Individualized Treatment Group Research Articles

The contributionof genotype-guided selection of P2Y12 inhibitor on prognosis in ACS /CCS patients undergoing percutaneous coronary intervention: aretrospective cohort study.

We aimed to explore the contribution of genotype-guided selection of P2Y12 inhibitors on prognosis in Chinese patients with acute coronary syndromes (ACS) or chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). Totally, 2063 patients were included. They were divided into empiric treatment group (n = 1025) and individualized treatment group (n = 1038) depending on whether taken CYP2C19 genetic testing. The incidences of clinical endpoint events were compared in two groups at 1-year follow-up. The effective endpoint events were major adverse cardiovascular events (MACEs), including all-cause mortality, in-stent restenosis, nonfatal myocardial infarction, nonfatal stroke and severe recurrent ischemia. Meanwhile, the safe endpoint was bleeding events defined by the Bleeding Academic Research Consortium (BARC) criteria. Finally, 66.83% patients were diagnosed with ACS and 33.17% patients were diagnosed with CCS in empiric group. 68.11% patients were diagnosed with ACS and 31.89% patients were diagnosed with CCS in individualized group. At 1-year follow-up, individualized group showed lower MACEs rate than empiric group (19.61% vs. 10.69%, HR: 1.915; 95% CI: 1.534 to 2.392; P < 0.0001, log-rank test; adjusted HR: 1.983; 95% CI: 1.573 to 2.501; P = 0.000, cox proportional hazards regression models), while bleeding events were significantly less common in empiric group than in individualized group (7.32% vs. 10.40%, HR: 0.693; 95% CI: 0.519 to 0.926; P = 0.0132, log-rank test; adjusted HR: 0.695; 95% CI: 0.518 to 0.933; P = 0.016, cox proportional hazards regression models). It was mainly manifested in BARC class 1 bleeding, which did not warrant the interruption of antiplatelet therapy (ITA). Further, subgroup analyses illustrated that no significant difference existed in cumulative MACEs-free survival rate between all treatment arms of individualized group (P = 0.6579 by log-rank test), and CYP2C19 intermediate metabolizer (IM) genetype appeared to be significantly associated with bleeding events for patients treated with ticagrelor (clopidogrel vs. ticagrelor: 6.80% vs. 14.88%; adjusted HR:0.440; 95% CI: 0.246 to 0.787; adjusted P = 0.006). Genotype-guided selection of P2Y12 inhibitor made a very positive contribution on the prognosis in Chinese ACS/CCS patients undergoing PCI. Instead of intensifying antiplatelet strategies, conventional-dose clopidogrel could be recommended as P2Y12 inhibitor after weighing MACEs and bleeding events in CYP2C19 IM patients.

Effect of individualized treatment strategy on postoperative nausea and vomiting in gynaecological laparoscopic surgery: a double-blind, randomized, controlled trial

BackgroundPostoperative nausea and vomiting (PONV) have always been a concern of clinicians and may increase medical costs for patients. Consensus guidelines recommend using multiple antiemetics with different mechanisms as prophylaxis in patients at high risk of PONV. Individualized risk scores for nausea and vomiting and individualized treatment strategies are feasible. This study evaluated the effect of individualized treatment strategies on postoperative nausea and vomiting after laparoscopic gynaecological operations.MethodsThis was a double-blind, randomized, controlled trial. A total of 119 adult patients who underwent gynaecological laparoscopic surgery under general anaesthesia were randomly divided into an individualized treatment group or a control group, with the individualized treatment group receiving individualized prevention according to a preoperative risk score of nausea and vomiting and the control group receiving no individualized prevention. Vomiting, retching, nausea, and use of rescue medication were all recorded for 24 h after the operation. The primary outcome variable was complete response, defined as no emesis or the use of rescue medication 24 h postoperatively.ResultsThe complete response rate was higher in the individualized treatment group (56.7%) than in the control group (23.7%) (95% CI, 0.01–0.27; P < 0.001). The incidences of emesis (18.3% vs. 44.1%, P = 0.002) were significantly lower in the individualized treatment group than in the control group. There were no differences in any nausea (26.7% vs. 33.9%, P = 0.391) or rescue medication use (6.7% vs. 8.5%, P = 0.743). Adverse events and laboratory and electrocardiogram abnormalities occurred no more frequently in the individualized treatment group than in the control group.ConclusionIn conclusion, this single-centre, double-blind, randomized study suggests that an individualized PONV prophylactic treatment strategy based on the number of PONV risk factors could be a safe and effective regimen to reduce the incidence of PONV in adult patients undergoing laparoscopic gynaecological surgery.

Evaluation of individualized treatment of nonproliferative diabetic retinopathy: a multicenter, randomized, parallel-controlled study.

To evaluate the differences in the efficacy of stationary treatment and individualized treatment for patients with nonproliferative diabetic retinopathy (NPDR). This study was a randomized, controlled, multicenter clinical trial. Participants with NPDR were randomized into the stationary treatment group or the individualized treatment group. The stationary treatment group was given the basic treatment and Qiming granules, and the individualized treatment group was given the basic treatment, Qiming granules, and individualized Chinese herbal medicines over a 12-week period. The individualized therapeutic formula was also changed over time to adjust to the changes in the clinical presentation of the patient. We conducted observations of fundus retinal exudation and hemorrhage, visual acuity, Traditional Chinese Medicine symptom scores and other indicators. A total of 140 participants with NPDR were randomized into the stationary treatment group or the individualized treatment group, and 132 participants completed this study. Following the 12-week treatment, significant improvements in both primary and secondary outcomes were observed in the stationary and individualized treatment groups. No remarkable difference in the primary outcomes between the two groups was observed. However, there was a significant difference in the Traditional Chinese Medicine symptom scores (18 ± 7 vs 15 ± 6; P < 0.05). There were no severe adverse effects. Compared with stationary treatment, individualized treatment is more effective at relieving the Traditional Chinese Medicine symptoms and improving vision and fundus lesions at 12 weeks post treatment.

Controlling Hypertension After Severe Cerebrovascular Event (CHASE): A randomized, multicenter, controlled study.

The optimal blood pressure lowering target in the acute phase of severe stroke is uncertain. Our aim was to compare the efficacy and safety of individualized blood pressure lowering with standard blood pressure lowering in severe stroke. Five-hundred consecutive patients with acute severe stroke and elevated BP were recruited from 26 Chinese hospitals. Eligible patients were randomized into an individualized blood pressure lowering group (with 10-15% reduction in systolic blood pressure from admission level or standard blood pressure lowering group (with a target SBP of <200 mm Hg in acute ischemic stroke and <180 mm Hg in intracerebral hemorrhage). The primary outcome was the proportion of patients with a poor functional outcome at day 90 of enrolment. Of 483 participants included in the analysis, 242 received individualized blood pressure lowering treatment and 241 received standard treatment. The primary outcome event was observed in 71.1% of the participants in the individualized treatment group and in 73.4% of the standard treatment group (odds ratio with individualized treatment for primary outcome, 0.75; 95% confidence interval, 0.47 to 1.19; p = 0.222). The rates of serious adverse events in the two groups were similar (27.7% vs. 28.2%). In patients with acute severe stoke, individualized blood pressure lowering treatment did not significantly reduce the rate of three-month death or dependence. Clinicaltrials.gov, NCT02982655. Registered in 5 December 2016, https://clinicaltrials.gov/ct2/show/NCT02982655.

Clinical research of individualized therapy in advanced esophageal cancer based on the ERCC1 C8092A genotype.

The present study aimed to explore the role and clinical value of the detection of Excision repair cross-complementing 1(ERCC1) C8092A polymorphisms in individualized therapy of patients with advanced esophageal cancer. A total of 127 patients with advanced esophageal cancer were enrolled between January 2010 and January 2014 in Anhui Provincial Hospital. Patients were randomly assigned in a 1:2 ratio to a standard treatment group or an individualized treatment group, respectively, prior to ERCC1 C8092A assessment. Patients in the standard treatment group were treated with paclitaxel and cisplatin. The DNA was obtained from the peripheral blood of individualized treatment patients, amplified by PCR and sequenced to determine the ERCC1 C8092A polymorphism prior to the administration of chemotherapies. Patients with the ERCC1 C8092A genotype of A/A or A/C received paclitaxel and cisplatin, and those with the genotype of C/C received paclitaxel and fluorouracil. The primary endpoint was response rate (RR). The secondary endpoints included toxicity of chemotherapy, progression-free survival (PFS) and overall survival (OS) times. Differences between the groups were evaluated by χ2 test. Differences in survival were analyzed by Kaplan-Meier survival curves. The survival rate was analyzed by log-rank test. Follow-up data was obtained until December 2015. The RR was obtained for 15 patients (34.8%) in the standard treatment group and 45 patients (53.6%) in the individualized treatment group (χ2=3.095; P=0.046). For adverse events, nausea and vomiting and anemia were significantly decreased in the individualized treatment group compared with the standard treatment group (P=0.001 and P=0.004, respectively). The median progression free survival time was 4.4 months [95% confidence interval (CI)3.8-5.0 months] in the standard treatment group and 6.6 months (95% CI, 5.8-7.4 months) in the individualized treatment group (P=0.018). The median overall survival time was 11.4 months (95% CI, 10.1-12.7 months) in the standard treatment group and 14.2 months (95% CI, 13.2-15.2 months) in the individualized treatment group (P=0.008). The RR, toxicity of chemotherapy, PFS and OS were significantly improved in the individualized treatment group compared with the standard treatment group. Detection of ERCC1 gene polymorphisms maybe performed for patients with advanced esophageal cancer to improve individualized therapy, which requires additional study.

The effectiveness of individualized treatment regimen on smear-positive retreatment pulmonary tuberculosis with mono- and poly-drug resistance

Objective: To analyze and evaluate the effectiveness of individualized treatment regimen in the therapy of smear-positive retreatment pulmonary tuberculosis with mono-and poly-drug resistance, and therefor to provide information on how to develop rational individualized regimen for retreatment tuberculosis cases with drug resistance. Methods: This was a multi-centered, prospective cohort study. Totally 254 cases of sputum positive tuberculosis with previous treatment history during the period from July 1, 2009 to August 30, 2016 were included in the analysis. All the cases were randomly divided into 3 groups and received therapy after randomization into treatment groups. After 3 months, cases with multidrug resistant tuberculosis, extensively drug-resistant tuberculosis, non-tuberculosis mycobacterial infection and those with smear-positive but culture-negative tuberculosis were excluded according to result of sputum culture and drug susceptibility test (DST). In treatment group A (individualized treatment group), 86 cases with an average age of (42.1±13.7) years for men and (38.5±12.8) years for women, were treated with individualized regimen, which allowed drug replacement on the basis of standard regimen (2SHRZE/6HRE) according to DST result. Treatment duration was recalculated after drug replacement and the total length should be 12 months or more. If the DST result did not show drug resistance, the patients would continue the 8 months' standard treatment. In treatment group B (intensified retreatment regimen group), 86 cases with an average age of (43.2±14.2) years for man and (37.9±14.1) years for women, received intensified retreatment regimen (2HL(2)EZS/2HL(2)EZS(3)/4HL(2)E). The dose for H was 0.3 g/d for patients with body weight <50 kg, and 0.4~0.5 g/d for higher body weight (≥50 kg); The doses for L(2,)E and Z were 0.6 g, 2/w; 0.75, 1/d and 0.5g, 3/d. In treatment group C (standard treatment group), 82 cases with an average of (42.5±11.9) years for man and (38.6±12.8) years for women, were treated with standardized regimen recommended by national tuberculosis program (2HREZS/6HRE). In both group B and C, the total treatment duration was 8 months and the drugs were not replaced for mono-and poly-drug resistance. Treatment outcomes of the 3 groups were analyzed, the status of drug replacement in group A was analyzed, and the adjustment of dose of H and R according to patients' body weight was observed. SPSS 19.0 was used for data analysis. Results: The treatment cure rates for group A, B and C were 73.3%(63/86), 76.7%(66/86) and 50%(41/82), and the treatment success rates were 80.2%(69/86), 84.9%(73/86) and 62.2%(51/82) respectively. Treatment failure was 8.1%(7/86), 4.7%(4/86) and 19.5%(16/82) in 3 groups. There were significant differences in the above indicators for group A and B in comparison with group C(χ(2)=13.127, P=0.001). However, there was no difference observed between group A and B(χ(2)=0.646, P=0.422). In group A, tuberculosis specialized hospitals using regular doses for R was only 38.7%(12/31). After 3 years' follow-up, no-relapse-success for group A was 66.7% (10/15). Conclusions: Inappropriate individualized treatment would increase treatment failure for retreatment tuberculosis. Higher doses of H and R and prolonged extensive therapy phase could contribute to increased treatment success.

Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery

Perioperative hypotension is associated with an increase in postoperative morbidity and mortality, but the appropriate management strategy remains uncertain. To evaluate whether an individualized blood pressure management strategy tailored to individual patient physiology could reduce postoperative organ dysfunction. The Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) study was a multicenter, randomized, parallel-group clinical trial conducted in 9 French university and nonuniversity hospitals. Adult patients (n = 298) at increased risk of postoperative complications with a preoperative acute kidney injury risk index of class III or higher (indicating moderate to high risk of postoperative kidney injury) undergoing major surgery lasting 2 hours or longer under general anesthesia were enrolled from December 4, 2012, through August 28, 2016 (last follow-up, September 28, 2016). Individualized management strategy aimed at achieving a systolic blood pressure (SBP) within 10% of the reference value (ie, patient's resting SBP) or standard management strategy of treating SBP less than 80 mm Hg or lower than 40% from the reference value during and for 4 hours following surgery. The primary outcome was a composite of systemic inflammatory response syndrome and dysfunction of at least 1 organ system of the renal, respiratory, cardiovascular, coagulation, and neurologic systems by day 7 after surgery. Secondary outcomes included the individual components of the primary outcome, durations of ICU and hospital stay, adverse events, and all-cause mortality at 30 days after surgery. Among 298 patients who were randomized, 292 patients completed the trial (mean [SD] age, 70 [7] years; 44 [15.1%] women) and were included in the modified intention-to-treat analysis. The primary outcome event occurred in 56 of 147 patients (38.1%) assigned to the individualized treatment strategy vs 75 of 145 patients (51.7%) assigned to the standard treatment strategy (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = .02; absolute risk difference, -14%, 95% CI, -25% to -2%). Sixty-eight patients (46.3%) in the individualized treatment group and 92 (63.4%) in the standard treatment group had postoperative organ dysfunction by day 30 (adjusted hazard ratio, 0.66; 95% CI, 0.52 to 0.84; P = .001). There were no significant between-group differences in severe adverse events or 30-day mortality. Among patients predominantly undergoing abdominal surgery who were at increased postoperative risk, management targeting an individualized systolic blood pressure, compared with standard management, reduced the risk of postoperative organ dysfunction. clinicaltrials.gov Identifier: NCT01536470.

Comparative study on eradication therapy of 1 440 newly diagnosed patients with Helicobacter pylori infection

Objective To evaluate the efficacy and safety of common therapy and individualized treatment in newly diagnosed patients with Helicobacter pylori (H. pylori) infection. Methods From March 2008 to February 2010, September 2013 to April 2014, January to October 2015, a total of 1 440 patients with H.pylori infection who received eradication therapy and with complete clinical data were retrospectively enrolled. Each was 350 cases in individualized treatment group, clarithromycin and bismuth containing quadruple therapy group and concomitant therapy group. A total of 100 cases were in standard triple therapy group, 90 cases in sequential therapy group, and 200 cases in levofloxacin and bismuth-containing quadruple therapy group. The eradication rate of H.pylori, incidence of adverse events and compliance rate were compared in the six groups. Chi square test was performed for statistical analysis. Results The results of intention-to-treat analysis indicated that there was no statistically significant difference in H.pylori eradication rates among six groups (χ2=0.985, P=0.323). However, the results of modified intention-to-treat analysis showed that H.pylori eradication rate of individualized treatment group was the highest (92.5% (282/305) and 93.3% (278/298)), second was levofloxacin and bismuth-containing quadruple therapy group (90.3% (167/185) and 91.6% (164/179)), and the differences were statistically significant (χ2=11.285 and 13.981, both P<0.01). There was statistically significant difference in indcidence of adverse events among the six groups (χ2=5.692, P=0.018), the incidence of adverse events in levofloxacin and bimuth-containing quadruple therapy group was lowest (16.2% (30/185)), and second was individualized treatment group (21.0% (64/305)). There was statistically significant difference in compliance rates among the six groups (χ2=4.712, P=0.023), the compliance rates of standard triple therapy group and sequential therapy group were highest (100% (100/100) and 100% (90/90)), and second was individualized treatment group (97.7% (298/305)). Conclusions Both the levofloxacin and bimuth-containing quadruple therapy group and individualized treatment group can effectively eradicate H.pylori infection. The former may be safe and effective to patients unable to receive individualized therapy. Key words: Helicobacter pylori; Eradication rate; Compliance; Safety; Individualized

Clinical research of individualized therapy in advanced non-small cell lung cancer guiding by detection of ERCC1 protein

Background and purpose: Excision repair cross-complementing 1(ERCC1) has been associated with cisplatin resistance.The study aimed to explore the role and clinical significance of detection of ERCC1 protein in individualized therapy of advanced non-small cell lung cancer(NSCLC) patients.Methods: From Aug.2006 to Jul.2009,222 stage ⅢB/Ⅳ NSCLC patients were enrolled.The expressions of ERCC1 protein in advanced stage NSCLC tissues were qualitatively detected by immunohistochemical methods.Patients were randomly assigned in a 2∶1 ratio to either the individualized treatment group or the standard treatment group before ERCC1 assessment.Patients in the control arm received gemcitabine plus cisplatin or vinorelbine plus cisplatin.In the genotypic arm,patients with low ERCC1 levels received gemcitabine plus cisplatin or vinorelbine plus cisplatin,and those with high levels received gemcitabine plus vinorelbine.Main outcome measures include response rate,overall survival and time to progression.Differences between the groups were statistically analyzed by chi-square test.Survival differences were analyzed by temporal inspection and Kaplan-Meier survival curves.Results: Follow-up data was up to Sep.30,2012.Objective response was obtained by 20 patients(26.6%) in the standard treatment group and 40 patients(27.2%) in the individualized treatment group(P=0.931).One year survival rate was 40.0% in the standard treatment group and 48.3% in the genotypic arm(P=0.24).The median survival time was 10.2 months(95%CI was 8.67 months to 11.73 months) in the standard treatment group and 13.3 months(95%CI was 12.46 months to 14.14 months) in the individualized treatment group(P=0.041).The time to progression was 4.8 months(95%CI was 4.12 months to 5.48 months) in the standard treatment group and 4.7 months(95%CI was 3.88 months to 5.52 months) in the individualized treatment group(P=0.395).Conclusion: The median survival time has extended in the individualized treatment group.But individualized therapy in advanced NSCLC guiding by detection of ERCC1 protein has not reflected advantage in response rate,overall survival and time to progression.Additional studies are warranted to optimize detections of biomarkers in guiding rational clinical chemotherapy regimens.

Late reactions after postoperative high-dose-rate intravaginal brachytherapy for endometrial cancer: a comparison of standardized and individualized target volumes

Purpose: To compare retrospectively two treatment protocols for postoperative intravaginal brachytherapy as to frequency of late radiation reactions and vaginal recurrence of disease. Methods and Materials: Two hundred seventeen patients with Stage I–II endometrial carcinoma underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by high-dose-rate (HDR) intracavitary irradiation, 5.5 Gy × 4 (22 Gy), to the upper 5 cm of the vagina. From 1988 to August 1991, the reference isodose was at 5 mm from the mucosal surface (standard treatment, 96 pts). From September 1991 to June 1996, the reference isodoses were chosen at 3 mm, 4 mm, or 5 mm depth depending on a clinical estimation of the mucosal thickness (individualized treatment, 121 pts). Maximum bladder and rectum doses were calculated from orthogonal X-ray films. Results: The patients were followed for 3 to 10 years. The rate of late vaginal reactions Grade 1 and 2 were 26% and 8%, respectively, after standard treatment, vs. 17% and 1% after individualized treatment ( p = 0.005). Bladder reaction rates were 9% Grade 1 and 1% Grade 2 after standard treatment vs. 1% Grade 1 after individualized treatment ( p = 0.005). Rectum reactions Grade 1 were seen in 5% and 1%, respectively. No Grade 3 reactions were observed. The reactions appeared after a median time interval of 9 months and 11 months, respectively. The rate of vaginal reactions was strongly correlated to the dose on the surface of the vaginal applicator, and the bladder reaction rate correlated with the calculated maximum bladder dose. Local vaginal recurrences were seen in 1 patient (1.0%) in the standard treatment group and in 3 patients (2.5%) in the individualized treatment group ( p = 0.78). Conclusions: By individualizing the depth of the reference dose in the vaginal mucosa according to its thickness and avoiding applicators with small diameters, the rate of reactions can be reduced without any significant increase in vaginal recurrences.