To establish the experts consensus on the management of delirium in critically ill patients.A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group.Each statement was assessed based on the GRADE (Grading of Recommendations Assessment,Development,and Evaluation) principle.Then the Delphi method was adopted by 36 experts to reassess all the statements.(1) Delirium is not only a mental change,but also a clinical syndrome with multiple pathophysiological changes.(2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function.(3) Pain is a common cause of delirium in critically ill patients.Analgesia can reduce the occurrence and development of delirium.(4) Anxiety or depression are important factors for delirium in critically ill patients.(5) The correlation between sedative and analgesic drugs and delirium is uncertain.(6) Pay attention to the relationship between delirium and withdrawal reactions.(7) Pay attention to the relationship between delirium and drug dependence/ withdrawal reactions.(8) Sleep disruption can induce delirium.(9) We should be vigilant against potential risk factors for persistent or recurrent delirium.(10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases,and can also be alleviated with the improvement of primary diseases.(11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis.(12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium,especially subclinical delirium.(13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium.(14) Daily assessment is helpful for early detection of delirium.(15) Hopoactive delirium and mixed delirium are common and should be emphasized.(16) Delirium may be accompanied by changes in electroencephalogram.Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant.(17) Pay attention to differential diagnosis of delirium and dementia/depression.(18) Pay attention to the role of rapid delirium screening method in delirium management.(19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium.(20) The key to the management of delirium is etiological treatment.(21) Improving environmental factors and making patient comfort can help reduce delirium.(22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium.(23) Communication with patients should be emphasized and strengthened.Family members participation can help reduce the incidence of delirium and promote the recovery of delirium.(24) Pay attention to the role of sleep management in the prevention and treatment of delirium.(25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium.(26) When using antipsychotics to treat delirium,we should be alert to its effect on the heart rhythm.(27) Delirium management should pay attention to brain functional exercise.(28) Compared with non-critically illness related delirium,the relief of critically illness related delirium will not accomplished at one stroke.(29) Multiple management strategies such as ABCDEF,eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients.(30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment.(31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management.Consensus can promote delirium management in critically ill patients,optimize analgesia and sedation therapy,and even affect prognosis.

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy. METHODS: ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed. RESULTS: The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS). CONCLUSIONS For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.
Adenocarcinoma ; blood ; drug therapy ; genetics ; mortality ; Adenocarcinoma of Lung ; Adult ; Aged ; Aged, 80 and over ; Cell-Free Nucleic Acids ; blood ; ErbB Receptors ; genetics ; Female ; Humans ; Lung Neoplasms ; blood ; drug therapy ; genetics ; mortality ; Male ; Middle Aged ; Molecular Targeted Therapy ; Mutation, Missense ; Prognosis

OBJECTIVETo conduct health economic evaluation of the prevention of mother-to-child HIV among pregnant women in Dehong prefecture, Yunnan province, China from 2004 to 2013.

METHODSData on cost were collected mainly from the annual prevention of mother-to-child transmission (PMTCT) reporting system of Dehong prefecture, and supplemented by HIV PMTCT-related resource allocation data from local health bureau. Effectiveness indexes were from local continuous HIV surveillance system and annual reported data. Cost-effectiveness and cost-utility analysis were used to conduct the health economic evaluation.

RESULTSFrom 2004 to 2013, 283980 pregnant women were screened for HIV, 2 059 were detected as positive, and the HIV positive rate was 0.73%. The total cost of the PMTCT program was 14 227 000 RMB after discounting, and the unit cost of positive case finding was 4 200 RMB. A total of 26 cases of adults and 325 infants were avoided HIV infection, and the cost-effectiveness ratio (CER) was 40 500 RMB/case. The total obtained quality adjusted life years (QALY) from the program was 8 911.5, each one of which cost 1 600 RMB/QALY. If the feeding pattern were breast feeding, CER would be 42 800 RMB/case and each one of QALY would cost 2 200 RMB.

CONCLUSIONBased on the cost-effectiveness and cost-utility analysis, the HIV PMTCT of Dehong prefecture had economic value, which indicates that continued investment is needed to strengthen local HIV PMTCT work.

Acquired Immunodeficiency Syndrome ; Adult ; Child ; China ; Cost-Benefit Analysis ; Costs and Cost Analysis ; Female ; HIV Infections ; Health ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; Mothers ; Pregnancy ; Quality-Adjusted Life Years

Humans ; Lung ; pathology ; Multiple Myeloma ; pathology

OBJECTIVETo understand the characteristics and retention situation of clients in extension clinic of methadone maintenance therapy.

METHODSFrom December 20, 2010 to March 10, 2011, the system sampling method was used to get the cases. A total of 462 heroin addicts from 22 methadone maintenance therapy clinics and extension clinics located in Mangshi, Ruili, Longchuan, Yingjiang, Lianghe of Dehong prefecture, Yunnan province were interviewed, and the demographic characteristics, quality of life, urine testing results for morphine of the patients between the extension MMT clinic and standard MMT clinic were also collected and compared. A cohort study was conducted to analyze retention situation of the new clients with Kaplan Meier method during 9 months treatment.

RESULTSOf the 462 cases, 239 cases were from standard MMT clinic, and 223 cases were from the extension MMT clinic. Among them, 117 cases were new research objects into the group during the investigation. Among the clients of extension MMT clinic, 96.7% (147/152) of them were males, 37.5% (57/152) were Dai nationality, and 61.2% (93/152) were married, 38.8% (59/152) with primary school education, 95.4% (145/152) lived with their family or relatives, 96.7% (147/152) could arrive at the clinic from their habitation within 15 minutes. The positive detection rates 72% (13/18), 71% (24/34), 58% (30/52), 29% (15/52), 14% (6/44), 14% (4/29), 15% (5/34), 17% (6/35), 6% (2/33), 16% (5/31) of urine-morphine testing among new clients of extension MMT clinics decreased as the period of treatment lengthened (χ(2) = 61.04, P < 0.05). The period of retention of the clients in extension MMT clinics was 175-days averagely, with an average retention 122 days of when withdrawing. The retention rates of the clients were 52% (37/71)and 61% (28/46) at 9th month of the extension MMT clinics and standard MMT clinics respectively. There was no difference in the retention rate between those of two types of clinics (χ(2) = 0.82, P = 0.37) .

CONCLUSIONMost of the clients in extension MMT clinics lived with their family or relatives, and spent less time on the way to the clinics. After 9 months methadone maintenance therapy, the quality of life of clients in extension clinics was improved while addiction among them decreased. The extension clinic was an effective strategy for retention in remote areas.

China ; Cohort Studies ; Demography ; Heroin Dependence ; Humans ; Male ; Methadone ; Opiate Substitution Treatment ; Quality of Life ; Substance-Related Disorders ; Treatment Outcome

Background and purpose:Herpes zoster is a common adverse event associated with the use of bortezomib. The objective of this study was to evaluate the efifcacy of different therapeutic regimens of valacyclovir prophylaxis: continuously administration and intermittent administration. Methods: We retrospectively analyzed the efficacy, side effects, expense of valacyclovir and emotional states of 31 patients with multiple myeloma who received bortezomib and valacyclovir prophylaxis. Among them, 14 patients underwent continuously administration of valacyclovir, the other 17 patients underwent intermittent administration. Continuously administration was deifned as daily oral valacyclovir 600 mg without cessation during entire period of bortezomib treatment. Intermittent administration was deifned as patients received valacyclovir at a dose of 600 mg daily during chemotherapy, while discontinue valacyclovir at the intermission time of bortezomib treatment. Results: There were no herpes zoster in patients of 2 arms. Adverse events over grade 3 associated with valacyclovir were not observed. Intermittent administration of valacyclovir showed a superiority of economic beneift. The emotional status were depended on the therapeutic effects of multiple myeloma. For those relapsed or refractory patients, continuously administration of valacyclovir might aggravate depression and anxiety. Conclusion:Intermittent administration of valacyclovir at a dose of 600 mg daily appears to be an effective prophylaxis for herpes zoster in patients receiving bortezomib.

Objective To understand the characteristics and retention situation of clients in extension clinic of methadone maintenance therapy.Methods From December 20,2010 to March 10,2011, the system sampling method was used to get the cases .A total of 462 heroin addicts from 22 methadone maintenance therapy clinics and extension clinics located in Mangshi , Ruili, Longchuan, Yingjiang, Lianghe of Dehong prefecture , Yunnan province were interviewed , and the demographic characteristics , quality of life, urine testing results for morphine of the patients between the extension MMT clinic and standard MMT clinic were also collected and compared.A cohort study was conducted to analyze retention situation of the new clients with Kaplan Meier method during 9 months treatment.Results Of the 462 cases,239 cases were from standard MMT clinic ,and 223 cases were from the extension MMT clinic . Among them,117 cases were new research objects into the group during the investigation .Among the clients of extension MMT clinic ,96.7%( 147/152 ) of them were males , 37.5%( 57/152 ) were Dai nationality , and 61.2%(93/152) were married,38.8%(59/152) with primary school education,95.4%(145/152) lived with their family or relatives ,96.7%( 147/152 ) could arrive at the clinic from their habitation within 15 minutes.The positive detection rates 72%(13/18),71%(24/34),58%(30/52),29%(15/52),14%(6/44),14%(4/29),15%(5/34),17%(6/35),6%(2/33),16%(5/31) of urine-morphine testing among new clients of extension MMT clinics decreased as the period of treatment lengthened (χ2 =61.04, P<0.05).The period of retention of the clients in extension MMT clinics was 175-days averagely , with an average retention 122 days of when withdrawing.The retention rates of the clients were 52%( 37/71 ) and 61%(28/46) at 9th month of the extension MMT clinics and standard MMT clinics respectively.There was no difference in the retention rate between those of two types of clinics (χ2 =0.82,P=0.37).Conclusion Most of the clients in extension MMT clinics lived with their family or relatives , and spent less time on the way to the clinics.After 9 months methadone maintenance therapy , the quality of life of clients in extension clinics was improved while addiction among them decreased.The extension clinic was an effective strategy for retention in remote areas.

Objective To understand the characteristics and retention situation of clients in extension clinic of methadone maintenance therapy.Methods From December 20,2010 to March 10,2011, the system sampling method was used to get the cases .A total of 462 heroin addicts from 22 methadone maintenance therapy clinics and extension clinics located in Mangshi , Ruili, Longchuan, Yingjiang, Lianghe of Dehong prefecture , Yunnan province were interviewed , and the demographic characteristics , quality of life, urine testing results for morphine of the patients between the extension MMT clinic and standard MMT clinic were also collected and compared.A cohort study was conducted to analyze retention situation of the new clients with Kaplan Meier method during 9 months treatment.Results Of the 462 cases,239 cases were from standard MMT clinic ,and 223 cases were from the extension MMT clinic . Among them,117 cases were new research objects into the group during the investigation .Among the clients of extension MMT clinic ,96.7%( 147/152 ) of them were males , 37.5%( 57/152 ) were Dai nationality , and 61.2%(93/152) were married,38.8%(59/152) with primary school education,95.4%(145/152) lived with their family or relatives ,96.7%( 147/152 ) could arrive at the clinic from their habitation within 15 minutes.The positive detection rates 72%(13/18),71%(24/34),58%(30/52),29%(15/52),14%(6/44),14%(4/29),15%(5/34),17%(6/35),6%(2/33),16%(5/31) of urine-morphine testing among new clients of extension MMT clinics decreased as the period of treatment lengthened (χ2 =61.04, P<0.05).The period of retention of the clients in extension MMT clinics was 175-days averagely , with an average retention 122 days of when withdrawing.The retention rates of the clients were 52%( 37/71 ) and 61%(28/46) at 9th month of the extension MMT clinics and standard MMT clinics respectively.There was no difference in the retention rate between those of two types of clinics (χ2 =0.82,P=0.37).Conclusion Most of the clients in extension MMT clinics lived with their family or relatives , and spent less time on the way to the clinics.After 9 months methadone maintenance therapy , the quality of life of clients in extension clinics was improved while addiction among them decreased.The extension clinic was an effective strategy for retention in remote areas.

Objective To investigate the response of multiple myeloma (MM) cells to 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP) and the impact of arsenic trioxide (As2O3) on the above reaction.Methods MM-derived cell lines RPMI8226 and U266 were used as in vitro models.Cell apoptosis was evaluated according to cellular morphology and DNA content measured by flow cytometry.Meanwhile,rhodamine 123 (Rh123) staining and flow cytometry assay were used to detect the changes of mitochondrial transmembrane potentials (△ψm) in MM cells before and after the treatment.The synergic effects of 8-Cl-cAMP and As2O3 were evaluated by King' s formula.Results The 8-Cl-cAMP could induce growth inhibition of RPMI8226 and U266 cells in dose and time-related manners.The 8-Cl-cAMP could trigger apoptosis and △ψm collapse in MM cells through cellular morphology and flow cytometry analysis.As2O3 accelerated 8-Cl-cAMP-mediated apoptosis of RPMI8226 cells,but there were few synergic effects observed.Conclusion 8-Cl-cAMP could induce cell proliferation inhibition and apoptosis in MM cells.Mitochondria may be one of targets in 8-Cl-cAMP-mediated apoptosis.Furthermore,As2O3 catalyzes 8-Cl-cAMP-induced apoptosis.

10.3969/j.issn.1007-3969.2013.04.010