Correct and logical inference on efficacy in subgroups and their mixture for binary outcomes

Targeted therapies are becoming more common. In targeted therapy development, suppose its companion diagnostic test divides patients into a marker‐positive subgroup and its complementary marker‐negative subgroup. To find the right patient population for the therapy to target, inference on efficacy in the marker‐positive and marker‐negative subgroups as well as efficacy in the overall mixture population are all of interest. Depending on the type of clinical endpoints, inference on mixture population can be nontrivial and commonly used efficacy measures may not be suitable for a mixture population. Correlations among estimates of efficacy in the marker‐positive, marker‐negative, and overall mixture population play a crucial role in using an earlier phase study to inform on the design of a confirmatory study (e.g., determination of sample size). This article first shows that when the clinical endpoint is binary (such as respond or not), odds ratio is inappropriate as an efficacy measure in this setting, but relative response (RR) is appropriate. We show a safe way of calculating estimated correlations is to consider mixing subgroup response probabilities within each treatment arm first, and then derive the joint distribution of RR estimates. We also show, if one calculates RR within each subgroup first, how wrong the correlations can be if the Delta method derivation fails to take randomness of estimating the mixing coefficient into account.     

Graphical procedures for evaluating overall and subject-specific incremental values from new predictors with censored event time data

Quantitative procedures for evaluating added values from new markers over a conventional risk scoring system for predicting event rates at specific time points have been extensively studied. However, a single summary statistic, for example, the area under the receiver operating characteristic curve or its derivatives, may not provide a clear picture about the relationship between the conventional and the new risk scoring systems. When there are no censored event time observations in the data, two simple scatterplots with individual conventional and new scores for "cases" and "controls" provide valuable information regarding the overall and the subject-specific level incremental values from the new markers. Unfortunately, in the presence of censoring, it is not clear how to construct such plots. In this article, we propose a nonparametric estimation procedure for the distributions of the differences between two risk scores conditional on the conventional score. The resulting quantile curves of these differences over the subject-specific conventional score provide extra information about the overall added value from the new marker. They also help us to identify a subgroup of future subjects who need the new predictors, especially when there is no unified utility function available for cost-risk-benefit decision making. The procedure is illustrated with two data sets. The first is from a well-known Mayo Clinic primary biliary cirrhosis liver study. The second is from a recent breast cancer study on evaluating the added value from a gene score, which is relatively expensive to measure compared with the routinely used clinical biomarkers for predicting the patient's survival after surgery.     

Symptoms Reported by Head and Neck Cancer Patients during Radiotherapy and Association with Mucosal Ulceration Site and Size: An Observational Study

Background

Self-reported pain and impairment of oral functions varies markedly and often in spite of extensive oral mucositis (OM). The aim of the current study was to appraise how patient-reported debilitation caused by OM is influenced by the extent and possibly location of the OM lesions.

Methods

Patients with head and neck cancer undergoing radiotherapy were examined before treatment, twice weekly during 6-7 weeks of therapy, and 3-4 weeks after therapy completion. OM signs of 33 participants were evaluated using the Oral Mucositis Assessment Scale (OMAS), while OM symptoms were recorded using Patient-Reported Oral Mucositis Symptom (PROMS)-questionnaires. Changes in OM experience as a function of OM signs was undertaken by comparing the aggregated and individual PROMS scale values at the point of transition of OMAS ulceration scores between 0 to 1, 1 to 2 and 2 to 3, respectively in the nine intra-oral locations designated in the OMAS. ANOVA with pairwise contrasts using the LSD procedure was applied for comparisons of mean changes of PROMS scale values for the participants who experienced an OMAS score of 2 or more during therapy (n=24).

Results

Impairment of eating hard foods was more when the OMAS score for ulceration anywhere in the mouth or in the soft palate changed from 1 to 2, compared to between score 0 and 1 (p=.002 and p=.05) or between score 2 and 3 (p=.001 and p=.02). Mouth pain increased more upon transition of OMAS score anywhere in the mouth from 1 to 2 compared to 0 to 1 (p=.05).

Conclusion

The relationship between patient-reported impairment of oral function and pain caused by OM ulceration is not linear, but rather curvilinear. Our findings should prompt investigators of future interventional trials to consider using a less severe outcome than maximum OM scores as the primary study outcome.     

Comparison of escitalopram alone and combined with zolpidem in treating major depression and related sleep impairments

Escitalopram has been shown to be effective for treating major depression (MDD); however, research is lacking regarding its effect on treating MDD-related sleep impairments. The purpose of this study was to assess the efficacy of escitalopram monotherapy and investigate changes in insomnia, depressive symptoms, and quality of life (QOL). Participants were 14 patients with MDD who enrolled in a clinical trial at Jikei University Katsushika Medical Center. Escitalopram monotherapy was used, and hypnotics were administered three times per week for individuals suffering from sleep impairments. The following variables were assessed: (1) sleep quality [Pittsburgh sleep quality index (PSQI)], (2) depression [Zung self-rating depression scale (ZSRDS)], and (3) quality of life (QOL) as determined by the Sheehan disability scale (SDISS) and short form (36) health survey (SF-36). These assessments were conducted prior to any treatment (pre-test) and again 8–12 weeks after treatment (post-test). Monotherapy (E = escitalopram alone; n = 6) and combination therapy (E+ = escitalopram + zolpidem; n = 8) groups were compared. All participants completed the full protocol (average 9.4 ± 1.8 weeks). Regardless of treatment group, participants improved on all assessments (including sleep impairment). However, groups did not differ in their level of improvement. A two-factor ANOVA revealed that the E+ group showed particular improvements in QOL. In treating MDD and associated sleep impairments, zolpidem did not confer additional benefits. Thus, clinicians should consider E monotherapy for patients with MDD-related sleep impairments before prescribing combination therapies.

     

ACPA-positive and ACPA-negative rheumatoid arthritis differ in their requirements for combination DMARDs and corticosteroids: secondary analysis of a randomized controlled trial

Introduction

UK guidelines recommend that all early active rheumatoid arthritis (RA) patients are offered combination disease-modifying antirheumatic drugs (DMARDs) and short-term corticosteroids. Anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA may differ in their treatment responses. We used data from a randomized controlled trial - the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trial - to examine whether responses to intensive combination treatments in early RA differ by ACPA status.

Methods

The CARDERA trial randomized 467 early active RA patients to receive: (1) methotrexate, (2) methotrexate/ciclosporin, (3) methotrexate/prednisolone or (4) methotrexate/ciclosporin/prednisolone in a factorial-design. Patients were assessed every six months for two years. In this analysis we evaluated 431 patients with available ACPA status. To minimize multiple testing we used a mixed-effects repeated measures ANOVA model to test for an interaction between ACPA and treatment on mean changes from baseline for each outcome (Larsen, disease activity scores on a 28-joint count (DAS28), Health Assessment Questionnaire (HAQ), EuroQol, SF-36 physical component summary (PCS) and mental component summary (MCS) scores). When a significant interaction was present, mean changes in outcomes were compared by treatment group at each time point using t-tests stratified by ACPA status. Odds ratios (ORs) for the onset of new erosions with treatment were calculated stratified by ACPA.

Results

ACPA status influenced the need for combination treatments to reduce radiological progression. ACPA-positive patients had significant reductions in Larsen score progression with all treatments. ACPA-positive patients receiving triple therapy had the greatest benefits: two-year mean Larsen score increases comprised 3.66 (95% confidence interval (CI) 2.27 to 5.05) with triple therapy and 9.58 (95% CI 6.76 to 12.39) with monotherapy; OR for new erosions with triple therapy versus monotherapy was 0.32 (95% CI 0.14 to 0.72; P = 0.003). ACPA-negative patients had minimal radiological progression irrespective of treatment. Corticosteroid’s impact on improving DAS28/PCS scores was confined to ACPA-positive RA.

Conclusions

ACPA status influences the need for combination DMARDs and high-dose tapering corticosteroids in early RA. In CARDERA, combination therapy was only required to prevent radiological progression in ACPA-positive patients; corticosteroids only provided significant disease activity and physical health improvements in ACPA-positive disease. This suggests ACPA is an important biomarker for guiding treatment decisions in early RA.

Trial registration

Current Controlled Trials ISRCTN32484878     

布地奈德福莫特罗粉吸入治疗肺癌合并慢阻肺患者的临床疗效及对患者生活质量的影响

目的:评价布地奈德福莫特罗粉吸入治疗肺癌合并慢性阻塞性肺气肿(COPD)患者的临床疗效及对患者生活质量的影响。方法:选择2015年1月~2016年12月我院收治的肺癌合并COPD患者68例,按照随机数字表法分为治疗组和对照组,每组34例。对照组给予常规对症治疗,治疗组在对照组的基础上给予布地奈德福莫特罗粉吸入剂治疗,2次/天,规律治疗3个月。比较两组患者治疗前后用力肺活量占预测值的百分比(FVC%)、第一秒用力呼气量占预测值的百分比(FEV1%)水平、COPD评估测试及圣乔治呼吸问卷(SGRQ)评分的变化。结果:治疗后,两组FVC%、FEV1%均较治疗前明显升高,且治疗组显著高于对照组(P0.05);两组CAT评分、症状评分、活动评分及总评分均较治疗前明显降低,且治疗组显著低于对照组(P0.05)。两组并发症发生率无显著性差异(P0.05)。结论:布地奈德福莫特罗粉吸入治疗肺癌合并COPD可有效改善患者的肺功能和生活质量。     

Identification of immune-related hub genes and construction of an immune-related gene prognostic index for low-grade glioma

Low-grade glioma (LGG) poses significant management challenges and has a dismal prognosis. While immunotherapy has shown significant promise in cancer treatment, its progress in glioma has confronted with challenges. In our study, we aimed to develop an immune-related gene prognostic index (IRGPI) which could be used to evaluate the response and efficacy of LGG patients with immunotherapy. We included a total of 529 LGG samples from TCGA database and 1152 normal brain tissue samples from the GTEx database. Immune-related differentially expressed genes (DEGs) were screened. Then, we used weighted gene co-expression network analysis (WGCNA) to identify immune-related hub genes in LGG patients and performed Cox regression analysis to construct an IRGPI. The median IRGPI was used as the cut-off value to categorize LGG patients into IRGPI-high and low subgroups, and the molecular and immune mechanism in IRGPI-defined subgroups were analysed. Finally, we explored the relationship between IRGPI-defined subgroups and immunotherapy related indicators in patients after immunotherapy. Three genes (RHOA, NFKBIA and CCL3) were selected to construct the IRGPI. In a survival analysis using TCGA cohort as a training set, patients in the IRGPI-low subgroup had a better OS than those in IRGPI-high subgroup, consistent with the results in CGGA cohort. The comprehensive results showed that IRGPI-low subgroup had a more abundant activated immune cell population and lower TIDE score, higher MSI, higher TMB score, lower T cell dysfunction score, more likely benefit from ICIs therapy. IRGPI is a promising biomarker in the field of LGG ICIs therapy to distinguish the prognosis, the molecular and immunological characteristics of patients.     

Restoration of leptin responsiveness in diet‐induced obese mice using an optimized leptin analog in combination with exendin‐4 or FGF21

The identification of leptin as a mediator of body weight regulation provided much initial excitement for the treatment of obesity. Unfortunately, leptin monotherapy is insufficient in reversing obesity in rodents or humans. Recent findings suggest that amylin is able to restore leptin sensitivity and when used in combination with leptin enhances body weight loss in obese rodents and humans. However, as the uniqueness of this combination therapy remains unclear, we assessed whether co‐administration of leptin with other weight loss‐inducing hormones equally restores leptin responsiveness in diet‐induced obese (DIO) mice. Accordingly, we report here the design and characterization of a series of site‐specifically enhanced leptin analogs of high potency and sustained action that, when administered in combination with exendin‐4 or fibroblast growth factor 21 (FGF21), restores leptin responsiveness in DIO mice after an initial body weight loss of 30%. Using either combination, body weight loss was enhanced compared with either exendin‐4 or FGF21 monotherapy, and leptin alone was sufficient to maintain the reduced body weight. In contrast, leptin monotherapy proved ineffective when identical weight loss was induced by caloric restriction alone over a comparable time. Accordingly, we find that a hypothalamic counter‐regulatory response to weight loss, assessed using changes in hypothalamic agouti related peptide (AgRP) levels, is triggered by caloric restriction, but blunted by treatment with exendin‐4. We conclude that leptin re‐sensitization requires pharmacotherapy but does not appear to be restricted to a unique signaling pathway. Our findings provide preclinical evidence that high activity, long‐acting leptin analogs are additively efficacious when used in combination with other weight‐lowering agents. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

Effects of photobiomodulation combined with MSCs transplantation on the repair of spinal cord injury in rat

Stem cell transplantation has shown promising regenerative effects against neural injury, and photobiomodulation (PBM) can aid tissue recovery. This study aims to evaluate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) and laser alone or combined on spinal cord injury (SCI). The animals were divided into SCI, hUCMSCs, laser treatment (LASER) and combination treatment (hUCMSCs + LASER) groups. Cell‐enriched grafts of hUCMSCs (1 × 10⁶ cells/ml) were injected at the site of antecedent trauma in SCI model rats. A 2 cm² damaged area was irradiated with 630 nm laser at 100 mW/cm² power for 20 min. Locomotion was evaluated using Basso–Beattie–Bresnahan (BBB) scores, and neurofilament repair were monitored by histological staining and diffusion tensor imaging (DTI). First, after SCI, the motor function of each group was restored with different degrees, the combination treatment significantly increased the BBB scores compared to either monotherapy. In addition, Nissl bodies were more numerous, and the nerve fibers were longer and thicker in the combination treatment group. Consistent with this, the in situ expression of NF‐200 and glial fibrillary acidic protein in the damaged area was the highest in the combination treatment group. Finally, DTI showed that the combination therapy optimally improved neurofilament structure and arrangement. These results may show that the combination of PBM and hUCMSCs transplantation is a feasible strategy for reducing secondary damage and promoting functional recovery following SCI.     

Four sequence positions of the movement protein of Cucumber mosaic virus determine the virulence against cmv1‐mediated resistance in melon

The resistance to a set of strains of Cucumber mosaic virus (CMV) in the melon accession PI 161375, cultivar ‘Songwhan Charmi’, is dependent on one recessive gene, cmv1, which confers total resistance, whereas a second set of strains is able to overcome it. We tested 11 strains of CMV subgroups I and II in the melon line SC12‐1‐99, which carries the gene cmv1, and showed that this gene confers resistance to strains of subgroup II only and that restriction is not related to either viral replication or cell‐to‐cell movement. This is the first time that a resistant trait has been correlated with CMV subgroups. Using infectious clones of the CMV strains LS (subgroup II) and FNY (subgroup I), we generated rearrangements and viral chimaeras between both strains and established that the determinant of virulence against the gene cmv1 resides in the first 209 amino acids of the movement protein, as this region from FNY is sufficient to confer virulence to the LS clone in the line SC12‐1‐99. A comparison of the sequences of the strains of both subgroups in this region shows that there are five main positions shared by all strains of subgroup II, which are different from those of subgroup I. Site‐directed mutagenesis of the CMV‐LS clone to substitute these residues for those of CMV‐FNY revealed that a combination of four of these changes [the group 64–68 (SNNLL to HGRIA), and the point mutations R81C, G171T and A195I] was required for a complete gain of function of the LS MP in the resistant melon plant.     

Comparison of design strategies for a three‐arm clinical trial with time‐to‐event endpoint: Power,time‐to‐analysis,and operational aspects

To optimize resources, randomized clinical trials with multiple arms can be an attractive option to simultaneously test various treatment regimens in pharmaceutical drug development. The motivation for this work was the successful conduct and positive final outcome of a three‐arm randomized clinical trial primarily assessing whether obinutuzumab plus chlorambucil in patients with chronic lympocytic lymphoma and coexisting conditions is superior to chlorambucil alone based on a time‐to‐event endpoint. The inference strategy of this trial was based on a closed testing procedure. We compare this strategy to three potential alternatives to run a three‐arm clinical trial with a time‐to‐event endpoint. The primary goal is to quantify the differences between these strategies in terms of the time it takes until the first analysis and thus potential approval of a new drug, number of required events, and power. Operational aspects of implementing the various strategies are discussed. In conclusion, using a closed testing procedure results in the shortest time to the first analysis with a minimal loss in power. Therefore, closed testing procedures should be part of the statistician's standard clinical trials toolbox when planning multiarm clinical trials.     

Elacestrant in metastatic breast cancer: Is the “standard of care” meeting standard requirements?

The EMERALD trial was an open label phase 3 trial evaluating elacestrant, the first oral selective estrogen receptor degrader (SERD), as compared to “standard of care”, in ER+/HER2- (hormone receptor positive, no HER2 overexpression) advanced or metastatic breast cancer.The EMERALD trial restricted the “standard of care” control arm to limited options that may have led to a substandard control arm. We describe how the EMERALD trial protocol allowed different clinically inappropriate scenarios in the control arm, according to prior therapy. The main relevant question remains the potential advantage of elacestrant over fulvestrant in fulvestrant-naive patients.Analyzing outcomes in subgroups according to prior and per-protocol therapy would help analyzing trial results. However, these subgroup results may be non-significant, and another randomized trial will be needed. Trials should be designed to answer directly clinical questions that are relevant.     

甲真菌病患者生活质量及口服伊曲康唑间歇冲击疗法对其的影响

目的研究伊曲康唑治疗对甲真菌病患者生活质量的影响。方法221例患者应用伊曲康唑冲击治疗前后填写调查表,其中43例患者完成伊曲康唑3个疗程随访。结果全甲营养不良型甲真菌病患者生活质量下降较为明显的指标为精神、心理状态4．79±2．81,日常生活、工作能力3．33±2．11（P〈0．05）。伊曲康唑治疗后甲真菌病患者生活质量分值随疗程延长逐渐降低。结论甲真菌病患者生活质量受到影响,伊曲康唑冲击治疗能改善患者生活质量。     

Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis

Background

Clostridium difficile infection (CDI) has become a global epidemiological problem for both hospitalized patients and outpatients. The most commonly used drugs to treat CDI are metronidazole and vancomycin. The aim of this study was to compare the efficacy and safety of metronidazole monotherapy with vancomycin monotherapy and combination therapy in CDI patients.

Methods

A comprehensive search without publication status or other restrictions was conducted. Studies comparing metronidazole monotherapy with vancomycin monotherapy or combination therapy in patients with CDI were considered eligible. Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated and reported.

Results

Of the 1910 records identified, seventeen studies from thirteen articles (n = 2501 patients) were included. No statistically significant difference in the rate of clinical cure was found between metronidazole and vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00), p = 0.05) or between either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58, 1.96), p = 0.83); however, the rate of clinical cure was lower for metronidazole than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80), p = 0.006). No statistically significant difference in the rate of CDI recurrence was found between metronidazole and vancomycin for mild CDI (OR = 0.99, 95% CI (0.40, 2.45), p = 0.98) or severe CDI (OR = 0.98, 95% CI (0.63, 1.53), p = 0.94) or between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI (0.66, 1.26), p = 0.56). In addition, there was no significant difference in the rate of adverse events (AEs) between metronidazole and vancomycin (OR = 1.18, 95% CI (0.80, 1.74), p = 0.41). In contrast, the rate of AEs was significantly lower for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17, 0.51), p<0.0001).

Conclusions

Metronidazole and vancomycin are equally effective for the treatment of mild CDI, but vancomycin is superior for the treatment of severe CDI. Combination therapy is not superior to monotherapy because it appears to be associated with an increase in the rate of AEs.     

Randomised comparison of combination chemotherapy plus supportive care with supportive care alone in patients with metastatic colorectal cancer.

OBJECTIVES--To compare the length of survival and quality of life in patients given combination chemotherapy in addition to supportive care and in patients given only supportive care. DESIGN--Randomised study. SETTING--Gastrointestinal oncology departments. PATIENTS--40 previously untreated patients with histologically confirmed, measurable colorectal cancer that was locally recurrent or metastatic. INTERVENTIONS--Patients were allocated randomly to receive chemotherapy or only supportive care in a ratio of 2:1 according to performance status, metastatic disease of the liver, and weight loss in the six months before entering the study. Chemotherapy consisted of four week cycles of intravenous leucovorin (200 mg/m2/day) followed by 5-fluorouracil (550 mg/m2/day) and cisplatin (20 mg/m2/day), each drug being given on the first four days of the cycle. MAIN OUTCOME MEASURES--Length of survival and quality of life score with an optimised functional living index-cancer scale. RESULTS--Overall survival was significantly longer for patients given chemotherapy (11.0 months) than for those receiving supportive care alone (5.0 months; p = 0.006). Despite common association of chemotherapy with mild to moderate gastrointestinal symptoms, there was no significant difference between the two groups in global or subgroup quality of life scores. In patients with abnormal scores before treatment, quality of life seemed better in the chemotherapy arm. CONCLUSIONS--In this sample of patients with disseminated colorectal cancer the chemotherapy regimen was an effective form of palliative treatment.     

Depression Affects the Scores of All Facets of the WHOQOL-BREF and May Mediate the Effects of Physical Disability among Community-Dwelling Older Adults

Background

Geriatric depression is associated with the overall quality of life (QOL). However, how depressive symptoms affect the different domains and facets of QOL in older adults, and whether depressive symptoms mediate the relationship between physical disability and QOL in older adults are unclear.

Methods

A total of 490 ambulatory community-dwelling older adults aged 65 years or above were interviewed using the brief version of the World Health Organisation Quality of Life instrument (WHOQOL-BREF), the Modified Barthel Index (MBI), the 15-item Geriatric Depression Scale (GDS-15), and the Mini-Mental State Examination (MMSE). Sequential models for multiple linear regressions were analysed to determine if the MBI, GDS-15 and MMSE scores predict the WHOQOL-BREF scores. The potential mediation effects of depression (as determined by the GDS-15) on the relationship between MBI and WHOQOL-BREF were also analysed.

Results

The GDS-15 score was predictive of the scores of the four domains and all 26 facets of the WHOQOL-BREF. The significant predictive effects of the MBI score on 15 of the 26 facets of the WHOQOL-BREF were reduced to three after the adjustment for the GDS-15 score. Depression (as assessed by the GDS-15) is a mediator of the relationship between MBI and the physical, psychological and environmental domains of the WHOQOL-BREF.

Conclusions

Depression (assessed by the GDS-15) may affect the scores of every domain and all facets of the WHOQOL-BREF in the elderly. Furthermore, it may mediate the relationship between the MBI and on QOL scores. We recommend taking depressive symptoms into consideration when measuring community-dwelling older adults’ QOL and providing active ageing programs.     

乳腺癌患者术后生命质量及影响因素的调查研究

目的:乳腺癌是我国女性最常见的恶性肿瘤。生命质量作为一种新的医学综合评价技术,包括了对患者身体状况、心理、社会功能以及与疾病或治疗有关的症状等情况的全面评估,其在癌症患者疗效评估中的应用日益增多。乳腺癌患者生命质量调查量表QLICP-BR具有中国文化特色、适合中国国情,具有较好的效度、信度和一定的反应度,适用于中国乳腺癌患者的生命质量测定。本研究旨在观察乳腺癌患者术后生命质量情况并评估各因素对其生命质量的影响,为进一步提高乳腺癌患者术后生命质量提供指导。方法:采用乳腺癌患者生命质量调查量表QLICP-BR收集资料,调查245名住院治疗的乳腺癌患者术后一般情况及生命质量,并分析其影响因素。结果:乳腺癌患者术后生存质量总分为88.44±12.32,其主要影响因素有患病年龄、居住环境、文化程度、家庭经济收入、工作状况、婚姻状况、治疗情况、术后时间及目前治疗情况等(P0.05)。其中年龄较长、居住城镇、文化水平较高、收入较高、在职、已婚、手术治疗联合化疗、术后时间较长以及当前正予以放疗的患者的生存质量评分较高。结论:乳腺癌患者术后生命质量为一般水平,多项因素对其有显著影响。临床上应针对主要影响因素制定综合有效的干预措施,提高乳腺癌患者术后的生命质量。     

心可舒片治疗冠心病患者PCI术后焦虑的疗效及对生活质量的影响

目的:探讨心可舒片治疗冠心病(CAD)患者经皮冠状动脉介入(PCI)术后焦虑的疗效及对生活质量的影响。方法:选择2015年1月~2017年1月我院心内科收治的68例行PCI术后合并焦虑的CAD患者并将其随机分为治疗组(n=34)、对照组(n=34)。对照组给予常规药物治疗,治疗组在此基础上给予心可舒片,4片/次,3次/d,治疗周期为3个月。比较两组患者治疗前后血液流变学指标、焦虑症状、生活质量的变化。结果:治疗3个月后,治疗组患者全血黏度、血浆黏度、红细胞压积及血小板聚集率均较治疗前显著下降,且均明显低于对照组(P0.05);治疗1个月后,两组HAMA评分均较治疗前明显减低(P0.05),而两组间比较差异无统计学意义(P0.05);治疗3个月后,治疗组HAMA评分明显低于对照组(P0.05);治疗1、3个月后,两组WHOQOL-BREF各维度评分均较治疗前明显升高(P0.05),且治疗组心理、社会关系维度评分显著高于对照组(P0.05)。结论:心可舒片可改善CAD患者PCI术后合并焦虑患者的血液流变学,缓解焦虑症状,提高患者的生活质量。     

The combination of atenolol and amlodipine is better than their monotherapy for preventing end‐organ damage in different types of hypertension in rats

Combinations therapy is often used in hypertensive patients whether combination therapy is necessary for preventing end‐organ damage is not known. The objective of this study was to determine in four different hypertensive animal models the necessity of adding the calcium channel blocker amlodipine to therapy with the ß‐blocker atenolol to modulate end‐organ damage. Spontaneously hypertensive rats, DOCA‐salt hypertensive rats, two‐kidney, one‐clip renovascular hypertensive rats and Lyon genetically hypertensive rats were used to study this objective. These animal models have different sensitivities to atenolol and amlodipine. The dosages of therapy employed were 10 mg/kg atenolol alone, 1 mg/kg amlodipine, 10 mg atenolol + 1 mg/kg amlodipine and 5 mg/kg atenolol+0.5 mg/kg amlodipine. BP was continuously recorded in all animals. After determination of baroreflex sensitivity, rats were sacrificed for end‐organ damage evaluation. The combination of amlodipine and atenolol had a synergistic inhibitory effect on blood pressure and blood pressure variability, and end‐organ damage as compared with monotherapy with atenolol or amlodipine in all animal models. Baroreflex sensitivity also improved with the combination therapy more than with monotherapy. In conclusion, atenolol and amlodipine combination exerts a superior effect on blood pressure, blood pressure variability, baroreflex sensitivity and end‐organ damage. The superior effect of the combination was observed in all four models of hypertension.