Diabetes care is often difficult without a proper collaboration between the patient and the care provider as the disease is mostly self-managed by patients through adjustments in their lifestyles,and medication doses ...Diabetes care is often difficult without a proper collaboration between the patient and the care provider as the disease is mostly self-managed by patients through adjustments in their lifestyles,and medication doses to optimise glycaemic control.Most clinical guidelines on the management of diabetes mellitus(DM)provide only broad principles on diabetes care,and the blind follow-up of such principles without a proper review and consideration of patient characteristics often results in inadequate glycaemic control and diabetes complications consequently.Therefore,a proper understanding of the pathobiology,clinical situation,and comorbidities of the individual case is of paramount importance to tailoring the most appropriate management strategy in real-world diabetes care.With the aid of five unique cases of DM[(1)Medically managed type 2 diabetes mellitus(T2DM)with severe obesity;(2)Management of T2DM with unreliable glycated haemoglobin(HbA1c);(3)Obesity in a patient with type 1 diabetes mellitus(T1DM);and(4)Late diagnosis and subsequent management of monogenic diabetes and 5.Sudden worsening of well-controlled T2DM)]we elaborate on the importance of individualised diabetes care and the practicalities in these situations.The review also provides an evidence update on the management of different forms of DM to guide physicians in optimising the care of their patients in day-to-day clinical practice.展开更多
Background Therapeutic drug monitoring guides clinical individualised medication by measuring plasma concentration, which could improve the curative effect, avoid drug overdose and reduce the incidence of adverse reac...Background Therapeutic drug monitoring guides clinical individualised medication by measuring plasma concentration, which could improve the curative effect, avoid drug overdose and reduce the incidence of adverse reactions. At present, there are few reports on the clinical detection of venlafaxine and its active metabolite O-desmethylvenlafaxine. In this paper, the detection method of venlafaxine and O-desmethylvenlafaxine in blood plasma was established, which provides an effective and convenient means for guiding clinical application of medication.Aim To establish a method for determination of venlafaxine and its active metabolite O-desmethylvenlafaxine in human plasma by highperformance liquid chromatography with fluorescence detection.Methods Chromatographic separation was achieved on an Agilent Eclipse XDB-C18 Column(4.6 × 150 mm, 5 μm) with water containing sodium dihydrogen phosphate(0.05 mol/L) and acetonitrile(72:28) as the mobile phases. The following parameters were employed: flow rate 0.5 mL/min, column temperature 30°C, fluorescence excitation wavelength 276 nm and emission wavelength 598 nm.Results The method showed good linearity in the concentration range 10–1000 ng/mL. The regression equation for venlafaxine was R=0.0054 C+0.0264, r2=0.99991. The regression equation for O-desmethylvenlafaxine was R=0.0034 C+0.0272, r2=0.99969. The intraday and interday precisions(relative SD) were less than 10%, and the quantitative limit was 10 ng/mL.Conclusion We established a sensitive, specific and simple method for the detection of venlafaxine and O-desmethylvenlafaxine. This method fully meets the needs of clinical trials of venlafaxine and the requirements of relevant guidelines. It provided a reference for the clinical detection of venlafaxine and O-desmethylvenlafaxine plasma concentrations and pharmacokinetic study.展开更多
Our individual metabolic phenotype is the result of the interaction between nutrients and DNA to modify gene expression. This is a combination of epigenetic interactions whereby nutrients modify the structure of DNA t...Our individual metabolic phenotype is the result of the interaction between nutrients and DNA to modify gene expression. This is a combination of epigenetic interactions whereby nutrients modify the structure of DNA to affect gene expression as well as individual genetic variation that alters our response to diet. Our metabolic phenotype is influenced by developmental plasticity, imprinting in early life and interactions with environmental factors over time. Unlike the human genome which is relatively fixed and stable throughout the body, the human metabolic phenotype is far more complex and dynamic, varying over time and among cells and varying greatly from person to person. Dietary recommendations are often generalized and intended to avert chronic illnesses such as diabetes and cardiovascular disease. In a climate where we are striving for personalisation of healthcare maybe we need a simpler approach;one that embraces genetic variation yet focuses on the optimum nutritional benefit of dietary components.展开更多
Continuous drug monitoring is a promising alternative to current therapeutic drug monitoring strategies and has a strong potential to reshape our understanding of pharmacokinetic variability and to improve individuali...Continuous drug monitoring is a promising alternative to current therapeutic drug monitoring strategies and has a strong potential to reshape our understanding of pharmacokinetic variability and to improve individualised therapy.This review highlights recent advances in biosensing technologies that support continuous drug monitoring in real time.We focus primarily on aptamer-based biosensors,wearable and implantable devices.Emphasis is given to the approaches employed in constructing biosensors.We pay attention to sensors’biocompatibility,calibration performance,long-term characteristics stability and measurement quality.Last,we discuss the current challenges and issues to be addressed in continuous drug monitoring to make it a promising,future tool for individualised therapy.The ongoing efforts are expected to result in fully integrated implantable drug biosensing technology.Thus,we may anticipate an era of advanced healthcare in which wearable and implantable biochips will automatically adjust drug dosing in response to patient health conditions,thus enabling the management of diseases and enhancing individualised therapy.展开更多
Aids are only one of the instruments with which the disabled person can often reach a good level of autonomy,he can improve his conditions of life and prevent the aggravating of his situation. Aids serve also to facil...Aids are only one of the instruments with which the disabled person can often reach a good level of autonomy,he can improve his conditions of life and prevent the aggravating of his situation. Aids serve also to facilitate care on the part of the family. The rights confirmed by Law 104 can also be achieved through the use of aids. The Italian state has planned a system of care with regards to aids so that some of them can be purchased with different tax concessions but essential aids,those necessary for the reaching of autonomy goals and prevention defined by an individual rehabilitative project,are supplied free of charge. In Italy essential aids are part therefore of a rehabilitation plan that is identified for each person with disabilities by a team made up of different professionals.展开更多
Purpose The transition into full-time training represents a key period in the development of young soccer players.Here we compared the weekly training loads(matches,field-,and resistance-training)of English Premier-Le...Purpose The transition into full-time training represents a key period in the development of young soccer players.Here we compared the weekly training loads(matches,field-,and resistance-training)of English Premier-League Academy soccer players from under-16(U16),under-18(U18)and under-23(U23)age-groups during a training meso-cycle.Methods Forty players(U16 n=13,U18 n=15 and U23 n=12)were monitored using global navigation satellite systems and differential ratings of perceived exertion(dRPE).External load metrics were total distance,high-speed running distance,[absolute:≥19.8 km/h,relative:≥87%of 30-15 final-velocity(vIFT)],sprint distance(absolute:≥25.2 km/h,relative:≥80%maximal sprint speed),and dynamic stress load.Internal load metrics were dRPE training loads.Results Other than relative sprint distance,overall weekly external training loads were substantially greater for U18s and U23s when compared with U16s[effect size range:1.09-1.99(moderate to large);±90%confidence limits~0.45].When compared with U16s,overall internal loads were substantially greater for U18s[0.69-0.95(moderate);±~0.40],but not U23s.Differences in weekly training loads between U18s and U23s were inconclusive.Conclusions Substantial differences in training loads between elite U16 players and their older counterparts,indicates the need for planned increases in training loads in anticipation of the transition into full-time training.展开更多
When there is substantial heterogeneity of treatment effectiveness for comparative treatmentselection, it is crucial to identify individualised treatment rules for patients who have heterogeneous responses to treatmen...When there is substantial heterogeneity of treatment effectiveness for comparative treatmentselection, it is crucial to identify individualised treatment rules for patients who have heterogeneous responses to treatment. Existing approaches include directly modelling clinical outcomeby defining the optimal treatment rule according to the interactions between treatment andcovariates and outcome weighted approach that uses clinical outcome as weights to maximise atarget function whose value directly reflects correct treatment assignment. All existing articles ofestimating individualised treatment rules are all assuming just two treatment assignments. Herewe propose an outcome weighted learning approach that uses a vector hinge loss to extend estimating individualised treatment rules in multi-category treatments case. The consistency of theresulting estimator is shown. We also demonstrate the performance of our approach in simulationstudies and a real data analysis.展开更多
In the present study, we aimed to develop a population pharmacokinetics(PPK) model of vancomycin(VCM) and propose the individualised dosage regimen for Chinese elderly patients. The data were collected prospectively f...In the present study, we aimed to develop a population pharmacokinetics(PPK) model of vancomycin(VCM) and propose the individualised dosage regimen for Chinese elderly patients. The data were collected prospectively from Chinese elderly patients receiving VCM therapy. Steady-state trough concentrations of VCM were determined using an enzyme-multiplied immunoassay. Patients’ sex, age, body weight, concomitant medications, infection type, and laboratory findings were recorded. The PPK model was developed using nonlinear mixed-effects model software. Moreover, we used Monte Carlo simulations to develop an initial dosage regimen targeting various VCM through concentration ranges based on the final model. We found that VCM clearance(CL) was significantly influenced by post-craniotomy meningitis(PCM) and glomerular filtration rate in elderly patients. Additionally, a new dosage regimen was proposed to individualise VCM regimen for PCM and non-PCM elderly patients. A PPK model was established to estimate the individual VCM CL for elderly patients, which could be applied for individualising doses in the target population.展开更多
There is in principle a close connection between individualisation and the state in both the European and Chinese contexts. But this connection can assume entirely different forms; indeed it can even point in diametri...There is in principle a close connection between individualisation and the state in both the European and Chinese contexts. But this connection can assume entirely different forms; indeed it can even point in diametrically opposed directions. From a sociological point of view it is important to distinguish between individualism as an ideology and individualisation as a real process resting on institutions. Individualisation means institutionalised individualism. By institutionalised individualism is not meant only a social ideology or an individual mode of perception. Rather, it designates central institutions of modem society such as, for example, civil and social basic rights, all of which are addressed to the individual; alternatively, it refers to the need, mediated through training and the labour market, to develop one's own biography and to extricate oneself from collective regulations; but it also refers to the neohberal global market regime which forces individuals to realise their self-interest as the innermost core of rationality.展开更多
文摘Diabetes care is often difficult without a proper collaboration between the patient and the care provider as the disease is mostly self-managed by patients through adjustments in their lifestyles,and medication doses to optimise glycaemic control.Most clinical guidelines on the management of diabetes mellitus(DM)provide only broad principles on diabetes care,and the blind follow-up of such principles without a proper review and consideration of patient characteristics often results in inadequate glycaemic control and diabetes complications consequently.Therefore,a proper understanding of the pathobiology,clinical situation,and comorbidities of the individual case is of paramount importance to tailoring the most appropriate management strategy in real-world diabetes care.With the aid of five unique cases of DM[(1)Medically managed type 2 diabetes mellitus(T2DM)with severe obesity;(2)Management of T2DM with unreliable glycated haemoglobin(HbA1c);(3)Obesity in a patient with type 1 diabetes mellitus(T1DM);and(4)Late diagnosis and subsequent management of monogenic diabetes and 5.Sudden worsening of well-controlled T2DM)]we elaborate on the importance of individualised diabetes care and the practicalities in these situations.The review also provides an evidence update on the management of different forms of DM to guide physicians in optimising the care of their patients in day-to-day clinical practice.
基金supported by Key Project of Pharmaceutical Research Fund of Shanghai Jiaotong University School of Medicine(JDYX2017ED003)
文摘Background Therapeutic drug monitoring guides clinical individualised medication by measuring plasma concentration, which could improve the curative effect, avoid drug overdose and reduce the incidence of adverse reactions. At present, there are few reports on the clinical detection of venlafaxine and its active metabolite O-desmethylvenlafaxine. In this paper, the detection method of venlafaxine and O-desmethylvenlafaxine in blood plasma was established, which provides an effective and convenient means for guiding clinical application of medication.Aim To establish a method for determination of venlafaxine and its active metabolite O-desmethylvenlafaxine in human plasma by highperformance liquid chromatography with fluorescence detection.Methods Chromatographic separation was achieved on an Agilent Eclipse XDB-C18 Column(4.6 × 150 mm, 5 μm) with water containing sodium dihydrogen phosphate(0.05 mol/L) and acetonitrile(72:28) as the mobile phases. The following parameters were employed: flow rate 0.5 mL/min, column temperature 30°C, fluorescence excitation wavelength 276 nm and emission wavelength 598 nm.Results The method showed good linearity in the concentration range 10–1000 ng/mL. The regression equation for venlafaxine was R=0.0054 C+0.0264, r2=0.99991. The regression equation for O-desmethylvenlafaxine was R=0.0034 C+0.0272, r2=0.99969. The intraday and interday precisions(relative SD) were less than 10%, and the quantitative limit was 10 ng/mL.Conclusion We established a sensitive, specific and simple method for the detection of venlafaxine and O-desmethylvenlafaxine. This method fully meets the needs of clinical trials of venlafaxine and the requirements of relevant guidelines. It provided a reference for the clinical detection of venlafaxine and O-desmethylvenlafaxine plasma concentrations and pharmacokinetic study.
文摘Our individual metabolic phenotype is the result of the interaction between nutrients and DNA to modify gene expression. This is a combination of epigenetic interactions whereby nutrients modify the structure of DNA to affect gene expression as well as individual genetic variation that alters our response to diet. Our metabolic phenotype is influenced by developmental plasticity, imprinting in early life and interactions with environmental factors over time. Unlike the human genome which is relatively fixed and stable throughout the body, the human metabolic phenotype is far more complex and dynamic, varying over time and among cells and varying greatly from person to person. Dietary recommendations are often generalized and intended to avert chronic illnesses such as diabetes and cardiovascular disease. In a climate where we are striving for personalisation of healthcare maybe we need a simpler approach;one that embraces genetic variation yet focuses on the optimum nutritional benefit of dietary components.
基金supported by the start-up funds from Westlake University to CenBRAIN lab and Bright Dream Joint Institute for Intelligent Robotics.
文摘Continuous drug monitoring is a promising alternative to current therapeutic drug monitoring strategies and has a strong potential to reshape our understanding of pharmacokinetic variability and to improve individualised therapy.This review highlights recent advances in biosensing technologies that support continuous drug monitoring in real time.We focus primarily on aptamer-based biosensors,wearable and implantable devices.Emphasis is given to the approaches employed in constructing biosensors.We pay attention to sensors’biocompatibility,calibration performance,long-term characteristics stability and measurement quality.Last,we discuss the current challenges and issues to be addressed in continuous drug monitoring to make it a promising,future tool for individualised therapy.The ongoing efforts are expected to result in fully integrated implantable drug biosensing technology.Thus,we may anticipate an era of advanced healthcare in which wearable and implantable biochips will automatically adjust drug dosing in response to patient health conditions,thus enabling the management of diseases and enhancing individualised therapy.
文摘Aids are only one of the instruments with which the disabled person can often reach a good level of autonomy,he can improve his conditions of life and prevent the aggravating of his situation. Aids serve also to facilitate care on the part of the family. The rights confirmed by Law 104 can also be achieved through the use of aids. The Italian state has planned a system of care with regards to aids so that some of them can be purchased with different tax concessions but essential aids,those necessary for the reaching of autonomy goals and prevention defined by an individual rehabilitative project,are supplied free of charge. In Italy essential aids are part therefore of a rehabilitation plan that is identified for each person with disabilities by a team made up of different professionals.
文摘Purpose The transition into full-time training represents a key period in the development of young soccer players.Here we compared the weekly training loads(matches,field-,and resistance-training)of English Premier-League Academy soccer players from under-16(U16),under-18(U18)and under-23(U23)age-groups during a training meso-cycle.Methods Forty players(U16 n=13,U18 n=15 and U23 n=12)were monitored using global navigation satellite systems and differential ratings of perceived exertion(dRPE).External load metrics were total distance,high-speed running distance,[absolute:≥19.8 km/h,relative:≥87%of 30-15 final-velocity(vIFT)],sprint distance(absolute:≥25.2 km/h,relative:≥80%maximal sprint speed),and dynamic stress load.Internal load metrics were dRPE training loads.Results Other than relative sprint distance,overall weekly external training loads were substantially greater for U18s and U23s when compared with U16s[effect size range:1.09-1.99(moderate to large);±90%confidence limits~0.45].When compared with U16s,overall internal loads were substantially greater for U18s[0.69-0.95(moderate);±~0.40],but not U23s.Differences in weekly training loads between U18s and U23s were inconclusive.Conclusions Substantial differences in training loads between elite U16 players and their older counterparts,indicates the need for planned increases in training loads in anticipation of the transition into full-time training.
基金The author would like to thank Jun Shao and Menggang Yu for their help with preparing the manuscript.This work was supported by the Chinese 111 Project[grant number B14019](for Lou and Shao).
文摘When there is substantial heterogeneity of treatment effectiveness for comparative treatmentselection, it is crucial to identify individualised treatment rules for patients who have heterogeneous responses to treatment. Existing approaches include directly modelling clinical outcomeby defining the optimal treatment rule according to the interactions between treatment andcovariates and outcome weighted approach that uses clinical outcome as weights to maximise atarget function whose value directly reflects correct treatment assignment. All existing articles ofestimating individualised treatment rules are all assuming just two treatment assignments. Herewe propose an outcome weighted learning approach that uses a vector hinge loss to extend estimating individualised treatment rules in multi-category treatments case. The consistency of theresulting estimator is shown. We also demonstrate the performance of our approach in simulationstudies and a real data analysis.
基金Guidance Project of Fujian Science and Technology Department(Grant No.2017Y0033)Fujian Medical Innovation Project(Grant No.2017-CX-31)+1 种基金Sail Project of Fujian Medical University(Grant No.2017XQ1068)“Weak Discipline Construction Project” of Shanghai Municipal Commission of Health and Family Planning(Grant No.2016ZB0301-01).
文摘In the present study, we aimed to develop a population pharmacokinetics(PPK) model of vancomycin(VCM) and propose the individualised dosage regimen for Chinese elderly patients. The data were collected prospectively from Chinese elderly patients receiving VCM therapy. Steady-state trough concentrations of VCM were determined using an enzyme-multiplied immunoassay. Patients’ sex, age, body weight, concomitant medications, infection type, and laboratory findings were recorded. The PPK model was developed using nonlinear mixed-effects model software. Moreover, we used Monte Carlo simulations to develop an initial dosage regimen targeting various VCM through concentration ranges based on the final model. We found that VCM clearance(CL) was significantly influenced by post-craniotomy meningitis(PCM) and glomerular filtration rate in elderly patients. Additionally, a new dosage regimen was proposed to individualise VCM regimen for PCM and non-PCM elderly patients. A PPK model was established to estimate the individual VCM CL for elderly patients, which could be applied for individualising doses in the target population.
文摘There is in principle a close connection between individualisation and the state in both the European and Chinese contexts. But this connection can assume entirely different forms; indeed it can even point in diametrically opposed directions. From a sociological point of view it is important to distinguish between individualism as an ideology and individualisation as a real process resting on institutions. Individualisation means institutionalised individualism. By institutionalised individualism is not meant only a social ideology or an individual mode of perception. Rather, it designates central institutions of modem society such as, for example, civil and social basic rights, all of which are addressed to the individual; alternatively, it refers to the need, mediated through training and the labour market, to develop one's own biography and to extricate oneself from collective regulations; but it also refers to the neohberal global market regime which forces individuals to realise their self-interest as the innermost core of rationality.