临床药师的最根本任务就是利用自身丰富的药学知识为临床药物治疗提供有效的服务,协助临床医生对药物治疗方案进行评估、监测和调整,保证患者用药的安全、经济、有效。PUIA模式由4个部分组成:①P(药理作用,pharmacological action...临床药师的最根本任务就是利用自身丰富的药学知识为临床药物治疗提供有效的服务,协助临床医生对药物治疗方案进行评估、监测和调整,保证患者用药的安全、经济、有效。PUIA模式由4个部分组成:①P(药理作用,pharmacological action),评估药物选择的合理性。②U(药物的用法用量,use),分析剂型、剂量及用法用量的合理性。③I(药物的相互作用interaction),考察药物问有无药效学和药动学间的相互作用。④A(不良反应,adverse drug reaction),分析实际的和潜在的ADR及药物过量引起的中毒反应,拟定监护、监测计划。我院临床药学工作刚刚起步,在临床药师参与肺科医师的查房工作中,尝试着用PUIA模式来分析医嘱中药疗方案的合理性,与医师沟通探讨并对治疗方案进行适当调整。现将采用PUIA模式分析的典型实例报告如下。展开更多
Recently introduced in the treatment algorithms and guidelines for the treatment of ulcerative colitis,biological therapy is an effective treatment option for patients with an acute severe flare not responsive to conv...Recently introduced in the treatment algorithms and guidelines for the treatment of ulcerative colitis,biological therapy is an effective treatment option for patients with an acute severe flare not responsive to conventional treatments and for patients with steroid dependent disease.The reduction in hospitalization and surgical intervention for patients affected by ulcerative colitis after the introduction of biologic treatment remains to be proven.Furthermore,these agents seem to be associated with increase in cost of treatment and risk for serious postoperative complications.Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice in ulcerative colitis patients.Surgery is traditionally recommended as salvage therapy when medical management fails,and,despite advances in medical therapy,colectomy rates remain unchanged between 20% and 30%.To overcome the reported increase in postoperative complications in patients on biologic therapies,several surgical strategies have been developed to maintain long-term pouch failure rate around 10%,as previously reported.Surgical staging along with the development of minimally invasive surgery are among the most promising advances in this field.展开更多
Prophylactic strategies against hepatitis B virus(HBV) recurrence after liver transplantation(LT) are essential for patients with HBV-related disease.Before LT, lamivudine(LAM) was proposed to be down-graded from firs...Prophylactic strategies against hepatitis B virus(HBV) recurrence after liver transplantation(LT) are essential for patients with HBV-related disease.Before LT, lamivudine(LAM) was proposed to be down-graded from first-to second-line therapy.In contrast, adefovir dipivoxil(ADV) has been approved not only as first-line therapy but also as rescue therapy for patients with LAM resistance.Furthermore, combination of ADV and LAM may result in lower risk of ADV resistance than ADV monotherapy.Other new drugs such as entecavir, telbivudine and tenofovir, are probably candidates for the treatment of hepatitis-B-surface-antigen-positive patients awaiting LT.After LT, low-dose intramuscular hepatitis B immunoglobulin(HBIG), in combination with LAM, has been regarded as the most cost-effective regimen for the prevention of post-transplant HBV recurrence in recipients without pretransplant LAM resistance and rapidly accepted in many transplant centers.With the introduction of new antiviral drugs, new hepatitis B vaccine and its new adjuvants, post-transplant HBIG-free therapeutic regimens with new oral antiviral drug combinations or active HBV vaccination combined with adjuvants will be promising, particularly in those patients with low risk of HBV recurrence.展开更多
Aim To develop a method to estimate population pharmacokinetic parameters with the limited sampling time points provided clinically during therapeutic drug monitoring. Methods Various simulations were attempted using ...Aim To develop a method to estimate population pharmacokinetic parameters with the limited sampling time points provided clinically during therapeutic drug monitoring. Methods Various simulations were attempted using a one-compartment open model with the first order absorption to determine PK parameter estimates with different sampling strategies as a validation of the method. The estimated parameters were further verified by comparing to the observed values. Results The samples collected at the single time point close to the non-informative sampling time point designed by this method led to bias and inaccurate parameter estimations. Furthermore, the relationship between the estimated non-informative sampling time points and the values of the parameter was examined. The non-informative sampling time points have been developed under some typical occasions and the results were plotted to show the tendency. As a result, one non-informative time point was demonstrated to be appropriate for clearance and two for both volume of distribution and constant of absorption in the present study. It was found that the estimates of the non-informative sampling time points developed in the method increase with increases of volume of distribution and the decrease of clearance and constant of absorption. Conclusion A rational sampling strategy during therapeutic drug monitoring can be established using the method present in the study.展开更多
Hepatitis C is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis C recurs universally in the transplanted liver and is the major cause of decreased graft an...Hepatitis C is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis C recurs universally in the transplanted liver and is the major cause of decreased graft and patient survival. The combination therapy of interferon and ribavirin has been shown to be the most effective therapy for recurrent hepatitis C. However, pre-and post-transplant hypersplenism often precludes patients from receiving the antiviral therapy. Splenectomy and partial splenic embolization are the two invasive modalities that can correct the cytopenia associated with hypersplenism. In this report we review the two treatment options, their associated outcomes and complications.展开更多
With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment reg...With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment regimens have emerged to cure Helicobacter pylori (H.pylori) infection.Novel first-line anti-H.pylori therapies in 2011 include sequential therapy,concomitant quadruple therapy,hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy.After the failure of standard triple therapy,a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI),bismuth,tetracycline and metronidazole can be employed as rescue treatment.Recently,triple therapy combining a PPI,levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy.This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects.The best second-line therapy for patients who fail to eradicate H.pylori with first-line therapies containing clarithromycin,amoxicillin and metronidazole is unclear.However,a levofloxacin-based triple therapy is an accepted rescue treatment.Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test.Nonetheless,an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H.pylori infection if antimicrobial sensitivity data are unavailable.展开更多
Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great...Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.展开更多
Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard ...Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.展开更多
Lung cancer is one of the most common malignant tumors in the world. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases, and approximately 75% of patients are diagnosed in the mid...Lung cancer is one of the most common malignant tumors in the world. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases, and approximately 75% of patients are diagnosed in the middle and late stages. The treatment methods mainly include surgery, chemotherapy, radiotherapy, molecular targeted therapy, traditional Chinese medicine therapy, and immune therapy. We summarize the current status of lung cancer-related treatment options and targets.展开更多
With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural ...With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural mechanism of bumetanide in children with ASD aged 3-6 years old.A total of 120 children were enrolled into the study and randomly assigned to either 0.5 mg bumetanide or placebo.In the final sample,119 children received at least one dose of bumetanide(59 children) or placebo(60 children) were included in the final analysis.The primary outcome was a reduction in the Childhood Autism Rating Scale(CARS) score,and the secondary outcomes were the Clinical Global Impressions Scale(CGI)-Global Improvement(CGI-I) score at 3 months and the change from baseline to 3-month in the Autism Diagnostic Observation Schedule(ADOS).Magnetic resonance spectroscopy(MRS) was used to measure y-aminobutyric acid(GABA) and glutamate neurotransmitter concentrations in the insular cortex(IC) before and after the treatment.As compared with the placebo,bumetanide treatment was significantly better in reducing the severity.No patient withdrew from the trial due to adverse events.The superiority of bumetanide to placebo in reducing insular GABA,measured using MRS,was demonstrated.The clinical improvement was associated with a decrease in insular GABA in the bumetanide group.In conclusion,this trial in a large group of young children with predominantly moderate and severe ASD demonstrated that bumetanide is safe and effective in improving the core symptoms of ASD.However,the clinical significance remains uncertain,and future multi-center clinical trials are required to replicate these findings and confirm the clinical significance using a variety of outcome measures.展开更多
Objective: To observe the clinical effects of moxibustion therapy on preventing and treating toxic and side effects of chemotherapy in malignant tumor patients. Methods: A total of 63 cases were randomly divided int...Objective: To observe the clinical effects of moxibustion therapy on preventing and treating toxic and side effects of chemotherapy in malignant tumor patients. Methods: A total of 63 cases were randomly divided into three groups. Twenty-three cases in the moxibustion group were treated by moxibustion, and 22 cases in the hydro-acupuncture group were treated by acupoint injection, and 18 cases in the control group were treated by oral administration of Batilol tablets. The changes of the white blood cell count and the content of immunoglobulin before and after the treatments were observed. Results: After treatments, the total leukocyte count and the content of immunoglobulin were all elevated in the moxibustion group and the hydro-acupuncture group, with statistical difference when compared with the control group (P〈0.05, P〈0.01). In the elevation of the white blood cell count, the hydro-acupuncture group was better than the moxibustion group (P〈0.05). Conclusion: Moxibustion and hydro-acupuncture can be used to treat and prevent toxic and side effects of chemotherapy. From this aspect, the different needling techniques possess different effects.展开更多
文摘临床药师的最根本任务就是利用自身丰富的药学知识为临床药物治疗提供有效的服务,协助临床医生对药物治疗方案进行评估、监测和调整,保证患者用药的安全、经济、有效。PUIA模式由4个部分组成:①P(药理作用,pharmacological action),评估药物选择的合理性。②U(药物的用法用量,use),分析剂型、剂量及用法用量的合理性。③I(药物的相互作用interaction),考察药物问有无药效学和药动学间的相互作用。④A(不良反应,adverse drug reaction),分析实际的和潜在的ADR及药物过量引起的中毒反应,拟定监护、监测计划。我院临床药学工作刚刚起步,在临床药师参与肺科医师的查房工作中,尝试着用PUIA模式来分析医嘱中药疗方案的合理性,与医师沟通探讨并对治疗方案进行适当调整。现将采用PUIA模式分析的典型实例报告如下。
文摘Recently introduced in the treatment algorithms and guidelines for the treatment of ulcerative colitis,biological therapy is an effective treatment option for patients with an acute severe flare not responsive to conventional treatments and for patients with steroid dependent disease.The reduction in hospitalization and surgical intervention for patients affected by ulcerative colitis after the introduction of biologic treatment remains to be proven.Furthermore,these agents seem to be associated with increase in cost of treatment and risk for serious postoperative complications.Restorative proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice in ulcerative colitis patients.Surgery is traditionally recommended as salvage therapy when medical management fails,and,despite advances in medical therapy,colectomy rates remain unchanged between 20% and 30%.To overcome the reported increase in postoperative complications in patients on biologic therapies,several surgical strategies have been developed to maintain long-term pouch failure rate around 10%,as previously reported.Surgical staging along with the development of minimally invasive surgery are among the most promising advances in this field.
文摘Prophylactic strategies against hepatitis B virus(HBV) recurrence after liver transplantation(LT) are essential for patients with HBV-related disease.Before LT, lamivudine(LAM) was proposed to be down-graded from first-to second-line therapy.In contrast, adefovir dipivoxil(ADV) has been approved not only as first-line therapy but also as rescue therapy for patients with LAM resistance.Furthermore, combination of ADV and LAM may result in lower risk of ADV resistance than ADV monotherapy.Other new drugs such as entecavir, telbivudine and tenofovir, are probably candidates for the treatment of hepatitis-B-surface-antigen-positive patients awaiting LT.After LT, low-dose intramuscular hepatitis B immunoglobulin(HBIG), in combination with LAM, has been regarded as the most cost-effective regimen for the prevention of post-transplant HBV recurrence in recipients without pretransplant LAM resistance and rapidly accepted in many transplant centers.With the introduction of new antiviral drugs, new hepatitis B vaccine and its new adjuvants, post-transplant HBIG-free therapeutic regimens with new oral antiviral drug combinations or active HBV vaccination combined with adjuvants will be promising, particularly in those patients with low risk of HBV recurrence.
基金National Natural Science Foundation of China(Grant No. 30472165) the 985 Projects of the State KeyLaboratory of Natural and Biomimetic Drugs (Grant No.268705077280).
文摘Aim To develop a method to estimate population pharmacokinetic parameters with the limited sampling time points provided clinically during therapeutic drug monitoring. Methods Various simulations were attempted using a one-compartment open model with the first order absorption to determine PK parameter estimates with different sampling strategies as a validation of the method. The estimated parameters were further verified by comparing to the observed values. Results The samples collected at the single time point close to the non-informative sampling time point designed by this method led to bias and inaccurate parameter estimations. Furthermore, the relationship between the estimated non-informative sampling time points and the values of the parameter was examined. The non-informative sampling time points have been developed under some typical occasions and the results were plotted to show the tendency. As a result, one non-informative time point was demonstrated to be appropriate for clearance and two for both volume of distribution and constant of absorption in the present study. It was found that the estimates of the non-informative sampling time points developed in the method increase with increases of volume of distribution and the decrease of clearance and constant of absorption. Conclusion A rational sampling strategy during therapeutic drug monitoring can be established using the method present in the study.
文摘Hepatitis C is the most common indication for orthotopic liver transplantation in the United States. Unfortunately, hepatitis C recurs universally in the transplanted liver and is the major cause of decreased graft and patient survival. The combination therapy of interferon and ribavirin has been shown to be the most effective therapy for recurrent hepatitis C. However, pre-and post-transplant hypersplenism often precludes patients from receiving the antiviral therapy. Splenectomy and partial splenic embolization are the two invasive modalities that can correct the cytopenia associated with hypersplenism. In this report we review the two treatment options, their associated outcomes and complications.
文摘With the rising prevalence of antimicrobial resistance,the treatment success of standard triple therapy has recently declined to unacceptable levels (i.e.,80% or less) in most countries.Therefore,several treatment regimens have emerged to cure Helicobacter pylori (H.pylori) infection.Novel first-line anti-H.pylori therapies in 2011 include sequential therapy,concomitant quadruple therapy,hybrid (dual-concomitant) therapy and bismuth-containing quadruple therapy.After the failure of standard triple therapy,a bismuth-containing quadruple therapy comprising a proton pump inhibitor (PPI),bismuth,tetracycline and metronidazole can be employed as rescue treatment.Recently,triple therapy combining a PPI,levofloxacin and amoxicillin has been proposed as an alternative to the standard rescue therapy.This salvage regimen can achieve a higher eradication rate than bismuth-containing quadruple therapy in some regions and has less adverse effects.The best second-line therapy for patients who fail to eradicate H.pylori with first-line therapies containing clarithromycin,amoxicillin and metronidazole is unclear.However,a levofloxacin-based triple therapy is an accepted rescue treatment.Most guidelines suggest that patients requiring third-line therapy should be referred to a medical center and treated according to the antibiotic susceptibility test.Nonetheless,an empirical therapy (such as levofloxacin-based or furazolidone-based therapies) can be employed to terminate H.pylori infection if antimicrobial sensitivity data are unavailable.
文摘Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.
文摘Pancreatic cancer is one of the most deadly cancers and is characterized by a poor prognosis. Single agent gemcitabine, despite its limited activity and modest impact on disease outcome, is considered as the standard therapy in pancreatic cancer. Most of the combination regimens used in the treatment of this disease, also including the targeted agents, did not improve the outcome of patients. Also, taxanes have been tested as single agent and in combination chemotherapy, both in first line and as salvage chemotherapy, as another possible option for treating pancreatic cancer. The inclusion of taxanes in combination with gemcitabine as upfront therapy obtained promising results. Accordingly, taxanes, and above all, new generation taxanes, appear to be suitable candidates for further testing to assess their role against pancreatic cancer in various clinical settings.
文摘Lung cancer is one of the most common malignant tumors in the world. Non-small cell lung cancer (NSCLC) accounts for approximately 80% of lung cancer cases, and approximately 75% of patients are diagnosed in the middle and late stages. The treatment methods mainly include surgery, chemotherapy, radiotherapy, molecular targeted therapy, traditional Chinese medicine therapy, and immune therapy. We summarize the current status of lung cancer-related treatment options and targets.
基金the Shanghai Municipal Commission of Health and Family Planning(2018BR33,2017EKHWYX-02,and GWV-10.1-XK07)the Shanghai Shenkang Hospital Development Center(16CR2025B)+9 种基金the Shanghai Clinical Key Subject Construction Project(shslczdzk02902)the National Natural Science Foundation of China(81761128035,81930095,81873909,82001771,and 31860306)the Shanghai Committee of Science and Technology(17XD1403200,20ZR1404900,and 19410713500)Xinhua Hospital of Shanghai Jiao Tong University School of Medicine(2018YJRC03)the National Human Genetic Resources Sharing Service Platform(2005DKA21300)the National Key Research and Development Program of China(2018YFC0910503)111 Project(B18015)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Guangdong Key Project in‘‘Development of New Tools for Diagnosis and Treatment of Autism”(2018B030335001)the Science and Technology Department of Yunnan Province(202001AV070010)。
文摘With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural mechanism of bumetanide in children with ASD aged 3-6 years old.A total of 120 children were enrolled into the study and randomly assigned to either 0.5 mg bumetanide or placebo.In the final sample,119 children received at least one dose of bumetanide(59 children) or placebo(60 children) were included in the final analysis.The primary outcome was a reduction in the Childhood Autism Rating Scale(CARS) score,and the secondary outcomes were the Clinical Global Impressions Scale(CGI)-Global Improvement(CGI-I) score at 3 months and the change from baseline to 3-month in the Autism Diagnostic Observation Schedule(ADOS).Magnetic resonance spectroscopy(MRS) was used to measure y-aminobutyric acid(GABA) and glutamate neurotransmitter concentrations in the insular cortex(IC) before and after the treatment.As compared with the placebo,bumetanide treatment was significantly better in reducing the severity.No patient withdrew from the trial due to adverse events.The superiority of bumetanide to placebo in reducing insular GABA,measured using MRS,was demonstrated.The clinical improvement was associated with a decrease in insular GABA in the bumetanide group.In conclusion,this trial in a large group of young children with predominantly moderate and severe ASD demonstrated that bumetanide is safe and effective in improving the core symptoms of ASD.However,the clinical significance remains uncertain,and future multi-center clinical trials are required to replicate these findings and confirm the clinical significance using a variety of outcome measures.
文摘Objective: To observe the clinical effects of moxibustion therapy on preventing and treating toxic and side effects of chemotherapy in malignant tumor patients. Methods: A total of 63 cases were randomly divided into three groups. Twenty-three cases in the moxibustion group were treated by moxibustion, and 22 cases in the hydro-acupuncture group were treated by acupoint injection, and 18 cases in the control group were treated by oral administration of Batilol tablets. The changes of the white blood cell count and the content of immunoglobulin before and after the treatments were observed. Results: After treatments, the total leukocyte count and the content of immunoglobulin were all elevated in the moxibustion group and the hydro-acupuncture group, with statistical difference when compared with the control group (P〈0.05, P〈0.01). In the elevation of the white blood cell count, the hydro-acupuncture group was better than the moxibustion group (P〈0.05). Conclusion: Moxibustion and hydro-acupuncture can be used to treat and prevent toxic and side effects of chemotherapy. From this aspect, the different needling techniques possess different effects.