The effect of initial local anesthetic dose with continuous interscalene analgesia on postoperative pain and diaphragmatic function in patients undergoing arthroscopic shoulder surgery: a double-blind, randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Interscalene block (ISB) is commonly performed using 20-40 mL of local anesthetic. Spread to adjacent structures and consequent adverse effects including paralysis of the ipsilateral hemidiaphragm are frequent. Pain ratings, analgesic requirements, adverse events, satisfaction, function and diaphragmatic excursion were compared following interscalene block (ISB) with reduced initial bolus volumes.</p> <p>Methods</p> <p>Subjects undergoing arthroscopic rotator cuff repair were randomized to receive 5, 10, or 20 mL ropivacaine 0.75% for ISB in a double-blind fashion (N = 36). Continuous infusion with ropivacaine 0.2% was maintained for 48 h. Pain and diaphragmatic excursion were assessed before block and in the recovery unit.</p> <p>Results</p> <p>Pain ratings in the recovery room were generally less than 4 (0-10 NRS) for all treatment groups, but a statistically significant difference was noted between the 5 and 20 mL groups (NRS: 2.67 vs. 0.62 respectively; p = 0.04). Pain ratings and supplemental analgesic use were similar among the groups at 24 h, 48 h and 12 weeks. There were no differences in the quality of block for surgical anesthesia. Dyspnea was significantly greater in the 20 mL group (p = 0.041). Subjects with dyspnea had significant diaphragmatic impairment more frequently (Relative risk: 2.5; 95%CI: 1.3-4.8; p = 0.042). Increased contralateral diaphragmatic motion was measured in 29 of the 36 subjects. Physical shoulder function at 12 weeks improved over baseline in all groups (baseline mean SST: 6.3, SEM: 0.6; 95%CI: 5.1-7.5; 12 week mean SST: 8.2, SEM: 0.46; 95%CI: 7.3-9.2; p = 0.0035).</p> <p>Conclusions</p> <p>ISB provided reliable surgical analgesia with 5 mL, 10 mL or 20 mL ropivacaine (0.75%). The 20 mL volume was associated with increased complaints of dyspnea. The 5 mL volume was associated with statistically higher pain scores in the immediate postoperative period. Lower volumes resulted in a reduced incidence of dyspnea compared to 20 mL, however diaphragmatic impairment was not eliminated. Compensatory increases in contralateral diaphragmatic movement may explain tolerance for ipsilateral paresis.</p> <p>Trial Registration</p> <p>clinicaltrials.gov. identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00672100">NCT00672100</a></p

Joint IARC/NCI International Cancer Seminar Series Report: Expert consensus on future directions for ovarian carcinoma research

Recently, ovarian cancer research has evolved considerably because of the emerging recognition that rather than a single disease, ovarian carcinomas comprise several different histotypes that vary by etiologic origin, risk factors, molecular profiles, therapeutic approaches, and clinical outcome. Despite significant progress in our understanding of the etiologic heterogeneity of ovarian cancer, as well as important clinical advances, it remains the eighth most frequently diagnosed cancer in women worldwide and the most fatal gynecologic cancer. The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) jointly convened an expert panel on ovarian carcinoma to develop consensus research priorities based on evolving scientific discoveries. Expertise ranged from etiology, prevention, early detection, pathology, model systems, molecular characterization, and treatment/clinical management. This report summarizes the current state of knowledge and highlights expert consensus on future directions to continue advancing etiologic, epidemiologic, and prognostic research on ovarian carcinoma

Would loss to follow-up bias the outcome evaluation of patients operated for degenerative disorders of the lumbar spine?: A study of responding and non-responding cohort participants from a clinical spine surgery registry

Loss to follow-up may bias the outcome assessments of clinical registries. In this study, we wanted to determine whether outcomes were different in responding and non-responding patients who were included in a clinical spine surgery registry, at two years of follow-up. In addition, we wanted to identify risk factors for failure to respond. 633 patients who were operated for degenerative disorders of the lumbar spine were followed for 2 years using a local clinical spine registry. Those who did not attend the clinic and those who did not answer a postal questionnaire—for whom 2 years of outcome data were missing—and who would be lost to follow-up according to the standard procedures of the registry protocols, were defined as non-respondents. They were traced and interviewed by telephone. Outcome measures were: improvement in health-related quality of life (EQ-5D), leg pain, and back pain; and also general state of health, employment status, and perceived benefits of the operation. We found no statistically significant differences in outcome between respondents (78% of the patients) and nonrespondents (22%). Receipt of postal questionnaires (not being summoned for a follow-up visit) was the strongest risk factor for failure to respond. Forgetfulness appeared to be an important cause. Older patients and those who had complications were more likely to respond. Interpretation A loss to follow-up of 22% would not bias conclusions about overall treatment effects and, importantly, there were no indications of worse outcomes in non-respondents

Fear of hypoglycaemia: defining a minimum clinically important difference in patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>To explore the concept of the Minimum Clinically Important Difference (MID) of the Worry Scale of the Hypoglycaemia Fear Survey (HFS-II) and to quantify the clinical importance of different types of patient-reported hypoglycaemia.</p> <p>Methods</p> <p>An observational study was conducted in Germany with 392 patients with type 2 diabetes mellitus treated with combinations of oral anti-hyperglycaemic agents. Patients completed the HFS-II, the Treatment Satisfaction Questionnaire for Medication (TSQM), and reported on severity of hypoglycaemia. Distribution- and anchor-based methods were used to determine MID. In turn, MID was used to determine if hypoglycaemia with or without need for assistance was clinically meaningful compared to having had no hypoglycaemia.</p> <p>Results</p> <p>112 patients (28.6%) reported hypoglycaemic episodes, with 15 patients (3.8%) reporting episodes that required assistance from others. Distribution- and anchor-based methods resulted in MID between 2.0 and 5.8 and 3.6 and 3.9 for the HFS-II, respectively. Patients who reported hypoglycaemia with (21.6) and without (12.1) need for assistance scored higher on the HFS-II (range 0 to 72) than patients who did not report hypoglycaemia (6.0).</p> <p>Conclusion</p> <p>We provide MID for HFS-II. Our findings indicate that the differences between having reported no hypoglycaemia, hypoglycaemia without need for assistance, and hypoglycaemia with need for assistance appear to be clinically important in patients with type 2 diabetes mellitus treated with oral anti-hyperglycaemic agents.</p

All-arthroscopic versus mini-open repair of small or moderate-sized rotator cuff tears: A protocol for a randomized trial [NCT00128076]

BACKGROUND: Rotator cuff tears are the most common source of shoulder pain and disability. Only poor quality studies have compared mini-open to arthroscopic repair, leaving surgeons with inadequate evidence to support optimal, minimally-invasive repair. METHODS/DESIGN: This randomized, multi-centre, national trial will determine whether an arthroscopic or mini-open repair provides better quality of life for patients with small or moderate-sized rotator cuff tears. A national consensus meeting of investigators in the Joint Orthopaedic Initiative for National Trials of the Shoulder (JOINTS Canada) identified this question as the top priority for shoulder surgeons across Canada. The primary outcome measure is a valid quality-of-life scale (Western Ontario Rotator Cuff (WORC)) that addresses 5 domains of health affected by rotator cuff disease. Secondary outcomes will assess rotator cuff functionality (ROM, strength, Constant score), secondary dimensions of health (general health status (SF-12) and work limitations), and repair integrity (MRI). Outcomes are measured at baseline, at 6 weeks, 3, 6, 12, and 24 months post-operatively by blinded research assistants and musculoskeletal radiologists. Patients (n = 250) with small or medium-sized cuff tears identified by clinical examination and MRI who meet eligibility criteria will be recruited. This sample size will provide 80% power to statistically detect a clinically important difference of 20% in WORC scores between procedures after controlling for baseline WORC score (α = 0.05). A central methods centre will manage randomization, data management, and monitoring under supervision of experienced epidemiologists. Surgeons will participate in either conventional or expertise-based designs according to defined criteria to avoid biases from differential surgeon expertise. Mini-open or all-arthroscopic repair procedures will be performed according to a standardized protocol. Central Adjudication (of cases), Trial Oversight and Safety Committees will monitor trial conduct. We will use an analysis of covariance (ANCOVA), where the baseline WORC score is used as a covariate, to compare the quality of life (WORC score) at 2 years post-operatively. As a secondary analysis, we will conduct the same statistical test but will include age and tear size as covariates with the baseline score. Enrollment will require 2 years and follow-up an additional 2 years. The trial will commence when funding is in place. DISCUSSION: These results will have immediate impact on the practice behaviors of practicing surgeons and surgical trainees at JOINTS centres across Canada. JOINTS Canada is actively engaged in knowledge exchange and will publish and present findings internationally to facilitate wider application. This trial will establish definitive evidence on this question at an international level

Copy number signatures and mutational processes in ovarian carcinoma.

The genomic complexity of profound copy number aberrations has prevented effective molecular stratification of ovarian cancers. Here, to decode this complexity, we derived copy number signatures from shallow whole-genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Measurement of signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes.NIHR, Ovarian Cancer Action, Cancer Research UK Cambridge Centre, Cambridge Experimental Cancer Medicine Centr

GEICO (Spanish Group for Investigation on Ovarian Cancer) treatment guidelines in ovarian cancer 2012

In 2006, under the auspices of The Spanish Research Group for Ovarian Cancer (Spanish initials GEICO), the first “Treatment Guidelines in Ovarian Cancer” were developed and then published in Clinical and Translational Oncology by Poveda Velasco et al. (Clin Transl Oncol 9(5):308–316, 2007). Almost 6 years have elapsed and over this time, we have seen some important developments in the treatment of ovarian cancer. Significant changes were also introduced after the GCIG-sponsored 4th Consensus Conference on Ovarian Cancer by Stuart et al. (Int J Gynecol Cancer 21:750–755, 2011). So we decided to update the treatment guidelines in ovarian cancer and, with this objective, a group of investigators of the GEICO group met in February 2012. This study summarizes the presentations, discussions and evidence that were reviewed during the meeting and during further discussions of the manuscript

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Characterisation of tumor microvessel density during progression of high-grade serous ovarian cancer: clinico-pathological impact. An OCTIPS Consortium study.

Background: High-grade serous ovarian cancer (HGSOC) intratumoural vasculature evolution remains unknown. The study investigated changes in tumour microvessel density (MVD) in a large cohort of paired primary and recurrent HGSOC tissue samples and its impact on patients’ clinico-pathological outcome. Methods: A total of 222 primary (pOC) and recurrent (rOC) intra-patient paired HGSOC were assessed for immunohistochemical expression of angiogenesis-associated biomarkers (CD31, to evaluate MVD, and VEGF-A). Expression profiles were compared between pOCs and rOCs and correlated with patients' data. Results: High intratumoural MVD and VEGF-A expression were observed in 75.7% (84/111) and 20.7% (23/111) pOCs, respectively. MVDhighand VEGF(+)samples were detected in 51.4% (57/111) and 20.7% (23/111) rOCs, respectively. MVDhigh/VEGF(+)co-expression was found in 19.8% (22/111) and 8.1% (9/111) of pOCs and rOCs, respectively (p = 0.02). Pairwise analysis showed no significant change in MVD (p = 0.935) and VEGF-A (p = 0.121) levels from pOCs to rOCs. MVDhighpOCs were associated with higher CD3(+)(p = 0.029) and CD8(+)(p = 0.013) intratumoural effector TILs, while VEGF(+)samples were most frequently encountered among BRCA-mutated tumours (p = 0.019). Multivariate analysis showed VEGF and MVD were not independent prognostic factors for OS. Conclusions: HGSOC intratumoural vasculature did not undergo significant changes during disease progression. High concentration of CD31(+)vessels seems to promote recruitment of effector TILs. The study also provides preliminary evidence of the correlation between VEGF-positivity and BRCA status