研究者发起的临床研究项目实施过程质量评估流程的探讨

近年来我国研究者发起的临床研究(ⅡT)项目数量快速增长,对ⅡT项目规范化实施提出了全新要求。本研究在国内外临床研究法规框架下,结合ⅡT项目实施过程质量评估工作实践探索了一套基本流程,主要包括质量评估前准备、项目组自评估、中心化核查、现场核查、撰写报告、综合评估,为提高ⅡT项目质量提供参考和借鉴。     

Evaluation of In Vivo Properties of Velosorb™ Fast Versus Vicryl™ Rapide in a Functional Rabbit Model of Intradermic Suture and Episiotomy

Objective: Fast-absorbing polyglactin 910 is commonly used to suture skin and vaginal incisions. In vitro studies have shown similar tensile strength properties between Velosorb? Fast and Vicryl? Rapide (Al-Qattan MM. J Hand Surg Br Eur. 2005;30(1):90–91). This randomized study compared Velosorb? Fast (Covidien) with Vicryl? Rapide (Ethicon) in a rabbit model of intradermic suture and episiotomy. Materials and Methods: This randomized prospective study was performed on 20 New Zealand rabbits, in which we realized a mediolateral perineo-vaginal incision and two vertical skin incisions of about 8 cm on the abdominal wall. The sutures were randomized between Velosorb? Fast (Covidien) and Vicryl? Rapide (Ethicon), and each rabbit was treated with the same suture on both vaginal incision and left abdominal incision, while the right abdominal incision was closed with an alternate suture. A macroscopic examination was performed on days 5 and 11. On day 11, animals were sacrificed for histological (Badylak quantitative score) and electron microscopic examinations. Differences were considered significant at p < .05. Results: All of the rabbits survived and were included in the final results. Fifty-one sutures were visible by histologic analysis (27 in the Velosorb? Fast group and 24 in the Vicryl? Rapide group). The power of the study was ≥80%. There was no significant difference between the two groups based on the total histologic Badylak score analysis or the Badylak sub-score analysis. Conclusions: Velosorb? Fast seems to be as efficient as Vicryl? Rapide for use in perineal and skin closure.     

Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV‐seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12‐month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non‐CMV infection, graft loss, and all‐cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve‐month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS‐adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01–0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29–0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late‐onset disease.     

Risk for emerging bipolar disorder,variants, and symptoms in children with attention deficit hyperactivity disorder,now grown up

AIM: To determine the prevalence of bipolar disorder (BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder (ADHD) through 14 years’ follow-up, when participants were between 21-24 years old.METHODS: First, we examined rates of BD type I and II diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD (MTA). We used the diagnostic interview schedule for children (DISC), administered to both parents (DISC-P) and youth (DISCY). We compared the MTA study subjects with ADHD (n = 579) to a local normative comparison group (LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts (TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic (PM) and non-specific manic (NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects.RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD (1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time (df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability (BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG (χ² = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM (df 3, 2538; F = 43.2; P < 0.0001).CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2 (A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies.     

Time-average albumin predicts the long-term prognosis of IgA nephropathy patients achieved remission

Objective To clarify the long-term renal prognosis and related risk factors of progression for IgA nephropathy (IgAN) patients who achieved remission under current therapy. To identify the target value of the serum albumin level for Chinese patients with IgAN. Methods The patients with biopsy-proven primary IgAN in Nephrology Department of Renji Hospital in Shanghai were studied．The survival of renal and the relationships between clinical parameters and renal outcome were assessed. Results A total of 369 patients between Jan 2005 and Dec 2010 were included with a median follow-up time of 49.0 (38.0-65.8) months. All the subjects had achieved a complete remission (CR) or partial remission (PR) following six months’ therapy after diagnosis. Progressive renal disease had occurred in 61 cases at the end of follow-up. Three variables had a significant independent effect on renal outcome in patients achieving remission under current therapy regimen for IgAN, including time-average serum creatinine (TA-Scr) [HR(95%CI): 1.03(1.01-1.04)], time-average serum albumin (TA-Alb) [HR(95%CI): 0.83 (0.69-0.99)], and eGFR ratio within one year [HR(95%CI): 0.00(0.00-0.01)]. By multivariate Cox analyses, each 1 g/L drop of TA-Alb was related with 17.2% increase in the risk of renal progression. The ROC curve indicated that combination of serum albumin at baseline and during a long-term had a more significant value in prediction of renal outcome than independent predictor alone. By Kaplan-Meier analyses, patients with TA-Alb﹤38 g/L had a 10.4 fold sincreased risk of progressive disease compared with that of TA-Alb﹥38 g/L. Conclusions IgAN patients with lower eGFR ratio, higher TA-Scr and lower TA-Alb would progress to ESRD more quickly, and serum albumin during follow-up is important for predicting IgAN progression.     

Left ventricular shape-luminal pressure relationship An open-chest study

Summary Left ventricular dimensions were measured in Cd²⁺ arrested (presumably diastolic), openchest rats. Aortic pressure was maintained at 137 cm H₂O (100 mm Hg) and left-ventricular (luminal) pressures were established and maintained at their chosen values, each by means of reservoir systems. The selected left-ventricular pressures were chosen to be within or to even broaden the range of conceivable diastolic pressures (–3 to 48 cm H₂O). After in situ fixation with 4 % formaldehyde and gelatin embedding, the hearts were serially sectioned in the apex base direction to obtain information at 11 levels (10, 20, ... 90, 100%). Tracings of selected sections were made along the edge of the left ventricular lumen and the pericardial surface. Volumes, surface areas, and mean external and internal radii of the left ventricle were derived. To quantify the circularity of sections a form factor (FF) was introduced (FF = 1 for a circular cross-section and less than one for other shapes). Ventricular lengths, radial dimensions, endocardial and epicardial surface areas, and total and luminal volumes increased with the increasing intraventricular pressures; as expected, the wall simultaneously thinned. Though its appearance was altered by the wall thinning, the curving muscle fascicular pattern was present over the entire pressure range examined. Endocardial surface areas increased more than did the epicardial surface areas. The endocardial FF value increased (more circular) at each section level as the pressure increased. The epicardial FF relationship was apparently constant (0.798 ± 0.014) for all section levels from 10 % through 90 %, regardless of luminal pressure. These results, when taken in conjunction with the results of our previous published studies, prompted the following speculation.The wall of the diastolic ventricle is a fluid-filled chamber with intramyocardial pressures that may be higher than ventricular pressures.     

Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe

Background

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.