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BACKGROUND: Vancomycin induced acute kidney injury (VI-AKI) is one of its serious adverse reactions. The purpose of this study is to discuss the risk factors for VI-AKI in overweight patients and construct a clinical prediction model based on the results of the analysis. METHODS: Multivariable logistic regression analysis was used to identify risk factors for VI-AKI and constructed nomogram models. The performance of the nomogram was evaluated based on the area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analysis (DCA). RESULT: Cancer (OR 4.186, 95% CI 1.473-11.896), vancomycin trough concentration >20.0 µg/mL (OR 6.251, 95% CI 2.275-17.180), concomitant furosemide (OR 2.722, 95% CI 1.071-6.919) and vasoactive agent (OR 2.824, 95% CI 1.086-7.340) were independent risk factors for VI-AKI. The AUC of the nomogram validation cohorts were 0.807 (95% CI 0.785-0.846). The calibration curve revealed that the predicted outcome was in agreement with the actual observations. Finally, the DCA curves showed that the nomogram had a good clinical applicability value. CONCLUSION: There are four independent risk factors for the occurrence of VI-AKI in overweight patients, and the nomogram prediction model has good predictive ability, which can provide reference for clinical decision-making.
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Informal caregivers of individuals affected by psychotic disorder can play a key role in the recovery process. However, little research has been conducted on the lived experiences of carers and family members. We conducted a bottom-up (from lived experience to theory) review of first-person accounts, co-written between academics and experts by experience, to identify key experiential themes. First-person accounts of carers, relatives, and individuals with psychosis were screened and discussed in collaborative workshops involving individuals with lived experiences of psychosis, family members, and carers, representing various organizations. The lived experiences of family members and carers were characterized by experiential themes related to dealing with the unexpected news, the search for a reason behind the disorder, living with difficult and negative emotions, dealing with loss, feeling lost in fragmented healthcare systems, feeling invisible and wanting to be active partners in care, struggling to communicate with the affected person, fighting stigma and isolation, dealing with an uncertain future, and learning from one's mistakes and building resilience and hope. Our findings bring forth the voices of relatives and informal carers of people with psychosis, by highlighting some of the common themes of their lived experiences from the time of the initial diagnosis and throughout the different clinical stages of the disorder. Informal carers are key stakeholders who can play a strategic role, and their contributions in the recovery process merit recognition and active support by mental health professionals.
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Cuidadores , Trastornos Psicóticos , Humanos , Cuidadores/psicología , Trastornos Psicóticos/psicología , Familia/psicologíaRESUMEN
BACKGROUND: The prescriptions of proton pump inhibitors (PPIs) have been widely concerned due to both huge increase in medical costs and possible long-term adverse events (AEs) caused by the improper route of drug administration. The aim of this study was to assess the effectiveness of pharmacist interventions on the clinical outcome and safety of switching from intravenous (IV) to oral PPIs therapy. PATIENTS AND METHODS: A retrospective, single-center, pre- intervention (early -stage)- and intervention (later -stage) study was performed in a Chinese hospital. RESULTS: A total of 1736 patients were included in the study. After 12 months of interventions, significant improvements in the number of rational IV to oral switch in patients with oral switch indications were found. The median duration of oral therapy was increased, while the duration of PPIs therapy was decreased. Pharmacist interventions led to significant reductions in mean PPI costs, mean total drug costs, mean hospitalization costs, and the risk for long-term adverse events. CONCLUSION: This study provides important evidence on the beneficial effect of pharmacist interventions on promoting an optimal IV to oral switch of PPIs and substantial cost saving by shortening the duration of IV PPIs therapy and reducing the risk for long-term AEs.
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Farmacéuticos , Inhibidores de la Bomba de Protones , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Estudios Retrospectivos , Hospitalización , Administración IntravenosaRESUMEN
Objective: Functional neurological disorder (FND) causes a high burden of disability and distress. Although it is a common disorder, there is a pressing need for improved access to evidence-based treatments. With difficulties in finding effective treatment, some people with FND may seek alternative means of symptom relief, such as legal and illicit psychoactive substances, although the prevalence and nature of such self-management strategies are currently unclear. Additionally, psychoactive substances may represent novel treatment research opportunities, particularly for those with suboptimal improvement. The investigators examined the use of self-management techniques, as well as perspectives on novel therapies, in this patient population. Methods: An online survey was created to assess self-management strategies and views on novel treatments for FND, including psychedelic therapy. The survey was accessible for 1 month, and respondents were recruited internationally through social media and patient groups. A total of 1,048 respondents from 16 countries completed the survey. Results: Almost half (46%) of 980 respondents reported having tried legal psychoactive substances for the management of their FND symptoms and, on average, nicotine, alcohol, and cannabidiol were reported as modestly effective. Additionally, 15% of respondents reported having used illicit substances, mostly cannabis, to manage FND, with the majority reporting moderate effectiveness and experiencing no or minimal physical (90%) and psychological (95%) sequelae. Many respondents (46%) reported that they would be willing to try medically supervised psychedelic therapy (with 19% of respondents ambivalent) if it were found to be safe and effective. Conclusions: Many people with FND seek alternative means of symptom management outside usual medical care, including legal and illicit psychoactive substances. Further research exploring novel treatment options, such as psychedelics, in FND may be warranted.
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Trastornos de Conversión , Automanejo , Trastornos Relacionados con Sustancias , Humanos , Psicotrópicos/uso terapéutico , Encuestas y Cuestionarios , Trastornos Relacionados con Sustancias/terapiaRESUMEN
Psychosis is the most ineffable experience of mental disorder. We provide here the first co-written bottom-up review of the lived experience of psychosis, whereby experts by experience primarily selected the subjective themes, that were subsequently enriched by phenomenologically-informed perspectives. First-person accounts within and outside the medical field were screened and discussed in collaborative workshops involving numerous individuals with lived experience of psychosis as well as family members and carers, representing a global network of organizations. The material was complemented by semantic analyses and shared across all collaborators in a cloud-based system. The early phases of psychosis (i.e., premorbid and prodromal stages) were found to be characterized by core existential themes including loss of common sense, perplexity and lack of immersion in the world with compromised vital contact with reality, heightened salience and a feeling that something important is about to happen, perturbation of the sense of self, and need to hide the tumultuous inner experiences. The first episode stage was found to be denoted by some transitory relief associated with the onset of delusions, intense self-referentiality and permeated self-world boundaries, tumultuous internal noise, and dissolution of the sense of self with social withdrawal. Core lived experiences of the later stages (i.e., relapsing and chronic) involved grieving personal losses, feeling split, and struggling to accept the constant inner chaos, the new self, the diagnosis and an uncertain future. The experience of receiving psychiatric treatments, such as inpatient and outpatient care, social interventions, psychological treatments and medications, included both positive and negative aspects, and was determined by the hope of achieving recovery, understood as an enduring journey of reconstructing the sense of personhood and re-establishing the lost bonds with others towards meaningful goals. These findings can inform clinical practice, research and education. Psychosis is one of the most painful and upsetting existential experiences, so dizzyingly alien to our usual patterns of life and so unspeakably enigmatic and human.
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BACKGROUND AND PURPOSE: Functional neurological disorder (FND) is common, and symptoms can be severe. There have been no international large-scale studies of patient experiences of FND. METHODS: A patient questionnaire was created to assess FND patient characteristics, symptom comorbidities and illness perceptions. Respondents were recruited internationally through an open access questionnaire via social media and patient groups over a month-long period. RESULTS: In total, 1048 respondents from 16 countries participated. Mean age was 42 years (86% female). Median FND symptom duration was 5 years, and median time from first symptom to diagnosis was 2 years. Mean number of current symptoms (core FND and associated) was 9.9. Many respondents had associated symptoms, for example fatigue (93%), memory difficulties (80%) and headache (70%). Self-reported psychiatric comorbidities were relatively common (depression, 43%; anxiety, 51%; panic, 20%; and post-traumatic stress disorder, 22%). Most respondents reported that FND had multiple causes, including physical and psychological. CONCLUSIONS: This large survey adds further evidence that people with FND typically have high levels of multiple symptom comorbidity with resultant distress. It also supports the notion that associated physical symptoms are of particular clinical significance in FND patients. Dualistic ideas of FND were not supported by respondents, who generally preferred to conceptualize the disorder as one at the interface of mind and brain. The need for a broad approach to this poorly served patient group is highlighted. Potential selection and response biases due to distribution of the survey online, mostly via FND patient groups, are a key limitation.
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Trastornos de Conversión , Enfermedades del Sistema Nervioso , Adulto , Ansiedad , Encéfalo , Femenino , Humanos , Masculino , Enfermedades del Sistema Nervioso/epidemiología , Encuestas y CuestionariosRESUMEN
Background: Inhalation therapy is the main treatment for asthma and chronic obstructive pulmonary disease (COPD) patients. Owing to the poor inhaler technique in using inhalers, we assessed the effect of a multidimensional pharmaceutical care on inhalation technique in patients with asthma and COPD. Materials and Methods: A 3-month controlled parallel-group study was undertaken in asthma and COPD patients using dry powder inhalers (DPIs). Patients in the intervention group received multidimensional pharmaceutical care, including establishment of a special dispensing window, face-to-face demonstration and education, brochure education, videos education, online consultation and education, and follow-up reeducation. Patients in the control group received usual pharmaceutical care. The inhaler technique score, correctness of inhaler usage, beliefs about medicines questionnaire (BMQ) score, asthma control test (ACT), and COPD assessment test (CAT) were measured pre- and postintervention. Quality of life improvement evaluated according to score changes of ACT in asthma and CAT in COPD and patient satisfaction were measured postintervention. Results: 259 patients finished the study with 133 in the intervention group and 126 in the control group. Compared to preintervention and control group postintervention, the inhaler technique score, correctness of inhaler usage, and ACT score significantly increased in the intervention group postintervention, while the BMQ score and CAT score decreased significantly (P < 0.05). Significant improvements in quality of life and patient satisfaction were found (P < 0.05). Conclusion: This study showed the multidimensional pharmaceutical care for asthma and COPD patients were effective in improving inhalation technique. By providing pharmaceutical care, pharmacists might help asthma and COPD patients to acquire better quality of life.
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Asma , Servicios Farmacéuticos , Enfermedad Pulmonar Obstructiva Crónica , Administración por Inhalación , Asma/tratamiento farmacológico , Broncodilatadores/uso terapéutico , Inhaladores de Polvo Seco , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Calidad de VidaRESUMEN
Background: Warfarin acts in heart valve replacement patients to minimize thromboembolic complications. We investigated whether patients can be distinguished based on their genotypes to efficiently and safely administer warfarin therapy after heart valve replacements.Research design and methods: A retrospective analysis was conducted in patients with warfarin therapy who underwent elective heart valve replacements between January 2013 and September 2018. The patients were divided into normal, sensitive, and highly sensitive bins based on their CYP2C9 and VKORC1 genotypes. The primary endpoints were over-anticoagulation and overt bleeding.Results: 375 patients were enrolled, with 65 classified as normal, 281 as sensitive, and 29 as highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders spent more time on over-anticoagulation in the first 28 (P < 0.001) and 90 (P = 0.001) days; experienced more frequent bleeding events in the first 28 days (P = 0.029; OR, 2.18; 95% CI, 1.15-4.13); required lower warfarin doses to obtain stable INR (P < 0.001); had higher warfarin sensitivity indices (P < 0.001).Conclusion: Predicting evidence have been obtained with CYP2C9 and VKORC1 genotypes in identifying heart valve replacement patients with higher efficient sensitivity and with a higher risk of bleeding and over-anticoagulation.
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Anticoagulantes/administración & dosificación , Citocromo P-450 CYP2C9/genética , Hemorragia/inducido químicamente , Vitamina K Epóxido Reductasas/genética , Warfarina/administración & dosificación , Adulto , Anciano , Anticoagulantes/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Genotipo , Implantación de Prótesis de Válvulas Cardíacas/métodos , Hemorragia/epidemiología , Hemorragia/genética , Humanos , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tromboembolia/prevención & control , Warfarina/efectos adversosRESUMEN
Background: Cefoperazone/sulbactam is a broad-spectrum antibacterial agent. Drug-induced immune hemolytic anemia is a rare but serious condition, and reactive thrombocytosis is caused by processes extrinsic to the megakaryocyte. Limited data are available for cefoperazone/sulbactam-associated hemolytic anemia and reactive thrombocytosis. Case presentation: We report the case of a 60-year-old woman undergoing surgical excision of the left atrial myxoma, who presented with hemolytic anemia and thrombocytosis following cefoperazone/sulbactam administration for lung infection. The duration of cefoperazone/sulbactam therapy was 8 days. Blood analysis showed markedly decreased hemoglobin, hematocrit, and red blood cell levels, with elevated lactate dehydrogenase, indirect bilirubin, platelets, and reticulocytes. Furthermore, the direct antiglobulin test was positive for anti-C3 and a diagnosis of hemolytic anemia and reactive thrombocytosis was made. Then, cefoperazone/sulbactam was discontinued and red blood cell transfusion was performed for 3 days. After 1 week, the patient's condition improved, and she was discharged. Conclusion: This is the first suspected case report of immune hemolytic anemia and reactive thrombocytosis related to cefoperazone/sulbactam. Caution should be taken for this reaction in patients undergoing cefoperazone/sulbactam therapy.
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OBJECTIVE: The Psychiatry Early Experience Programme (PEEP) is a novel enrichment activity at Kings College London medical school. Throughout their five-year degree, students shadow trainee psychiatry doctors. The study aimed to evaluate whether more regular early exposure affects attitudes towards psychiatry. METHODS: Forty first-year medical students joined PEEP and completed a baseline survey, including questions on demographics, current top three choices of medical specialty and the 30-item Attitudes Towards Psychiatry questionnaire (ATP-30). Participants completed annual follow up surveys, incorporating free-text questions about what students had learned and whether their views about psychiatry had changed. RESULTS: Over three years there was a sustained improvement in mean ATP-30 scores (8.27 points higher at three years than at baseline [95% CI 2.86-13.7, T=3.2, p=0.005]). There was no significant difference between baseline specialty choice and specialty choice at three-year follow-up. At three years there was a 55% response rate. There was no significant association between non-responders at three years and baseline ATP-30, specialty choice or demographic factors. Thematic analysis of qualitative data suggested that PEEP challenged preconceptions towards psychiatry and highlighted its relevance in medicine. CONCLUSIONS: The results offer some support that exposure to clinical psychiatry through longitudinal shadowing experiences can sustain positive attitudes. Areas for development include using a control group and following-up participants to the point when they specialize. It remains unclear whether it is most effective to select participants based on established commitment to psychiatry or to try to influence students who are still undecided.
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Actitud del Personal de Salud , Psiquiatría , Estudiantes de Medicina , Selección de Profesión , Humanos , Psiquiatría/educación , Facultades de Medicina , Estudiantes de Medicina/psicología , Encuestas y Cuestionarios , Reino UnidoRESUMEN
BACKGROUND: In an ageing world facing an epidemic of chronic diseases, there is great interest in the burden of multimorbidity on individuals and caregivers, yet no studies have examined the longitudinal association between multimorbidity and care dependence in low and middle income countries. Mental and cognitive disorders are associated with dependence but little is known about their role in the pathway to dependence in the context of multimorbidity. This study aims to determine (1) the association of multimorbidity with the onset of care dependence in older adults, accounting for mortality and controlling for sociodemographic factors, and (2) the independent effects of physical multimorbidity, mental and cognitive disorders. METHODS: A population-based cohort study of people aged 65 years and older in six countries in Latin America, and China. Data on chronic conditions and sociodemographic factors were collected at baseline. Multimorbidity was ascertained as a count of up to 15 mental, cognitive and physical health conditions. Dependence was ascertained through informant interviews at baseline and follow-up. We used competing risk regression to assess the association between multimorbidity and the onset of care dependence, acknowledging the possibility of dependence-free death. We also assessed the independent effects of physical multimorbidity and depression, anxiety and dementia individually. RESULTS: 12,965 participants, with no needs for care at baseline, were followed up for a median of 3.0-4.9 years. Each unit increase in multimorbidity count increased the cumulative risk of dependence by 20% in the fully adjusted model. Age was the only variable to confound this relationship. Physical multimorbidity was associated with only a modest increased risk of care dependence. Dementia, depression and anxiety were independently associated with incident care dependence at every level of physical multimorbidity, and depression and anxiety attenuated the effect of physical multimorbidity. CONCLUSION: Multimorbidity consistently predicts care dependence with little variation between countries. Physical multimorbidity imparts a lower risk than multimorbidity with mental and cognitive disorders included. Mental and cognitive disorders independently increase the risk of care dependence. Comprehensive and holistic assessment of disorders of body, brain and mind can help to identify older people at high risk of care dependence.
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Cuidadores/estadística & datos numéricos , Enfermedad Crónica/epidemiología , Países en Desarrollo/estadística & datos numéricos , Multimorbilidad , Pobreza/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Ansiedad/epidemiología , China/epidemiología , Trastornos del Conocimiento/epidemiología , Estudios de Cohortes , Demencia/epidemiología , Depresión/epidemiología , Femenino , Humanos , Renta , América Latina/epidemiología , Estudios Longitudinales , Masculino , Análisis de RegresiónRESUMEN
BACKGROUND: Total knee arthroplasty (TKA) is associated with blood loss and an increased risk of transfusion. Guidelines for antifibrinolytic drug tranexamic acid (TXA) treatment in TKA patients are available. We evaluated the effects of anticoagulant pharmacist intervention on perioperative blood conservation treatment in TKA patients. METHODS: In a retrospective, observational experimental study, patients admitted for TKA were allocated into the control or pharmacist intervention group. In the intervention phase, multiple interventions of TXA treatment based on guidelines were implemented. The primary endpoint was blood loss. Other outcome included postoperative haemoglobin and haematocrit levels, allogeneic blood transfusion, cost savings and safety. RESULTS: A total of 177 patients were included (88 and 89 in the control and intervention group, respectively). In the intervention group, 24.72% orders of TXA dosage, 20.22% orders of drug choice, 26.97% orders of TXA timing and 30.34% orders of TXA administration manner were adjusted. Eighty-nine (100%) patients received blood conservation therapy compared with 21 (23.86%) patients in the control group (P < 0.001). Total blood loss was 1133.31 ± 627.08 mL in the control group compared with 604.34 ± 459.09 mL in the intervention group (P < 0.001). Postoperative drops in haemoglobin and haematocrit in the control group were greater than in the intervention group (P < 0.001). The rate of allogeneic blood transfusion was 40.91% in the control group compared with 21.35% in the intervention group (P = 0.01). Pharmacist intervention was conducted to cost savings resulting from reduced transfusion, but with comparable safety profile. CONCLUSIONS: Anticoagulant pharmacist intervention on blood conservation treatment of TKA patients leads to favourable clinical and economic outcome.
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Antifibrinolíticos/uso terapéutico , Artroplastia de Reemplazo de Rodilla , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Transfusión Sanguínea/estadística & datos numéricos , Ácido Tranexámico/uso terapéutico , Anciano , Antifibrinolíticos/administración & dosificación , China/epidemiología , Femenino , Hematócrito , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Farmacéuticos/economía , Estudios Retrospectivos , Seguridad/estadística & datos numéricos , Ácido Tranexámico/administración & dosificaciónRESUMEN
This multi-centered study was designed to evaluate the biological effects of exposure to antineoplastic drugs (ADs) at PIVAS (Pharmacy Intravenous Admixture Service) across ten Chinese hospitals. 8-hydroxy-2-deoxyguanosine (8-OHdG) was used as a biomarker of DNA oxidative damage and lymphocyte apoptosis assays using peripheral lymphocyte cells were used to detect primary DNA damage. The mutagenicity activity was estimated with the Ames fluctuation test. 158 exposed and 143 unexposed workers participated in this study. The urinary 8-OHdG/Cr concentrations of the exposed group was 22.05±17.89ng/mg Cr, which was significantly higher than controls of 17.36±13.50ng/mg Cr (P<0.05). The rate of early lymphocyte apoptosis was slightly increased in exposed group than that of the control group (P=0.087). The mutagenic activity was significantly higher in the exposed group relative to the control group (P<0.05). Moreover, while no statistically significant difference was observed, higher concentrations of 8-OHdG/Cr in urine and an early lymphocyte apoptosis rate were found in exposed group II as compared to exposed group I. In addition, a significant correlation between early lymphocyte apoptosis and exposure time to ADs was also observed (P<0.05). In conclusion, our study identified elevated biomarkers in PIVAS workers exposed to ADs. However whether these findings could lead to increased incidence of genotoxic responses remains to be further investigated.
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Antineoplásicos/efectos adversos , Exposición Profesional/efectos adversos , Servicio de Farmacia en Hospital , 8-Hidroxi-2'-Desoxicoguanosina , Adulto , Apoptosis , Biomarcadores/orina , China/epidemiología , Daño del ADN , Desoxiguanosina/análogos & derivados , Desoxiguanosina/orina , Composición de Medicamentos , Femenino , Humanos , Linfocitos , Masculino , Enfermeras y Enfermeros , Farmacéuticos , Adulto JovenRESUMEN
Pharmacists' role may be ideal for improving rationality of drug prescribing practice. We aimed to study the impact of multifaceted pharmacist interventions on antibiotic prophylaxis in patients undergoing clean or clean-contaminated operations in cardiothoracic department. A pre-test-post-test quasiexperimental study was conducted in a cardiothoracic ward at a tertiary teaching hospital in Suzhou, China. Patients admitted to the ward were collected as baseline group (2011.7-2012.12) and intervention group (2013.7-2014.12), respectively. The criteria of prophylaxis antibiotic utilization were established on the basis of the published guidelines and official documents. During the intervention phase, a dedicated pharmacist was assigned and multifaceted interventions were implemented in the ward. Then we compared the differences in antibiotic utilization, bacterial resistance, clinical and economic outcomes between the 2 groups. Furthermore, patients were collected after the intervention (2015.1-2015.6) to evaluate the sustained effects of pharmacist interventions. 412 and 551 patients were included in the baseline and intervention groups, while 156 patients in postintervention group, respectively. Compared with baseline group, a significant increase was found in the proportion of antibiotic prophylaxis, the proportion of rational antibiotic selection, the proportion of suitable prophylactic antibiotic duration, and the proportion of suitable timing of administration of the first preoperative dose (Pâ<â0.001). Meanwhile, a significant reduction was seen in the rate of unnecessary replacement of antibiotics and the rate of unnecessary combinations (Pâ<â0.001). Besides, pharmacist intervention resulted in favorable outcomes with significantly decreased rates of surgical site infections, prophylactic antibiotic cost, and significantly shortened length of stay (Pâ<â0.05). Furthermore, there were also significant decreases of the rates of antibiotic resistant enterobacter cloacae, klebsiella pneumonia, and staphylococcus aureus (Pâ<â0.05). Moreover, the effects were sustained after discontinuation of the active interventions, as shown in prophylactic antibiotic utilization data. Pharmacist interventions in cardiothoracic surgery result in a high adherence to evidence-based treatment guidelines and a profound culture change in drug prescribing with favorable outcomes. The effects of pharmacist intervention are sustained and the role of pharmacists is emphasized for rational medication and optimal outcomes in clinical treatment.
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Profilaxis Antibiótica , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Farmacéuticos , Infección de la Herida Quirúrgica/prevención & control , Cirugía Torácica , Profilaxis Antibiótica/métodos , Profilaxis Antibiótica/estadística & datos numéricos , Procedimientos Quirúrgicos Cardíacos/métodos , China , Análisis Costo-Beneficio , Adhesión a Directriz , Humanos , Registros Médicos Orientados a Problemas/estadística & datos numéricos , Política Organizacional , Rol Profesional , Estudios Prospectivos , Mejoramiento de la Calidad , Infección de la Herida Quirúrgica/economía , Centros de Atención Terciaria/estadística & datos numéricos , Cirugía Torácica/métodos , Cirugía Torácica/normasRESUMEN
In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS. G. biloba extract (12 and 24 mg·kg(-1)) and dexamethasone (2 mg·kg(-1)), as a positive control, were given by i.p. injection. The cells in the bronchoalveolar lavage fluid (BALF) were counted. The degree of animal lung edema was evaluated by measuring the wet/dry weight ratio. The superoxidase dismutase (SOD) and myeloperoxidase (MPO) activities were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-a, interleukin-1b, and interleukin-6, were assayed by enzyme-linked immunosorbent assay. Pathological changes of lung tissues were observed by H&E staining. The levels of NF-κB p65 and COX-2 expression were detected by Western blotting. Compared to the LPS group, the treatment with the G. biloba extract at 12 and 24 mg·kg(-1) markedly attenuated the inflammatory cell numbers in the BALF, decreased NF-κB p65 and COX-2 expression, and improved SOD activity, and inhibited MPO activity. The histological changes of the lungs were also significantly improved. The results indicated that G. biloba extract has a protective effect on LPS-induced acute lung injury in mice. The protective mechanism of G. biloba extract may be partly attributed to the inhibition of NF-κB p65 and COX-2 activation.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Ciclooxigenasa 2/metabolismo , Ginkgo biloba/química , Fitoterapia , Extractos Vegetales/farmacología , Factor de Transcripción ReIA/metabolismo , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Ciclooxigenasa 2/genética , Ensayo de Inmunoadsorción Enzimática , Expresión Génica/efectos de los fármacos , Interleucina-1beta/análisis , Interleucina-6/análisis , Lipopolisacáridos , Pulmón/inmunología , Pulmón/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Peroxidasa/metabolismo , Edema Pulmonar , Superóxido Dismutasa/metabolismo , Factor de Transcripción ReIA/genética , Factor de Necrosis Tumoral alfa/análisisRESUMEN
BACKGROUND: Cyclosporine (CsA), a potent immunosuppressive agent used to prevent rejection, is characterized by large individual variability. The purpose of this study was to explore the pharmacokinetic characteristics of CsA and establish a CsA population pharmacokinetic model that could be used for personalized therapy in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients. METHODS: Clinical data were obtained from 117 allo-HSCT patients. The data analysis was performed using NONMEM software. A first-order conditional estimation with interaction (FOCE-I) method within NONMEM was used to estimate the parameters. The covariates, including demographics, hematological indices, biochemical levels, concurrent drugs, and genetic polymorphisms of CYP3A4, CYP3A5, and ABCB1, were evaluated quantitatively. The stability of the final model was validated by a nonparametric bootstrap procedure. RESULTS: A total of 1,571 observed concentrations were collected. A 1-compartment model with first-order absorption and elimination adequately described the pharmacokinetics of CsA. The typical values for clearance (CL), volume of distribution (V), and bioavailability were 29.6 L/hr, 605 L, and 0.619, respectively. The interindividual variability of these parameters was 20.4, 66.1, and 30.4%, respectively. The residual error was 31.4% and 23.7 ng/mL. The duration of CsA therapy, hematocrit, antifungal agent administration, triglycerides, and weight were identified as the main covariates that influenced CL, and hematocrit had a significant effect on V. The internal validation showed that the final model was stable and accurate. CONCLUSIONS: This study established a population pharmacokinetic model of CsA in allo-HSCT patients that could provide the foundation for personalized use of CsA in the clinic.