Protocol for a randomized, placebo-controlled, double-blind clinical trial investigating sacral neuromodulation for neurogenic lower urinary tract dysfunction

BACKGROUND Sacral neuromodulation has become a well-established and widely accepted treatment for refractory non-neurogenic lower urinary tract dysfunction, but its value in patients with a neurological cause is unclear. Although there is evidence indicating that sacral neuromodulation may be effective and safe for treating neurogenic lower urinary tract dysfunction, the number of investigated patients is low and there is a lack of randomized controlled trials. METHODS AND DESIGN This study is a prospective, randomized, placebo-controlled, double-blind multicenter trial including 4 sacral neuromodulation referral centers in Switzerland. Patients with refractory neurogenic lower urinary tract dysfunction are enrolled. After minimally invasive bilateral tined lead placement into the sacral foramina S3 and/or S4, patients undergo prolonged sacral neuromodulation testing for 3-6 weeks. In case of successful (defined as improvement of at least 50% in key bladder diary variables (i.e. number of voids and/or number of leakages, post void residual) compared to baseline values) prolonged sacral neuromodulation testing, the neuromodulator is implanted in the upper buttock. After a 2 months post-implantation phase when the neuromodulator is turned ON to optimize the effectiveness of neuromodulation using sub-sensory threshold stimulation, the patients are randomized in a 1:1 allocation in sacral neuromodulation ON or OFF. At the end of the 2 months double-blind sacral neuromodulation phase, the patients have a neuro-urological re-evaluation, unblinding takes place, and the neuromodulator is turned ON in all patients. The primary outcome measure is success of sacral neuromodulation, secondary outcome measures are adverse events, urodynamic parameters, questionnaires, and costs of sacral neuromodulation. DISCUSSION It is of utmost importance to know whether the minimally invasive and completely reversible sacral neuromodulation would be a valuable treatment option for patients with refractory neurogenic lower urinary tract dysfunction. If this type of treatment is effective in the neurological population, it would revolutionize the management of neurogenic lower urinary tract dysfunction. TRIAL REGISTRATION TRIAL REGISTRATION NUMBER http://www.clinicaltrials.gov; Identifier: NCT02165774.

How much Entrepreneurial Orientation (EO) is needed for Long-term Success?

According to the STEP research framework, entrepreneurial orientation (EO) is one key element of transgenerational value creation. EO refers to key entrepreneurial processes in a company, i.e. to the methods, practices and decision-making styles managers use to act entrepreneurially. 3 EO consists of five main dimensions and several sub dimensions. However, there is a puzzle. Many studies suggest that the higher EO, the more successful a company is. But this seems not always to be true. Just think of many of the dot.com firms at the end of the 1990s. Firm members could act very autonomously, the companies were very innovative, took high risks, were very proactive and very aggressive in the market. However, most of them were not able to survive for more than a few years. So how entrepreneurial has a firm to be in order to achieve long-term success?

Factors determining the success of radiofrequency denervation in lumbar facet joint pain: a prospective study

Background and aims Radiofrequency denervation (RF) of the lumbar facet joints has been shown to be effective in well-selected patients. However, long-term success varies between studies. We evaluated the influence of selected psychosocial and constitutional factors on the outcome of RF, expressed as the duration of pain relief. Methods This prospective observational study included 44 patients who received RF denervations at the University Hospital of Berne. Success was defined as at least 50% pain reduction 7–21 days, 6 months and 1 year after RF therapy. The Cox-regression analysis was performed to evaluate the influence of the following factors on the duration of success: age, sex, depression, work inability and previous surgery. Results Complete follow-up was available for 41 patients. The success rate 7–21 days after the denervation was 76%. It decreased to 32% at 6 months and to 22% at 1 year. The median success duration was 17 weeks (95% CI 10–26). The Cox-regression analysis showed a significant shorter duration of success for patients with depression (hazard ratio [HR] 2.97, 95% CI 1.32–6.65), previous surgery (HR 2.39, 95% CI 1.10–5.21) and number of treated joints (HR 1.95 for each increase in the number of joints, 95% CI 1.14–3.33). In bivariate analyses, only depression was kept to be significant. Conclusions Depression seems to be related with a short duration of success. Based on these findings, a comprehensive study is warranted to evaluate whether psychosocial factors have to be considered when recruiting patients for radiofrequency denervation.

Coastal upwelling is linked to temporal genetic variability in the acorn barnacle Balanus glandula

Dispersal and recruitment are central processes that shape the geographic and temporal distributions of populations of marine organisms. However, significant variability in factors such as reproductive output, larval transport, survival, and settlement success can alter the genetic identity of recruits from year to year. We designed a temporal and spatial sampling protocol to test for genetic heterogeneity among adults and recruits from multiple time points along a similar to 400 km stretch of the Oregon (USA) coastline. In total, 2824 adult and recruiting Balanus glandula were sampled between 2001 and 2008 from 9 sites spanning the Oregon coast. Consistent with previous studies, we observed high mitochondrial DNA diversity at the cytochrome oxidase I locus (884 unique haplotypes) and little to no spatial genetic population structure among the 9 sites (Phi(ST) = 0.00026, p = 0.170). However, subtle but significant temporal shifts in genetic composition were observed among year classes (Phi(ST) = 0.00071, p = 0.035), and spatial Phi(ST) varied from year to year. These temporal shifts in genetic structure were correlated with yearly differences in the strength of coastal upwelling (p = 0.002), with greater population structure observed in years with weaker upwelling. Higher levels of barnacle settlement were also observed in years with weaker upwelling (p < 0.001). These data suggest the hypothesis that low upwelling intensity maintains more local larvae close to shore, thereby shaping the genetic structure and settlement rate of recruitment year classes.

Ultrasonographic-guided ilioinguinal/iliohypogastric nerve block in pediatric anesthesia: what is the optimal volume?

Recently, our study group demonstrated the usefulness of ultrasonographic guidance in ilioinguinal/iliohypogastric nerve blocks in children. As a consequence, we designed a follow-up study to evaluate the optimal volume of local anesthetic for this regional anesthetic technique. Using a modified step-up-step-down approach, with 10 children in each study group, a starting dose of 0.2 mL/kg of 0.25% levobupivacaine was administered to perform an ilioinguinal/iliohypogastric nerve block under ultrasonographic guidance. After each group of 10 patients, the results were analyzed, and if all blocks were successful, the volume of local anesthetic was decreased by 50%, and a further 10 patients were enrolled into the study. Failure to achieve a 100% success rate within a group subjected patients to an automatic increase of half the previous volume reduction to be used in the subsequent group. Using 0.2 and 0.1 mL/kg of 0.25% levobupivacaine, the success rate was 100%. With a volume of 0.05 mL/kg of 0.25% levobupivacaine, 4 of 10 children received additional analgesia because of an inadequate block. Therefore, according to the protocol, the amount was increased to 0.075 mL/kg of 0.25% levobupivacaine, where the success rate was again 100%. We conclude that ultrasonographic guidance for ilioinguinal/iliohypogastric nerve blocks in children allowed a reduction of the volume of local anesthetic to 0.075 mL/kg.

Adiponectin as a marker of success in intracytoplasmic sperm injection/embryo transfer cycles

Adiponectin (Acrp30) is an adipose tissue-derived protein whose serum concentrations, in contrast to leptin, are reported to be negatively correlated to body mass. In spite of the comparatively high circulating adiponectin concentrations, this protein has not been studied in the context of assisted reproduction to date. The aim of this preliminary project was thus to examine the potential of adiponectin to serve as a marker for fertility. We compared adiponectin levels in serum before and after controlled ovarian hyperstimulation, as well as in follicular fluid (FF), between two groups: those with successful outcome (clinical pregnancies) and those with implantation failure. In the former, adiponectin concentrations were higher than in the negative outcome group; this difference was statistically significant (p < 0.05) in serum on the day of oocyte pick-up (OPU) as well as two or three days before OPU, but not in FF or in serum at the beginning of the stimulation phase. This finding adds a new perspective to the suggested but still controversial reduction in FF leptin concentrations in the positive outcome group, and may become a useful tool for early prediction of success of in vitro fertilization treatment for a given patient.

Success rate and efficiency of activator treatment

In a retrospective multicentre study, the success rate and efficiency of activator treatment were analysed. All patients from two University clinics (Giessen, Germany and Berne, Switzerland) that fulfilled the selection criteria (Class II division 1 malocclusion, activator treatment, no aplasia, no extraction of permanent teeth, no syndromes, no previous orthodontic treatment except transverse maxillary expansion, full available records) were included in the study. The subject material amounted to 222 patients with a mean age of 10.6 years. Patient records, lateral head films, and dental casts were evaluated. Treatment was classified as successful if the molar relationship improved by at least half to three-fourths cusp width depending on whether or not the leeway space was used during treatment. Group comparisons were carried out using Wilcoxon two-sample and Kruskal-Wallis tests. For discrete data, chi-square analysis was used and Fisher's exact test when the sample size was small. Stepwise logistic regression was also employed. The success rate was 64 per cent in Giessen and 66 per cent in Berne. The only factor that significantly (P < 0.001) influenced treatment success was the level of co-operation. In approximately 27 per cent of the patients at both centres, the post-treatment occlusion was an 'ideal' Class I. In an additional 38 per cent of the patients, marked improvements in occlusal relationships were found. In subjects with Class II division 1 malocclusions, in which orthodontic treatment is performed by means of activators, a marked improvement of the Class II dental arch relationships can be expected in approximately 65 per cent of subjects. Activator treatment is more efficient in the late than in the early mixed dentition.

Small is beautiful: why profundaplasty should not be forgotten

BACKGROUND: Surgical profundaplasty (SP)is used mainly as an adjunct to endovascular management of peripheral vascular disease (PAD) today. Results from earlier series of profundaplasty alone have been controversial, especially regarding its hemodynamic effect. The question is: Can profundaplasty alone still be useful? Our aim was to evaluate its role in the modern management of vascular patients. METHODS: This was a retrospective outcome study. A consecutive series of 97 patients (106 legs) from January 2000 through December 2003 were included. In 55 (52%) legs, the superficial femoral artery was occluded. These patients were included in the current analysis. Of these patients 14 (25%) were female. Mean age was 71 ((11) years. Nineteen (35%) were diabetic. The indication for operation was claudication in 29 (53%), critical leg ischemia (CLI) in 26 (47%), either with rest pain in 17 (31%), or ulcer/gangrene in 9 (16%). Endarterectomy with patch angioplasty with bovine pericardium was performed in all cases. Mean follow-up was 33 ( 14 months. Mean preoperative ankle brachial index (ABI) was 0.6. Sustained clinical efficacy was defined as upward shift of 1 or greater on the Rutherford scale without repeat target limb revascularization (TLR) or amputation. Mortality, morbidity, need for TLR, or amputation were separate endpoints. RESULTS: Postoperatively, ABI was significantly improved (mean = 0.7), in 24 (44%) by more than 0.15. At three years, cumulative clinical success rate was 80%. Overall, patients with claudication had a better outcome than those with CLI (p = 0.04). Two (4%) major amputations and 2 (4%) minor ones were performed, all in patients with CLI. None of the 9 (16%) ulcers healed. CONCLUSION: Profundaplasty is still a valuable option for patients with femoral PAD and claudication without tissue loss. It is a straightforward procedure that combines good efficacy with low complication rates. Further endovascular treatment may be facilitated. It is not useful for patients with the combination of critical ischemia and tissue loss.

Occlusion length is a crucial determinant of efficiency and complication rate in thrombectomy for acute ischemic stroke

BACKGROUND AND PURPOSE: Although mechanical thrombectomy (MT) has an encouragingly high recanalization rate in treating stroke, it is associated with severe complications of which the underlying factors have yet to be identified. Because MT is a mechanical approach, the mechanical properties of the thrombus might be crucial for its success. The present study assesses the effect of thrombus length on the in vivo effectiveness and complication rate of MT. MATERIALS AND METHODS: Angiography and embolization of 21 cranial vessels with radiopaque whole-blood thrombi 10, 20, and 40 mm in length (7 occlusions each) were performed in 7 swine. MT was carried out using a distal snarelike device (BCR Roadsaver) with proximal balloon occlusion. A total of 61 retrievals were attempted. RESULTS: In the group of 10-mm occlusions, 77.8% of the attempts achieved complete recanalisation. For longer occlusions, the success rates decreased significantly to 20% of attempts for 20-mm occlusions (odds ratio [OR], 14; 95% confidence interval [CI], 2.2-89.2) and 11.1% for 40-mm occlusions (OR, 28; 95% CI, 3.9-202.2; P < .005). The low success rates were largely due to complications associated with thrombus compaction during retrieval. Similarly, the rate of thromboembolic events increased from 0% in 10-mm occlusions to 14.8% in 40-mm occlusions. CONCLUSIONS: MT using a distal device proved to be a fast, effective, and safe procedure for recanalizing short (10-mm) occlusions in the animal model. However, occlusion length emerged as a crucial determinant for MT with a significant decrease in recanalization success per attempt and increased complication rates. These findings suggest limitations of MT in the clinical application.

Where the land is greener: Case studies and analysis of soil and water conservation initiatives worldwide

‘where the land is greener’ looks at soil and water conservation from a global perspective. In total, 42 soil and water conservation technologies and 28 approaches are described – each fully illustrated with photographs, graphs and line drawings – as applied in case studies in more than 20 countries around the world. This unique presentation of case studies draws on WOCAT’s extensive database, gathered in over 12 years of field experience. The book is intended as a prototype for national and regional compilations of sustainable land management practices a practical – instrument for making field knowledge available to decision makers. Various land use categories are covered, from crop farming to grazing and forestry. The technologies presented range from terrace-building to agroforestry systems; from rehabilitation of common pastures to conservation agriculture; from Vermiculture to water harvesting. Several of these technologies are already well-established successes – others are innovative, relatively unknown, but full of promise. Descriptions of the various technologies are complemented by studies of the ‘approaches’ that have underpinned their development and dissemination. Some of these approaches were developed specifically for individual projects; others developed and spread spontaneously in fascinating processes that offer a new perspective for development policy. In addition to the case studies, the book includes two analytical sections on the technologies and approaches under study. By identifying common elements of success, these analyses offer hope for productive conservation efforts at the local level with simultaneous global environmental benefits. Policy pointers for decision makers and donors offer a new impetus for further investment – to make the land greener.

Percutaneous aortic valve replacement for severe aortic stenosis in high-risk patients using the second- and current third-generation self-expanding CoreValve prosthesis: device success and 30-day clinical outcome

OBJECTIVES: We sought to determine both the procedural performance and safety of percutaneous implantation of the second (21-French [F])- and third (18-F)-generation CoreValve aortic valve prosthesis (CoreValve Inc., Irvine, California). BACKGROUND: Percutaneous aortic valve replacement represents an emerging alternative therapy for high-risk and inoperable patients with severe symptomatic aortic valve stenosis. METHODS: Patients with: 1) symptomatic, severe aortic valve stenosis (area <1 cm2); 2) age > or =80 years with a logistic EuroSCORE > or =20% (21-F group) or age > or =75 years with a logistic EuroSCORE > or =15% (18-F group); or 3) age > or =65 years plus additional prespecified risk factors were included. Introduction of the 18-F device enabled the transition from a multidisciplinary approach involving general anesthesia, surgical cut-down, and cardiopulmonary bypass to a truly percutaneous approach under local anesthesia without hemodynamic support. RESULTS: A total of 86 patients (21-F, n = 50; 18-F, n = 36) with a mean valve area of 0.66 +/- 0.19 cm2 (21-F) and 0.54 +/- 0.15 cm2 (18-F), a mean age of 81.3 +/- 5.2 years (21-F) and 83.4 +/- 6.7 years (18-F), and a mean logistic EuroSCORE of 23.4 +/- 13.5% (21-F) and 19.1 +/- 11.1% (18-F) were recruited. Acute device success was 88%. Successful device implantation resulted in a marked reduction of aortic transvalvular gradients (mean pre 43.7 mm Hg vs. post 9.0 mm Hg, p < 0.001) with aortic regurgitation grade remaining unchanged. Acute procedural success rate was 74% (21-F: 78%; 18-F: 69%). Procedural mortality was 6%. Overall 30-day mortality rate was 12%; the combined rate of death, stroke, and myocardial infarction was 22%. CONCLUSIONS: Treatment of severe aortic valve stenosis in high-risk patients with percutaneous implantation of the CoreValve prosthesis is feasible and associated with a lower mortality rate than predicted by risk algorithms.

A systematic review of the success of sinus floor elevation and survival of implants inserted in combination with sinus floor elevation. Part II: transalveolar technique

OBJECTIVES: The objectives of this systematic review were to assess the survival rate of implants placed in sites with transalveolar sinus floor elevation. MATERIAL AND METHODS: An electronic search was conducted to identify prospective and retrospective cohort studies on transalveolar sinus floor elevation, with a mean follow-up time of at least 1 year after functional loading. Failure and complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates/ year proportions. RESULTS: The search provided 849 titles. Full-text analysis was performed for 176 articles, resulting in 19 studies that met the inclusion criteria. Meta-analysis of these studies indicated an estimated annual failure rate of 2.48% (95% confidence interval (95% CI): 1.37-4.49%) translating to an estimated survival rate of 92.8% (95% CI): 87.4-96.0%) for implants placed in transalveolarly augmented sinuses, after 3 years in function. Furthermore, subject-based analysis revealed an estimated annual failure of 3.71% (95% CI: 1.21-11.38%), translating to 10.5% (95% CI: 3.6-28.9%) of the subjects experiencing implant loss over 3 years. CONCLUSION: Survival rates of implants placed in transalveolar sinus floor augmentation sites are comparable to those in non-augmented sites. This technique is predictable with a low incidence of complications during and post-operatively.

A systematic review of the success of sinus floor elevation and survival of implants inserted in combination with sinus floor elevation

OBJECTIVES: The objectives of this systematic review were to assess the survival rate of grafts and implants placed with sinus floor elevation. MATERIAL AND METHODS: An electronic search was conducted to identify studies on sinus floor elevation, with a mean follow-up time of at least 1 year after functional loading. RESULTS: The search provided 839 titles. Full-text analysis was performed for 175 articles resulting in 48 studies that met the inclusion criteria, reporting on 12,020 implants. Meta-analysis indicated an estimated annual failure rate of 3.48% [95% confidence interval (CI): 2.48%-4.88%] translating into a 3-year implant survival of 90.1% (95% CI: 86.4%-92.8%). However, when failure rates was analyzed on the subject level, the estimated annual failure was 6.04% (95% CI: 3.87%-9.43%) translating into 16.6% (95% CI: 10.9%-24.6%) of the subjects experiencing implant loss over 3 years. CONCLUSION: The insertion of dental implants in combination with maxillary sinus floor elevation is a predictable treatment method showing high implant survival rates and low incidences of surgical complications. The best results (98.3% implant survival after 3 years) were obtained using rough surface implants with membrane coverage of the lateral window.

Analysis of mRNA transcripts improves the success rate of molecular genetic testing in OTC deficiency

BACKGROUND: Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of urea metabolism that can lead to hyperammonemic crises and orotic aciduria. To date, a total of 341 causative mutations within the OTC gene have been described. However, in about 20% of the patients with enzymatically confirmed OTC deficiency no mutation can be detected when sequencing of genomic DNA analyzing exons and adjacent intronic segments of the OTC gene is performed. METHODS: Standard genomic DNA analysis of the OTC gene in five consecutive patients from five families revealed no mutation. Hence, liver tissue was obtained by needle sampling or open biopsy and RNA extracted from liver was analyzed. RESULTS: Complex rearrangements of the OTC transcript (three insertions and two deletions) were found in all five patients. CONCLUSION: In patients with a strong suspicion of OTC deficiency despite normal results of sequencing exonic regions of the OTC gene, characterization of liver OTC mRNA is highly effective in resolving the genotype. Liver tissue sampling by needle aspiration allows for both enzymatic analysis and RNA based diagnostics of OTC deficiency.