Nonanesthesiologist-administered propofol sedation: from the exception to standard practice. Sedation and monitoring trends over 20 years.

The practice of sedation, including monitoring practice for digestive endoscopy, continues to evolve throughout the world. In many countries, including Switzerland, there is a trend towards increased utilization of sedation during both routine and advanced endoscopic procedures. Sedation improves patient satisfaction with endoscopy and also improves the quality of the examination. In addition, a trend can be observed towards an increasing use of propofol as the preferred sedative drug. Here we review the latest published data from surveys describing sedation and monitoring practice in different countries and compare them with our own data from successive nationwide surveys among Swiss gastroenterologists over a period of 20 years. This development between these socioeconomically very similar Western industrialized countries, however, shows some unique and surprising differences. In Germany and Switzerland, propofol use has become increasingly widespread, in Switzerland even to the extent that during the last few years propofol has overtaken benzodiazepine sedation, with an absolute majority of Swiss gastroenterologists using it without the assistance of an anesthesiologist. In addition, the change in Switzerland reflects a successful generalization of nonanesthesiologist-administered propofol (NAAP) sedation from the hospital setting to private practice.

Percepció de dificultat i esforç en la mobilització de persones dependents, en el seu entorn domiciliari, per part dels seus cuidadors, abans i després de la utilització de llençols lliscants

Les persones amb dependència necessiten ajuda en la mobilització al llit, que suposa un esforç per a la persona cuidadora. La percepció de dificultat en dur a terme aquestes tasques pot afectar negativament la qualitat de vida de les persones cuidadores i també la de les persones dependents. L’objectiu d’aquest estudi va ser investigar si la utilització de superfícies de reducció de la fricció (tipus llençols lliscants) redueix la dificultat percebuda per les persones cuidadores i les persones dependents en la mobilització al llit. Mètodes: es va dur a terme un estudi quasi experimental a domicili en una mostra seleccionada a conveniència de 12 persones amb dependència i els seus cuidadors en diverses localitats. Es va avaluar la percepció de dificultat en la mobilització per part dels cuidadors i les persones dependents abans i després d’una intervenció formativa simultània a la utilització de llençols lliscants. Resultats: el perfil del cuidador és el d’una dona de mitjana edat amb una relació filial amb la persona dependent i sense formació específica en mètodes de mobilització de persones dependents. El perfil de la persona dependent és el d’una dona major de 80 anys amb una gran dependència que necessita ajuda de la persona que la cuida en les maniobres de redreçament i trasllat al llit. En una escala de percepció de la dificultat de 0 a 10, les mitjanes de les puntuacions observades en els cuidadors abans de la intervenció van ser de 6,9 (DE: 3,1) en el redreçament cap amunt i de 7,1 (DE: 3,1) en el trasllat lateral; després de la intervenció van ser d’1,25 (DE: 1,8) en el redreçament cap amunt i d’1,45 (DE: 1,6) en la mobilització lateral. En la mateixa escala, les mitjanes de les puntuacions observades en les persones dependents abans de la intervenció van ser de 8,6 (DE: 2,3) en el redreçament cap amunt i de 8,6 (DE: 2,3) en el trasllat cap als costats, i després de la intervenció van ser de 2 (DE: 2,6) en els redreçaments cap amunt i de 2 (DE: 2,6) en els trasllats cap als costats. Comparant les puntuacions d’abans i després de la intervenció, observem que la dificultat percebuda per part dels cuidadors de les persones dependents va disminuir de manera significativa (p & 0,001); en les persones dependents també va disminuir, però la disminució no va arribar a ser significativa (p = 0,057). Conclusions: els resultats observats mostren que la utilització de llençols lliscants millora la qualitat de vida dels cuidadors, mesurada per la percepció de la dificultat en les maniobres de mobilització al llit. Així mateix, la seva utilització pot contribuir a un millor envelliment actiu. Caldria fer estudis que permetin quantificar l’esforç físic necessari i el cost-benefici que suposa la utilització d’aquests dispositius.

Dynamic changes in brain functional connectivity during concurrent dual-task performance.

This study investigated the spatial, spectral, temporal and functional proprieties of functional brain connections involved in the concurrent execution of unrelated visual perception and working memory tasks. Electroencephalography data was analysed using a novel data-driven approach assessing source coherence at the whole-brain level. Three connections in the beta-band (18-24 Hz) and one in the gamma-band (30-40 Hz) were modulated by dual-task performance. Beta-coherence increased within two dorsofrontal-occipital connections in dual-task conditions compared to the single-task condition, with the highest coherence seen during low working memory load trials. In contrast, beta-coherence in a prefrontal-occipital functional connection and gamma-coherence in an inferior frontal-occipitoparietal connection was not affected by the addition of the second task and only showed elevated coherence under high working memory load. Analysis of coherence as a function of time suggested that the dorsofrontal-occipital beta-connections were relevant to working memory maintenance, while the prefrontal-occipital beta-connection and the inferior frontal-occipitoparietal gamma-connection were involved in top-down control of concurrent visual processing. The fact that increased coherence in the gamma-connection, from low to high working memory load, was negatively correlated with faster reaction time on the perception task supports this interpretation. Together, these results demonstrate that dual-task demands trigger non-linear changes in functional interactions between frontal-executive and occipitoparietal-perceptual cortices.

Artérite á cellules géantes et vitesse de sédimentation normale: plus qu'une exception [Giant cell arteritis and normal sedimentation rate: more than an exception!]

BACKGROUND: Giant cell arteritis (GCA) is a systemic segmental vasculitis of unknown etiology, typically affecting elderly patients. Elevated erythrocyte-sedimentation rate (ESR) is usually found in such patients. PATIENTS AND METHODS: One hundred and twenty three patients underwent temporal artery biopsy in our institution between 1977 and 1995. Among them, 66 (53.7%) biopsies were positive (i.e. histologic findings were very suggestive of GCA). The clinical charts from all patients with positive biopsies were retrieved and 47 were eligible for our study (inadequate data in 19 cases). RESULTS: Seven of the 47 patients with positive biopsies (15%) had a normal ESR and 70% (33/47 cases) had neuro-ophthalmic complications including anterior ischemic optic neuropathy, central retinal artery occlusion, choroidal ischemia and extraocular muscle and/or cranial nerve palsy (III, IV, VI). No differences were found between the groups with normal or elevated ESR as 87.5% (6/7 cases) of the group with normal ESR exhibited neuro-ophthalmic complications. CONCLUSIONS: ESR was normal in 15% of our GCA patients and these patients had the same frequency of neuro-ophthalmic complications as the GCA patients with elevated ESR. Thus, our study does not support the previous concept that patients with higher ESR are more at risk for neuro-ophthalmic complications. GCA with normal ESR is not rare and such patients should be investigated with other blood studies (C-reactive protein) and with fluorescein angiography.

Les traitements de l'ostéoporose (à l'exception de la substitution hormonale et de ses dérivés) [Treatment of osteoporosis (with the exception of hormone replacement and its derivates]

Calcium and vitamin D supplementation are warranted for the treatment of osteoporosis, when other specific drugs are used. Vitamin D supplementation is necessary when the plasma level of 25-hydroxy-vitamin D is below 30 nmol/l (12 pg/l) in order to avoid any increase of the plasma parathyroid hormone level. Bisphosphonates are the most widely drugs used. Recent advances will provide patients with a more convenient therapeutically equivalent alternative: the once-weekly oral dosing regimen and probably the possibility to give infusions at intervals of up to one year. Parathyroid hormone administered subcutaneously daily produced a dramatic increase of trabecular and cortical bone mineral density, and an important decrease of vertebral and nonvertebral fracture risk. Strontium is a new original drug, which stimulates bone formation, and inhibits bone resorption. It significantly improves trabecular and cortical bone mass. Calcitonin not only prevents the recurrence of vertebral fractures, but possibly could decrease hip fractures risk. Hydrochlorothiazide preserves the bone mineral density, and decreases nonvertebral fracture risk, as showed in epidemiological studies. Large clinical trials with statins therapy in appropriate populations are required to find out whether these drugs have any role in preventing fractures.

Concurrent or Sequential Adjuvant Hormonoradiotherapy after Conservative Surgery for Early-Stage Breast Cancer: Clinical Results of the CO-HO-RT Phase II Randomized Trial.

Purpose: Letrozole (LET) has recently been shown to be superior to tamoxifen for postmenopausal patients (pts). In addition, LET radiosensitizes breast cancer cells in vitro. We conducted a phase II randomized study to evaluate concurrent and sequential radiotherapy (RT)-LET in the adjuvant setting. We present here clinical results with a minimum follow-up of 24 months. Patients and Methods: Postmenopausal pts with early-stage breast cancer were randomized after conservative surgery to either: A) concurrent RT-LET (LET started 3 weeks before the first day of RT) or B) sequential RT-LET (LET started 3 weeks after the end of RT). Whole breast RT was delivered to a total dose of 50 Gy. A 10-16 Gy boost was allowed according to age and pathological prognostic factors. Pts were stratified by center, adjuvant chemotherapy, boost, and radiation-induced CD8 apoptosis (RILA). RILA was performed before RT as previously published (Ozsahin et al. Clin Cancer Res, 2005). An independent monitoring committee reviewed individual safety data. Skin toxicities were evaluated by two different clinicians at each medical visit (CTCAE v3.0). Lung CT-scan and functional pulmonary tests were performed regularly. DNA samples were screened for SNPs in candidate genes as recently published (Azria et al., Clin Cancer Res, 2008). Results: A total of 150 pts were randomized between 01/05 and 02/07. Median follow-up is 26 months (range, 3-40 months). No statistical differences were identified between the two arms in terms of mean age; initial TNM; median surgical bed volume; post surgical breast volume. Chemotherapy and RT boost were delivered in 19% and 38% of pts, respectively. Nodes received 50 Gy in 23% of patients without differences between both arms. During RT and within the first 6 weeks after RT, 10 patients (6.7%) presented grade 3 acute skin dermatitis during RT but no differences were observed between both arms (4 and 6 patients in arm A and B, respectively). At 26 month of follow-up, grade 2 and more radiation-induced subcutaneous fibrosis (RISCF) was present in 4 patients (3%) without any difference between arm A (n = 2) and B (n = 2), p=0.93. In both arms, all patients that presented a RICSF had a RILA lower than 16%. Sensitivity and specificity were 100% and 39%, respectively.No acute lung toxicities were observed and quality of life was good to excellent for all patients.SNPs analyses are still on-going (Pr Rosenstein, NY). Conclusion: Acute and early late grade 2 dermatitis were similar in both arms. The only factor that influenced RISCF was a low radiation-induced lymphocyte apoptosis yield. We confirmed prospectively the capacity of RILA for identifying hypersensitive patients to radiation. Indeed, patients with RILA superior to 16% did not present late effects to radiation and confirmed the first prospective trial we published in 2005 (Ozsahin et al., Clin Cancer Res).

High rate of severe radiation dermatitis during radiation therapy with concurrent cetuximab in head and neck cancer: results of a survey in EORTC institutes.

OBJECTIVE: Examination of the rate of grade III or grade IV radiation dermatitis during treatment of head and neck cancer (HNC) with radiotherapy (RT) and concurrent cetuximab in EORTC centres. MATERIALS AND METHOD: A questionnaire was sent to all members of the EORTC Radiation Oncology Group and Head and Neck Group (111 institutions) to evaluate the widespread use of cetuximab and radiotherapy in HNC and to estimate the frequency of grades III and IV skin reactions in the radiation portals associated with this protocol. Co-morbidities, RT schedules and co-medications were also recorded. RESULTS: We received responses from 28 institutions in 11 countries. A total of 125 HNC patients from 15 institutions were treated with cetuximab and concurrent RT. Information about the skin reactions was available from 71 patients. Of these 36 had no grade III/IV adverse effects in the RT field, 15 had a grade III and 20 had grade IV radiation dermatitis. No detectable relation of grades III and IV radiation dermatitis with co-morbidities such as liver insufficiency or renal dysfunction was found. CONCLUSION: According to the results of the questionnaire, grade III/IV radiation dermatitis is observed in 49% of HNC patients treated with cetuximab and concurrent RT. A systematic clinical monitoring of cutaneous side effects during RT plus cetuximab is advised to ensure the safety of this protocol.

Radiation therapy and concurrent plus adjuvant temsirolimus (CCI-779) versus chemoirradiation with temozolomide in newly diagnosed glioblastoma without methylation of the MGMT gene promoter.

Background: Preclinical data indicate activity of mammalian target of rapamycin inhibitors and synergistic activity together with radiotherapy in glioblastoma. The aim of this trial is to assess the therapeutic activity of temsirolimus (CCI-779), an intravenous mTOR inhibitor, in patients with newly diagnosed glioblastoma with unmethylated O6 methlyguanine-DNA-methlytransferase (MGMT)promoter. Methods: Patients (n=257) with newly diagnosed glioblastoma after open surgical biopsy or resection fulfilling basic eligibility criteria underwent a central MGMT promoter analysis using quantitative methylation specific PCR. Patients with glioblastoma harboring an unmethylated MGMT promoter (n=111) were randomized 1:1 between radiotherapy (60 Gy; 5 times 2 Gy per week) plus concomitant and six cycles of maintenance temozolomide or radiotherapy plus weekly temsirolimus at 25 mg flat dose to be continued until progression or undue toxicity. Primary endpoint was overall survival at 12 months (OS12). Sample size of the investigational treatment arm required 54 patients to assess adequacy of temsirolimus activity set at 80%. More than 38 patients alive at 12 months in the per protocol population was considered a positive signal. A control arm of 54 patients treated with the standard of care was implemented to evaluate the assumptions on OS12. Results: Between December 2009 and October 2012, 111 pts in 14 centers were randomized and treated. Median age was 55 and 58 years in the temsirolimus and standard arm, respectively. Most patients (95.5%) had a WHO performance status of 0 or 1. Both therapies were properly administered with a median of 13 cycles of maintenance temsirolimus. In the per protocolpopulation, exactly 38 patients treated with temsirolimus (out of 54 eligible) reached OS12. In the intention to treat population OS12 was 72.2% [95% CI (58.2, 82.2)] in the temozolomide arm and 69.6% [95% CI (55.8, 79.9) in the temsirolimus arm [HR=1.16 95% CI (0.77, 1.76), p=0.47]. Conclusions: The therapeutic activity of temsirolimus in patients with newly diagnosed glioblastoma with an unmethylated MGMT promoter is too low.

Mynodbcsv: Lightweight Zero-Config Database Solution for Handling Very Large CSV Files.

Volumes of data used in science and industry are growing rapidly. When researchers face the challenge of analyzing them, their format is often the first obstacle. Lack of standardized ways of exploring different data layouts requires an effort each time to solve the problem from scratch. Possibility to access data in a rich, uniform manner, e.g. using Structured Query Language (SQL) would offer expressiveness and user-friendliness. Comma-separated values (CSV) are one of the most common data storage formats. Despite its simplicity, with growing file size handling it becomes non-trivial. Importing CSVs into existing databases is time-consuming and troublesome, or even impossible if its horizontal dimension reaches thousands of columns. Most databases are optimized for handling large number of rows rather than columns, therefore, performance for datasets with non-typical layouts is often unacceptable. Other challenges include schema creation, updates and repeated data imports. To address the above-mentioned problems, I present a system for accessing very large CSV-based datasets by means of SQL. It's characterized by: "no copy" approach - data stay mostly in the CSV files; "zero configuration" - no need to specify database schema; written in C++, with boost [1], SQLite [2] and Qt [3], doesn't require installation and has very small size; query rewriting, dynamic creation of indices for appropriate columns and static data retrieval directly from CSV files ensure efficient plan execution; effortless support for millions of columns; due to per-value typing, using mixed text/numbers data is easy; very simple network protocol provides efficient interface for MATLAB and reduces implementation time for other languages. The software is available as freeware along with educational videos on its website [4]. It doesn't need any prerequisites to run, as all of the libraries are included in the distribution package. I test it against existing database solutions using a battery of benchmarks and discuss the results.

Assessment of the COOP charts with and without pictures in a Swiss population.

OBJECTIVES: This study aimed to assess the validity of COOP charts in a general population sample, to examine whether illustrations contribute to instrument validity, and to establish general population norms. METHODS: A general population mail survey was conducted among 20-79 years old residents of the Swiss canton of Vaud. Participants were invited to complete COOP charts, the SF-36 Health Survey; they also provided data on health service use in the previous month. Two thirds of the respondents received standard COOP charts, the rest received charts without illustrations. RESULTS: Overall 1250 persons responded (54%). The presence of illustrations did not affect score distributions, except that the illustrated 'physical fitness' chart drew greater non-response (10 vs. 3%, p < 0.001). Validity tests were similar for illustrated and picture-less charts. Factor analysis yielded two principal components, corresponding to physical and mental health. Six COOP charts showed strong and nearly linear relationships with corresponding SF36 scores (all p < 0.001), demonstrating concurrent validity. Similarly, most COOP charts were associated with the use of medical services in the past month. Only the chart on 'social support' partly deviated from construct validity hypotheses. Population norms revealed a generally lower health status in women and an age-related decline in physical health. CONCLUSIONS: COOP charts can be used to assess the health status of a general population. Their validity is good, with the possible exception of the 'social support' chart. The illustrations do not affect the properties of this instrument.

Effects of group size and early handling on some behavioural and physiological welfare parameters in farmed blue foxes

Selostus: Ryhmäkoon ja varhaisen käsittelyn vaikutus tarhattujen sinikettujen hyvinvointiin