Background Mycophenolic acid (MPA) is an effective oral immunosuppressive drug used to treat lupus nephritis (LN), which exhibits large pharmacokinetic variability. This study aimed to characterize MPA pharmacokinetic behaviour in Mexican LN patients and to develop a population pharmacokinetic model which identified factors that influence MPA pharmacokinetic variability. Methods Blood samples from LN patients treated with mycophenolate mofetil (MMF) were collected pre dose and up to six hours post dose. MPA concentrations were determined by a validated ultra-performance liquid chromatography tandem mass spectrometry technique. Patients were genotyped for polymorphisms in enzymes (UGT1A8, 1A9 and 2B7) and transporters (ABCC2 and SLCO1B3). The anthropometric, clinical, genetic and co-medication characteristics of each patient were considered as potential covariates to explain the variability. Results A total of 294 MPA concentrations from 40 LN patients were included in the development of the model. The data were analysed using NONMEM software and were best described by a two-compartment linear model. MPA CL, Vc, Vp, Ka and Q were 15.4 L/h, 22.86 L, 768 L, 1.28 h-1 and 20.3 L/h, respectively. Creatinine clearance and prednisone co-administration proved to have influence on clearance, while body weight influenced Vc. The model was internally validated, proving to be stable. MMF dosing guidelines were obtained through stochastic simulations performed with the final model. Conclusions This is the first MPA population pharmacokinetic model to have found that co-administration of prednisone results in a considerable increase on clearance. Therefore, this and the other covariates should be taken into account when prescribing MMF in order to optimize the immunosuppressant therapy in patients with LN.In 1950, Hench, Kendall and Reichstein were awarded with the Nobel Prize in Physiology and Medicine for the isolation and first therapeutic use of glucocorticoids. Since then, they have become one of the main agents in the treatment of systemic lupus erythematosus (SLE). https://www.selleckchem.com/products/sw-100.html The use of high-dose oral glucocorticoids (usually 1 mg/kg/day of prednisone equivalent) have become the rule for treating moderate to severe lupus activity. In addition, tapering schemes have not been well defined, all this leading to prolonged exposures to potentially damaging amounts of glucocorticoids. Several studies have shown that glucocorticoids are a major cause of toxicity in SLE in a dose-dependent manner, with prolonged doses greater than 7.5 mg/day being associated with damage accrual. Thus, there is an urgent need for different therapeutic schedules that can achieve a rapid and durable control of lupus activity while reducing the many unwanted effects of glucocorticoids. Recent data show that pulses of methyl-prednisolone are an effective first-line therapy to treat lupus flares (not only severe ones) without major short or long-term toxicity and allowing a reduction in oral prednisone doses. Universal use of hydroxychloroquine - always recommended, infrequently accomplished - and early therapy with immunosuppressive drugs also help control SLE and reduce prednisone load. Results from observational studies confirm the more rapid achievement of remission and the reduction of long-term damage using these combination schedules with reduced prednisone doses. Seventy years after their first therapeutic use, we are learning to use glucocorticoids in a more efficient and safe manner.We present the neuroimaging findings of three cases of non-ketotic hyperglycaemia (NKH) associated with focal seizures and a review of the previous cases and series reported in literature. NKH is a cause of seizures in both long-standing and newly diagnosed diabetic patients. They are usually focal motor seizures, rarely with a secondary generalisation. This condition does not fully respond to anticonvulsant therapy if glycaemic levels are not normalised. Of interest, magnetic resonance imaging (MRI) of NKH could be different from those observed during other kinds of seizures. Indeed, seizure-related MRI abnormalities mainly involve the cortical grey matter, while NKH-related seizures usually appear as reversible subcortical T2/fluid attenuation inversion recovery (FLAIR) hypointensity. This latter abnormality shows a good spatial correlation with the area of the ictal focus on electroencephalogram and could be associated with other more common post-ictal MRI changes (cortical grey matter T2/FLAIR hyperintensity, cortical or leptomeningeal enhancement). Although these abnormalities tend to be transient, a focal volume loss or gliosis can result on follow-up imaging. Our cases confirm T2/FLAIR subcortical hypointensity as a main neuroradiological hallmark of NKH-induced seizures.Aim To compare the efficacy of a high-intensity psychosocial intervention with standardized usual care in countering psychosocial complexity among child-parent units in a pediatric oncology setting. Methods Two hundred pediatric oncology patients and their parents were recruited from Italian hospitals. A total of 81 child-parent units were assigned to the high-intensity psychosocial intervention and 119 child-parent units to standardized usual care. Psychosocial factors were assessed before and 1 year after intervention to measure efficacy. Results More improvements over time were observed in the high-intensity intervention group of child-parent units compared to the standard intervention group. Conclusion An intensive, structured, and tailored high-intensity intervention positively affects the psychosocial factors of child-parent units. Patients and families should have access to intensive psychosocial support throughout the cancer trajectory.Purpose Symptom monitoring has demonstrated improved outcomes in patients with cancer, including quality of life, resource utilization, ability to continue treatment, and survival. The use of disease-specific patient-reported outcome (PRO) measures facilitates symptom monitoring. While the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC), a PRO measure of symptom burden in lung cancer, is psychometrically validated for use in patients with NSCLC, its content validity has not been verified through direct patient input. Our purpose is to describe the symptom experience of patients with NSCLC and to confirm that the MDASI-LC contains the key symptoms specific to NSCLC from the patient perspective. Methods Patients with NSCLC described their symptom experience in single qualitative interviews. Content analysis was used to define the content domain for a PRO measure of NSCLC symptom burden. Results Participants (N = 40) had a mean age of 66.1 years (standard deviation, 10.9 years); 60.0% were male, 77.5% were White, and 56.
Background Mycophenolic acid (MPA) is an effective oral immunosuppressive drug used to treat lupus nephritis (LN), which exhibits large pharmacokinetic variability. This study aimed to characterize MPA pharmacokinetic behaviour in Mexican LN patients and to develop a population pharmacokinetic model which identified factors that influence MPA pharmacokinetic variability. Methods Blood samples from LN patients treated with mycophenolate mofetil (MMF) were collected pre dose and up to six hours post dose. MPA concentrations were determined by a validated ultra-performance liquid chromatography tandem mass spectrometry technique. Patients were genotyped for polymorphisms in enzymes (UGT1A8, 1A9 and 2B7) and transporters (ABCC2 and SLCO1B3). The anthropometric, clinical, genetic and co-medication characteristics of each patient were considered as potential covariates to explain the variability. Results A total of 294 MPA concentrations from 40 LN patients were included in the development of the model. The data were analysed using NONMEM software and were best described by a two-compartment linear model. MPA CL, Vc, Vp, Ka and Q were 15.4 L/h, 22.86 L, 768 L, 1.28 h-1 and 20.3 L/h, respectively. Creatinine clearance and prednisone co-administration proved to have influence on clearance, while body weight influenced Vc. The model was internally validated, proving to be stable. MMF dosing guidelines were obtained through stochastic simulations performed with the final model. Conclusions This is the first MPA population pharmacokinetic model to have found that co-administration of prednisone results in a considerable increase on clearance. Therefore, this and the other covariates should be taken into account when prescribing MMF in order to optimize the immunosuppressant therapy in patients with LN.In 1950, Hench, Kendall and Reichstein were awarded with the Nobel Prize in Physiology and Medicine for the isolation and first therapeutic use of glucocorticoids. Since then, they have become one of the main agents in the treatment of systemic lupus erythematosus (SLE). https://www.selleckchem.com/products/sw-100.html The use of high-dose oral glucocorticoids (usually 1 mg/kg/day of prednisone equivalent) have become the rule for treating moderate to severe lupus activity. In addition, tapering schemes have not been well defined, all this leading to prolonged exposures to potentially damaging amounts of glucocorticoids. Several studies have shown that glucocorticoids are a major cause of toxicity in SLE in a dose-dependent manner, with prolonged doses greater than 7.5 mg/day being associated with damage accrual. Thus, there is an urgent need for different therapeutic schedules that can achieve a rapid and durable control of lupus activity while reducing the many unwanted effects of glucocorticoids. Recent data show that pulses of methyl-prednisolone are an effective first-line therapy to treat lupus flares (not only severe ones) without major short or long-term toxicity and allowing a reduction in oral prednisone doses. Universal use of hydroxychloroquine - always recommended, infrequently accomplished - and early therapy with immunosuppressive drugs also help control SLE and reduce prednisone load. Results from observational studies confirm the more rapid achievement of remission and the reduction of long-term damage using these combination schedules with reduced prednisone doses. Seventy years after their first therapeutic use, we are learning to use glucocorticoids in a more efficient and safe manner.We present the neuroimaging findings of three cases of non-ketotic hyperglycaemia (NKH) associated with focal seizures and a review of the previous cases and series reported in literature. NKH is a cause of seizures in both long-standing and newly diagnosed diabetic patients. They are usually focal motor seizures, rarely with a secondary generalisation. This condition does not fully respond to anticonvulsant therapy if glycaemic levels are not normalised. Of interest, magnetic resonance imaging (MRI) of NKH could be different from those observed during other kinds of seizures. Indeed, seizure-related MRI abnormalities mainly involve the cortical grey matter, while NKH-related seizures usually appear as reversible subcortical T2/fluid attenuation inversion recovery (FLAIR) hypointensity. This latter abnormality shows a good spatial correlation with the area of the ictal focus on electroencephalogram and could be associated with other more common post-ictal MRI changes (cortical grey matter T2/FLAIR hyperintensity, cortical or leptomeningeal enhancement). Although these abnormalities tend to be transient, a focal volume loss or gliosis can result on follow-up imaging. Our cases confirm T2/FLAIR subcortical hypointensity as a main neuroradiological hallmark of NKH-induced seizures.Aim To compare the efficacy of a high-intensity psychosocial intervention with standardized usual care in countering psychosocial complexity among child-parent units in a pediatric oncology setting. Methods Two hundred pediatric oncology patients and their parents were recruited from Italian hospitals. A total of 81 child-parent units were assigned to the high-intensity psychosocial intervention and 119 child-parent units to standardized usual care. Psychosocial factors were assessed before and 1 year after intervention to measure efficacy. Results More improvements over time were observed in the high-intensity intervention group of child-parent units compared to the standard intervention group. Conclusion An intensive, structured, and tailored high-intensity intervention positively affects the psychosocial factors of child-parent units. Patients and families should have access to intensive psychosocial support throughout the cancer trajectory.Purpose Symptom monitoring has demonstrated improved outcomes in patients with cancer, including quality of life, resource utilization, ability to continue treatment, and survival. The use of disease-specific patient-reported outcome (PRO) measures facilitates symptom monitoring. While the MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC), a PRO measure of symptom burden in lung cancer, is psychometrically validated for use in patients with NSCLC, its content validity has not been verified through direct patient input. Our purpose is to describe the symptom experience of patients with NSCLC and to confirm that the MDASI-LC contains the key symptoms specific to NSCLC from the patient perspective. Methods Patients with NSCLC described their symptom experience in single qualitative interviews. Content analysis was used to define the content domain for a PRO measure of NSCLC symptom burden. Results Participants (N = 40) had a mean age of 66.1 years (standard deviation, 10.9 years); 60.0% were male, 77.5% were White, and 56.
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