Adulto , Femenino , Humanos , Aprendizaje , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto JovenRESUMEN
INTRODUCTION:: Peripherally inserted central catheters are venous devices intended for short to medium periods of intravenous treatment. Positioning of the catheter tip at the cavoatrial junction is necessary for optimum performance of a peripherally inserted central catheter. In this study, safety, effectiveness and cost-effectiveness of electrocardiographic-guided peripherally inserted central catheter positioning in a Dutch teaching hospital were evaluated. METHODS:: All patients who received a peripherally inserted central catheter in 2016 using electrocardiographic guidance were compared to those where fluoroscopy guidance was used in a prospective non-randomized cohort study. Relevant data were extracted from electronic health records. Cost-effectiveness analysis was performed. RESULTS:: A total of 162 patients received a peripherally inserted central catheter using fluoroscopy guidance and 103 patients using electrocardiographic guidance in 2016. No significant difference was found in malposition, infection or other complications between these groups. Due to personnel reduction and omission of fluoroscopy costs, cost reduction for each catheter insertion was 120 in the first year and, as a result of discounted acquisition costs, 190 in subsequent years. DISCUSSION:: The positioning results and complication rate are comparable to the previously reported literature. The cost reduction may vary in different hospitals. Other benefits of the electrocardiographic-guided technique are omission of X-ray exposure and improved patient service. CONCLUSION:: Implementation of electrocardiographic-guided tip positioning for peripherally inserted central catheter was safe and effective in this study and led to an improved high value and cost-conscious care.
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Cateterismo Venoso Central/economía , Cateterismo Periférico/economía , Catéteres de Permanencia/economía , Catéteres Venosos Centrales/economía , Electrocardiografía/economía , Costos de Hospital , Hospitales de Enseñanza/economía , Adulto , Anciano , Anciano de 80 o más Años , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Cateterismo Venoso Central/métodos , Cateterismo Periférico/efectos adversos , Cateterismo Periférico/instrumentación , Cateterismo Periférico/métodos , Catéteres de Permanencia/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Ahorro de Costo , Análisis Costo-Beneficio , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Valor Predictivo de las Pruebas , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Radiografía Intervencional/economía , Adulto JovenRESUMEN
AIMS: We aimed to re-assess the previously shown but recently disputed association between HbA1c and severe hypoglycemia. METHODS: 52 Patients with T1D and IAH participated in an earlier reported randomized, crossover trial with two 16-week intervention periods comparing continuous glucose monitoring (CGM) with self-monitoring of blood glucose (SMBG). In this previous study, time spent in normoglycemia (the primary outcome), was improved by 9.6% (p<0.0001). We performed post-hoc analyses using a zero-inflated Poisson regression model to assess the relationship between severe hypoglycemia and HbA1c, glucose variability and duration of diabetes. RESULTS: During SMBG use, HbA1c and the number of severe hypoglycemic events were negatively associated (OR 0.20 [95% CI 0.09 to 0.44]). During CGM use, this relationship showed an odds ratio of 0.65 (95% CI 0.42 to 1.01). There was no significant relationship between glucose variability or duration of diabetes and severe hypoglycemia. CONCLUSIONS: In patients with T1D and IAH, treated with standard SMBG, a negative association exists between HbA1c and the number of severe hypoglycemic events. Thus, reaching target HbA1c values still comes with a higher risk of severe hypoglycemia. CGM weakens this association, suggesting CGM enables patients to reach their target HbA1c more safely.
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Concienciación , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/psicología , Hemoglobina Glucada/análisis , Hipoglucemia/diagnóstico , Hipoglucemia/psicología , Adulto , Glucemia/análisis , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea , Estudios Cruzados , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemia/sangre , Hipoglucemia/inducido químicamente , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios RetrospectivosRESUMEN
BACKGROUND The VU University Medical Center, a tertiary-care hospital in the Netherlands, has adopted a dress code based on national guidelines. It includes uniforms provided by the hospital and a 'bare-below-the-elbow' policy for all healthcare workers (HCWs) in direct patient care. Because compliance was poor, we sought to improve adherence by interventions targeted at the main causes of noncompliance. OBJECTIVE To measure compliance with the dress code, to assess causes of noncompliance and to assess whether a behavioral approach (combing a nominal group technique with participatory action) is effective in improving compliance METHODS Between March 2014 and June 2016, a total of 1,920 HCWs were observed in hospital hallways for adherence to the policy, at baseline, and at follow-up measurements. Based on the outcome of the baseline measurement, a nominal group technique was applied to assess causes of noncompliance. The causes revealed served as input for interventions that were developed, prioritized, and tailored to specific groups of HCWs and specific departments through participatory action. RESULTS We identified lack of knowledge, lack of facilities, and negative attitudes as the main causes of noncompliance. The importance of each cause varied for different groups of HCWs. Tailored interventions targeted at these causes increased overall compliance by 39.6% (95% CI, 31.7-47.5). CONCLUSION The combination of a nominal group technique and participatory action approach is an effective method to increase and sustain compliance with hospital dress code. This combined approach may also be useful to improve adherence to other guidelines. Infect Control Hosp Epidemiol 2017;38:1435-1440.
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Vestuario/normas , Infección Hospitalaria/prevención & control , Adhesión a Directriz/estadística & datos numéricos , Personal de Hospital , Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Humanos , Países Bajos , Centros de Atención TerciariaRESUMEN
OBJECTIVE To investigate whether the safety culture of a hospital unit is associated with the ability to improve. DESIGN Qualitative investigation of safety culture on hospital units following a before-and-after trial on hand hygiene. SETTING VU University Medical Center, a tertiary-care hospital in the Netherlands. METHODS With support from hospital management, we implemented a hospital-wide program to improve compliance. Over 2 years, compliance was measured through direct observation, twice before, and 4 times after interventions. We analyzed changes in compliance from baseline, and selected units to evaluate safety culture using a positive deviance approach: the hospital unit with the highest hand hygiene compliance and 2 units that showed significant improvement (21% and 16%, respectively) were selected as high performing. Another 2 units showed no improvement and were selected as low performing. A blinded, independent observer conducted interviews with unit management, physicians, and nurses, based on the Hospital Survey on Patient Safety Culture. Safety culture was categorized as pathological (lowest level), reactive, bureaucratic, proactive, or generative (highest level). RESULTS Overall, 3 units showed a proactive or generative safety culture and 2 units had bureaucratic or pathological safety cultures. When comparing compliance and interview results, high-performing units showed high levels of safety culture, while low-performing units showed low levels of safety culture. CONCLUSIONS Safety culture is associated with the ability to improve hand hygiene. Interventions may not be effective when applied in units with low levels of safety culture. Although additional research is needed to corroborate our findings, the safety culture on a unit can benefit from enhancement strategies such as team-building exercises. Strengthening the safety culture before implementing interventions could aid improvement and prevent nonproductive interventions. Infect Control Hosp Epidemiol 2017;38:1277-1283.
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Higiene de las Manos/métodos , Seguridad del Paciente , Mejoramiento de la Calidad , Centros Médicos Académicos/organización & administración , Estudios Controlados Antes y Después , Higiene de las Manos/normas , Humanos , Cultura Organizacional , Seguridad del Paciente/normas , Prueba de Estudio Conceptual , Mejoramiento de la Calidad/organización & administración , Centros de Atención Terciaria/organización & administraciónRESUMEN
There are several studies on bioaccumulation and biomagnification of nonylphenol (NP) and its ethoxylates (NPEOs), but their toxico-kinetic mechanisms remain unclear. In the present investigation, we explored the accumulation of NP and NPEOs in estuarine-marine food chains with a bioaccumulation model comprising five trophic levels. Using this model, we estimated uptake and elimination rate constants for NPEOs based on the organisms' weight and lipid content and the chemicals' Kow. Further, we calculated accumulation factors for NP and NPEOs, including biota-sediment accumulation factors (BSAF) and biomagnification factors (BMF), and compared these to independent field measurements collected in the Western Scheldt estuary in The Netherlands and field data reported in the literature. The estimated BSAF values for NP and total NPEOs were below 1 for all trophic levels. The estimated BMF values were around 1 for all trophic levels except for the highest level (carnivorous mammals and birds). For this trophic level, the estimated BMF value varied between 0.1 and 2.4, depending on the biotransformation capacity. For all trophic levels, except primary producers, the accumulation estimates that accounted for biotransformation of NPEOs into NP were closer to the field data than model estimates that did not include biotransformation, indicating that NP formation by biotransformation of NPEOs might occur in organisms.
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Organismos Acuáticos/metabolismo , Éteres de Etila/análisis , Fenoles/análisis , Contaminantes Químicos del Agua/análisis , Animales , Biotransformación , Aves/metabolismo , Éteres de Etila/química , Éteres de Etila/farmacocinética , Cadena Alimentaria , Modelos Teóricos , Países Bajos , Fenoles/química , Fenoles/farmacocinética , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/farmacocinéticaAsunto(s)
Reacciones Falso Negativas , Ensayos de Liberación de Interferón gamma/métodos , Interferón gamma/metabolismo , Tuberculosis/diagnóstico , Adulto , Estudios Transversales , Femenino , Variación Genética , Humanos , Cooperación Internacional , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Análisis de Regresión , Estudios Retrospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
BACKGROUND: There is increasing evidence to suggest that different Mycobacterium tuberculosis lineages cause variations in the clinical presentation of tuberculosis (TB). Certain M. tuberculosis genotypes/lineages have been shown to be more likely to cause active TB in human populations from a distinct genetic ancestry. This study describes the genetic biodiversity of M. tuberculosis genotypes in Mwanza city, Tanzania and the clinical presentation of the disease caused by isolates of different lineages. METHODS: Two-hundred-fifty-two isolates from pulmonary TB patients in Mwanza, Tanzania were characterized by spoligotyping, and 45 isolates were further characterized by mycobacterium interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR). The patients' level of the acute phase reactants AGP, CRP and neutrophil counts, in addition to BMI, were measured and compared to the M. tuberculosis lineage of the infectious agent for each patient. RESULTS: The most frequent genotype was ST59 (48 out of 248 [19.4%]), belonging to the Euro-American lineage LAM11_ZWE, followed by ST21 (CAS_KILI lineage [44 out of 248 [17.7%]). A low degree of diversity (15.7% [39 different ST's out of 248 isolates]) of genotypes, in addition to a high level of mixed M. tuberculosis sub-populations among isolates with an unreported spoligotype pattern (10 out of 20 isolates [50.0%]) and isolates belonging to the ST53 lineage (13 out of 25 [52%]) was observed. Isolates of the 'modern' (TbD1-) Euro-American lineage induced higher levels of α1-acid glycoprotein (ß = 0.4, P = 0.02; 95% CI [0.06-0.66]) and neutrophil counts (ß = 0.9, P = 0.02; 95% CI [0.12-1.64]) and had lower BMI score (ß = -1.0, P = 0.04; 95% CI[-1.89 - (-0.03)]). LAM11_ZWE ('modern') isolates induced higher levels of CRP (ß = 24.4, P = 0.05; 95% CI[0.24-48.63]) and neutrophil counts (ß = 0.9, P = 0.03; 95% CI[0.09-1.70]). CONCLUSION: The low diversity of genotypes may be explained by an evolutionary advantage of the most common lineages over other lineages combined with optimal conditions for transmission, such as overcrowding and inadequate ventilation. The induction of higher levels of acute phase reactants in patients infected by 'modern' lineage isolates compared to 'ancient' lineages may suggest increased virulence among 'modern' lineage isolates.
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Proteínas de Fase Aguda/metabolismo , Mycobacterium tuberculosis/genética , Tuberculosis Pulmonar/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Estudios Transversales , Femenino , Genotipo , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite , Mycobacterium tuberculosis/aislamiento & purificación , Tanzanía , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/diagnóstico , Adulto JovenRESUMEN
OBJECTIVE: Strong evidence suggests diabetes may be associated with tuberculosis (TB) and could influence TB treatment outcomes. We assessed the role of diabetes on sputum culture conversion and mortality among patients undergoing TB treatment. METHODS: A total of 1250 Tanzanian TB patients were followed prospectively during TB treatment with sputum culture after 2 and 5 months. Survival status was assessed at least 1 year after initiation of treatment. At baseline, all participants underwent testing for diabetes and HIV, and the serum concentration of the acute phase reactant alpha-1 glycoprotein (AGP) was determined. RESULTS: There were no differences between participants with and without diabetes regarding the proportion of positive cultures at 2 (3.8% vs. 5.8%) and 5 (1.3% vs. 0.9%) months (P > 0.46). However, among patients with a positive TB culture, relatively more patients with diabetes died before the 5-month follow-up. Within the initial 100 days of TB treatment, diabetes was associated with a fivefold increased risk of mortality (RR 5.09, 95% CI 2.36; 11.02, P < 0.001) among HIV uninfected, and a twofold increase among HIV co-infected patient (RR 2.33 95% CI 1.20; 4.53, P = 0.012), while diabetes was not associated with long-term mortality. Further adjustment with AGP did not change the estimates. CONCLUSION: Diabetes considerably increases risk of early mortality during TB treatment. The effect may not be explained by increased severity of TB, but could be due to impaired TB treatment response. Research is needed to clarify the mechanism and to assess whether glycaemic control improves survival.
Asunto(s)
Glucemia/metabolismo , Complicaciones de la Diabetes/mortalidad , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/mortalidad , Complicaciones de la Diabetes/sangre , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Infecciones por VIH/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Orosomucoide/metabolismo , Estudios Prospectivos , Factores de Riesgo , Tanzanía/epidemiología , Resultado del Tratamiento , Tuberculosis Pulmonar/sangre , Tuberculosis Pulmonar/terapia , Adulto JovenRESUMEN
INTRODUCTION: One third of the world's population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute phase reactant: alpha-1-acid glycoprotein (AGP) in neighborhood controls. METHODS: The study was nested within the framework of two nutrition studies among TB patients in Mwanza, Tanzania. Household contacts- and neighborhood controls were invited to participate. The study involved a questionnaire, BMI determination and blood samples to measure AGP, HIV testing and a Quantiferon Gold In tube (QFN-IT) test to detect signs of LTBI. RESULTS: 245 household contacts and 192 neighborhood controls had available QFN-IT data. Among household contacts, the proportion of QFT-IT positive was 59% compared to 41% in the neighborhood controls (pâ=â0.001). In a linear regression model adjusted for sex, age, CD4 and HIV, a QFT-IT positive test was associated with a 10% higher level of alpha-1-acid glycoprotein(AGP) (10(B) 1.10, 95% CI 1.01; 1.20, pâ=â0.03), compared to individuals with a QFT-IT negative test. CONCLUSION: LTBI is highly prevalent among apparently healthy urban Tanzanians even without known exposure to TB in the household. LTBI was found to be associated with elevated levels of AGP. The implications of this observation merit further studies.