Late Onset Cystoid Macular Oedema Following Surgery for Radiation Induced Cataract in Patient With Retinoblastoma

Purpose: Cystoid macular oedema (CMO) is a very rare condition following cataract surgery in paediatric population. Nevertheless, we report a case series of patients with radiation induced cataract after retinoblastoma (Rb) treatment that underwent cataract surgery and developed subsequently late onset CMO. Methods: Between January 1984 and December 2009, 25 consecutive eyes (25 patients) with Rb presented with radiation induced cataract surgery at the Jules Gonin Eye Hospital. Sixteen eyes (16 patients) had prior radiation induced retinopathy and maculopathy (IRM). Out of these, 3 eyes (3 patients) developed CMO after cataract surgery. Results: One eye had Rb stage B, and 2 eyes had stage D International classification. All of them developed IRM following brachytherapy and/or external beam irradiation. Patients underwent phako-aspiration and in bag intraocular lens implantation after IRM had resolved. Mean age at cataract surgery was 10.7 ± 2.8 (SEM) (range 5-14) years old. Mean time between resolution of IRM and cataract surgery was 76.0 ± 27.2 (SEM) (range 24-116) months. Mean time of onset CMO after cataract surgery was 81.0 ± 34.4 (SEM) (range 13-124) months. There was no other underlying vascular or tractional factor for CMO development. All of them were treated with a combination of oral carbonic anhydrase inhibitor, topical steroid and topical non-steroid. Mean macular thickness pre-, during-, and post CMO were 134.0 ± 10.3, 298.0 ± 37.1, and 154.0 ± 4.0 (SEM) µm, respectively. Mean best corrected visual acuity pre-, during-, and post CMO were 0.31 ± 0.19, 0.46 ± 0.12, and 0.34 ± 0.18 (SEM) LogMAR, respectively. Mean time for CMO reabsorption was 17.0 ± 9.8 (SEM) months. Conclusions: To the best of our knowledge, CMO following paediatric cataract surgery is a very uncommon condition. Moreover, late onset CMO after phako-aspiration for radiation induced cataract in Rb patients has never been described. It is a rare complication but can be treated successfully.

Simultaneous renal oncocytoma and lymphoma: interest of lymphadenectomy

Kidney lesions may be difficult to diagnose only by radiological exams, often requiring proof by tissue biopsy. Moreover, if enlarged regional lymph nodes are also present, the spectrum of differential diagnoses is even greater. The role of regional lymph node dissection in this setting is not clearly established. We show the case of a patient with a kidney mass associated with a conglomerate of para-aortic and iliac lymphadenopathies corresponding to an oncocytoma and a nodular lymphocyte predominant Hodgkin' lymphoma, respectively. Diagnosis of these two lesions was performed by morphology and immunohistochemistry. This case reflects how imaging can mislead to diagnosis and how histological confirmation helps decide treatment management.

Determination of catecholamines in plasma and urine.

For more than 20 years, measurement of catecholamines in plasma and urine in clinical chemistry laboratories has been the cornerstone of the diagnosis of neuroendocrine tumors deriving from the neural crest such as pheochromocytoma (PHEO) and neuroblastoma (NB), and is still used to assess sympathetic stress function in man and animals. Although assay of catecholamines in urine are still considered the biochemical standard for the diagnosis of NB, they have been progressively abandoned for excluding/confirming PHEOs to the advantage of metanephrines (MNs). Nevertheless, catecholamine determinations are still of interest to improve the biochemical diagnosis of PHEO in difficult cases that usually require a clonidine-suppression test, or to establish whether a patient with PHEO secretes high concentrations of catecholamines in addition to metanephrines. The aim of this chapter is to provide an update about the catecholamine assays in plasma and urine and to show the most common pre-analytical and analytical pitfalls associated with their determination.

Blood corticosterone levels and intersexual selection games: best-of-bad-job strategies of male common lizards

Glucocorticoids affect physiology and behaviour, reproduction and potentially sexual selection as well. Shortterm and moderate glucocorticoid elevations are suggested to be adaptive, and prolonged and high elevations may be extremely harmful. This suggests that optimal reproductive strategies, and thus sexual selection, may be dose dependent. Here, we investigate effects of moderate and high elevations of blood corticosterone levels on intra- and intersexual behaviour and mating success of male common lizards Lacerta vivipara. Females showed less interest and more aggressive behaviour towards high corticosterone males and blood corticosterone levels affected male reproductive strategy. Males of moderate and high corticosterone elevations, compared with Control males, showed increased interest (i.e., higher number of chases, tongue extrusions, and approaches) towards females and high corticosterone males initiated more copulation attempts. However, neither increased male interest nor increased copulation attempts resulted in more copulations. This provides evidence for a best-of-a-bad-job strategy, where males with higher corticosterone levels compensated for reduced female interest and increased aggressive female behaviour directed towards them, by showing higher interest and by conducting more copulation attempts. Blood corticosterone levels affected intrasexual selection as well since moderate corticosterone levels positively affected male dominance, but dominance did not affect mating success. These findings underline the importance of female mate choice and are in line with adaptive compensatory behaviours of males. They further show that glucocorticoid effects on behaviour are dose dependent and that they have important implications for sexual selection and social interactions, and might potentially affect Darwinian fitness.

Risk-benefit balance assessment of SSRI antidepressant use during pregnancy and lactation based on best available evidence.

INTRODUCTION: Psychiatric disorders are among the leading causes of disability in Western societies. Selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressant drugs during pregnancy and the postpartum period. Over the last decade, conflicting findings regarding the safety of SSRI drugs during pregnancy and lactation have questioned whether such treatments should be used during this period. AREAS COVERED: We discuss the main criteria that should be considered in the risk/benefit assessment of SSRI treatment in pregnant and/or breastfeeding patients (i.e., risks associated with SSRI use and with untreated depression as well as therapeutic benefits of SSRI and some alternative treatment strategies). For each criterion, available evidence has been synthesized and stratified by methodological quality as well as discussed for clinical impact. EXPERT OPINION: Currently, it is impossible for most of the evaluated outcomes to distinguish between the effects related to the mother's underlying disease and those inherent to SSRI treatment. In women suffering from major depression and responding to a pharmacological treatment, introduction or continuation of an SSRI should be encouraged in order to prevent maternal complications and to preserve maternal-infant bonding. The choice of the right drug depends above all on individual patient characteristics such as prior treatment response, diagnoses and comorbid conditions.

Patient, primary care physician and specialist expectations of primary care physician involvement in cancer care.

BACKGROUND: In Canada, many health authorities recommend that primary care physicians (PCP) stay involved throughout their patients' cancer journey to increase continuity of care. Few studies have focused on patient and physician expectations regarding PCP involvement in cancer care. OBJECTIVE: To compare lung cancer patient, PCP and specialist expectations regarding PCP involvement in coordination of care, emotional support, information transmission and symptom relief at the different phases of cancer. DESIGN: Canadian survey of lung cancer patients, PCPs and cancer specialists PARTICIPANTS: A total of 395 patients completed questionnaires on their expectations regarding their PCP participation in several aspects of care, at different phases of their cancer. Also, 45 specialists and 232 community-based PCP involved in these patients' care responded to a mail survey on the same aspects of cancer care. RESULTS: Most specialists did not expect participation of the PCP in coordination of care in the diagnosis and treatment phases (65% and 78% respectively), in contrast with patients (83% and 85%) and PCPs (80% and 59%) (p < 0.0001). At these same phases, the best agreement among the 3 groups was around PCP role in emotional support: 84% and more of all groups had this expectation. PCP participation in symptom relief was another shared expectation, but more unanimously at the treatment phase (p = 0.85). In the advanced phase, most specialists expect a major role of PCP in all aspects of care (from 81% to 97%). Patients and PCP agree with them mainly for emotional support and information transmission. CONCLUSION: Lung cancer patient, PCP and specialist expectations regarding PCP role differ with the phase of cancer and the specific aspect of cancer care. There is a need to reach a better agreement among them and to better define PCP role, in order to achieve more collaborative and integrated cancer care.

Swiss DRGs : patient heterogeneity and hospital payments

In this paper, we analyze the prospective method of paying hospitals when the within-DRG variance is high. To avoid patients dumping, an outlier payment system is implemented. In the APDRG Swiss System, it consists in a mixture of fully prospective payments for low costs patients and partially cost-based system for high cost patients. We show how the optimal policy depends on the degree to which hospitals take patients' interest into account. A fixed-price policy is optimal when the hospital is sufficiently benevolent. When the hospital is weakly benevolent, a mixed policy solving a trade-off between rent extraction, efficiency and dumping deterrence must be preferred. Following Mougeot and Naegelen (2008), we show how the optimal combination of fixed price and partially costbased payment depends on the degree of benevolence of the hospital, the social cost of public funds and the distribution of patients severity. [Authors]

Impact of etanercept-methotrexate therapy on patient-reported outcomes in rheumatoid arthritis patients with up to 12 months of symptoms.

Background/Purpose: Patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) are critical in evaluating RA treatment effects on function and health-related quality of life (HR-QoL). Significant improvement in PROs has been reported in RA studies of biologic agents, including etanercept (ETN), but most studies have been conducted in patients with established disease. In addition to assessing treatment effects in early RA, there is interest in therapeutic strategies that allow dose reduction or withdrawal of biologic therapy (biologic-free) after induction of response. The PRIZE trial is an ongoing, 3-period study to evaluate the efficacy of combined ETN and methotrexate (MTX) therapy in patients with early, moderate-to-severe RA and to assess whether efficacy (remission) can be maintained with ETN dose reduction or biologic-free (Period 2) or drug-free (Period 3). Herein we report PROs associated with ETN 50 mg QW plus MTX (ETN50/MTX) therapy administered for 52 wks in Period 1 (induction) of the PRIZE trial. Methods: In Period 1, MTX- and biologic-naı‥ve patients with early, active RA (symptom onset 12 mo from enrollment; DAS28 _3.2) received open-label ETN50/MTX for 52 wks. The starting dose of MTX was 10 mg QW; at the discretion of the investigator, titration was permitted up to a maximum of 25 mg QW to achieve remission. Corticosteroid boosts were administered to patients not achieving low disease state at wks 13 and 26, unless contraindicated or not tolerated. PROs were assessed using the Health Assessment Questionnaire (HAQ) total score; Patient Acceptable Symptom State (PASS); EuroQol-5 Dimensions (EQ-5D) total index; Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue; Work Instability Scale for Rheumatoid Arthritis (RAWIS); and Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI:RA). Results: A total of 306 patients received treatment in Period 1 (mITT population); 222 (73%) patients completed the period. The majority of patients were female (70%), with a mean age of 50 y, mean DAS28 of 6.0 (median, 6.0), and duration of disease symptoms from onset of 6.5 months (median, 6.3 mo). Significant and clinically meaningful improvements in PROs, including in HAQ, EQ-5D, SF-36, and FACIT-Fatigue, were demonstrated with ETN50/MTX therapy from baseline to the final on therapy visit (Table; P_0.0001). Similar improvements were observed in all dimensions of RA-WIS and WPAI:RA (Table; P_0.0001). Conclusion: Combination therapy with ETN50/MTX for 52 wks in patients with _12 mo of symptomatic, active RA resulted in significant, clinically important improvements in measures of physical function, including normal HAQ (66.6% of patients), HR-QoL, fatigue, and work productivity. These outcomes are consistent with those reported in prior studies in patients with more established disease.

The future of patient safety: Surgical trainees accept virtual reality as a new training tool.

BACKGROUND: The use of virtual reality (VR) has gained increasing interest to acquire laparoscopic skills outside the operating theatre and thus increasing patients' safety. The aim of this study was to evaluate trainees' acceptance of VR for assessment and training during a skills course and at their institution. METHODS: All 735 surgical trainees of the International Gastrointestinal Surgery Workshop 2006-2008, held in Davos, Switzerland, were given a minimum of 45 minutes for VR training during the course. Participants' opinion on VR was analyzed with a standardized questionnaire. RESULTS: Fivehundred-twenty-seven participants (72%) from 28 countries attended the VR sessions and answered the questionnaires. The possibility of using VR at the course was estimated as excellent or good in 68%, useful in 21%, reasonable in 9% and unsuitable or useless in 2%. If such VR simulators were available at their institution, most course participants would train at least one hour per week (46%), two or more hours (42%) and only 12% wouldn't use VR. Similarly, 63% of the participants would accept to operate on patients only after VR training and 55% to have VR as part of their assessment. CONCLUSION: Residents accept and appreciate VR simulation for surgical assessment and training. The majority of the trainees are motivated to regularly spend time for VR training if accessible.

Au-delà de l'ennui: l'effort pour rendre l'autre intéressant [Beyond boredom: the effort to make a patient interesting]

The doctors' emotional reaction towards the patients has an impact on the doctor-patient relationship. This article focuses on a particular emotion, boredom which is evoked by certain patients. By means of a case vignette, this phenomenon is elucidated and confronted with the psycho-analytical concept of "pensée opératoire", and ways are identified to raise the interest in patients.

Subgroup And Quality Of Life Analyses Of The Phase Iii Clinical Trial Of Novottf-100a Versus Best Standard Chemotherapy For Recurrent Glioblastoma

BACKGROUND: NovoTTF is a portable device delivering low-intensity, intermediate-frequency, electric fields using noninvasive, disposable scalp electrodes. These fields physically interfere with cell division. Preliminary studies in recurrent and newly diagnosed glioblastoma (GBM) have shown promising results. A phase III study in recurrent GBM has recently been concluded. METHODS: Adults (KPS ≥ 70%) with recurrent GBM (any recurrence) were randomized (stratified by surgery and center) to either NovoTTF administered continuously (20-24 hours/day, 7 days/week) or the best available chemotherapy (best physician choice [BPC]). Primary endpoint was overall survival (OS); 6-month progression-free survival (PFS6), 1-year survival, and QOL were secondary endpoints. RESULTS: Two hundred thirty-seven patients were randomized (28 centers in the United States and Europe) to either NovoTTF alone (120 patients) or BPC (117 patients). Patient characteristics were balanced, median age was 54 years (range, 23-80 years), median KPS was 80% (range, 50-100). One quarter had surgery for recurrence, and over half were at their second or more recurrence. A survival advantage for the device group was seen in patients treated according to protocol (median OS, 7.8 months vs. 6.1 months; n = 185; p = 0.01). Moreover, subgroup analysis in patients with better prognostic baseline characteristics (KPS ≥ 80%; age ≤ 60; 1st-3rd recurrence) demonstrated a robust survival benefit for NovoTTF patients compared to matched BPC patients (median OS, 8.8 months vs. 6.6 months; n = 110; p < 0.01). In this group, 1-year survival was 35% vs. 20% and PFS6 was 25.6% vs. 7.7%. Interestingly, in patients who failed bevacizumab prior to the trial, OS was also significantly extended by NovoTTF (4.4 months vs. 3.1 months; n = 23 vs. n = 21; p < 0.02). Quality of life was equivalent or superior in NovoTTF patients. CONCLUSIONS: NovoTTF, a noninvasive, novel cancer treatment modality shows significant therapeutic efficacy with improved quality of life. The impact of NovoTTF was more pronounced when patients with better baseline prognostic factors were treated. A large scale phase III clinical trial in newly diagnosed GBM is currently being conducted.

Brachial or wrist blood pressure in obese patients : which is the best ?

RESUME L'obésité et l'hypertension atteignent des niveaux épidémiques aussi bien dans les pays industrialisés que dans ceux en voie de développement. La coexistence de ces deux pathologies est associée à un risque cardiovasculaire augmenté. Traditionnellement on mesure la pression artérielle (PA) au bras au moyen d'un brassard qui détermine la pression systolique et diastolique en utilisant soit la méthode auscultatoire ou oscillométrique. L'utilisation d'un brassard de taille standard chez le patient avec un tour de bras augmenté peut surestimer la pression artérielle. Il semble même qu'il existe un rapport idéal entre le tour de bras, et la taille du brassard La mesure à domicile de la pression artérielle avec des appareils validés donne des valeurs de la PA valables. Plusieurs appareils existent sur le marché et depuis quelques années les appareils de mesure de la PA au poignet font leur apparition sur le marché. Cette étude vise à comparer chez des sujets sains et obèses les valeurs de PA obtenues au poignet avec celles obtenues au bras en utilisant deux appareils validés l'OMRON HEM 705-CP et l'OMRON R6. L'OMRON HEM 705-CP permet l'utilisation soit d'un brassard standard (13x30 cm) ou d'un brassard large (16x38 cm), et l'OMRON R6 mesure la PA au poignet. Nous avons comparé un groupe de sujets obèses [Body Mass Index (BMI) >35kg/m2] avec un groupe de sujets sains (BMI <25kg/m2). Ont été exclues de l'étudé les personnes prenant un traitement antihypertenseur ainsi que celles souffrant d'arythmies. La PA a été mesurée en position assise avec le bras gauche sur une table à hauteur du coeur. Un brassard large a été employé pour les sujets obèses et un brassard standard pour les sujets sains. Trois mesures ont été effectuées, la première après une pause de 5 min et chacune des suivantes avec un intervalle de 2 min. La pression d'inflation maximale a été fixée à 170 mmHg. Nous avons utilisé la formule proposée par Marks LA et al pour déterminer si le rapport entre la taille des brassards fournis avec l'OMRON .HEM 705-CP et le tour de bras de nos sujets était optimal (taille du brassard = 9.34 x log10 taille du bras). Nos résultats ne montrent pas de différence statistiquement significative de la PA diastolique entre les deux groupes, qu'elle soit mesurée au bras ou au poignet. La PA systolique mesurée au bras s'est par contre avérée significativement plus basse chez les sujets obèses que chez les sujets sains. Aucune différence n'a été trouvée lorsque la mesure est effectuée au poignet. En utilisant la formule fournie par Marks le rapport entre taille du brassard (large chez les obèses) et tour de bras a été de 10.30±30 chez les sujets obèses et 9.630.45 chez les sujets sains (p<0.001). Le rapport entre tour de bras et brassard chez les sujets obèses est nettement au-dessus de la valeur optimale, ce qui suggère une possible sous-estimation de la PA systolique chez ces sujets. Ces résultats suggèrent qu'il existe un risque de sous-estimer la PA chez le patient obèse lors de l'utilisation d'un brassard large. Cette erreur pourrait être réduite par l'utilisation d'appareils de mesure au poignet. validés chez le sujet obèse.

Medical record search engines, using pseudonymised patient identity: an alternative to centralised medical records

Purpose The purpose of our multidisciplinary study was to define a pragmatic and secure alternative to the creation of a national centralised medical record which could gather together the different parts of the medical record of a patient scattered in the different hospitals where he was hospitalised without any risk of breaching confidentiality. Methods We first analyse the reasons for the failure and the dangers of centralisation (i.e. difficulty to define a European patients' identifier, to reach a common standard for the contents of the medical record, for data protection) and then propose an alternative that uses the existing available data on the basis that setting up a safe though imperfect system could be better than continuing a quest for a mythical perfect information system that we have still not found after a search that has lasted two decades. Results We describe the functioning of Medical Record Search Engines (MRSEs), using pseudonymisation of patients' identity. The MRSE will be able to retrieve and to provide upon an MD's request all the available information concerning a patient who has been hospitalised in different hospitals without ever having access to the patient's identity. The drawback of this system is that the medical practitioner then has to read all of the information and to create his own synthesis and eventually to reject extra data. Conclusions Faced with the difficulties and the risks of setting up a centralised medical record system, a system that gathers all of the available information concerning a patient could be of great interest. This low-cost pragmatic alternative which could be developed quickly should be taken into consideration by health authorities.

Méta-analyses d'essais randomisés sur données individuelles dans le traitement des cancers ORL non métastatiques : principes, résultats, perspectives [Individual patient data meta-analyses of randomized trials for the treatment of non-metastatic head and neck squamous cell carcinomas: Principles, results and perspectives].

Meta-analyses are considered as an important pillar of evidence-based medicine. The aim of this review is to describe the main principles of a meta-analysis and to use examples of head and neck oncology to demonstrate their clinical impact and methodological interest. The major role of individual patient data is outlined, as well as the superiority of individual patient data over meta-analyses based on published summary data. The major clinical breakthrough of head and neck meta-analyses are summarized, regarding concomitant chemotherapy, altered fractionated chemotherapy, new regimens of induction chemotherapy or the use of radioprotectants. Recent methodological developments are described, including network meta-analyses, the validation of surrogate markers. Lastly, the future of meta-analyses is discussed in the context of personalized medicine.

Implementation of bayesian therapeutic drug monitoring in modern patient care

The variability observed in drug exposure has a direct impact on the overall response to drug. The largest part of variability between dose and drug response resides in the pharmacokinetic phase, i.e. in the dose-concentration relationship. Among possibilities offered to clinicians, Therapeutic Drug Monitoring (TDM; Monitoring of drug concentration measurements) is one of the useful tool to guide pharmacotherapy. TDM aims at optimizing treatments by individualizing dosage regimens based on blood drug concentration measurement. Bayesian calculations, relying on population pharmacokinetic approach, currently represent the gold standard TDM strategy. However, it requires expertise and computational assistance, thus limiting its large implementation in routine patient care. The overall objective of this thesis was to implement robust tools to provide Bayesian TDM to clinician in modern routine patient care. To that endeavour, aims were (i) to elaborate an efficient and ergonomic computer tool for Bayesian TDM: EzeCHieL (ii) to provide algorithms for drug concentration Bayesian forecasting and software validation, relying on population pharmacokinetics (iii) to address some relevant issues encountered in clinical practice with a focus on neonates and drug adherence. First, the current stage of the existing software was reviewed and allows establishing specifications for the development of EzeCHieL. Then, in close collaboration with software engineers a fully integrated software, EzeCHieL, has been elaborated. EzeCHieL provides population-based predictions and Bayesian forecasting and an easy-to-use interface. It enables to assess the expectedness of an observed concentration in a patient compared to the whole population (via percentiles), to assess the suitability of the predicted concentration relative to the targeted concentration and to provide dosing adjustment. It allows thus a priori and a posteriori Bayesian drug dosing individualization. Implementation of Bayesian methods requires drug disposition characterisation and variability quantification trough population approach. Population pharmacokinetic analyses have been performed and Bayesian estimators have been provided for candidate drugs in population of interest: anti-infectious drugs administered to neonates (gentamicin and imipenem). Developed models were implemented in EzeCHieL and also served as validation tool in comparing EzeCHieL concentration predictions against predictions from the reference software (NONMEM®). Models used need to be adequate and reliable. For instance, extrapolation is not possible from adults or children to neonates. Therefore, this work proposes models for neonates based on the developmental pharmacokinetics concept. Patients' adherence is also an important concern for drug models development and for a successful outcome of the pharmacotherapy. A last study attempts to assess impact of routine patient adherence measurement on models definition and TDM interpretation. In conclusion, our results offer solutions to assist clinicians in interpreting blood drug concentrations and to improve the appropriateness of drug dosing in routine clinical practice.