Randomized controlled trial on single dose steroid before thyroidectomy for benign disease to improve postoperative nausea, pain, and vocal function

OBJECTIVE: To evaluate the effects of a single preoperative dose of steroid on thyroidectomy outcomes. BACKGROUND: Nausea, pain, and voice alteration frequently occur after thyroidectomy. Because steroids effectively reduce nausea and inflammation, a preoperative administration of steroids could improve these thyroidectomy outcomes. METHODS: Seventy-two patients (men = 20, women = 52) undergoing thyroidectomy for benign disease were included in this randomized, controlled, 2 armed (group D: 8 mg dexamethasone, n = 37; group C: 0.9% NaCl, n = 35), double-blinded study (clinical trial number NCT00619086). Anesthesia, surgical procedures, antiemetics, and analgesic treatments were standardized. Nausea (0-3), pain (visual analog scale), antiemetic and analgesic requirements, and digital voice recording were documented before and 4, 8, 16, 24, 36, and 48 hours after surgery. Patients were followed-up 30 days after hospital discharge. RESULTS: Baseline characteristics were similar among the 2 treatment groups. Nausea was pronounced in the first 16 hours postoperatively (scores were <0.3 and 0.8-1.0 for group D and C, respectively (P = 0.005)), and was significantly lower in group D compared with group C during the observation period (P = 0.001). Pain diminished within 48 hours after surgery (visual analog scale 20 and 35 in group D and C, respectively (P = 0.009)). Antiemetic and analgesic requirements were also significantly diminished. Changes in voice mean frequency were less prominent in the dexamethasone group compared with the placebo group (P = 0.015). No steroid-related complications occurred. CONCLUSION: A preoperative single dose of steroid significantly reduced nausea, vomiting, and pain, and improved postoperative voice function within the first 48 hours (most pronounced within 16 hours) after thyroid resection; this strategy should be routinely applied in thyroidectomies.

To stent or not to stent perioperatively the ureteroileal anastomosis of ileal orthotopic bladder substitutes and ileal conduits? Results of a prospective randomized trial

PURPOSE: We evaluated the impact of stenting the ureteroileal anastomosis on its competence, upper urinary tract dilatation, gastrointestinal recovery, metabolic parameters and patency rate after cystectomy with ileal bladder substitution or ileal conduit. MATERIALS AND METHODS: A total of 54 patients (37 with an ileal bladder substitute and 17 with an ileal conduit) were prospectively randomized into 2 groups, with (29) or without (25) perioperative stenting of the ureteroileal anastomosis. In all cases an end-to-side ureteroileal refluxing anastomosis was performed. The stents were removed after 5 to 10 days. The parameters assessed postoperative days 1, 3 and 7 were creatinine concentration from the wound drains, upper urinary tract dilatation, time to bowel function recovery, serum creatinine, as well as urea and incidence of metabolic acidosis. RESULTS: Median patient age was 68 years (range 45 to 85). Urine leak on postoperative day 1 was more frequent in those anastomoses without stents, and on postoperative days 3 and 7 the values were comparable. Stenting of the ureteroileal anastomosis resulted in significantly decreased early postoperative upper urinary tract dilatation, improved recovery of bowel function and decreased metabolic acidosis. In either group no patient had clinical evidence of ureteroileal anastomotic stricture during the early postoperative period. Three patients with perioperative stenting required surgical or endoscopic treatment for a stricture of the ureteroileal anastomosis during the 12-month followup. CONCLUSIONS: Stenting of the ureteroileal anastomosis allows for significantly less frequent incidence of early postoperative dilatation of the pelvicaliceal system, bowel activity resumes significantly earlier and metabolic acidosis is significantly less frequent.

Individual versus standard quality of life assessment in a phase II clinical trial in mesothelioma patients: feasibility and responsiveness to clinical changes

In patients with malignant pleural mesothelioma undergoing a multimodality therapy, treatment toxicity may outweigh the benefit of progression-free survival. The subjective experience across different treatment phases is an important clinical outcome. This study compares a standard with an individual quality of life (QoL) measure used in a multi-center phase II trial.

Trial-to-trial size variability of motor-evoked potentials. A study using the triple stimulation technique

Motor-evoked potentials (MEPs) vary in size from one stimulus to the next. The objective of this study was to determine the cause and source of trial-to-trial MEP size variability. In two experiments involving 10 and 14 subjects, the variability of MEPs to cortical stimulation (cortical-MEPs) in abductor digiti minimi (ADM) and abductor hallucis (AH) was compared to those responses obtained using the triple stimulation technique (cortical-TST). The TST eliminates the effects of motor neuron (MN) response desynchronization and of repetitive MN discharges. Submaximal stimuli were used in both techniques. In six subjects, cortical-MEP variability was compared to that of brainstem-MEP and brainstem-TST. Variability was greater for MEPs than that for TST responses, by approximately one-third. The variability was the same for cortical- and brainstem-MEPs and was similar in ADM and AH. Variability concerned at least 10-15% of the MN pool innervating the target muscle. With the stimulation parameters used, repetitive MN discharges did not influence variability. For submaximal stimuli, approximately two-third of the observed MEP size variability is caused by the variable number of recruited alpha-MNs and approximately one-third by changing synchronization of MN discharges. The source of variability is most likely localized at the spinal segmental level.

United we stand, divided we fall: a meta-analysis of experiments on clonal integration and its relationship to invasiveness

Fragmentation and vegetative regeneration from small fragments may contribute to population expansion, dispersal and establishment of new populations of introduced plants. However, no study has systematically tested whether a high capacity of vegetative regeneration is associated with a high degree of invasiveness. For small single-node fragments, the presence of internodes may increase regeneration capacity because internodes may store carbohydrates and proteins that can be used for regeneration. We conducted an experiment with 39 stoloniferous plant species to examine the regeneration capacity of small, single-node fragments with or without attached stolon internodes. We asked (1) whether the presence of stolon internodes increases regeneration from single-node fragments, (2) whether regeneration capacity differs between native and introduced species in China, and (3) whether regeneration capacity is positively associated with plant invasiveness at a regional scale (within China) and at a global scale. Most species could regenerate from single-node fragments, and the presence of internodes increased regeneration rate and subsequent growth and/or asexual reproduction. Regeneration capacity varied greatly among species, but showed no relationship to invasiveness, either in China or globally. High regeneration capacity from small fragments may contribute to performance of clonal plants in general, but it does not appear to explain differences in invasiveness among stoloniferous clonal species.

Effect of a chitosan additive to a Sn(2+)-containing toothpaste on its anti-erosive/anti-abrasive efficacy-a controlled randomised in situ trial

OBJECTIVES It is well known that Sn(2+) is a notable anti-erosive agent. There are indications that biopolymers such as chitosan can enhance the effect of Sn(2+), at least in vitro. However, little information exists about their anti-erosive/anti-abrasive in situ effects. In the present in situ study, the efficacy of Sn(2+)-containing toothpastes in the presence or absence of chitosan was tested. METHODS Ten subjects participated in the randomised crossover study, wearing mandibular appliances with human enamel specimens. Specimens were extraorally demineralised (7 days, 0.5 % citric acid, pH 2.6; 6 × 2 min/day) and intraorally exposed to toothpaste suspensions (2 × 2 min/day). Within the suspension immersion time, one half of the specimens were additionally brushed intraorally with a powered toothbrush (5 s, 2.5 N). Tested preparations were a placebo toothpaste (negative control), two experimental toothpastes (F/Sn = 1,400 ppm F(-), 3,500 ppm Sn(2+); F/Sn/chitosan = 1,400 ppm F(-), 3,500 ppm Sn(2+), 0.5 % chitosan) and an SnF2-containing gel (positive control, GelKam = 3,000 ppm Sn(2+), 1,000 ppm F(-)). Substance loss was quantified profilometrically (μm). RESULTS In the placebo group, tissue loss was 11.2 ± 4.6 (immersion in suspension) and 17.7 ± 4.7 (immersion in suspension + brushing). Immersion in each Sn(2+)-containing suspension significantly reduced tissue loss (p ≤ 0.01); after immersion in suspension + brushing, only the treatments with GelKam (5.4 ± 5.5) and with F/Sn/chitosan (9.6 ± 5.6) significantly reduced loss [both p ≤ 0.05 compared to placebo; F/Sn 12.8 ± 6.4 (not significant)] CONCLUSION Chitosan enhanced the efficacy of the Sn(2+)-containing toothpaste as an anti-erosive/anti-abrasive agent. CLINICAL RELEVANCE The use of Sn(2+)- and chitosan-containing toothpaste is a good option for symptomatic therapy in patients with regular acid impacts.

Differences in Time to Disease Progression Do Not Predict for Cancer-specific Survival in Patients Receiving Immediate or Deferred Androgen-deprivation Therapy for Prostate Cancer: Final Results of EORTC Randomized Trial 30891 with 12 Years of Follow-up

BACKGROUND Trials assessing the benefit of immediate androgen-deprivation therapy (ADT) for treating prostate cancer (PCa) have often done so based on differences in detectable prostate-specific antigen (PSA) relapse or metastatic disease rates at a specific time after randomization. OBJECTIVE Based on the long-term results of European Organization for Research and Treatment of Cancer (EORTC) trial 30891, we questioned if differences in time to progression predict for survival differences. DESIGN, SETTING, AND PARTICIPANTS EORTC trial 30891 compared immediate ADT (n=492) with orchiectomy or luteinizing hormone-releasing hormone analog with deferred ADT (n=493) initiated upon symptomatic disease progression or life-threatening complications in randomly assigned T0-4 N0-2 M0 PCa patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Time to first objective progression (documented metastases, ureteric obstruction, not PSA rise) and time to objective castration-resistant progressive disease were compared as well as PCa mortality and overall survival. RESULTS AND LIMITATIONS After a median of 12.8 yr, 769 of the 985 patients had died (78%), 269 of PCa (27%). For patients receiving deferred ADT, the overall treatment time was 31% of that for patients on immediate ADT. Deferred ADT was significantly worse than immediate ADT for time to first objective disease progression (p<0.0001; 10-yr progression rates 42% vs 30%). However, time to objective castration-resistant disease after deferred ADT did not differ significantly (p=0.42) from that after immediate ADT. In addition, PCa mortality did not differ significantly, except in patients with aggressive PCa resulting in death within 3-5 yr after diagnosis. Deferred ADT was inferior to immediate ADT in terms of overall survival (hazard ratio: 1.21; 95% confidence interval, 1.05-1.39; p [noninferiority]=0.72, p [difference] = 0.0085). CONCLUSIONS This study shows that if hormonal manipulation is used at different times during the disease course, differences in time to first disease progression cannot predict differences in disease-specific survival. A deferred ADT policy may substantially reduce the time on treatment, but it is not suitable for patients with rapidly progressing disease.

Myocardial Infarction - Stress PRevention INTervention (MI-SPRINT) to reduce the incidence of posttraumatic stress after acute myocardial infarction through trauma-focused psychological counseling: study protocol for a randomized controlled trial

BACKGROUND Posttraumatic Stress Disorder (PTSD) may occur in patients after exposure to a life-threatening illness. About one out of six patients develop clinically relevant levels of PTSD symptoms after acute myocardial infarction (MI). Symptoms of PTSD are associated with impaired quality of life and increase the risk of recurrent cardiovascular events. The main hypothesis of the MI-SPRINT study is that trauma-focused psychological counseling is more effective than non-trauma focused counseling in preventing posttraumatic stress after acute MI. METHODS/DESIGN The study is a single-center, randomized controlled psychological trial with two active intervention arms. The sample consists of 426 patients aged 18 years or older who are at 'high risk' to develop clinically relevant posttraumatic stress symptoms. 'High risk' patients are identified with three single-item questions with a numeric rating scale (0 to 10) asking about 'pain during MI', 'fear of dying until admission' and/or 'worrying and feeling helpless when being told about having MI'. Exclusion criteria are emergency heart surgery, severe comorbidities, current severe depression, disorientation, cognitive impairment and suicidal ideation. Patients will be randomly allocated to a single 45-minute counseling session targeting either specific MI-triggered traumatic reactions (that is, the verum intervention) or the general role of psychosocial stress in coronary heart disease (that is, the control intervention). The session will take place in the coronary care unit within 48 hours, by the bedside, after patients have reached stable circulatory conditions. Each patient will additionally receive an illustrated information booklet as study material. Sociodemographic factors, psychosocial and medical data, and cardiometabolic risk factors will be assessed during hospitalization. The primary outcome is the interviewer-rated posttraumatic stress level at three-month follow-up, which is hypothesized to be at least 20% lower in the verum group than in the control group using the t-test. Secondary outcomes are posttraumatic stress levels at 12-month follow-up, and psychosocial functioning and cardiometabolic risk factors at both follow-up assessments. DISCUSSION If the verum intervention proves to be effective, the study will be the first to show that a brief trauma-focused psychological intervention delivered within a somatic health care setting can reduce the incidence of posttraumatic stress in acute MI patients. TRIAL REGISTRATION ClinicalTrials.gov: NCT01781247.

Atorvastatin added to interferon beta for relapsing multiple sclerosis: 12-month treatment extension of the randomized multicenter SWABIMS trial

BACKGROUND Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. OBJECTIVES To report the 12-month extension of a phase II trial evaluating the efficacy, safety and tolerability of atorvastatin 40 mg/d added to interferon beta-1b (IFNB-1b) in relapsing-remitting multiple sclerosis (RRMS). METHODS In the randomized, multicenter, parallel-group, rater-blinded core study, 77 RRMS patients started IFNB-1b. At month three they were randomized 1∶1 to receive atorvastatin 40 mg/d or not in addition to IFNB-1b until month 15. In the subsequent extension study, patients continued with unchanged medication for another 12 months. Data at study end were compared to data at month three of the core study. RESULTS 27 of 72 patients that finished the core study entered the extension study. 45 patients were lost mainly due to a safety analysis during the core study including a recruitment stop for the extension study. The primary end point, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.926; 95% CI 0.265-14.0007; p = 0.51). All secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of Gd-enhancing lesions on T1-weighted images, volume of grey and white matter, EDSS, MSFC, relapse rate, number of relapse-free patients and neutralizing antibodies did not show significant differences either. The combination therapy was well tolerated. CONCLUSIONS Atorvastatin 40 mg/day in addition to IFNB-1b did not have any beneficial effects on RRMS compared to IFNB-1b monotherapy over a period of 24 months.

High-speed rotational atherectomy before paclitaxel-eluting stent implantation in complex calcified coronary lesions: the randomized ROTAXUS (Rotational Atherectomy Prior to Taxus Stent Treatment for Complex Native Coronary Artery Disease) trial

OBJECTIVES This study sought to determine the effect of rotational atherectomy (RA) on drug-eluting stent (DES) effectiveness. BACKGROUND DES are frequently used in complex lesions, including calcified stenoses, which may challenge DES delivery, expansion, and effectiveness. RA can adequately modify calcified plaques and facilitate stent delivery and expansion. Its impact on DES effectiveness is widely unknown. METHODS The ROTAXUS (Rotational Atherectomy Prior to TAXUS Stent Treatment for Complex Native Coronary Artery Disease) study randomly assigned 240 patients with complex calcified native coronary lesions to RA followed by stenting (n = 120) or stenting without RA (n = 120, standard therapy group). Stenting was performed using a polymer-based slow-release paclitaxel-eluting stent. The primary endpoint was in-stent late lumen loss at 9 months. Secondary endpoints included angiographic and strategy success, binary restenosis, definite stent thrombosis, and major adverse cardiac events at 9 months. RESULTS Despite similar baseline characteristics, significantly more patients in the standard therapy group were crossed over (12.5% vs. 4.2%, p = 0.02), resulting in higher strategy success in the rotablation group (92.5% vs. 83.3%, p = 0.03). At 9 months, in-stent late lumen loss was higher in the rotablation group (0.44 ± 0.58 vs. 0.31 ± 0.52, p = 0.04), despite an initially higher acute lumen gain (1.56 ± 0.43 vs. 1.44 ± 0.49 mm, p = 0.01). In-stent binary restenosis (11.4% vs. 10.6%, p = 0.71), target lesion revascularization (11.7% vs. 12.5%, p = 0.84), definite stent thrombosis (0.8% vs. 0%, p = 1.0), and major adverse cardiac events (24.2% vs. 28.3%, p = 0.46) were similar in both groups. CONCLUSIONS Routine lesion preparation using RA did not reduce late lumen loss of DES at 9 months. Balloon dilation with only provisional rotablation remains the default strategy for complex calcified lesions before DES implantation.

Caries-preventive effectiveness of fluoride varnish as adjunct to oral health promotion and supervised tooth brushing in preschool children: a double-blind randomized controlled trial.

OBJECTIVES To evaluate the effect of biannual fluoride varnish applications in preschool children as an adjunct to school-based oral health promotion and supervised tooth brushing with 1000ppm fluoride toothpaste. METHODS 424 preschool children, 2-5 year of age, from 10 different pre schools in Athens were invited to this double-blind randomized controlled trial and 328 children completed the 2-year programme. All children received oral health education with hygiene instructions twice yearly and attended supervised tooth brushing once daily. The test group was treated with fluoride varnish (0.9% diflurosilane) biannually while the control group had placebo applications. The primary endpoints were caries prevalence and increment; secondary outcomes were gingival health, mutans streptococci growth and salivary buffer capacity. RESULTS The groups were balanced at baseline and no significant differences in caries prevalence or increment were displayed between the groups after 1 and 2 years, respectively. There was a reduced number of new pre-cavitated enamel lesions during the second year of the study (p=0.05) but the decrease was not statistically significant. The secondary endpoints were unaffected by the varnish treatments. CONCLUSIONS Under the present conditions, biannual fluoride varnish applications in preschool children did not show significant caries-preventive benefits when provided as an adjunct to school-based supervised tooth brushing with 1000ppm fluoride toothpaste. CLINICAL SIGNIFICANCE In community based, caries prevention programmes, for high caries risk preschool children, a fluoride varnish may add little to caries prevention, when 1000ppm fluoride toothpaste is used daily.

The Effect of 6 versus 9 Years of Zoledronic Acid Treatment in Osteoporosis: A Randomized Second Extension to the HORIZON-Pivotal Fracture Trial (PFT).

While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n=95) and Z6P3 (n=95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was -0.54% in Z9 vs. -1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: -0.37%, 1.93%; p=0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. This article is protected by copyright. All rights reserved.