Cumulative Failure Rate Research Articles

Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous (MUSTANG), an EAST Multicenter Study.

We sought to describe contemporary presentation, treatment, and outcomes of patients presenting with acute (A), perforated (P), and gangrenous (G) appendicitis in the United States. Recent European trials have reported that medical (antibiotics only) treatment of acute appendicitis is an acceptable alternative to surgical appendectomy. However, the type of operation (open appendectomy) and average duration of stay are not consistent with current American practice and therefore their conclusions do not apply to modern American surgeons. This multicenter prospective observational study enrolled adults with appendicitis from January 2017 to June 2018. Descriptive statistics were performed. P and G were combined into a "complicated" outcome variable and risk factors were assessed using multivariable logistic regression. A total 3597 subjects were enrolled across 28 sites: median age was 37 (27-52) years, 1918 (53%) were male, 90% underwent computed tomography (CT) imaging, 91% were initially treated by appendectomy (98% laparoscopic), and median hospital stay was 1 (1-2) day. The 30-day rates of Emergency Department (ED) visit and readmission were 10% and 6%. Of 219 initially treated with antibiotics, 35 (16%) required appendectomy during index hospitalization and 12 (5%) underwent appendectomy within 30 days, for a cumulative failure rate of 21%. Overall, 2403 (77%) patients had A, whereas 487 (16%) and 218 (7%) patients had P and G, respectively. On regression analysis, age, symptoms >48 hours, temperature, WBC, Alvarado score, and appendicolith were predictive of "complicated" appendicitis, whereas co-morbidities, smoking, and ED triage to appendectomy >6 hours or >12 hours were not. In the United States, the majority of patients presenting with appendicitis receive CT imaging, undergo laparoscopic appendectomy, and stay in the hospital for 1 day. One in five patients selected for initial non-operative management required appendectomy within 30 days. In-hospital delay to appendectomy is not a risk factor for "complicated" appendicitis.

Cumulative sum analysis of the learning curve for the preclosure technique using Proglide.

Our study aims to assess the technical quality and the learning curve of the preclosure technique for a vascular surgeon using Proglide using cumulative sum analysis (CUSUM analysis). This study was designed retrospectively and enrolled 81 consecutive patients with 88 access sites who underwent endovascular aortic repair or thoracic endovascular aortic repair with the preclosure technique using Proglide between July 2017 and February 2018. The patients were divided into 2 groups chronologically: (A) the first 40 cases and (B) the latter 41 cases. Logistic regression analysis was used to assess the impact of technical risk factors on the success of the preclosure technique, and the χ2 test and 1-way ANOVA were applied to analyse the distribution of individual characteristics and risk factors between the 2 groups. CUSUM analysis was adapted to analyse the learning curve and to monitor the technical quality, with a predetermined target failure rate of 5%, an alternative failure rate of 20% and calculated 80% 'alert', 95% 'alarm' and 80% 'reassurance' lines. Primary technical success was obtained in 81 (92.05%) access sites. There were no significant correlations between primary technical success and risk factors, including, common femoral artery diameter (P = 0.88), common femoral artery depth from the skin (P =0.94), the level of common femoral artery calcification (P =0.86) and size of sheath (P =0.96). Moreover, the distribution of related risk factors was not significantly different between groups A and B. CUSUM analysis showed that the cumulative failure rate never crossed the 80% 'alert' and 95% 'alarm' lines. Additionally, the failure rate began to approach the 80% 'reassurance' line after ∼22 cases and crossed the 80% 'reassurance' line after 36 cases. The technique of totally percutaneous access using Proglide is safe and effective for an experienced vascular surgeon, even if the operator has no previous experience with any preclosure techniques. CUSUM analysis showed that 36 cases are necessary to achieve the target failure rate of 5%.

Clinical and OCT outcomes of a universal adhesive in a randomized clinical trial after 12 months

ObjectivesTo assess the performance of a universal adhesive in different application modes in non-carious cervical lesions clinically and by optical coherence tomography (OCT). Methods55 adult patients with three non-carious cervical lesions (NCCL) each participated in the study. Lesions were restored with Scotchbond™ Universal (SBU, 3 M) applied in the self-etch (SBU-SE) and the selective-enamel-etch mode (SBU-SEE) in combination with Filtek™ Supreme XTE (3 M). OptiBond™ FL (OFL, Kerr) was used as a control. Restorations were clinically assessed (FDI criteria) after 14 days, 6 and 12 months and in parallel imaged by OCT (interfacial adhesive defects), starting immediately after filling placement. Cumulative failure rates (CFR) and means of interfacial adhesive defect were statistically evaluated. ResultsAfter 12 months, CFRs were lower in the SBU groups (0.0% each) than in the OFL group (20.0%, p = 0.001). Clinically, small marginal fractures occurred three times more often in the SBU-SE than in the SBU-SEE group (p = 0.001). Immediately after filling placement and at each reassessment OCT revealed more interfacial defects at enamel interfaces for SBU/SE compared to SBU/SEE and OFL (pi ≤ 0.044). At dentin/cement more defects were seen with OFL compared to SBU/SE and SBU/SEE (pi ≤ 0.001). Before restoration loss, more interfacial defects appeared compared to remaining restorations (pimmediately/6M = 0.132/0.002). ConclusionsClinical evaluation and OCT imaging revealed higher interfacial integrity for SBU in both application modes compared to OFL. OCT detected interfacial bond failures prior to clinical deterioration or restoration loss. Clinical significanceScotchbond Universal showed an equivalent or improved bonding performance compared to the reference adhesive. Selective enamel etching is recommended. The parameter interfacial adhesive defect seems to be a valuable predictor for evaluation of adhesive restoration systems.

A randomized controlled 10 years follow up of a glass ionomer restorative material in class I and class II cavities

ObjectiveTo evaluate the durability of a glass ionomer restorative material in Class I and Class II cavities during 10 years compared with a micro filled composite resin. MethodsFifty-nine participants (mean age 24 years) received 140 (80 Class I and 60 Class II) glass ionomer (GI) or composite resin (CR) restorations. Evaluation was performed with slightly modified USPHS criteria at baseline, and yearly during the 10 years. Data were analyzed with Cohran's Q and McNemar's tests. ResultsFifty-one patients and 124 restorations (61 GI / 38 Class I - 23 Class II, 63 CR / 38 Class I, 25 Class II) were evaluated after 10 years. The recall rate was 86.4%. The overall clinical recall rate of restorations was 88.6%. The success rate of Class I and II restorations were calculated as 100% for both materials. The cumulative failure rate (CRF) of all Cl I and Cl II GI restorations was 3.17% in total, but CFR was 8 % for Cl II GI restorations. A significant difference was observed between the marginal discoloration scores of restorations at 10 years (p = 0.022). No significant difference was seen between two restorative materials in terms of marginal adaptation (p > 0.05). A significant change was seen in color match of GI restorations at 10 years (p < 0.05). No significant change was found for the anatomical form, secondary caries, postoperative sensitivity, surface texture, and retention for either restorative material (p > 0.05). ConclusionsBoth tested restorative materials showed an acceptable success rate in the restoration of Class I and Class II cavities during the 10-year follow up.

Cause-Specific Risk Factors of Death in Individuals with Diabetes: A Competing Risks Modeling.

BackgroundDiabetes is on the rise worldwide.ObjectivesThis study aimed to evaluate the risk factors of various causes of death in people with type 2 diabetes (T2D).MethodsIn this cohort study on 2638 people with T2D, we applied cause-specific and sub-distribution hazards models to assess the impact of various factors on the risk of death. Moreover, we plotted a cumulative incidence curve to summarize cumulative failure rates over time.ResultsAbout 75% of individuals with T2D died from cardiovascular disease (CVD) and cerebrovascular accidents (CVA). Death from CVD was associated with the increased risk of hypertension (hazard ratio (HR) = 1.83, 95% CI: 1.37 - 2.46), hypercholesterolemia (HR = 1.58, 95% CI: 1.17 - 2.14), and diabetes duration. The risk of death from CVA was related to hypertension (HR = 2.76, 95% CI: 1.67 - 4.55) and hyperglycemia (HR = 4.34, 95% CI: 1.75 - 10.79). The CVA risk in patients with diabetes duration of 10 - 20 years was higher than the risk in patients with diabetes duration > 20 years (diabetes duration of ≤ 10 years as the reference category). Diabetes duration of longer than 20 years was associated with a higher risk of death from cancer (HR = 2.65, 95% CI: 1.05 - 6.68). The risk of death from foot infection and diabetic nephropathy increased in patients with longer diabetes duration after adjustment for sex, age, and body mass index.ConclusionsRegardless of the cause, death rates in people with T2D increase over time and risk factors have different impacts on death from each cause. This should be acknowledged in risk management in individuals with T2D.

Effect of a hydrophobic bonding resin on the 36-month performance of a universal adhesive-a randomized clinical trial.

To evaluate if the addition of a layer of a hydrophobic bonding resin to the recommended application sequence of a universal adhesive improves the respective clinical behavior in non-carious cervical lesions (NCCLs) after 36months. Scotchbond Universal Adhesive (SBU, 3M Oral Care) was applied in NCCLs of 39 subjects using four adhesion strategies: (1) three-step ER (etch-and-rinse), (2) two-step ER, (3) two-step SE (self-etch), and (4) one-step SE. An extra layer of a hydrophobic bonding resin was applied for strategies three-step ER and two-step SE. The same composite resin (Filtek Supreme XTE, 3M Oral Care) was used for all strategies. Restorations were evaluated at baseline and 18 and 36months using the modified United States Public Health Service (USPHS) criteria. Kruskal-Wallis, Mann-Whitney U, Friedman, and Wilcoxon non-parametric tests were computed. The cumulative failure rate was 8.6%. The 36-month retention rates were 100% for both 3-ER and 2-ER, 76.0% for 2-SE, and 86.2% for 1-SE. A lower retention rate was observed for two-step SE at 36months compared with both three-ER (p < 0.01) and two-ER (p < 0.01). Identical retention rates were measured for the two SE groups. When retention rate was compared at baseline versus 36months for each adhesion strategy, a significant decrease was observed for 2-SE. The restorations performed with 3-ER, 2-SE, and 1-SE had a significant deterioration in marginal discoloration at the 18-month recall. The 36-month clinical performance of Scotchbond Universal Adhesive improved for both etch-and-rinse strategies. Phosphoric acid etching is still recommended to provide retention to composite restorations in NCCLs.

Reliability of 4H-SiC (0001) MOS Gate Oxide by NO Post-Oxide-Annealing

In this work, we investigated the oxide reliability of 4H-SiC (0001) MOS capacitors, the oxide was fabricated about 60 nm by thermal oxidation temperature at 1350°C, the oxides than annealed at different temperatures and times in diluted NO (10% in N2). The 4H-SiC MOS structure was analyzed by C-V and I-V measurement. Compared the J-E curves and Weibull distribution curves of charge-to-breakdown for fives samples under different annealing temperature and time, it shows that the high annealing temperature improves the electrical properties as the lifetime enhanced. The mode value of field-to-breakdown (EBD) for thermal oxides by post-oxide-annealing in NO for 30 min at 1350°C was 10.09 MV/cm, the charge-to-breakdown (QBD) of this sample was the highest in all samples, and the QBD value at 63.2% cumulative failure rate was 0.15 C/cm2. The QBD of the sample annealing at 1200°C for 120 min was 0.06 C/ cm2. The effects of NO annealing in high temperature enhance the lifetime of electrical properties and field-to-breakdown obviously. It can be demonstrated that the annealing temperature as high as 1300°C for 30 min can be used to accelerate TDDB of SiC MOS gate oxide.

Intermediate-Term Outcomes of an Affordable Aqueous Drainage Implant in Adults with Refractory Glaucoma

To report the outcomes of Aurolab Aqueous Drainage Implant (AADI) (Aurolab, Madurai, India) surgery in adults with refractory glaucoma. Retrospective, noncomparative, interventional case series. Patients 18 years of age or older who underwent AADI surgery between January 2012 and December 2015 for refractory glaucoma with a minimum follow-up of 2 years. Case records of eligible patients were evaluated for demographics, best-corrected visual acuity (BCVA), and indication for AADI surgery. The intraocular pressure (IOP) and the number of antiglaucoma medications (AGMs) were recorded at baseline, at 1, 3, 6, 9, 12, 18, and 24 months, and at the last visit after 24 months if any from the case files. Complications during or at any time point after surgery were also recorded. Cumulative failure rate of the AADI was defined as IOP > 18 mmHg or not reduced by 30% below baseline on 2 consecutive follow-up visits after 3 months, IOP ≤ 6 mmHg on 2 consecutive follow-up visits after 3 months, reoperation for glaucoma, or loss of light perception vision. A total of 158 eyes of 158 patients with a mean age of 45.4±17.4 years and mean follow-up of 41.9±14.7 months were included in the analysis. Secondary open-angle glaucoma (n= 71, 45%) was the most common form of glaucoma. The mean preoperative IOP was 34.7±9.9 mmHg with 3.2±0.7 AGMs. At 1 year, the mean IOP decreased to 15.10±6.7 mmHg with 1.5±1.1 medications, and this was maintained at 2 years. Kaplan-Meier estimates showed that the cumulative probability of failure was 9.5% (95% confidence interval [CI], 5.8-15.2) at 1 year, 27.8% (95% CI, 21.5-35.5) at 2 years, 38.9% (95% CI, 31.1-47.8) at 3 years, and 50.1% (95% CI, 40.5-60.6) at 4 years. Forty-seven complications were observed in 38 eyes (24%), most of which were transient and did not require surgical intervention. The AADI tube exposure (n= 1), retraction (n= 1), plate exposure (n= 1), and plate displacement (n= 1) were seen rarely. The AADI appears to have good efficacy and safety for managing eyes with refractory glaucoma. Longer follow-up studies are required to determine long-term cumulative failure rates.

A Retrospective Cohort Study of the Survival Rate of 88 Zygomatic Implants Placed Over an 18-year Period.

The management of patients with a severely atrophic or resected maxilla with zygomatic implants can be surgically challenging, but postoperative complications are relatively uncommon. This retrospective cohort study evaluated the percentage survival rates of zygomatic implants placed over an 18-year period. This study evaluated patients receiving zygomatic implants in primary-care (specialist referral dental practice) and secondary-care (hospital) settings over an 18-year period. In total, 88 zygomatic implants were placed in 45 patients aged between 42 and 88 years. Of the 88 implants, 54 were immediately loaded. The implant survival rate was 94.32%, with five implants failing during the study period (implant-level cumulative failure rate: 5.68%; mean follow-up: 7.5 years; maximum: 18 years). The failures were not significantly associated with sex, surface finish, implant length, zygomatic anatomy-guided approach (ZAGA) classification, or implant position (all P values > .05). All failed implants were fitted with fixed prostheses. Failures occurred between 6 months and 15 years after placement. This study of zygomatic implants placed in patients with a severely atrophic and resected maxilla confirms that this approach is a predictable method for supporting fixed or removable prostheses up to 18 years, demonstrating high survival rates. Given the low number of failures, no potential risk factors for failure could be identified.

Cervical laser vaporization for women with cervical intraepithelial neoplasia-3.

This study evaluated outcomes of laser vaporization of the cervix for women with cervical intraepithelial neoplasia (CIN)-3. We retrospectively reviewed 161 consecutive patients with CIN3 who were treated with cervical laser vaporization between January 2008 and December 2012. At each follow-up visit, histologically confirmed CIN2, CIN3 and invasive carcinoma were defined as treatment failures, as were high-grade squamous intraepithelial lesion (HSIL) or atypical squamous cells that cannot exclude HSIL with subsequent treatment or lost to follow-up. Primary endpoints included long-term follow-up (at least 5 years of regular hospital visits) and treatment failure rate. Treatment failure rates were estimated by the Kaplan-Meier method. Patients' median age was 31 years old. Median follow-up period was 67 months (interquartile range: 52-74 months). Over 5 years, 70.8% continued their follow-up visits, but significantly more patients aged ≥35 years did so (86.4%) than did those aged ≤34 years (61.8%, P = 0.0009). Treatment failure was observed in 14 (8.7%) patients, 1 of whom progressed to invasive cancer (0.6%). Cumulative treatment failure rates were 1-year: 5.1%, 2-year: 6.4% and 5-year: 9.5%. Among patients who suffered treatment failures, 57.1% initial failures occurred within the first year and 71.4% within the first 2 years. Long-term oncologic outcomes of cervical vaporization in CIN3 remain at a suboptimal level. The importance of a minimum of 5 years of regular hospital visits should be emphasized to patients with CIN3 who are candidates for cervical laser vaporization, especially those aged ≤34 years.

Can We Jump Out of the Periodic Circles of Hope and Disappointment in the Anterior Cruciate Ligament Reconstruction Using Synthetic Ligament? A Nationwide Multicenter Study by the China Artificial Ligament Study Group (CALSG)

Background: The application of synthetic ligaments for theanterior cruciate ligament (ACL) reconstruction was never untroubled. Their history was commented as Periodic cycles of hope and disappointment. Currently, their long-term clinical outcome was still controversial despite satisfactory short and mid-term results. If we want to spare us from another disappointment, we have to clarify the long-term rate of adverse events and the fundamental reason for failure. Methods: The national multicenter research was backed by the China Artificial Ligament Study Group (CALSG). The ACL reconstruction using synthetic ligaments between July 2004 and December 2010 were screened. The adverse events consisted of cumulative failure and complications. For failure cases, the symptoms, the clinical outcomes, the reason for failure, and the activity level were investigated. Findings: A total of 1705 cases from 20 centers were screened with 1393 cases included. And 1146 cases fulfilled evaluation at meanly 87 months postoperative. Adverse events were confirmed in 83 cases with the rate of 7.2% (83/1146). Among them, the cumulative failure was confirmed in 36 cases; complications in 32 cases; cumulative failure combined with complications in 15 cases. Generally, the cumulative failure rate was 4.5% (51/1146), and the complication rate was 4.1% (47/1146). For failure cases, the bone tunnel position was evaluated in 49 of them. The bone tunnel malposition, an error caused by the surgeon, was confirmed in 32 cases with the constituent ratio of 65.3% (32/49); trauma in 25 cases with the constituent ratio of 49.0% (25/51); screw loosening in 8 cases with the constituent ratio of 15.7% (8/51). Conclusion: Currently, the failure rate of ACL reconstruction using synthetic ligament was 4.5% at meanly 87 months postoperative. Bone tunnel malposition was the primary cause of failure. We need to pay attention to the technique error when ACL reconstruction using synthetic ligaments failed, instead of merely blaming the graft. Funding Statement: China Artificial Ligament Study Group Declaration of Interests: The authors state no conflict reported. Ethics Approval Statement: KY2017-334 (Huashan Hospital Institutional Review Board)

Comparing the Efficiency of Two Treatment Methods of Hydrocephalus: Shunt Implantation and Endoscopic Third Ventriculostomy.

Introduction:Hydrocephalus is one of the most common diseases in children, and its treatment requires brain operation. However, the pathophysiology of the disease is very complicated and still unknown.Methods:Endoscopic Third Ventriculostomy (ETV) and Ventriculoperitoneal Shunt (VPS) implantation are among the common treatments of hydrocephalus. In this study, Cerebrospinal Fluid (CSF) hydrodynamic parameters and efficiency of the treatment methods were compared with numerical simulation and clinical follow-up of the treated patients.Results:Studies have shown that in patients under 19 years of age suffering from hydrocephalus related to a Posterior Fossa Brain Tumor (PFBT), the cumulative failure rate was 21% and 29% in ETV and VPS operation, respectively. At first, the ETV survival curve shows a sharp decrease and after two months it gets fixed while VPS curve makes a gradual decrease and reaches to a level lower than ETV curve after 5.7 months. Post-operative complications in ETV and VPS methods are 17% and 31%, respectively. In infants younger than 12 months with hydrocephalus due to congenital Aqueduct Stenosis (AS), and also in the elderly patients suffering from Normal Pressure Hydrocephalus (NPH), ETV is a better treatment option. Computer simulations show that the maximum CSF pressure is the most reliable hydrodynamic index for the evaluation of the treatment efficacy in these patients. After treatment by ETV and shunt methods, CSF pressure decreases about 9 and 5.3 times, respectively and 2.5 years after shunt implantation, this number returns to normal range.Conclusion:In infants with hydrocephalus, initial treatment by ETV was more reasonable than implanting the shunt. In adult with hydrocephalus, the initial failure in ETV occurred sooner compared to shunt therapy; however, ETV was more efficient.

An Analysis of Dental Implants Survival and Success

Osseointegration of a dental implant may encounter a variety of problems caused by various factors, as prior health-related problems, patients� habits and the technique of the implant inserting. Retrospective cohort study of 70 patients who received implants between January 2011- April 2016 in one dental unit, with Kaplan-Meier method to calculate the probability of implants�s survival at 60 months. The analysis included demographic data, age, gender, medical history, behavior risk factors, type and location of the implant. For this cohort the implants�survival for the first 6 months was 92.86% compared to the number of patients and 97.56% compared to the number of total implants performed, with a cumulative failure rate of 2.43% after 60 months. Failures were focused exclusively on posterior mandible implants, on the percentage of 6.17%, odds ratio (OR) for these failures being 16.76 (P = 0.05) compared with other localisations of implants, exclusively in men with median age of 42 years.

Advancement flap procedure in Crohn and non-Crohn perineal fistulas: a simple surgical approach.

Rectal flap advancement is still a part of therapeutic management of anal fistulas. Data on the outcome of rectal flap advancement in patients with Crohn's disease (CD) is scarce. Our objective was to ascertain rates of failure of rectal flap advancement and to determine predictive factors for failure, with a special focus on CD METHOD: The patients' details, the characteristics of the fistula and the main clinical and therapeutic events were prospectively assessed among patients who underwent rectal flap advancement. All patients had a partial-thickness rectal flap advancement. Failure of primary rectal flap advancement was defined as the occurrence of at least one of the following: abscess, discharge, visible external opening, further drainage procedure. The rates of failure of rectal flap and the predictive factors of failure were assessed. Eighty-seven patients (34 patients with CD) were included. The median (interquartile range) follow-up was 13.3 (3.8-38.1) months. The cumulative failure rates were 15.9% (10.3-23.6), 23.0% (16.0-31.8), 31.6% (22.9-41.8) and 41.3% (30.5-53.0) at 3, 6, 12 and 24months respectively. These data were comparable in Crohn's patients. Those with a supralevator fistula [hazard ratio2.53 (1.01-7.71), P=0.0476] and patients who had fewer than two fistula drainages before rectal flap [hazard ratio3.19 (1.40-8.23), P=0.005] were associated with higher rectal flap failure rates. In CD patients, the absence of biological therapy at referral was predictive of failure. Rectal flap advancement is a satisfactory option for the therapeutic management of anal fistula, including CD populations. Fistula drainage is needed before performing this surgical technique.

Is Optical Coherence Tomography a Potential Tool to Evaluate Marginal Adaptation of Class III/IV Composite Restorations In Vivo?

Margin analysis of Class III and IV composite restorations in vitro and in vivo occurred by scanning electron microscopy (SEM) and optical coherence tomography (OCT). The results were compared and related to clinical evaluation. Eight Class III composite restorations were imaged in vitro using OCT and SEM. The margins were analyzed quantitatively. OCT signals were verified by assignment to the criteria perfect margin, gap, and positive/negative ledge. In vivo quantitative margin analysis of Class III/IV composite restorations made of the micro-hybrid composite Venus combined with the self-etch adhesive iBond Gluma inside (1-SE) or etch-and-rinse adhesive Gluma Comfort Bond (2-ER) (all Heraeus Kulzer) was carried out using OCT and SEM after 90 months of clinical function. The results were compared with clinical evaluation (US Public Health Service criteria; marginal integrity, marginal discoloration). In vitro, the correlation between OCT and SEM was high for all four margin criteria (Kendall tau b [τb] correlation: 0.64-0.92, pi≤0.026), with no significant differences between OCT and SEM (pi≥0.63). In vivo, a moderate correlation was observed (τb: 0.38-0.45, pi<0.016). Clinically, the cumulative failure rate in the criterion marginal integrity was higher for the 1-SE group (baseline 90 M, p=0.011). Similarly, OCT and SEM detected higher percentages of the criterion gap in the 1-SE group (p: 0.027/0.002), in contrast to perfect margin. Both, gap and perfect margin ranged widely between 0.0% and 88.7% (OCT) and between 0.0% and 89.0% (SEM). Despite the positive selection bias after 90 months with only a few patients left, quantitative margin analysis allows for differentiation between the two adhesives at this specific date. OCT in particular offers the possibility to evaluate marginal integrity directly in vivo.

Contraceptive efficacy and safety of estradiol valerate/dienogest in a healthy female population: a multicenter, open-label, uncontrolled Phase III study.

BackgroundTo investigate the efficacy and safety of a combined oral contraceptive containing estradiol valerate and dienogest (EV/DNG) in healthy Asian women.MethodsIn this multicenter Phase III study, women received oral EV/DNG in a 28-day regimen for 13 cycles. The primary efficacy endpoint was the number of unintended pregnancies, measured by the Pearl Index (PI); secondary efficacy endpoints included bleeding pattern and cycle control parameters. Adverse events were monitored during the study and overall satisfaction with treatment was determined on completion of the study.ResultsA total of 954 Asian women (97.7% of subjects assigned to study medication; mean age 33.4 years) were treated. Five pregnancies were reported during EV/DNG treatment over 796.34 relevant woman-years of exposure, giving an unadjusted PI of 0.63 and a cumulative failure rate of 0.0049; 3 pregnancies during EV/DNG treatment over 760.35 relevant woman-years of exposure gave an adjusted PI of 0.39. The bleeding pattern improved during the reporting periods within the study. The proportion of women who experienced withdrawal bleeding decreased with treatment (84.9% of women during Cycle 1 vs 79.3% in Cycle 13), and the mean length of withdrawal bleeding decreased with treatment (4.2 vs 3.4 days). The number and maximum length of intracyclic bleeding/spotting episodes also decreased with EV/DNG. EV/DNG was well tolerated, and 92% of women included in the study were very satisfied or somewhat satisfied with EV/DNG.ConclusionEV/DNG showed high contraceptive efficacy, was well tolerated in Asian women, and may be effectively used in this population.Clinical trials registryClinicalTrials.gov identifier: NCT01638910.

Clinical Effectiveness of a Resin-modified Glass Ionomer Cement and a Mild One-step Self-etch Adhesive Applied Actively and Passively in Noncarious Cervical Lesions: An 18-Month Clinical Trial

To evaluate the clinical effectiveness of two methods of application of a mild one-step self-etch adhesive and composite resin as compared with a resin-modified glass ionomer cement (RMGIC) control restoration in noncarious cervical lesions (NCCLs). A total of 294 restorations were placed in 56 patients, 98 in each one of the following groups: 1) G-Bond active application combined with Solare-X composite resin (A-1SEA), 2) G-Bond passive application combined with Solare-X composite resin (P-1SEA), and 3) GC II LC RMGIC. The restorations were evaluated at baseline and after six, 12, and 18 months according to the FDI criteria for fractures/retention, marginal adaptation, marginal staining, postoperative sensitivity, and secondary caries. Cumulative failure rates were calculated for each criterion at each recall period. The effect of adhesive, method of application, and recall period were assessed. The Kruskal-Wallis test for intergroup comparison and Friedman and Wilcoxon signed ranks tests for intragroup comparison were used for each criterion ( α=0.05). The retention rates at 18 months were 93.26% for the A-1SEA group, 86.21% for the P-1SEA group, and 90.91% for the RMGIC group. The active application improved the retention rates compared with the passive application of mild one-step self-etch adhesive; however, no statistically significant difference was observed between the groups. Marginal staining was observed in 13 restorations (1 in A-1SEA, 4 in P-1SEA, and 8 in RMGIC) with no significant difference between the groups. The RMGIC group showed a significant increase in marginal staining at 12 and 18 months from the baseline. There was no significant difference between the groups for marginal adaptation, secondary caries, or postoperative sensitivity. Within the limitations of the study, we can conclude that mild one-step self-etch adhesive followed by a resin composite restoration can be an alternative to RMGIC with similar retention and improved esthetics in restoration of NCCLs. Agitation could possibly benefit the clinical performance of mild one-step self-etch adhesives, but this study did not confirm that the observed benefit was statistically significant.

Radiotherapy is essential after complete response to asparaginase-containing chemotherapy in early-stage extranodal nasal-type NK/T-cell lymphoma: A multicenter study from the China Lymphoma Collaborative Group (CLCG)

PurposeThis study aimed to clarify the benefit of radiotherapy (RT) in patients with early-stage extranodal NK/T-cell lymphoma (NKTCL) who achieve a complete response (CR) after asparaginase-containing chemotherapy (CT). Patients and methodsOf 240 patients achieved a CR after asparaginase-containing CT, 202 patients received additional RT (CT + RT), and 38 patients did not (CT alone). ResultsCompared to CT alone, CT + RT significantly improved overall survival (OS), disease-free survival (DFS) and locoregional control (LRC). The 5-year OS, DFS and LRC rates were 84.9%, 76.2% and 84.9% for CT + RT, compared to 58.9% (P = 0.006), 43.6% (P = 0.001) and 62.1% (P = 0.026) for CT alone. The 5-year cumulative disease recurrence rate was 18.8% for CT + RT compared to 46.9% (P = 0.003) for CT alone. High-dose RT (≥50 Gy) significantly decreased the risk of locoregional recurrence. The 5-year cumulative locoregional failure rate was 35.5% for patients receiving <50 Gy compared to 8.8% for patients receiving ≥50 Gy (P = 0.028). ConclusionsFor patients with early-stage NKTCL who achieve a CR after asparaginase-containing CT, omission of RT results in frequent locoregional recurrence and a poor prognosis; RT is essential to improve locoregional control and survival.

The fate of preserved sphincter in rectal cancer patients.

Sphincter-saving surgery is widely accepted operative modality to treat rectal cancer. It often requires temporary diverting stoma to avoid the complications of anastomotic failure. This study investigates the cumulative failure rate in sphincter preservation for rectal cancer and the risk factors associated with the permanent stoma. A retrospective study on 358 patients diagnosed with primary rectal cancer from 2009 to 2013 was conducted at a single institute. Three hundred and thirty-one out of 358 patients with rectal cancer located within 12cm from the anal verge, who underwent sphincter-preserving surgery, were included in this study. The cumulative rate for permanent stoma was calculated. Univariate and multivariate analysis were performed, comparing the patients with stoma to the ones without. Temporary diverting stoma was created in 223 (82%) patients. After median follow-up of 42months, 18 patients (6.6%) persistently used temporary stoma or required re-creation of stoma. Univariate analysis revealed that BMI, tumor location below 4cm from the anal verge, coloanal anastomosis, anastomotic leakage, and local recurrence were significantly associated with persistent use or re-formation of stoma. Multivariate analysis showed that anastomotic leakage (OR 50.3; 95% CI, 10.1-250.1; p < 0.0001) and local recurrence (OR 11.3; 95% CI, 1.61-78.5; p = 0.015) were the independent risk factors. Patients with anastomotic leakage and local recurrence are at high risk for permanent stoma. Not only should patients be fully informed of possible failure in sphincter preservation preoperatively, but also patient-oriented decision should be made on patient-tailored surgical plan.

DAHANCA 10 – Effect of darbepoetin alfa and radiotherapy in the treatment of squamous cell carcinoma of the head and neck. A multicenter, open-label, randomized, phase 3 trial by the Danish head and neck cancer group

PurposeTo evaluate if correction of low hemoglobin (Hb) levels by means of darbepoetin alfa improves the outcomes of radiotherapy in patients with squamous cell carcinoma of the head and neck (HNSCC). Patients and methodsPatients eligible for primary radiotherapy and who had Hb values below 14.0 g/dl were randomized to receive accelerated fractionated radiotherapy with or without darbepoetin alfa. Patients also received the hypoxic radiosensitizer nimorazole. Darbepoetin alfa was given weekly during radiotherapy or until the Hb value exceeded 15.5 g/dl. ResultsFollowing a planned interim analysis which showed inferiority of the experimental treatment the trial was stopped after inclusion of 522 patients (of a planned intake of 600). Of these, 513 were eligible for analysis (254 patients treated with darbepoetin alfa and 259 patients in the control group). Overall, the patients were distributed according to the stratification parameters (gender, T and N staging, tumor site). Treatment with darbepoetin alfa increased the Hb level to the planned value in 81% of the patients. The compliance was good without excess serious adverse events.The results showed a poorer outcome with a 5-year cumulative loco-regional failure rate of 47% vs. 34%, Hazard Ratio (HR): 1.53 [1.16–2.02], for the darbepoetin alfa vs. control arm, respectively. This was also seen for the endpoints of event-free survival (HR: 1.36 [1.09–1.69]), disease-specific death (HR: 1.43 [1.08–1.90]), and overall survival (HR: 1.30 [1.02–1.64]). There was no enhanced risk of cardio-vascular events observed in the experimental arm or any significant differences in acute or late radiation related morbidity. All univariate analyses were confirmed in a multivariate setting. ConclusionCorrection of the Hb level with darbepoetin alfa during radiotherapy of patients with HNSCC resulted in a significantly poorer tumor control and survival.