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1.
ObjectiveTo review the effectiveness of computer support for determining optimum drug dose.DesignSystematic review of comparative studies where computers gave advice to clinicians on the most appropriate drug dose. Search methods used were standard for the Cochrane Collaboration on Effective Professional Practice.SubjectsComparative studies conducted worldwide and published between 1966 and 1996.ResultsEighteen studies met the inclusion criteria. The drugs studied were theophylline, warfarin, heparin, aminoglycosides, nitroprusside, lignocaine, oxytocin, fentanyl, and midazolam. The computer programs used individualised pharmacokinetic models to calculate the most appropriate dose. Meta-analysis of data from 671 patients showed higher blood concentrations of drug with computer support (effect size 0.69, 95% confidence interval 0.36 to 1.02) and reduced time to achieve therapeutic control (0.44, 0.17 to 0.71). The total dose of drug used was unchanged, and there were fewer unwanted effects of treatment. Five of six studies measuring outcomes of care showed benefit from computer assistance.ConclusionsThis review suggests that using computers to determine the correct dose of certain drugs in acute hospital settings is beneficial. Computers may give doctors the confidence to use higher doses when necessary, adjusting the drug dose more accurately to individual patients. Further research is necessary to evaluate the benefits in general use.

Key messages

  • This systematic review of studies examining computer support for determining optimum drug dose showed benefits from computer use
  • Computer support led to patients having increased blood concentrations of drug, reduced time to achieve therapeutic benefits, and fewer unwanted effects of treatment
  • Computer support helps doctors to tailor drug doses more closely to the needs of individual patients
  • All the studies took place in hospitals, and further research is needed to determine the risks and benefits of widespread use of computer support, particularly in general practice, where most prescribing takes place
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2.
ObjectiveTo determine the effectiveness of anticholinergic drugs for the treatment of overactive bladder syndrome.DesignSystematic review of randomised controlled trials.ConclusionsAlthough statistically significant, the differences between anticholinergic drugs and placebo were small, apart from the increased rate of dry mouth in patients receiving active treatment. For many of the outcomes studied, the observed difference between anticholinergics and placebo may be of questionable clinical significance. None of these studies provided data on long term outcome.

What is already known on this topic

Anticholinergics are the first line medical treatment for overactive bladderThe effectiveness of these drugs is unclear

What this study adds

Anticholinergics produce significant improvements in overactive bladder symptoms compared with placeboThe benefits are, however, of limited clinical significance  相似文献   

3.
BackgroundRadiotherapy is one of the most important and common therapies for cancer patients. Selenium has been shown to be capable of reducing the side effects of radiotherapy because selenoproteins have anti-oxidative functions against reactive oxygen species that are induced by the radiation. They also function in DNA-repair and cytokine control.PurposeWe explored the benefits and risks of selenium supplementation in radiotherapy in our previous review to establish guidelines. In the current study, we expanded the search to cover recent advances in clinical studies of selenium supplementation in radiotherapy.MethodsWe conducted an initial screening in the PubMed using the MeSH terms and keywords “selenium”, “radiation”, “therapy”, and “radiotherapy” using the same methodology applied in our previous review. We identified 121 articles published between January 2013 and December 2019. We then identified eight articles (six studies) on selenium and radiotherapy by excluding 113 articles.ResultsIn selenium supplementation studies, selenium doses of 300−500 μg/day with duration of 10 days to 6 months were used. Selenium supplementation improved the selenium nutritional conditions of the patients and reduced the side effects of radiotherapy. Selenium supplementation did not reduce the effectiveness of radiotherapy, and no toxicities were reported.ConclusionThe results of our previous and current reviews showed that selenium supplementation offers specific benefits for several cancer types treated with radiotherapy. Here, we suggest a new guideline for selenium supplementation in radiotherapy. We recommend determining the selenium status of the patients before radiotherapy, and in cases of deficiency (<100 μg/L serum selenium level), selenium supplement can be beneficial.  相似文献   

4.
BackgroundPulmonary artery catheters (PAC) are used widely to monitor hemodynamics in patients undergoing coronary bypass graft (CABG) surgery. However, recent studies have raised concerns regarding both the effectiveness and safety of PAC. Therefore, our aim was to determine the effects of the use of PAC on the short- and long-term health and economic outcomes of patients undergoing CABG.Methods1361 Chinese patients who consecutively underwent isolated, primary CABG at the Cardiovascular Institute of Fuwai Hospital from June 1, 2012 to December 31, 2012 were included in this study. Of all the patients, 453 received PAC during operation (PAC group) and 908 received no PAC therapy (control group). Short-term and long-term mortality and major complications were analyzed with multivariate regression analysis and propensity score matched-pair analysis was used to yield two well-matched groups for further comparison.ResultsThe patients who were managed with PAC more often received intraoperative vasoactive drugs dopamine (70.9% vs. 45.5%; P<0.001) and epinephrine (7.7% vs. 2.6%; P<0.001). In addition, costs for initial hospitalization were higher for PAC patients ($14,535 vs. $13,873, respectively, p = 0.004). PAC use was neither associated with the perioperative mortality or major complications, nor was it associated with long-term mortality and major adverse cardiac and cerebrovascular events. In addition, comparison between two well-matched groups showed no significant differences either in baseline characteristics or in short-term and long-term outcomes.ConclusionsThere is no clear indication of any benefit or harm in managing CABG patients with PAC. However, use of PAC in CABG is more expensive. That is, PAC use increased costs without benefit and thus appears unjustified for routine use in CABG surgery.  相似文献   

5.
Koh  Vivien  Kwan  Hsueh Yin  Tan  Woei Loon  Mah  Tzia Liang  Yong  Wei Peng 《BMC genomics》2016,17(13):1029-96
Background

Gemcitabine is used as a standard drug treatment for non-small cell lung cancer (NSCLC), but treatment responses vary among patients. Our previous studies demonstrated that POLA2 + 1747 GG/GA single nucleotide polymorphism (SNP) improves differential survivability and mortality in NSCLC patients. Here, we determined the association between POLA2 and gemcitabine treatment in human lung cancer cells.

Results

Human PC9, H1299 and H1650 lung cancer cell lines were treated with 0.01-100 μM gemcitabine for 72 h. Although all 3 cell lines showed decreased cell viability upon gemcitabine treatment, H1299 was found to be the most sensitive to gemcitabine treatment. Next, sequencing was performed to determine if POLA2 + 1747 SNP might be involved in gemcitabine sensitivity. Data revealed that all 3 cell lines harbored the wild-type POLA2 + 1747 GG SNP, indicating that the POLA2 + 1747 SNP might not be responsible for gemcitabine sensitivity in the cell lines studied. Silencing of POLA2 gene in H1299 was then carried out by siRNA transfection, followed by gemcitabine treatment to determine the effect of POLA2 knockdown on chemosensitivity to gemcitabine. Results showed that H1299 exhibited increased resistance to gemcitabine after POLA2 knockdown, suggesting that POLA2 does not act alone and may cooperate with other interacting partners to cause gemcitabine resistance.

Conclusions

Collectively, our findings showed that knockdown of POLA2 increases gemcitabine resistance in human lung cancer cells. We propose that POLA2 may play a role in gemcitabine sensitivity and can be used as a prognostic biomarker of patient outcome in NSCLC pathogenesis.

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6.
Periampullary adenocarcinoma, including pancreatic cancer, is a heterogeneous group of tumours with dismal prognosis, for which there is an urgent need to identify novel treatment strategies. The human epithelial growth factor receptors EGFR, HER2 and HER3 have been studied in several tumour types, and HER-targeting drugs have a beneficial effect on survival in selected types of cancer. However, these effects have not been evident in pancreatic cancer, and remain unexplored in other types of periampullary cancer. The prognostic impact of HER-expression in these cancers also remains unclear. The aim of this study was therefore to examine the expression and prognostic value of EGFR, HER2 and HER3 in periampullary cancer, with particular reference to histological subtype. To this end, protein expression of EGFR, HER2 and HER3, and HER2 gene amplification was assessed by immunohistochemistry and silver in situ hybridization, respectively, on tissue microarrays with tumours from 175 periampullary adenocarcinomas, with follow-up data on recurrence-free survival (RFS) and overall survival (OS) for up to 5 years. EGFR expression was similar in pancreatobiliary (PB) and intestinal (I) type tumours, but high HER2 and HER3 expression was significantly more common in I-type tumours. In PB-type cases receiving adjuvant gemcitabine, but not in untreated cases, high EGFR expression was significantly associated with a shorter OS and RFS, with a significant treatment interaction in relation to OS (pinteraction = 0.042). In I-type cases, high EGFR expression was associated with a shorter OS and RFS in univariable, but not in multivariable, analysis. High HER3 expression was associated with a prolonged RFS in univariable, but not in multivariable, analysis. Neither HER2 protein expression nor gene amplification was prognostic. The finding of a potential interaction between the expression of EGFR and response to adjuvant chemotherapy in PB-type tumours needs validation, and merits further study.  相似文献   

7.
8.
《Endocrine practice》2009,15(7):750-762
ObjectiveTo discuss the effects and clinical benefit provided by combining various orally administered antidiabetic drugs (OADs) for the treatment of type 2 diabetes and to examine the advantages of single-tablet combinations with respect to targeting hyperglycemia and adherence.MethodsA review of randomized controlled trials that studied OAD combinations for the treatment of type 2 diabetes was conducted by using search terms in PubMed.ResultsReported data have documented that OAD combination therapies have additional benefits over monotherapy in terms of glycemic efficacy. Results from randomized controlled trials on a range of OAD combinations have demonstrated differences in safety and efficacy. The use of single-tablet OAD combinations has been shown to improve adherence in patients.ConclusionThe development of single-tablet OAD combinations that can address all aspects of glycemia with a favorable tolerability profile has the potential to help patients manage their glycemic control more effectively and to minimize the risk of long-term diabetes-related complications. In addition, single-tablet combinations of agents offer improved convenience for patients as well as potential cost benefits. Thus, they represent an important treatment option for type 2 diabetes. (Endocr Pract. 2009;15:750-762)  相似文献   

9.
多杀性巴氏杆菌分子分型方法简述   总被引:3,自引:0,他引:3  
彭忠  梁婉  吴斌 《微生物学报》2016,56(10):1521-1529
多杀性巴氏杆菌是一种能感染多种动物甚至是人的重要革兰氏阴性病原菌。目前临床上用于多杀性巴氏杆菌诊断的分型方法主要包括血清学分型方法和分子分型方法。其中血清学分型方法主要基于免疫学实验技术建立,操作过程繁琐,技术要求高,工作量大,不适用于临床上大规模快速开展多杀性巴氏杆菌流行病学调查的需要;而基于分子生物学手段建立的分子分型方法相对于传统的血清学分型方法而言具有快速、简单、灵敏、灵活等特点,特别是某些分子分型方法与传统的分型方法形成了较为精确的对应关系,因而在临床上得到了广泛的应用。目前适用于临床上开展多杀性巴氏杆菌分离鉴定的分子分型方法主要包括多重PCR方法及多位点序列分型法(MLST),其中多重PCR方法又包括基于荚膜编码区及脂多糖外核编码簇建立的PCR方法。本文将重点就这3种常用的多杀性巴氏杆菌分子分型方法进行综述,介绍其建立原理、实现手段以及各自的优缺点,为临床上开展多杀性巴氏杆菌的流行病学调查特别是分子流行病学调查提供参考。  相似文献   

10.
11.
BackgroundThe pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1), a class B G protein-coupled receptor (GPCR), has emerged as a promising target for treating neurodegenerative conditions. Unfortunately, despite years of research, no PAC1-specific agonist has been discovered, as activity on two other GPCRs, VPAC1 and VPAC2, is retained with current analogs. Cell signaling is related to structural modifications in the intracellular loops (ICLs) of GPCRs. Thus, we hypothesized that peptides derived from the ICLs (called pepducins) of PAC1 might initiate, as allosteric ligands, signaling cascades after recognition of the parent receptor and modulation of its conformational landscape.MethodsThree pepducins were synthesized and evaluated for their ability to 1) promote cell survival; 2) stimulate various signaling pathways associated with PAC1 activation; 3) modulate selectively PAC1, VPAC1 or VPAC2 activation; and 4) sustain mobility and prevent death of dopaminergic neurons in a zebrafish model of neurodegeneration.ResultsAssays demonstrated that these molecules promote SH-SY5Y cell survival, a human neuroblastoma cell line expressing PAC1, and activate signaling via Gαs and Gαq, with distinct potencies and efficacies. Also, PAC1-Pep1 and PAC1-Pep2 activated selectively PAC1-mediated Gαs stimulation. Finally, experiments, using a zebrafish neurodegeneration model, showed a neuroprotective action with all three pepducins and in particular, revealed the ability of PAC1-Pep1 and PAC1-Pep3 to preserve fish mobility and tyrosine hydroxylase expression in the brain.ConclusionWe have developed the first neuroprotective pepducins derived from PAC1, a class B GPCR.General significancePAC1-derived pepducins represent attractive templates for the development of innovative neuroprotecting molecules.  相似文献   

12.
BackgroundCOPD is currently the fourth leading cause of death worldwide. Statins are lipid lowering agents with documented cardiovascular benefits. Observational studies have shown that statins may have a beneficial role in COPD. The impact of statins on blood gene expression from COPD patients is largely unknown.ObjectiveIdentify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.MethodsWhole blood gene expression was measured on 168 statin users and 451 non-users from the ECLIPSE study using the Affymetrix Human Gene 1.1 ST microarray chips. Factor Analysis for Robust Microarray Summarization (FARMS) was used to process the expression data. Differential gene expression analysis was undertaken using the Linear Models for Microarray data (Limma) package adjusting for propensity score and surrogate variables. Similarity of the expression signal with published gene expression profiles was performed in ProfileChaser.Results25 genes were differentially expressed between statin users and non-users at an FDR of 10%, including LDLR, CXCR2, SC4MOL, FAM108A1, IFI35, FRYL, ABCG1, MYLIP, and DHCR24. The 25 genes were significantly enriched in cholesterol homeostasis and metabolism pathways. The resulting gene signature showed correlation with Huntington’s disease, Parkinson’s disease and acute myeloid leukemia gene signatures.ConclusionThe blood gene signature of statins’ use in COPD patients was enriched in cholesterol homeostasis pathways. Further studies are needed to delineate the role of these pathways in lung biology.  相似文献   

13.
《Endocrine practice》2014,20(1):70-74
ObjectiveSince the 1980s, it has been discussed whether the preoperative treatment of prolactinomas with dopamine agonists (DAs) is beneficial or detrimental regarding postoperative residue or recurrence. Many neurosurgeons have emphasized the difficulties caused by fibrosis during the ablation of such prolactinomas.MethodsFrom February to December 2012, the authors searched electronic databases and book chapters published from 1991 to 2012; a total of 3,771 articles and 37 book chapters were searched. Ten articles that explicitly addressed this issue were identified.ResultsFive articles reported that preoperative treatment did not affect postoperative status. One article described a positive influence of preoperative treatment with DAs (P < .01), and 3 articles found a negative influence (P = .040, P = .02, no significance value reported). One article described histopathological evidence of tumor fibrosis that was found intraoperatively after preoperative DA treatment.ConclusionsThis systematic review did not identify any strong evidence that preoperative treatment of prolactinomas with DAs is harmful or beneficial. Therefore, further studies are needed. (Endocr Pract. 2014;20:70-74)  相似文献   

14.
ObjectiveTo determine whether a period of starvation (nil by mouth) after gastrointestinal surgery is beneficial in terms of specific outcomes.DesignSystematic review and meta-analysis of randomised controlled trials comparing any type of enteral feeding started within 24 hours after surgery with nil by mouth management in elective gastrointestinal surgery. Three electronic databases (PubMed, Embase, and the Cochrane controlled trials register) were searched, reference lists checked, and letters requesting details of unpublished trials and data sent to pharmaceutical companies and authors of previous trials.ResultsEleven studies with 837 patients met the inclusion criteria. In six studies patients in the intervention group were fed directly into the small bowel and in five studies patients were fed orally. Early feeding reduced the risk of any type of infection (relative risk 0.72, 95% confidence interval 0.54 to 0.98, P=0.036) and the mean length of stay in hospital (number of days reduced by 0.84, 0.36 to 1.33, P=0.001). Risk reductions were also seen for anastomotic dehiscence (0.53, 0.26 to 1.08, P=0.080), wound infection, pneumonia, intra-abdominal abscess, and mortality, but these failed to reach significance (P>0.10). The risk of vomiting was increased among patients fed early (1.27, 1.01 to 1.61, P=0.046).ConclusionsThere seems to be no clear advantage to keeping patients nil by mouth after elective gastrointestinal resection. Early feeding may be of benefit. An adequately powered trial is required to confirm or refute the benefits seen in small trials.

What is already known on this topic

Enteral feeding within 24 hours after gastrointestinal surgery is toleratedTheoretically, early enteral feeding improves tissue healing and reduces septic complications after gastrointestinal surgery

What this study adds

There is no benefit in keeping patients “nil by mouth” after gastrointestinal surgerySeptic complications and length of hospital stay were reduced in those patients who received early enteral feedingIn patients who received early enteral feeding there were no significant reductions in incidence of anastomotic dehiscence, wound infection, pneumonia, intra-abdominal abscess, and mortality  相似文献   

15.
BackgroundAlthough great achievements have been made in the field of cancer therapy, chemotherapy and radiotherapy remain the mainstay cancer therapeutic modalities. However, they are associated with various side effects, including cardiocytotoxicity, nephrotoxicity, myelosuppression, neurotoxicity, hepatotoxicity, gastrointestinal toxicity, mucositis, and alopecia, which severely affect the quality of life of cancer patients. Plants harbor a great chemical diversity and flexible biological properties that are well-compatible with their use as adjuvant therapy in reducing the side effects of cancer therapy.PurposeThis review aimed to comprehensively summarize the molecular mechanisms by which phytochemicals ameliorate the side effects of cancer therapies and their potential clinical applications.MethodsWe obtained information from PubMed, Science Direct, Web of Science, and Google scholar, and introduced the molecular mechanisms by which chemotherapeutic drugs and irradiation induce toxic side effects. Accordingly, we summarized the underlying mechanisms of representative phytochemicals in reducing these side effects.ResultsRepresentative phytochemicals exhibit a great potential in reducing the side effects of chemotherapy and radiotherapy due to their broad range of biological activities, including antioxidation, antimutagenesis, anti-inflammation, myeloprotection, and immunomodulation. However, since a majority of the phytochemicals have only been subjected to preclinical studies, clinical trials are imperative to comprehensively evaluate their therapeutic values.ConclusionThis review highlights that phytochemicals have interesting properties in relieving the side effects of chemotherapy and radiotherapy. Future studies are required to explore the clinical benefits of these phytochemicals for exploitation in chemotherapy and radiotherapy.  相似文献   

16.
[目的]建立并评估1种适宜的脑膜炎奈瑟菌(Neisseria meningitidis,Nm)基因组分子分型方法.[方法]本研究以125株代表性Nm菌株的基因组序列为对象,建立了基于核心基因SNP的基因组分型方法,并与pubMLST网站公布的MLST和cgMLST分型方法进行比较.[结果]基于核心基因SNP的基因组分型...  相似文献   

17.
《Endocrine practice》2014,20(1):84-93
ObjectiveTo review and evaluate medical therapies for Cushing’s disease (CD), with an emphasis on recent clinical trial experience with pasireotide and mifepristone, and to discuss the therapeutic potential and appropriate selection of these compounds in this patient population.MethodsRecently published Phase III trial data for each compound are reviewed and assessed, and relative benefits and risks are examined and compared where possible.ResultsMifepristone and pasireotide are both potentially beneficial for CD patients but have greatly dissimilar mechanisms of action and adverse event (AE) profiles. Pasireotide acts at the level of the pituitary adenoma, reducing cortisol levels through inhibition of adrenocorticotropic hormone (ACTH) release. However, pasireotide reduces insulin secretion and incretin hormone response and is associated with significant risk for new or worsening hyperglycemia. Mifepristone ameliorates the signs and symptoms of hypercortisolemia via glucocorticoid receptor (GR2) blockade, but this approach raises serum cortisol levels and increases risk for adrenal insufficiency (AI), hypokalemia, and endometrial thickening. While response to pasireotide can be monitored via measurements of serum, urine, or late-night salivary cortisol, evaluation of response to mifepristone is solely based on changes in clinical parameters (e.g., hyperglycemia, hypertension, body weight/composition).ConclusionManagement of persistent CD is challenging, and the decision to initiate medical treatment hinges on many factors. Pasireotide may be a more attractive option for most patients due to its action at the underlying tumor and the ability to monitor biochemical responses. However, mifepristone may be more appropriate when it is necessary to avoid or minimize risk for hyperglycemiarelated complications. (Endocr Pract. 2014;20:84-93)  相似文献   

18.
Designsystematic review and trial sequential analysis of randomized controlled trials.DatabasePubmed, Scopus, EBSCO and EMBASE were searched from inception to August 5, 2014.MethodsMortality was dichotomized as binary outcome variable and odds ratio (OR) was chosen to be the summary statistic. Pooled OR was calculated by using DerSimonian and Laird method. Statistical heterogeneity was assessed by using the statistic I2. Trial sequential analysis was performed to account for the small number of trials and patients.Conclusionour study fails to identify any beneficial effect of antipyretic therapy on ICU patients with established diagnosis of sepsis. Due to limited number of total participants, more studies are needed to make a conclusive and reliable analysis.  相似文献   

19.
BackgroundThe application of mushrooms for health purposes has a long tradition and is very common in Asian countries. This trend is also becoming increasingly popular in the western hemisphere. However, mushrooms from European tradition are being treated in a restrained manner despite having significant potential as drugs or as sources of pure bioactive substances.Aim: The present review provides an overview of the most important mushrooms used in European ethnomedical traditions and explores their pharmacological potential and the challenges for the development of new drugs from these sources of natural products.Method: Mushroom species were selected based on information in old herbal books and dispensaries, uninterrupted use and scientific literature in the PubMed database up to June 2019.Results: Traditional experiences and modern studies have demonstrated that medical mushrooms used in European traditions have promising distinct pharmacological potential mediated through defined mechanisms (anti-tumour, anti-inflammatory, anti-oxidative and anti-bacterial). However, the number of modern chemical, biological and pharmacological studies remains relatively small, and some mushroom species have not been studied at all. Unfortunately, no valid clinical studies can be found. Unlike the case with herbal and fungal drugs from traditional Chinese medicine, we are far from comprehensively exploring this potential.Conclusions: Mushrooms from traditional European medicine have the potential to be used in modern medicine. Considerable research, interdisciplinary collaboration, involvement of the pharmaceutical industry, time and money are necessary to explore this potential not only in the form of dietary supplements but also in the form of approved drugs.  相似文献   

20.
Background and aimsHepatic steatosis is the most common histopathological finding on liver biopsy, with the most prevalent etiology being NAFLD. The pathogenesis of hepatic steatosis and NAFLD is multifactorial, however, studies on the importance of manganese in NAFLD are limited. We aimed to study hepatic manganese content, and other trace elements, in relation to hepatic steatosis in patients with chronic liver diseases of different etiology, mainly NAFLD.MethodsPatients with chronically elevated liver function tests underwent a diagnostic work-up, including routine blood tests and two liver biopsies. One of the biopsies was sent for histopathological evaluation, and the other for ultra-trace elemental determinations. Steatosis was graded using conventional histopathological methodology, and fat content was also quantitated in biopsy samples by measuring the steatotic area of the section using stereological point counting (SPC). Ultra-trace elemental analysis was utilized for determining manganese, iron, and copper using inductively coupled plasma sector field mass spectrometry (ICP-SFMS).Results76 patients were included in the study. Hepatic manganese concentrations in patients with steatosis were lower than in patients without hepatic steatosis (3.8 ± 1.1 vs. 6.4 ± 1.8, P < 0.001). Similar results were seen for blood manganese levels and hepatic steatosis. We found a strong inverse correlation between steatosis grade and hepatic manganese content (ρ=-0.743, P < 0.001). Also, low levels of manganese independently predicted the presence of steatosis (aOR 0.07 [95%CI: 0.01−0.63]).ConclusionPatients with NAFLD, or other CLD and concomitant hepatic steatosis, showed lower levels of hepatic manganese content with increasing grade of steatosis.  相似文献   

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