Comparison of the effects of cetylpyridinium chloride with an essential oil mouth rinse on dental plaque and gingivitis - a six-month randomized controlled clinical trial

OBJECTIVE: To compare the effects of an experimental mouth rinse containing 0.07% cetylpyridinium chloride (CPC) (Crest Pro-Health) with those provided by a commercially available mouth rinse containing essential oils (EOs) (Listerine) on dental plaque accumulation and prevention of gingivitis in an unsupervised 6-month randomized clinical trial. MATERIAL AND METHODS: This double-blind, 6-month, parallel group, positively controlled study involved 151 subjects balanced and randomly assigned to either positive control (EO) or experimental (CPC) mouth rinse treatment groups. At baseline, subjects received a dental prophylaxis procedure and began unsupervised rinsing twice a day with 20 ml of their assigned mouthwash for 30 s after brushing their teeth for 1 min. Subjects were assessed for gingivitis and gingival bleeding by the Gingival index (GI) of Löe ; Silness (1963) and plaque by the Silness ; Löe (1964) Plaque index at baseline and after 3 and 6 months of rinsing. At 3 and 6 months, oral soft tissue health was assessed. Microbiological samples were also taken for community profiling by the DNA checkerboard method. RESULTS: Results show that after 3 and 6 months of rinsing, there were no significant differences (p=0.05) between the experimental (CPC) and the positive control mouth rinse treatment groups for overall gingivitis status, gingival bleeding, and plaque accumulation. At 6 months, the covariant (baseline) adjusted mean GI and bleeding sites percentages for the CPC and the EO rinses were 0.52 and 0.53 and 8.7 and 9.3, respectively. Both mouth rinses were well tolerated by the subjects. Microbiological community profiles were similar for the two treatment groups. Statistically, a significant greater reduction in bleeding sites was observed for the CPC rinse versus the EO rinse. CONCLUSION: The essential findings of this study indicated that there was no statistically significant difference in the anti-plaque and anti-gingivitis benefits between the experimental CPC mouth rinse and the positive control EO mouth rinse over a 6-month period.

Six-month angiographic follow-up of the PAS-Port II clinical trial

BACKGROUND: The PAS-Port device (Cardica, Redwood City, CA) allows the rapid deployment of a clampless proximal anastomosis between a vein graft and the aorta. METHODS: Fifty-four patients awaiting elective coronary artery bypass graft surgery were enrolled. Outcome variables were intraoperative device performance, early and 6- month angiographic graft patency, and 12-month clinical follow-up. RESULTS: Sixty-three PAS-Port devices were deployed in 54 patients. Two deployments were unsuccessful. There were no reoperations for bleeding. Two patients died of causes unrelated to the device. Patency evaluation at discharge was performed by angiogram on 49 implants and computed tomography in 2 implants (86% follow-up). At discharge, all evaluated grafts were patent (100%) and rated Fitzgibbon A. At 6-month follow-up, there was no additional mortality; 47 implants (88% follow-up) were evaluated by angiography (Fitzgibbon O [n = 1], Fitzgibbon B [n = 1], and Fitzgibbon A [n = 45]) and 5 by computed tomography. All grafts but 1 were patent (98.1%). At 12 months, 2 additional patients died of causes unrelated to the PAS-Port implant. Forty-six of 50 alive patients (95.8%) were followed up without any reports of device-related major adverse cardiac events. CONCLUSIONS: Discharge (100%) and 6-month patency (98%) are excellent; patency and 12 months' clinical follow-up compares favorably with data from historical hand-sewn controls. The PAS-Port system safely allows the clampless creation of a proximal anastomosis.

One-year outcomes of repeated adjunctive photodynamic therapy during periodontal maintenance: a proof-of-principle randomized-controlled clinical trial

BACKGROUND: Single photodynamic therapy (PDT) has been effective in initial periodontal therapy, but only improved bleeding on probing (BoP) in maintenance patients after a single use. Repeated PDT has not been addressed. OBJECTIVES: To study the possible added benefits of repeated adjunctive PDT to conventional treatment of residual pockets in patients enrolled in periodontal maintenance. MATERIAL AND METHODS: Ten maintenance patients with 70 residual pockets [probing pocket depth (PPD)>or=5 mm] were randomly assigned for treatment five times in 2 weeks (Days 0, 1, 2, 7, 14) with PDT (test) or non-activated laser (control) following debridement. The primary outcome variable was PPD, and the secondary variables were clinical attachment level (CAL) and BoP. These were assessed at 3, 6 and 12 months following the interventions. RESULTS: Greater PPD reductions were observed in the test (-0.67 +/- 0.34; p=0.01) compared with the control patients (-0.04 +/- 0.33; NS) after 6 months. Significant CAL gain (+0.52 +/- 0.31; p=0.01) was noted for the test, but not in the control (-0.27 +/- 0.52; NS) patients after 6 months. BoP percentages decreased significantly in test (97-64%, 67%, 77%), but not control patients after 3, 6 and 12 months. CONCLUSIONS: Repeated (five times) PDT adjunctive to debridement yielded improved clinical outcomes in residual pockets in maintenance patients. The effects were best documented after 6 months.

Anti-infective therapy of peri-implantitis with adjunctive local drug delivery or photodynamic therapy: 12-month outcomes of a randomized controlled clinical trial

OBJECTIVE: The objective of the study is to compare the clinical, microbiological and host-derived effects in the non-surgical treatment of initial peri-implantitis with either adjunctive local drug delivery (LDD) or adjunctive photodynamic therapy (PDT) after 12 months. MATERIALS AND METHODS: Forty subjects with initial peri-implantitis, that is, pocket probing depths (PPD) 4-6 mm with bleeding on probing (BoP) and radiographic bone loss ≤2 mm, were randomly assigned to two treatment groups. All implants were mechanically debrided with titanium curettes and with a glycine-based powder airpolishing system. Implants in the test group (N = 20) received adjunctive PDT, whereas minocycline microspheres were locally delivered into the peri-implant pockets of control implants (N = 20). At sites with residual BoP, treatment was repeated after 3, 6, 9 and 12 months. The primary outcome variable was the change in the number of peri-implant sites with BoP. Secondary outcome variables included changes in PPD, clinical attachment level (CAL), mucosal recession (REC) and in bacterial counts and crevicular fluid (CF) levels of host-derived biomarkers. RESULTS: After 12 months, the number of BoP-positive sites decreased statistically significantly (P < 0.05) from baseline in both groups (PDT: 4.03 ± 1.66-1.74 ± 1.37, LDD: 4.41 ± 1.47-1.55 ± 1.26). A statistically significant (P < 0.05) decrease in PPD from baseline was observed at PDT-treated sites up to 9 months (4.19 ± 0.55 mm to 3.89 ± 0.68 mm) and up to 12 months at LDD-treated sites (4.39 ± 0.77 mm to 3.83 ± 0.85 mm). Counts of Porphyromonas gingivalis and Tannerella forsythia decreased statistically significantly (P < 0.05) from baseline to 6 months in the PDT and to 12 months in the LDD group, respectively. CF levels of IL-1β decreased statistically significantly (P < 0.05) from baseline to 12 months in both groups. No statistically significant differences (P > 0.05) were observed between groups after 12 months with respect to clinical, microbiological and host-derived parameters. CONCLUSIONS: Non-surgical mechanical debridement with adjunctive PDT was equally effective in the reduction of mucosal inflammation as with adjunctive delivery of minocycline microspheres up to 12 months. Adjunctive PDT may represent an alternative approach to LDD in the non-surgical treatment of initial peri-implantitis.

The effects of erythritol air-polishing powder on microbiologic and clinical outcomes during supportive periodontal therapy: Six-month results of a randomized controlled clinical trial.

OBJECTIVES To characterize the physical characteristics of a new low abrasive erythritol powder (EPAP) and to evaluate its influence on the clinical and microbiologic parameters over a period of 6 months in patients undergoing supportive periodontal therapy (SPT). METHOD AND MATERIALS Prior to the clinical application, the particle size and abrasion level of EPAP were compared to glycine air-polishing powder (GPAP) ex vivo. Subsequently, 40 chronic periodontitis patients previously enrolled in SPT were randomly assigned into two groups for the treatment with subgingival EPAP or repeated scaling and root planing (SRP). At baseline (BL), bleeding on probing positive (BOP+) sites with probing pocket depth (PPD) of ≥ 4 mm but no detectable calculus were defined as study sites. During SPT, these sites were either treated by EPAP or SRP at BL, 3, and 6 months (3M, 6M). When indicated, additional SRP was provided. Plaque Index, BOP, PPD, clinical attachment level (CAL), and subgingival plaque were evaluated at BL and 6M. RESULTS EPAP yielded lower abrasiveness and smaller particle sizes when compared to GPAP. In 38 patients completing the study, EPAP and SRP resulted in significant reductions of BOP% (EPAP, 40.45%; SRP, 42.53%), PPD (EPAP, -0.67; SRP, -0.68), and increase of CAL (EPAP, 0.48; SRP, 0.61) while at 6M no statistically significant between-group differences were observed (P > .05). Microbiologic evaluation revealed minor shifts in the composition of the subgingival biofilm without influence on periodontopathogenic bacteria. CONCLUSION The subgingival use of EPAP by means of an air-polishing device may be considered safe and may lead to comparable clinical and microbiologic outcomes to those obtained with SRP. CLINICAL RELEVANCE The subgingival use of EPAP appears to represent a promising modality for the removal of subgingival biofilm during SPT.

Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial.

BACKGROUND REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding. METHODS We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions. FINDINGS 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80-1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73-16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19-2·25; p=0·002). INTERPRETATION The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin. FUNDING Regado Biosciences Inc.

Time-differentiated target temperature management after out-of-hospital cardiac arrest: a multicentre, randomised, parallel-group, assessor-blinded clinical trial (the TTH48 trial): study protocol for a randomised controlled trial

BACKGROUND The application of therapeutic hypothermia (TH) for 12 to 24 hours following out-of-hospital cardiac arrest (OHCA) has been associated with decreased mortality and improved neurological function. However, the optimal duration of cooling is not known. We aimed to investigate whether targeted temperature management (TTM) at 33 ± 1 °C for 48 hours compared to 24 hours results in a better long-term neurological outcome. METHODS The TTH48 trial is an investigator-initiated pragmatic international trial in which patients resuscitated from OHCA are randomised to TTM at 33 ± 1 °C for either 24 or 48 hours. Inclusion criteria are: age older than 17 and below 80 years; presumed cardiac origin of arrest; and Glasgow Coma Score (GCS) <8, on admission. The primary outcome is neurological outcome at 6 months using the Cerebral Performance Category score (CPC) by an assessor blinded to treatment allocation and dichotomised to good (CPC 1-2) or poor (CPC 3-5) outcome. Secondary outcomes are: 6-month mortality, incidence of infection, bleeding and organ failure and CPC at hospital discharge, at day 28 and at day 90 following OHCA. Assuming that 50 % of the patients treated for 24 hours will have a poor outcome at 6 months, a study including 350 patients (175/arm) will have 80 % power (with a significance level of 5 %) to detect an absolute 15 % difference in primary outcome between treatment groups. A safety interim analysis was performed after the inclusion of 175 patients. DISCUSSION This is the first randomised trial to investigate the effect of the duration of TTM at 33 ± 1 °C in adult OHCA patients. We anticipate that the results of this trial will add significant knowledge regarding the management of cooling procedures in OHCA patients. TRIAL REGISTRATION NCT01689077.

Stapled haemorrhoidopexy vs. Milligan-Morgan haemorrhoidectomy for grade III haemorrhoids: a randomized clinical trial

The aim of this double blind randomized clinical trial was to compare the short-term and long-term outcomes of stapled haemorrhoidopexy (SH group) performed using a circular stapler with that of the Milligan-Morgan haemorrhoidectomy (MMH group). A total of 79 consecutive patients with grade III haemorrhoids were randomized into two groups treated with SH (n. 39) and MMH (n. 40). The outcomes of the procedures were evaluated postoperatively and over a follow-up period of minimum 2 years. Patients undergoing the SH procedure showed greater short term advantages than MMH group with reduced pain, shorter length of hospital stay, earlier return to work and high patient satisfaction. Long-term follow-up has indicated more favourable results in MMH group in terms of resumption of symptoms with absence of residual prolapse and risk of recurrence of prolapse. At two years follow-up recurrent prolapse was confirmed in six patients of SH group (13%) whereas in none of the MMH group. At six months follow-up there weren’t significant difference in the mean satisfaction score for the two groups. At two years the mean satisfaction score was higher in the MMH group vs SH group. Seven patients in the SH group needed a reoperation whereas none in MMH group. From January 2009, in our Surgery Unit the patients are always informed about a higher recurrence rate of SH and we perform this technique only when the patient choices to accept this risk to take advantage of the short-term benefits of this procedure.

Therapeutic failure with thalidomide in patients with recurrent intestinal bleeding due to angiodysplasias

Angiodysplasias are one of the reasons of gastrointestinal bleeding, whose origin is usually due to vascular malformations. There are different types of therapies for angiodysplasia such as endoscopic, angiographic and pharmacological techniques. Among the last ones, there is little variety of effective drugs to treat the disease. We describe the therapeutic failure with thalidomide in a male with recurrent gastrointestinal bleeding due to angiodysplasias. A thorough diagnostic work-up, including gastroscopy, enteroscopy, angiography and capsule endoscopy were performed. Despite treatment with high-dose somatostatin analogues and oral iron, the patient continued bleeding. The patient was administered then thalidomide for three months with no clinical response. Thalidomide had to be withdrawn owing to adverse effects.

Prospective, non-randomized phase 2 clinical trial of carboplatin plus paclitaxel with sequential radical pelvic radiotherapy for uterine papillary serous carcinoma

Objective Uterine Papillary Serous Carcinoma (UPSC) is uncommon and accounts for less than 5% of all uterine cancers. Therefore the majority of evidence about the benefits of adjuvant treatment comes from retrospective case series. We conducted a prospective multi-centre non-randomized phase 2 clinical trial using four cycles of adjuvant paclitaxel plus carboplatin chemotherapy followed by pelvic radiotherapy, in order to evaluate the tolerability and safety of this approach. Methods This trial enrolled patients with newly diagnosed, previously untreated patients with stage 1b-4 (FIGO-1988) UPSC with a papillary serous component of at least 30%. Paclitaxel (175 mg/m2) and carboplatin (AUC 6) were administered on day 1 of each 3-week cycle for 4 cycles. Chemotherapy was followed by external beam radiotherapy to the whole pelvis (50.4 Gy over 5.5 weeks). Completion and toxicity of treatment (Common Toxicity Criteria, CTC) and quality of life measures were the primary outcome indicators. Results Twenty-nine of 31 patients completed treatment as planned. Dose reduction was needed in 9 patients (29%), treatment delay in 7 (23%), and treatment cessation in 2 patients (6.5%). Hematologic toxicity, grade 3 or 4 occurred in 19% (6/31) of patients. Patients' self-reported quality of life remained stable throughout treatment. Thirteen of the 29 patients with stages 1–3 disease (44.8%) recurred (average follow up 28.1 months, range 8–60 months). Conclusion This multimodal treatment is feasible, safe and tolerated reasonably well and would be suitable for use in multi-institutional prospective randomized clinical trials incorporating novel therapies in patients with UPSC.

Clinical trial of the Norton Scale in acute care settings

This study investigated the effect of using Norton Scale assessment data in the nursing care of patients at risk of developing pressure ulcers. The results indicated that incorporating the Norton Scale in care planning resulted in benefits to patients through earlier and more effective nursing interventions.

Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis

Background Chaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS). Methods A total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10. Results No significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen. Conclusions Cpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.