Intravitreal ranibizumab for age-related macular degeneration : optical coherence tomography guided retreatment intervals and their intra- and inter-individual variability

Purpose: To determine whether the need for retreatment after an initial phase of 3 monthly intravitreal injections of ranibizumab shows an intra-individual regular rhythm and to what degree it varies between different patients. Methods: Prospective study with 42 patients with exudative AMD, treatment naïve. Loading dose of 3 monthly doses of ranibizumab (0,5 mg), followed by a 12 months pro re nata (PRN) regimen according to early exudative signs on HD-OCT Cirrus, Zeiss. The follow-up visits were intensified (week 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, etc after each injection) in order to detect recurrences early, and injection followed within 3 days in cases of subretinal fluid, cysts, or central thickness increase of>50microns. Intervals were calculated between injections for the 12 month follow-up with PRN treatment. Variability was expressed as standard deviation (SD). Results: Visual acuity (VA) improved from a mean ETDRS score of 61.6 (SD 10.8) at baseline to 68.0 (SD 10.2) at month 3 and to 74.7(SD 9.0) at month 12. The 15 patients who have already completed the study showed maintenance of the VA improvement. Central foveal thickness improved from a mean value of 366 microns (baseline) to 253 microns (month 3), well maintained thereafter. Mean number of injections was 8.8 (SD 3.5,range 0-12) per 12 months of follow-up (after 3 doses), with mean individual treatment-recurrence (TR) intervals ranging from 28->365 days (mean 58). Intraindividual variability of TR intervals (SD) was 7.1 days as a mean value (range 1.7¡V22.6). It ranged within 20% of the mean intra-individual interval for 30 (91%) and within 15% for 21 patients (64%). The first interval was within 1 week of the mean intra-individual interval in 64% and within 2 weeks in 89% of patients. Conclusions: The majority of AMD patients showed a relatively stable rhythm for PRN injections of ranibizumab after initial loading phase, associated with excellent functional/anatomical results. The initial interval last loading dose-first recurrence may have a predictive value for further need of treatment, potentially facilitating follow-up and patient care.

Que cache l'agenda caché [What is behind the hidden agenda?]

The physicians often forget to ask their patients if they would like to discuss other complaints or topics. It is sometimes quite difficult to explore the patient's complaints; while the physicians tend to focus on the immediate problem, the patients may have not only one, but several hidden agendas during a visit. In a caring relation there is a clear advantage to clarify the implicit. The search for the hidden agenda is to improve the care of i) biomedical problems ii) the social quest presented to the physicians. The sentence "Oh, by the way, doctor..." should not be only understood as an information but also as a relational expression and a reaction to the imminent separation from the physician.

Transgenerational transmission of trauma in families of Holocaust survivors: The consequences of extreme family functioning on resilience, Sense of Coherence, anxiety and depression.

BACKGROUND: The psychological transmission of the noxious effects of a major trauma from one generation to the next remains unclear. The present study aims to identify possible mechanisms explaining this transmission among families of Holocaust Survivors (HS). We hypothesized that the high level of depressive and anxiety disorders (DAD) among HS impairs family systems, which results in damaging coping strategies of their children (CHS) yielding a higher level of DAD. METHODS: 49 CHS completed the Resilience Scale for Adults, the Hopkins Symptom Check List-25, the 13-Item Sense of Coherence (SOC) scale, and the Family Adaptability and Cohesion Scale. We test a mediation model with Family types as the predictor; coping strategies (i.e. Resilience or SOC) as the mediator; and DAD as the outcome variable. RESULTS: Results confirm that the CHS׳ family types are more often damaged than in general population. Moreover, growing in a damaged family seems to impede development of coping strategies and, therefore, enhances the occurrence of DAD. LIMITATIONS: The present investigation is correlational and should be confirmed by other prospective investigations. CONCLUSIONS: At a theoretical level we propose a mechanism of transmission of the noxious effects of a major trauma from one generation to the next through family structure and coping strategies. At a clinical level, our results suggest to investigate the occurrence of trauma among parents of patients consulting for DAD and to reinforce their coping strategies.

Que cache l'hypertension arterielle masquée? [What is behind masked hypertension?]

In approximately 10% of adults, ambulatory blood pressures recorded during everyday activities or selfmeasured blood pressures are abnormally elevated whereas office blood pressures are in a normal range. This type of blood pressure behavior, known as masked hypertension, is associated with an increased cardiovascular risk. It may be pertinent to search for the presence of masked hypertension in individuals having sometimes elevated, sometimes normal office blood pressures, as well as in very high risk patients and in patients requiring an optimal blood pressure control, such as for instance in those with diabetes or nephropathy.

Sleep deprivation (SD) on focal brain ischemia in the rat : effects of different SD protocols

Sleep-wake disturbances are frequently observed in stroke patients and are associated with poorer functional outcome. Until now the effects of sleep on stroke evolution are unknown. The purpose of the present study was to evaluate the effects of three sleep deprivation (SD) protocols on brain damages after focal cerebral ischemia in a rat model. Permanent occlusion of distal branches of the middle cerebral artery was induced in adult rats. The animals were then subjected to 6h SD, 12h SD or sleep disturbances (SDis) in which 3 x 12h sleep deprivation were performed by gentle handling. Infarct size and brain swelling were assessed by Cresyl violet staining, and the number of damaged cells was measured by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Behavioral tests, namely tape removal and cylinder tests, were performed for assessing sensorimotor function. In the 6h SD protocol, no significant difference (P > 0.05) was found either in infarct size (42.5 ± 30.4 mm3 in sleep deprived animals vs. 44.5 ± 20.5 mm3 in controls, mean ± s.d.), in brain swelling (10.2 ± 3.8 % in sleep deprived animals vs. 11.3 ± 2.0 % in controls) or in number of TUNEL-positive cells (21.7 ± 2.0/mm2 in sleep deprived animals vs. 23.0 ± 1.1/mm2 in controls). In contrast, 12h sleep deprivation increased infarct size by 40 % (82.8 ± 10.9 mm3 in SD group vs. 59.2 ± 13.9 mm3 in control group, P = 0.008) and number of TUNEL-positive cells by 137 % (46.8 ± 15/mm in SD group vs. 19.7 ± 7.7/mm2 in control group, P = 0.003). There was no significant difference (P > 0.05) in brain swelling (12.9 ± 6.3 % in sleep deprived animals vs. 11.6 ± 6.0 % in controls). The SDis protocol also increased infarct size by 76 % (3 x 12h SD 58.8 ± 20.4 mm3 vs. no SD 33.8 ± 6.3 mm3, P = 0.017) and number of TUNEL-positive cells by 219 % (32.9 ± 13.2/mm2 vs. 10.3 ± 2.5/mm2, P = 0.008). Brain swelling did not show any difference between the two groups (24.5 ± 8.4 % in SD group vs. 16.7 ± 8.9 % in control group, p > 0.05). Both behavioral tests did not show any concluding results. In summary, we demonstrate that sleep deprivation aggravates brain damages in a rat model of stroke. Further experiments are needed to unveil the mechanisms underlying these effects.

Improving telecommunication security level by integrating quantum key distribution in communication protocols

Résumé La cryptographie classique est basée sur des concepts mathématiques dont la sécurité dépend de la complexité du calcul de l'inverse des fonctions. Ce type de chiffrement est à la merci de la puissance de calcul des ordinateurs ainsi que la découverte d'algorithme permettant le calcul des inverses de certaines fonctions mathématiques en un temps «raisonnable ». L'utilisation d'un procédé dont la sécurité est scientifiquement prouvée s'avère donc indispensable surtout les échanges critiques (systèmes bancaires, gouvernements,...). La cryptographie quantique répond à ce besoin. En effet, sa sécurité est basée sur des lois de la physique quantique lui assurant un fonctionnement inconditionnellement sécurisé. Toutefois, l'application et l'intégration de la cryptographie quantique sont un souci pour les développeurs de ce type de solution. Cette thèse justifie la nécessité de l'utilisation de la cryptographie quantique. Elle montre que le coût engendré par le déploiement de cette solution est justifié. Elle propose un mécanisme simple et réalisable d'intégration de la cryptographie quantique dans des protocoles de communication largement utilisés comme les protocoles PPP, IPSec et le protocole 802.1li. Des scénarios d'application illustrent la faisabilité de ces solutions. Une méthodologie d'évaluation, selon les critères communs, des solutions basées sur la cryptographie quantique est également proposée dans ce document. Abstract Classical cryptography is based on mathematical functions. The robustness of a cryptosystem essentially depends on the difficulty of computing the inverse of its one-way function. There is no mathematical proof that establishes whether it is impossible to find the inverse of a given one-way function. Therefore, it is mandatory to use a cryptosystem whose security is scientifically proven (especially for banking, governments, etc.). On the other hand, the security of quantum cryptography can be formally demonstrated. In fact, its security is based on the laws of physics that assure the unconditional security. How is it possible to use and integrate quantum cryptography into existing solutions? This thesis proposes a method to integrate quantum cryptography into existing communication protocols like PPP, IPSec and the 802.l1i protocol. It sketches out some possible scenarios in order to prove the feasibility and to estimate the cost of such scenarios. Directives and checkpoints are given to help in certifying quantum cryptography solutions according to Common Criteria.

Intravitreal ranibizumab for age-related macular degeneration - optical coherence tomography guided retreatment intervals and their intra- and inter-individual variability

PURPOSE:To determine whether the need for retreatment after an initial loading phase of 3 monthly intravitreal injections of ranibizumab shows an intra-individual regular rhythm and to what degree it varies between different patients.SETTING:Prospective mono-centre cohort study.METHODS:Prospective study with 42 patients with exudative age-related macular degeneration (AMD), treatment na?ve, giving informed consent. Loading dose of 3 monthly doses of ranibizumab (0,5mg), followed by a 12 months pro re nata (PRN) regimen according to early exudative signs on spectral domain optical coherence tomography (HD-OCT Cirrus Zeiss?, cube 512x126). The follow-up visits were intensified (week 4, 5, 6, 7, 8, 10, 12, 14, 16, 20, 24, etc after each injection) in order to detect exudative recurrences early, and injection followed within 3 days in cases of subretinal fluid, or intraretinal cysts, or central thickness increase of >50?m. Intervals were calculated between injections and the following recurrence was calculated for the 12 month follow-up with PRN treatment. Variability was expressed as standard deviation (SD). RESULTS Visual acuity (VA) improved from a mean ETDRS letter score of 61.6 (SD 10.8) at baseline to 68.0 (SD 10.2, +6.4 letters) at month 3 and increased further to 74.7 (SD 9.0, +13.1 letters from baseline) at month 12. The 15 patients who have completed the study by October 2010 showed maintenance of the VA improvement. Retinal thickness of the central foveal subfield improved from a mean value of 366?m(baseline) to 253?m(month 3), well maintained thereafter. Mean number of injections was 8.8 (SD 3.5) per 12 months of follow-up (after 3 loading doses), ranging from 0 to 12, with mean individual treatment-recurrence intervals ranging from 28 to >365 days (mean 58 days). Intraindividual variability of treatment-recurrence intervals, measured as SD of the individual intervals, was 7.1days as a mean value(range 1.7 ? 22.6 days) for the 33 patients with more than 1 injection during follow-up. SD was higher for longer intervals of an individual patient. It ranged within 20% of the mean intra-individual interval for 30 patients(91%) and within 15% for 21 patients(64%). The first interval was within 1 week of the mean intra-individual interval in 64% of patients and within 2 weeks in 89% of patients.CONCLUSIONS:The majority of AMD patients showed a relatively stable rhythm for PRN injections of intravitreal ranibizumab after initial loading phase, associated with excellent functional and anatomical results. The initial interval between last loading dose and first recurrence may have a predictive value for further need of treatment, therefore potentially facilitating follow-up and patient care.

Visualization of aqueous shunt position and patency using anterior segment optical coherence tomography.

PURPOSE: To describe the use of anterior segment optical coherence tomography (AS-OCT) to clarify the position and patency of aqueous shunt devices in the anterior chamber of eyes where corneal edema or tube position does not permit a satisfactory view. DESIGN: Noncomparative observational case series. METHODS: Four cases are reported in which aqueous shunt malposition or obstruction was suspected but the shunt could not be seen on clinical examination. The patients underwent AS-OCT to identify the position and patency of the shunt tip. RESULTS: In each case, AS-OCT provided data regarding tube position and/or patency that could not be obtained by slit-lamp examination or by gonioscopy that influenced management. CONCLUSIONS: AS-OCT can be used to visualize anterior chamber tubes in the presence of corneal edema that precludes an adequate view or in cases where the tube is retracted into the cornea. In such cases, AS-OCT is useful in identifying shunt patency and position, which helps guide clinical decision making.

Fate of clinical research studies after ethical approval--follow-up of study protocols until publication.

BACKGROUND: Many clinical studies are ultimately not fully published in peer-reviewed journals. Underreporting of clinical research is wasteful and can result in biased estimates of treatment effect or harm, leading to recommendations that are inappropriate or even dangerous. METHODS: We assembled a cohort of clinical studies approved 2000-2002 by the Research Ethics Committee of the University of Freiburg, Germany. Published full articles were searched in electronic databases and investigators contacted. Data on study characteristics were extracted from protocols and corresponding publications. We characterized the cohort, quantified its publication outcome and compared protocols and publications for selected aspects. RESULTS: Of 917 approved studies, 807 were started and 110 were not, either locally or as a whole. Of the started studies, 576 (71%) were completed according to protocol, 128 (16%) discontinued and 42 (5%) are still ongoing; for 61 (8%) there was no information about their course. We identified 782 full publications corresponding to 419 of the 807 initiated studies; the publication proportion was 52% (95% CI: 0.48-0.55). Study design was not significantly associated with subsequent publication. Multicentre status, international collaboration, large sample size and commercial or non-commercial funding were positively associated with subsequent publication. Commercial funding was mentioned in 203 (48%) protocols and in 205 (49%) of the publications. In most published studies (339; 81%) this information corresponded between protocol and publication. Most studies were published in English (367; 88%); some in German (25; 6%) or both languages (27; 6%). The local investigators were listed as (co-)authors in the publications corresponding to 259 (62%) studies. CONCLUSION: Half of the clinical research conducted at a large German university medical centre remains unpublished; future research is built on an incomplete database. Research resources are likely wasted as neither health care professionals nor patients nor policy makers can use the results when making decisions.