Hepatitis C virus(HCV)is a global health concern associated with significant morbidity and mortality.Before the approval of second-generation direct-acting antiviral agents(DAAs),interferon therapy and liver transplan...Hepatitis C virus(HCV)is a global health concern associated with significant morbidity and mortality.Before the approval of second-generation direct-acting antiviral agents(DAAs),interferon therapy and liver transplantation constituted the mainstay of treatment.The introduction of well-tolerated oral DAAs in late 2013 has revolutionized HCV management with over 95%cure rates.The predominance of HCV-related liver transplantations has declined following the widespread approval of DAAs.Despite the unparallel efficacy observed among these novel therapies,pharmaceutical costs continue to limit equitable access to healthcare and likely contribute to the differential HCV infection rates observed globally.To reduce the burden of disease worldwide,essential agenda items for all countries must include the prioritization of integrated care models and access to DAAs therapies.Through transparent negotiations with the pharmaceutical industry,the consideration for compassionate release of medications to promote equitable division of care is paramount.Here we provide a literature review of HCV,changes in epidemiologic trends,access issues for current therapies,and global inequities in disease burden.展开更多
Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 ...Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 years is rare.We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period.A 69-year-old man was diagnosed with LEMS and SCLC(cT0N2M0,stage ⅢA) 13 years ago.Chemoradiotherapy was performed and a complete response was achieved.With anticancer treatment,the LEMS symptoms was alleviated.At the age of 82 years,gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC.Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.展开更多
The overall goal of this project is to develop a humane non-human primate model of traumatic spinal cord injury that will facilitate the development and evaluation of therapeutic interventions. The model utilizes neur...The overall goal of this project is to develop a humane non-human primate model of traumatic spinal cord injury that will facilitate the development and evaluation of therapeutic interventions. The model utilizes neurophysiological techniques to identify the location of the upper motor neuron axons that innervate the lower motor neurons that control tail musculature. This facilitates the placement of a selective lesion that partially disconnects the upper and lower motor neuron supply to the musculature of the tail. An implanted transmitter quantitatively measures electromyography data from the tail. The preliminary data indicates that this model is feasible. The subject was able to tolerate the implantation of the transmitter, without adverse effects. As well, there was no limb impairment, bowel dysfunction or bladder dysfunction. The histopathologic and electromyographic features of the selective experimental lesion were similar to human spinal cord injury.展开更多
This study examines the relationship between childhood exposure to air pollution and diagnosis with chronic non-respiratory health outcomes in adulthood. This prospective cohort study uses data collected in the 1970/1...This study examines the relationship between childhood exposure to air pollution and diagnosis with chronic non-respiratory health outcomes in adulthood. This prospective cohort study uses data collected in the 1970/1980s from 395 children, including exposure to air pollution. Over thirty years later, a survey collected data on various health outcomes, including diagnosis with arthritis, high blood pressure, long-term skin conditions, and hay fever allergies. Logistic regression modeling was performed to examine the relative contribution of childhood exposure to air pollution on chronic non-respiratory health outcomes in adulthood. Childhood exposure to SO2 emerged as a significant predictor of arthritis (OR = 2.73, 95% CI 1.20 - 6.18) and high blood pressure (OR = 2.82, 95% CI 1.23 - 6.47). Other significant predictors include respiratory symptoms during childhood, family income during childhood and adulthood, property tenure, employment status, residential exposures, life events, physical activity, and body mass index. Childhood exposure to air pollution did not emerge as a significant predictor of long-term skin conditions or hay fever allergies. Findings contribute to the debate on the health effects of air pollution, indicating that the health impacts of childhood exposure to air pollution may include chronic inflammatory disorders in adulthood.展开更多
A valid non human primate model of traumatic spinal cord injury (TSCI) is essential to evaluate and develop new treatments. In previous experiments, it has been demonstrated that a transmitter can be implanted in the ...A valid non human primate model of traumatic spinal cord injury (TSCI) is essential to evaluate and develop new treatments. In previous experiments, it has been demonstrated that a transmitter can be implanted in the macaque fasicularis monkey that measures electromyographic data from the musculature of the tail. As well, previous experiments have demonstrated that selective lesions can be created in the lower thoracic spinal cord that does not cause limb weakness and/or bowel dysfunction. The histopathological features of these lesions appear similar to human TSCI. This paper describes a method by which the EMG data can be transformed into a quantitative metric of volitional limb movement (“Q”). This metric permits an objective assessment of injury, natural recovery as well as potential efficacy of candidate treatments.展开更多
Mortality is a well-established patient-important outcome in critical care studies.In contrast,morbidity is less uniformly reported(given the myriad of critical care illnesses and complications of each)but may have a ...Mortality is a well-established patient-important outcome in critical care studies.In contrast,morbidity is less uniformly reported(given the myriad of critical care illnesses and complications of each)but may have a common end-impact on a patient’s functional capacity and health-related quality-of-life(HRQoL).Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences.Hence,as mortality decreases within critical care,it becomes increasingly important to measure intensive care unit(ICU)survivor HRQoL.HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0(representing death)and 1(representing full health).They can be combined with survival to calculate quality-adjusted life-years(QALY),which are one of the most widely used methods of combining morbidity and mortality into a composite outcome.Although QALYs have been use for health-technology assessment decision-making,an emerging and novel role would be to inform clinical decision-making for patients,families and healthcare providers about what expected HRQoL may be during and after ICU care.Critical care randomized control trials(RCTs)have not routinely measured or reported HRQoL(until more recently),likely due to incapacity of some patients to participate in patient-reported outcome measures.Further differences in HRQoL measurement tools can lead to non-comparable values.To this end,we propose the validation of a gold-standard HRQoL tool in critical care,specifically the EQ-5D-5L.Both combined health-utility and mortality(disaggregated)and QALYs(aggregated)can be reported,with disaggregation allowing for determination of which components are the main drivers of the QALY outcome.Increased use of HRQoL,health-utility,and QALYs in critical care RCTs has the potential to:(1)Increase the likelihood of finding important effects if they exist;(2)improve research efficiency;and(3)help inform optimal management of critically ill patients allowing for decision-making about their HRQoL,in additional to traditional health-technology assessments.展开更多
近年来实效性临床试验受到更多重视,尤其在传统医学临床评价研究领域。为了提高实效性临床试验报告的质量,CONSORT声明组和医疗保健体系中的实效性随机对照临床试验(pragmatic randomized controlled trials in health care systems,PRA...近年来实效性临床试验受到更多重视,尤其在传统医学临床评价研究领域。为了提高实效性临床试验报告的质量,CONSORT声明组和医疗保健体系中的实效性随机对照临床试验(pragmatic randomized controlled trials in health care systems,PRACTIHC)小组对《CONSORT声明》进行了修改,以帮助读者评估试验质量和结果的可靠性。实效性试验报告指南,作为《CONSORT声明》的一个特殊扩展,能在报告、评价和应用实效性试验方面帮助编辑、系统评价者、试验设计者和决策者评估实效性试验报告中的信息,判定其结论是否适用,以及干预措施是否可行、可否被接受。2005年1月和2008年3月,在加拿大多伦多分别举行了为期两天的会议来探讨提高随机对照试验对卫生保健决策贡献的方法,焦点集中于实效性试验。2005年会,后扩展版草案修订清单发送至编写组成员,经过几次修订,编写组起草了一份摘要草案。在2008年讨论并修改了这一草案。这份草案发给CONSORT声明组以供修改并发表。这份声明的扩展版提出了对8个条目的补充。及时向国内读者和临床试验研究人员介绍该指南有重要的现实意义和学术价值。北京中医药大学循证医学中心刘建平教授等在短时间内翻译了该指南。本刊希望通过介绍中文版"提高实效性临床试验报告的质量——《CONSORT声明》的扩展"以提高国内实效性临床试验报告的质量,相信也有助于改进试验设计的方法学质量。展开更多
Clinical practice guidelines:The challenge of grading Clinical practice guidelines have improved in quality over the past ten years by adhering to a few basic principles,such as conducting thorough systematic reviews ...Clinical practice guidelines:The challenge of grading Clinical practice guidelines have improved in quality over the past ten years by adhering to a few basic principles,such as conducting thorough systematic reviews of relevant evidence,and grading the recommendations and the quality of the underlying evidence.The large number of systems of measuring the quality of evidence and recommendations that have emerged are,however,confusing.An international group of guideline developers, systematic reviewers,and clinical展开更多
Context: Implantable cardioverter defibrillator(ICD) therapy is effective but is associated with high-voltage shocks that are painful. Objective: To determine whether amiodarone plus β -blocker or sotalol are better ...Context: Implantable cardioverter defibrillator(ICD) therapy is effective but is associated with high-voltage shocks that are painful. Objective: To determine whether amiodarone plus β -blocker or sotalol are better than β -blocker alone for prevention of ICD shocks. Design, Setting, and Patients: A randomized controlled trial with blinded adjudication of events of 412 patients from 39 outpatient ICD clinical centers located in Canada, Germany, United States, England, Sweden, and Austria, conducted from January 13, 2001, to September 28, 2004. Patients were eligible if they had received an ICD within 21 days for inducible or spontaneously occurring ventricular tachycardia or fibrillation. Intervention: Patients were randomized to treatment for 1 year with amiodarone plus β -blocker, sotalol alone, or β -blocker alone. Main Outcome Measure: Primary outcome was ICD shock for any reason. Results: Shocks occurred in 41 patients(38.5% ) assigned to β -blocker alone, 26(24.3% ) assigned to sotalol, and 12(10.3% ) assigned to amiodarone plus β -blocker. A reduction in the risk of shock was observed with use of either amiodarone plus β -blocker or sotalol vs β -blocker alone(hazard ratio[HR], 0.44; 95% confidence interval[CI], 0.28- 0.68; P< .001). Amiodarone plus β -blocker significantly reduced the risk of shock compared with β -blocker alone(HR, 0.27; 95% CI, 0.14- 0.52; P< .001) and sotalol(HR, 0.43; 95% CI, 0.22- 0.85; P=.02). There was a trend for sotalol to reduce shocks compared with β -blocker alone(HR, 0.61; 95% CI, 0.37- 1.01; P=.055). The rates of study drug discontinuation at 1 year were 18.2% for amiodarone, 23.5% for sotalol, and 5.3% for β -blocker alone. Adverse pulmonary and thyroid events and symptomatic bradycardia were more common among patients randomized to amiodarone. Conclusions: Despite use of advanced ICD technology and treatment with a β -blocker, shocks occur commonly in the first year after ICD implant. Amiodarone plus β -blocker is effective for preventing these shocks and is more effective than sotalol but has an increased risk of drug-related adverse effects. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT00257959.展开更多
This paper presents an analysis of the recently published Justification for the Use of statins in Prevention(JUPITER:an intervention trial evaluating rosuvastatin) trial,which tested the statin rosuvastatin in apparen...This paper presents an analysis of the recently published Justification for the Use of statins in Prevention(JUPITER:an intervention trial evaluating rosuvastatin) trial,which tested the statin rosuvastatin in apparently healthy individuals with no prior cardiovascular(CVD) disease and with normal plasma low density lipoprotein(LDL) cholesterol concentrations but with raised plasma high sensitivity C-reactive protein(hsCRP) levels.The rate of the combined primary CVD endpoint was significantly reduced in the treatment arm after a median of under 2 years.The JUPITER trial is distinct from previous studies examining statin use in primary prevention groups because the target group for drug therapy was apparently healthy men and women at low or intermediate risk for developing CVD.On the basis of JUPITER's findings,there are key questions that should be assessed on the therapeutic intervention of CVD regarding:the primary prevention groups that should be targeted for statin therapy,the utility of targets in addition to plasma LDL cholesterol levels,and the need to consider the metabolic state of individuals targeted for therapy(including the presence of obesity and inflammation).The conclusion from the current analysis is that the JUPITER results warrant further LDL cholesterol lowering than is currently targeted in primary prevention groups that have a pre-existing condition or lifestyle that elevates CVD risk but still do not have a high global CVD risk(as assessed with current algorithms).This group is not captured in current widely used CVD risk calculations,however,with the identification of useful biomarkers,such as hsCRP,this group can be better identified and targeted for intervention.展开更多
Patients with muscular dystrophy may be prone to nutrient deficiency due to mo bility limitations or oropharyngeal weakness. Patients with myotonic muscular dy strophy (DM1) may be particularly prone to nutritional de...Patients with muscular dystrophy may be prone to nutrient deficiency due to mo bility limitations or oropharyngeal weakness. Patients with myotonic muscular dy strophy (DM1) may be particularly prone to nutritional deficiencies from associa ted dysmotility of the entire gastrointestinal tract. We prospectively evaluated nutritional intake, body composition, and muscle strength in adult patients wit h DM1 (n=29) and other muscular dystrophies (n=22) on two occasions separated by ~6 months. Handgrip was significantly lower and knee extension higher for DM1 compared to other dystrophies, with no between-group differences in nutritional intakes. Many patients in both groups demonstrated inadequate nutrient intake o f protein, energy, vitamins (water and fat soluble), and minerals (calcium and m agnesium). Significant correlations were found between measures of strength and certain individual nutrients (e.g., copper and water-soluble vitamins). These d ata indicate that a substantial number of adults with muscular dystrophy do not meet current dietary intake recommendations. The potential clinical implications of these findings are discussed.展开更多
Introduction.With the development of novel therapeutic options and treatment pathways for critically ill patients,innovative methods to assess treatment efficacy in a timely manner are greatly needed.Not only that,but...Introduction.With the development of novel therapeutic options and treatment pathways for critically ill patients,innovative methods to assess treatment efficacy in a timely manner are greatly needed.Not only that,but the traditional methods of conducting randomized controlled trials(RCTs)are often inefficient and exceedingly expensive.展开更多
Evidence-based medicine is widely promoted for decision-making in health care and is associated with improved patient outcomes.Critics have suggested that evidence-based medicine focuses primarily on groups of patient...Evidence-based medicine is widely promoted for decision-making in health care and is associated with improved patient outcomes.Critics have suggested that evidence-based medicine focuses primarily on groups of patients rather than individuals,but often fail to consider subgroup analyses,N-of-1 trials,and the incorporation of patient values and preferences.Precision medicine has been promoted as an approach to individualize diagnosis and treatment of diseases through genetic,biomarker,phenotypic,and psychosocial characteristics.However,there are often high costs associated with personalized medicine,and high-quality evidence is lacking for effectiveness in many applications.For the potential of personalized medicine to be realized,it must adhere to the principles of evidencebased medicine:(1)evidence in isolation is not sufficient to make clinical decisions—patient’s values and preferences as well as resource implications must be considered,and(2)there is a hierarchy of evidence to guide clinical decision-making and studies at lower risk of bias are likely to provide more trustworthy findings.展开更多
文摘Hepatitis C virus(HCV)is a global health concern associated with significant morbidity and mortality.Before the approval of second-generation direct-acting antiviral agents(DAAs),interferon therapy and liver transplantation constituted the mainstay of treatment.The introduction of well-tolerated oral DAAs in late 2013 has revolutionized HCV management with over 95%cure rates.The predominance of HCV-related liver transplantations has declined following the widespread approval of DAAs.Despite the unparallel efficacy observed among these novel therapies,pharmaceutical costs continue to limit equitable access to healthcare and likely contribute to the differential HCV infection rates observed globally.To reduce the burden of disease worldwide,essential agenda items for all countries must include the prioritization of integrated care models and access to DAAs therapies.Through transparent negotiations with the pharmaceutical industry,the consideration for compassionate release of medications to promote equitable division of care is paramount.Here we provide a literature review of HCV,changes in epidemiologic trends,access issues for current therapies,and global inequities in disease burden.
文摘Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 years is rare.We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period.A 69-year-old man was diagnosed with LEMS and SCLC(cT0N2M0,stage ⅢA) 13 years ago.Chemoradiotherapy was performed and a complete response was achieved.With anticancer treatment,the LEMS symptoms was alleviated.At the age of 82 years,gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC.Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.
文摘The overall goal of this project is to develop a humane non-human primate model of traumatic spinal cord injury that will facilitate the development and evaluation of therapeutic interventions. The model utilizes neurophysiological techniques to identify the location of the upper motor neuron axons that innervate the lower motor neurons that control tail musculature. This facilitates the placement of a selective lesion that partially disconnects the upper and lower motor neuron supply to the musculature of the tail. An implanted transmitter quantitatively measures electromyography data from the tail. The preliminary data indicates that this model is feasible. The subject was able to tolerate the implantation of the transmitter, without adverse effects. As well, there was no limb impairment, bowel dysfunction or bladder dysfunction. The histopathologic and electromyographic features of the selective experimental lesion were similar to human spinal cord injury.
文摘This study examines the relationship between childhood exposure to air pollution and diagnosis with chronic non-respiratory health outcomes in adulthood. This prospective cohort study uses data collected in the 1970/1980s from 395 children, including exposure to air pollution. Over thirty years later, a survey collected data on various health outcomes, including diagnosis with arthritis, high blood pressure, long-term skin conditions, and hay fever allergies. Logistic regression modeling was performed to examine the relative contribution of childhood exposure to air pollution on chronic non-respiratory health outcomes in adulthood. Childhood exposure to SO2 emerged as a significant predictor of arthritis (OR = 2.73, 95% CI 1.20 - 6.18) and high blood pressure (OR = 2.82, 95% CI 1.23 - 6.47). Other significant predictors include respiratory symptoms during childhood, family income during childhood and adulthood, property tenure, employment status, residential exposures, life events, physical activity, and body mass index. Childhood exposure to air pollution did not emerge as a significant predictor of long-term skin conditions or hay fever allergies. Findings contribute to the debate on the health effects of air pollution, indicating that the health impacts of childhood exposure to air pollution may include chronic inflammatory disorders in adulthood.
文摘A valid non human primate model of traumatic spinal cord injury (TSCI) is essential to evaluate and develop new treatments. In previous experiments, it has been demonstrated that a transmitter can be implanted in the macaque fasicularis monkey that measures electromyographic data from the musculature of the tail. As well, previous experiments have demonstrated that selective lesions can be created in the lower thoracic spinal cord that does not cause limb weakness and/or bowel dysfunction. The histopathological features of these lesions appear similar to human TSCI. This paper describes a method by which the EMG data can be transformed into a quantitative metric of volitional limb movement (“Q”). This metric permits an objective assessment of injury, natural recovery as well as potential efficacy of candidate treatments.
基金Supported by the EuroQol Research Foundation,No. 299-RA
文摘Mortality is a well-established patient-important outcome in critical care studies.In contrast,morbidity is less uniformly reported(given the myriad of critical care illnesses and complications of each)but may have a common end-impact on a patient’s functional capacity and health-related quality-of-life(HRQoL).Survival with a poor quality-of-life may not be acceptable depending on individual patient values and preferences.Hence,as mortality decreases within critical care,it becomes increasingly important to measure intensive care unit(ICU)survivor HRQoL.HRQoL measurements with a preference-based scoring algorithm can be converted into health utilities on a scale anchored at 0(representing death)and 1(representing full health).They can be combined with survival to calculate quality-adjusted life-years(QALY),which are one of the most widely used methods of combining morbidity and mortality into a composite outcome.Although QALYs have been use for health-technology assessment decision-making,an emerging and novel role would be to inform clinical decision-making for patients,families and healthcare providers about what expected HRQoL may be during and after ICU care.Critical care randomized control trials(RCTs)have not routinely measured or reported HRQoL(until more recently),likely due to incapacity of some patients to participate in patient-reported outcome measures.Further differences in HRQoL measurement tools can lead to non-comparable values.To this end,we propose the validation of a gold-standard HRQoL tool in critical care,specifically the EQ-5D-5L.Both combined health-utility and mortality(disaggregated)and QALYs(aggregated)can be reported,with disaggregation allowing for determination of which components are the main drivers of the QALY outcome.Increased use of HRQoL,health-utility,and QALYs in critical care RCTs has the potential to:(1)Increase the likelihood of finding important effects if they exist;(2)improve research efficiency;and(3)help inform optimal management of critically ill patients allowing for decision-making about their HRQoL,in additional to traditional health-technology assessments.
文摘近年来实效性临床试验受到更多重视,尤其在传统医学临床评价研究领域。为了提高实效性临床试验报告的质量,CONSORT声明组和医疗保健体系中的实效性随机对照临床试验(pragmatic randomized controlled trials in health care systems,PRACTIHC)小组对《CONSORT声明》进行了修改,以帮助读者评估试验质量和结果的可靠性。实效性试验报告指南,作为《CONSORT声明》的一个特殊扩展,能在报告、评价和应用实效性试验方面帮助编辑、系统评价者、试验设计者和决策者评估实效性试验报告中的信息,判定其结论是否适用,以及干预措施是否可行、可否被接受。2005年1月和2008年3月,在加拿大多伦多分别举行了为期两天的会议来探讨提高随机对照试验对卫生保健决策贡献的方法,焦点集中于实效性试验。2005年会,后扩展版草案修订清单发送至编写组成员,经过几次修订,编写组起草了一份摘要草案。在2008年讨论并修改了这一草案。这份草案发给CONSORT声明组以供修改并发表。这份声明的扩展版提出了对8个条目的补充。及时向国内读者和临床试验研究人员介绍该指南有重要的现实意义和学术价值。北京中医药大学循证医学中心刘建平教授等在短时间内翻译了该指南。本刊希望通过介绍中文版"提高实效性临床试验报告的质量——《CONSORT声明》的扩展"以提高国内实效性临床试验报告的质量,相信也有助于改进试验设计的方法学质量。
文摘Clinical practice guidelines:The challenge of grading Clinical practice guidelines have improved in quality over the past ten years by adhering to a few basic principles,such as conducting thorough systematic reviews of relevant evidence,and grading the recommendations and the quality of the underlying evidence.The large number of systems of measuring the quality of evidence and recommendations that have emerged are,however,confusing.An international group of guideline developers, systematic reviewers,and clinical
文摘Context: Implantable cardioverter defibrillator(ICD) therapy is effective but is associated with high-voltage shocks that are painful. Objective: To determine whether amiodarone plus β -blocker or sotalol are better than β -blocker alone for prevention of ICD shocks. Design, Setting, and Patients: A randomized controlled trial with blinded adjudication of events of 412 patients from 39 outpatient ICD clinical centers located in Canada, Germany, United States, England, Sweden, and Austria, conducted from January 13, 2001, to September 28, 2004. Patients were eligible if they had received an ICD within 21 days for inducible or spontaneously occurring ventricular tachycardia or fibrillation. Intervention: Patients were randomized to treatment for 1 year with amiodarone plus β -blocker, sotalol alone, or β -blocker alone. Main Outcome Measure: Primary outcome was ICD shock for any reason. Results: Shocks occurred in 41 patients(38.5% ) assigned to β -blocker alone, 26(24.3% ) assigned to sotalol, and 12(10.3% ) assigned to amiodarone plus β -blocker. A reduction in the risk of shock was observed with use of either amiodarone plus β -blocker or sotalol vs β -blocker alone(hazard ratio[HR], 0.44; 95% confidence interval[CI], 0.28- 0.68; P< .001). Amiodarone plus β -blocker significantly reduced the risk of shock compared with β -blocker alone(HR, 0.27; 95% CI, 0.14- 0.52; P< .001) and sotalol(HR, 0.43; 95% CI, 0.22- 0.85; P=.02). There was a trend for sotalol to reduce shocks compared with β -blocker alone(HR, 0.61; 95% CI, 0.37- 1.01; P=.055). The rates of study drug discontinuation at 1 year were 18.2% for amiodarone, 23.5% for sotalol, and 5.3% for β -blocker alone. Adverse pulmonary and thyroid events and symptomatic bradycardia were more common among patients randomized to amiodarone. Conclusions: Despite use of advanced ICD technology and treatment with a β -blocker, shocks occur commonly in the first year after ICD implant. Amiodarone plus β -blocker is effective for preventing these shocks and is more effective than sotalol but has an increased risk of drug-related adverse effects. Clinical Trials Registration: ClinicalTrials.gov Identifier: NCT00257959.
文摘This paper presents an analysis of the recently published Justification for the Use of statins in Prevention(JUPITER:an intervention trial evaluating rosuvastatin) trial,which tested the statin rosuvastatin in apparently healthy individuals with no prior cardiovascular(CVD) disease and with normal plasma low density lipoprotein(LDL) cholesterol concentrations but with raised plasma high sensitivity C-reactive protein(hsCRP) levels.The rate of the combined primary CVD endpoint was significantly reduced in the treatment arm after a median of under 2 years.The JUPITER trial is distinct from previous studies examining statin use in primary prevention groups because the target group for drug therapy was apparently healthy men and women at low or intermediate risk for developing CVD.On the basis of JUPITER's findings,there are key questions that should be assessed on the therapeutic intervention of CVD regarding:the primary prevention groups that should be targeted for statin therapy,the utility of targets in addition to plasma LDL cholesterol levels,and the need to consider the metabolic state of individuals targeted for therapy(including the presence of obesity and inflammation).The conclusion from the current analysis is that the JUPITER results warrant further LDL cholesterol lowering than is currently targeted in primary prevention groups that have a pre-existing condition or lifestyle that elevates CVD risk but still do not have a high global CVD risk(as assessed with current algorithms).This group is not captured in current widely used CVD risk calculations,however,with the identification of useful biomarkers,such as hsCRP,this group can be better identified and targeted for intervention.
文摘Patients with muscular dystrophy may be prone to nutrient deficiency due to mo bility limitations or oropharyngeal weakness. Patients with myotonic muscular dy strophy (DM1) may be particularly prone to nutritional deficiencies from associa ted dysmotility of the entire gastrointestinal tract. We prospectively evaluated nutritional intake, body composition, and muscle strength in adult patients wit h DM1 (n=29) and other muscular dystrophies (n=22) on two occasions separated by ~6 months. Handgrip was significantly lower and knee extension higher for DM1 compared to other dystrophies, with no between-group differences in nutritional intakes. Many patients in both groups demonstrated inadequate nutrient intake o f protein, energy, vitamins (water and fat soluble), and minerals (calcium and m agnesium). Significant correlations were found between measures of strength and certain individual nutrients (e.g., copper and water-soluble vitamins). These d ata indicate that a substantial number of adults with muscular dystrophy do not meet current dietary intake recommendations. The potential clinical implications of these findings are discussed.
文摘Introduction.With the development of novel therapeutic options and treatment pathways for critically ill patients,innovative methods to assess treatment efficacy in a timely manner are greatly needed.Not only that,but the traditional methods of conducting randomized controlled trials(RCTs)are often inefficient and exceedingly expensive.
文摘Evidence-based medicine is widely promoted for decision-making in health care and is associated with improved patient outcomes.Critics have suggested that evidence-based medicine focuses primarily on groups of patients rather than individuals,but often fail to consider subgroup analyses,N-of-1 trials,and the incorporation of patient values and preferences.Precision medicine has been promoted as an approach to individualize diagnosis and treatment of diseases through genetic,biomarker,phenotypic,and psychosocial characteristics.However,there are often high costs associated with personalized medicine,and high-quality evidence is lacking for effectiveness in many applications.For the potential of personalized medicine to be realized,it must adhere to the principles of evidencebased medicine:(1)evidence in isolation is not sufficient to make clinical decisions—patient’s values and preferences as well as resource implications must be considered,and(2)there is a hierarchy of evidence to guide clinical decision-making and studies at lower risk of bias are likely to provide more trustworthy findings.