IVA in addition to BMD can change the osteoporosis management in 25% of clinical routine patients.

Vertebral fracture is one of the major osteoporotic fractures which are unfortunately very often undetected. In addition, it is well known that prevalent vertebral fracture increases dramatically the risk of future additional fracture. Instant Vertebral Assessment (IVA) has been introduced in DXA device couple years ago to ease the detection of such fracture when routine DXA are performed. To correctly use such tool, ISCD provided clinical recommendation on when and how to use it. The aim of our study was to evaluate the ISCD guidelines in clinical routine patients and see how often it may change of patient management. During two months (March and April 2010), a medical questionnaire was systematically given to our clinical routine patient to check the validity of ISCD IVA recommendations in our population. In addition, all women had BMD measurement at AP spine, Femur and 1/3 radius using a Discovery A System (Hologic, Waltham, USA). When appropriate, IVA measurement had been performed on the same DXA system and had been centrally evaluated by two trained Doctors for fracture status according to the semi-quantitative method of Genant. The reading had been performed when possible between L5 and T4. Out of 210 women seen in the consultation, 109 (52%) of them (mean age 68.2±11.5 years) fulfilled the necessary criteria to have an IVA measurement. Out of these 109 women, 43 (incidence 39.4%) had osteoporosis at one of the three skeletal sites and 31 (incidence 28.4%) had at least one vertebral fracture. 14.7% of women had both osteoporosis and at least one vertebral fracture classifying them as "severe osteoporosis" while 46.8% did not have osteoporosis not vertebral fracture. 24.8% of the women had osteoporosis but no vertebral fracture while 13.8% of women did have osteoporosis but vertebral fracture (Clinical osteoporosis). In conclusion, in 52% of our patients, IVA was needed according to ISCD criteria. In half of them the IVA test influenced of patient management either my changing the type of treatment of simply by classifying patient as "clinical osteoporosis". IVA appears to be an important tool in clinical routine but unfortunately is not yet very often use in most of the centers.

Reproducibility of straylight measurement by C-Quant for assessment of retinal straylight using the compensation comparison method.

BACKGROUND: Straylight gives the appearance of a veil of light thrown over a person's retinal image when there is a strong light source present. We examined the reproducibility of the measurements by C-Quant, and assessed its correlation to characteristics of the eye and subjects' age. PARTICIPANTS AND METHODS: Five repeated straylight measurements were taken using the dominant eye of 45 healthy subjects (age 21-59) with a BCVA of 20/20: 14 emmetropic, 16 myopic, eight hyperopic and seven with astigmatism. We assessed the extent of reproducibility of straylight measures using the intraclass correlation coefficient. RESULTS: The mean straylight value of all measurements was 1.01 (SD 0.23, median 0.97, interquartile range 0.85-1.1). Per 10 years of age, straylight increased in average by 0.10 (95%CI 0.04 to 0.16, p < 0.01]. We found no independent association of refraction (range -5.25 dpt to +2 dpt) on straylight values (0.001; 95%CI -0.022 to 0.024, p = 0.92). Compared to emmetropic subjects, myopia reduced straylight (-.011; -0.024 to 0.02, p = 0.11), whereas higher straylight values (0.09; -0.01 to 0.20, p = 0.09) were observed in subjects with blue irises as compared to dark-colored irises when correcting for age. The intraclass correlation coefficient (ICC) of repeated measurements was 0.83 (95%CI 0.76 to 0.90). CONCLUSIONS: Our study showed that straylight measurements with the C-Quant had a high reproducibility, i.e. a lack of large intra-observer variability, making it appropriate to be applied in long-term follow-up studies assessing the long-term effect of surgical procedures on the quality of vision.

Intraocular Straylight And Contrast Sensitivity Two Months After Lasik: Intraocular Straylight Measurement As A New Parameter In Visual Quality Assessment

PROPÒSIT: Estudiar l'efecte de la cirurgia LASIK en la llum dispersa i la sensibilitat al contrast. MÈTODES: Vint-i-vuit pacients van ser tractats amb LASIK. La qualitat visual es va avaluar abans de l'operació i dos mesos després. RESULTATS: La mitjana de llum dispersa i la sensibilitat al contrast abans de l'operació no va canviar en dos mesos després. Només un ull tenia un marcat augment en la llum dispersa. Nou ulls van presentar una lleugera disminució en la sensibilitat al contrast. S'han trobat dues complicacions. CONCLUSIÓ: Després de LASIK la majoria dels pacients (80%) no van tenir complicacions i van mantenir la seva qualitat visual. Uns pocs pacients (16%) van tenir una mica de qualitat visual disminuïda. Molt pocs (4%) van tenir complicacions clíniques amb disminució en la qualitat visual.

Telehealth system (e-CUIDATE) to improve quality of life in breast cancer survivors: rationale and study protocol for a randomized clinical trial.

BACKGROUND Breast cancer survivors suffer physical impairment after oncology treatment. This impairment reduces quality of life (QoL) and increase the prevalence of handicaps associated to unhealthy lifestyle (for example, decreased aerobic capacity and strength, weight gain, and fatigue). Recent work has shown that exercise adapted to individual characteristics of patients is related to improved overall and disease-free survival. Nowadays, technological support using telerehabilitation systems is a promising strategy with great advantage of a quick and efficient contact with the health professional. It is not known the role of telerehabilitation through therapeutic exercise as a support tool to implement an active lifestyle which has been shown as an effective resource to improve fitness and reduce musculoskeletal disorders of these women. METHODS / DESIGN This study will use a two-arm, assessor blinded, parallel randomized controlled trial design. People will be eligible if: their diagnosis is of stages I, II, or IIIA breast cancer; they are without chronic disease or orthopedic issues that would interfere with ability to participate in a physical activity program; they had access to the Internet and basic knowledge of computer use or living with a relative who has this knowledge; they had completed adjuvant therapy except for hormone therapy and not have a history of cancer recurrence; and they have an interest in improving lifestyle. Participants will be randomized into e-CUIDATE or usual care groups. E-CUIDATE give participants access to a range of contents: planning exercise arranged in series with breathing exercises, mobility, strength, and stretching. All of these exercises will be assigned to women in the telerehabilitation group according to perceived needs. The control group will be asked to maintain their usual routine. Study endpoints will be assessed after 8 weeks (immediate effects) and after 6 months. The primary outcome will be QoL measured by The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 version 3.0 and breast module called The European Organization for Research and Treatment of Cancer Breast Cancer-Specific Quality of Life questionnaire. The secondary outcomes: pain (algometry, Visual Analogue Scale, Brief Pain Inventory short form); body composition; physical measurement (abdominal test, handgrip strength, back muscle strength, and multiple sit-to-stand test); cardiorespiratory fitness (International Fitness Scale, 6-minute walk test, International Physical Activity Questionnaire-Short Form); fatigue (Piper Fatigue Scale and Borg Fatigue Scale); anxiety and depression (Hospital Anxiety and Depression Scale); cognitive function (Trail Making Test and Auditory Consonant Trigram); accelerometry; lymphedema; and anthropometric perimeters. DISCUSSION This study investigates the feasibility and effectiveness of a telerehabilitation system during adjuvant treatment of patients with breast cancer. If this treatment option is effective, telehealth systems could offer a choice of supportive care to cancer patients during the survivorship phase. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01801527.

Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration.

Measurement with an automated oscillometric wrist device with position sensor leads to lower values than measurements obtained with an automated oscillometric arm device from the same manufacturer in elderly persons.

OBJECTIVE: Home blood pressure (BP) monitoring is recommended by several clinical guidelines and has been shown to be feasible in elderly persons. Wrist manometers have recently been proposed for such home BP measurement, but their accuracy has not been previously assessed in elderly patients. METHODS: Forty-eight participants (33 women and 15 men, mean age 81.3±8.0 years) had their BP measured with a wrist device with position sensor and an arm device in random order in a sitting position. RESULTS: Average BP measurements were consistently lower with the wrist than arm device for systolic BP (120.1±2.2 vs. 130.5±2.2 mmHg, P<0.001, means±SD) and diastolic BP (66.0±1.3 vs. 69.7±1.3 mmHg, P<0.001). Moreover, a 10 mmHg or greater difference between the arm and wrist device was observed in 54.2 and 18.8% of systolic and diastolic measures, respectively. CONCLUSION: Compared with the arm device, the wrist device with position sensor systematically underestimated systolic as well as diastolic BP. The magnitude of the difference is clinically significant and questions the use of the wrist device to monitor BP in elderly persons. This study points to the need to validate BP measuring devices in all age groups, including in elderly persons.

Acupuncture and rehabilitation of the painful shoulder: study protocol of an ongoing multicentre randomised controlled clinical trial [ISRCTN28687220]

BACKGROUND Although the painful shoulder is one of the most common dysfunctions of the locomotor apparatus, and is frequently treated both at primary healthcare centres and by specialists, little evidence has been reported to support or refute the effectiveness of the treatments most commonly applied. According to the bibliography reviewed, physiotherapy, which is the most common action taken to alleviate this problem, has not yet been proven to be effective, because of the small size of sample groups and the lack of methodological rigor in the papers published on the subject. No reviews have been made to assess the effectiveness of acupuncture in treating this complaint, but in recent years controlled randomised studies have been made and these demonstrate an increasing use of acupuncture to treat pathologies of the soft tissues of the shoulder. In this study, we seek to evaluate the effectiveness of physiotherapy applied jointly with acupuncture, compared with physiotherapy applied with a TENS-placebo, in the treatment of painful shoulder caused by subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). METHODS/DESIGN Randomised controlled multicentre study with blind evaluation by an independent observer and blind, independent analysis. A study will be made of 465 patients referred to the rehabilitation services at participating healthcare centres, belonging to the regional public health systems of Andalusia and Murcia, these patients presenting symptoms of painful shoulder and a diagnosis of subacromial syndrome (rotator cuff tendinitis and subacromial bursitis). The patients will be randomised into two groups: 1) experimental (acupuncture + physiotherapy); 2) control (TENS-placebo + physiotherapy); the administration of rescue medication will also be allowed. The treatment period will have a duration of three weeks. The main result variable will be the change produced on Constant's Shoulder Function Assessment (SFA) Scale; as secondary variables, we will record the changes in diurnal pain intensity on a visual analogue scale (VAS), nocturnal pain intensity on the VAS, doses of non-steroid anti-inflammatory drugs (NSAIDs) taken during the study period, credibility scale for the treatment, degree of improvement perceived by the patient and degree of improvement perceived by the evaluator. A follow up examination will be made at 3, 6 and 12 months after the study period has ended. Two types of population will be considered for analysis: per protocol and per intention to treat. DISCUSSION The discussion will take into account the limitations of the study, together with considerations such as the choice of a simple, safe method to treat this shoulder complaint, the choice of the control group, and the blinding of the patients, evaluators and those responsible for carrying out the final analysis.

Imagerie cardiaque non invasive: apport spécifique en clinique des nouvelles modalités (I). Evaluation morphologique [Cardiac imaging: specific clinical role of newly developed non invasive techniques. Part 1: Morphological evaluation].

Echocardiography is the preferred initial test to assess cardiac morphology and ventricular function. Cardiac MRI enables an optimal visualisation of heart muscle without contrast injection, and precise measurement of the ventricular volumes and systolic function. It is therefore an ideal test for patients with poor echocardiographic windows or for the specific evaluation of right heart chambers. Heart CT also remarkably images heart muscle and precisely measures ventricular systolic function after intravenous injection of iodinated contrast. Coronary CT may also, in selected cases, avoid the need for diagnostic coronary angiography. Although very accurate, these imaging modalities are expensive and may be contra-indicated for a particular patient. Their use in clinical practice has to follow the accepted guidelines.

IVA in addition to BMD can change the osteoporosis management in 25% of clinical routine patients

Introduction Vertebral fracture is one of the major osteoporoticfractures which are unfortunately very often undetected. In addition,it is well known that prevalent vertebral fracture increases dramaticallythe risk of future additional fracture. Instant Vertebral Assessment(IVA) has been introduced in DXA device a couple of years ago toease the detection of such fracture when routine DXA are performed.To correctly use such tool, ISCD provided clinical recommendationon when and how to use it. The aim of our study was to evaluate theISCD guidelines in clinical routine patients and see how often itmay change of patient management.Methods During two months (March and April 2010), a medicalquestionnaire was systematically given to our clinical routine patientto check the validity of ISCD IVA recommendations in our population.In addition, all women had BMD measurement at AP spine,femur and 1/3 radius using a Discovery A System (Hologic, Waltham,USA). When appropriate, IVA measurement had been performedon the same DXA system and had been centrally evaluated by twotrained doctors for fracture status according to the semi-quantitativemethod of Genant. The reading had been performed when possiblebetween L5 and T4.Results Out of 210 women seen in the consultation, 109 (52 %)of them (mean age 68.2 ± 11.5 years) fulfilled the necessary criteriato have an IVA measurement. Out of these 109 women, 43 (incidence39.4 %) had osteoporosis at one of the three skeletal sitesand 31 (incidence 28.4 %) had at least one vertebral fracture. 14.7 %of women had both osteoporosis and at least one vertebral fractureclassifying them as "severe osteoporosis" while 46.8 % did not haveosteoporosis and no vertebral fracture. 24.8 % of the women hadosteoporosis but no vertebral fracture while 13.8 % of women didhave osteoporosis but vertebral fracture (clinical osteoporosis).Conclusions In 52 % of our patients, IVA was needed accordingto ISCD criteria. In half of them the IVA test influenced of patientmanagement either may changing the type of treatment of simplyby classifying patient as "clinical osteoporosis". IVA appears to bean important tool in clinical routine but unfortunately is not yetvery often use in most of the centers.

Suivi thérapeutique des médicaments (II). La pratique clinique [Therapeutic drug monitoring: clinical practice].

When requesting a blood level measurement in the context of "Therapeutic drug monitoring" (TDM), numerous aspects have to be considered in the pre-analytical and analytical area, as in the integration of associated clinical data. This review presents therapeutic classes for which a clinical benefit of TDM is established or suggested, at least in some settings. For each class of drugs, the main pharmacokinetic, pre-analytical, analytical and clinical aspects are evaluated in the scope of such a monitoring. Each step of the TDM process is important and none should be neglected. Additional clinical trials are however warranted to better establish the exact conditions of use for such a monitoring.

Use of new biochemical plasmatic markers, plasma free and total metanephrines, for the diagnosis and follow-up of neuroblastoma in children with clinical correlation

Background: Neuroblastoma is a paediatrictumour derived from the neural crest. Biochemical diagnosis and follow up rely on quantitation of urinary catecholamines (dopamine and noradrenaline) and their metabolites vanillylmandelic acid (VMA) and homovanillic acid (HVA) (gold-standard). When combined, these analyses have a sensitivity of 95%. However, they are clearly limited by inaccuracy of urine collection in young children and normalisation of catecholamine concentrations by creatininuria. Recent development in biochemical diagnosis of pheochromocytoma, another neural crest tumour found in adults, shows that plasmatic measurement of methoxylated catecholamines called metanephrines are more sensitive and specific than other biomarkers. Moreover, a study to determine the reference intervals for metanephrines in a pediatric population has recently been completed. The aim of this work is to describe the role of metanephrines monitoring in the follow up of neuroblastoma. Method: This retrospective study included patients with neuroblastoma in whom the following parameters were determined: plasma free and total metanephrines, plasma catecholamines, 24h urinary catecholamines and metanephrines in absolute value and corrected by creatinine, VMA and HVA at the diagnosis and during treatment at the University Hospital of Lausanne (Switzerland). Eleven patients aged between the first day of life and 7 years old were followed between 2005 and 2012. Clinical outcome and biochemical concentrations of the analytes were correlated. Results: At diagnosis, plasma free and total normetanephrines and methoxytyramine have a sensitivity of 100% compared to 85% for the actual gold standard. Metanephrine remain below the upper reference limit as expected since these tumours do not produce adrenaline. The relationship between biochemical markers and clinical outcome is illustrated graphically. Plasma or urinary normetanephrine and methoxytyramine correlate better with the history of the patient than VMA and HVA, as evaluated by ordinal logistic regression. Concentrations of analytes in urine show a better correlation with clinical events when the results are corrected by creatininuria. Conclusion: Normetanephrine and methoxytyramine reflect disease history in neuroblastoma patients and could play a significant role in the follow up of this type of tumour. Formal studies in a sufficient number of patients are needed to confirm this preliminary observation.

Protocol of the COSMIN study: consensus-based standards for the selection of health measurement instruments

Background: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist.Method: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist.Discussion: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase.

Total knee arthroplasty - a clinical and numerical study of the micromovements of the tibial implant

Introduction The importance of the micromovements in the mechanism of aseptic loosening is clinically difficult to evaluate. To complete the analysis of a series of total knee arthroplasties (TKA), we used a tridimensional numerical model to study the micromovements of the tibial implant.Material and Methods Fifty one patients (with 57 cemented Porous Coated Anatomic TKAs) were reviewed (mean follow-up 4.5 year). Radiolucency at the tibial bone-cement interface was sought on the AP radiographs and divided in 7 areas. The distribution of the radiolucency was then correlated with the axis of the lower limb as measured on the orthoradiograms.The tridimensional numerical model is based on the finite element method. It allowed the measurement of the cemented prosthetic tibial implant's displacements and the microvements generated at bone-ciment interface. A total load (2000 Newton) was applied at first vertically and asymetrically on the tibial plateau, thereby simulating an axial deviation of the lower limbs. The vector's posterior inclination then permitted the addition of a tangential component to the axial load. This type of effort is generated by complex biomechanical phenomena such as knee flexion.Results 81 per cent of the 57 knees had a radiolucent line of at least 1 mm, at one or more of the tibial cement-epiphysis jonctional areas. The distribution of these lucent lines showed that they came out more frequently at the periphery of the implant. The lucent lines appeared most often under the unloaded margin of the tibial plateau, when axial deviation of lower limbs was present.Numerical simulations showed that asymetrical loading on the tibial plateau induced a subsidence of the loaded margin (0-100 microns) and lifting off at the opposite border (0-70 microns). The postero-anterior tangential component induced an anterior displacement of the tibial implant (160-220 microns), and horizontal micromovements with non homogenous distribution at the bone-ciment interface (28-54 microns).Discussion Comparison of clinical and numerical results showed a relation between the development of radiolucent lines and the unloading of the tibial implant's margin. The deleterious effect of lower limbs' axial deviation is thereby proven. The irregular distribution of lucent lines under the tibial plateau was similar of the micromovements' repartition at the bone-cement interface when tangential forces were present. A causative relation between the two phenomenaes could not however be established.Numerical simulation is a truly useful method of study; it permits to calculate micromovements which are relative, non homogenous and of very low amplitude. However, comparative clinical studies remain as essential to ensure the credibility of results.

Usefulness of methadone plasma concentration measurement in patients receiving nevirapine or efavirenz.

Objective: To determine methadone plasma trough and peak concentrations in patients presenting opiate withdrawal symptoms after introduction of nevirapine or efavirenz. To describe the disappearance of these symptoms after methadone titration based on plasma concentrations rather than on the symptoms. Methods: Nine patients undergoing highly active antiretroviral therapy (HAART) and either nevirapine or efavirenz treatment were monitored daily for opiate withdrawal in a specialized drug addiction center. Methadone dose was titrated daily, and plasma concentrations were measured. The data are retrospective (case series). Results: Several patients complained of symptoms such as nausea, vomiting, accelerated intestinal transit, or insomnia. Even after methadone titration based on clinical symptoms, patients and health-care providers trained in infectious disease did not classify these as withdrawal symptoms and considered them as the side effects of HAART or anxiety. Methadone plasma trough concentration showed low levels of (R)- and (R,S)-methadone. Further methadone dose adjustment according to plasma level resulted in the disappearance of these withdrawal symptoms. The daily methadone dose was split when the peak/trough (R)-methadone ratio was more than 2. Conclusions: When introducing efavirenz or nevirapine to patients undergoing methadone treatment, withdrawal symptoms should be monitored, especially those such as insomnia, vomiting, or nausea. Methadone plasma trough and peak measurements can be of value in preventing unnecessary side effects of HAART.

Clinical relevance of cerebral autoregulation following subarachnoid haemorrhage.

Subarachnoid haemorrhage (SAH) is a form of stroke that is associated with substantial morbidity, often as a result of cerebral ischaemia that occurs in the following days. These delayed deficits in blood flow have been traditionally attributed to cerebral vasospasm (the narrowing of large arteries), which can lead to cerebral infarction and poor neurological outcome. Data from recent studies, however, show that treatment of vasospasm in patients with SAH, using targeted medication, does not translate to better neurological outcomes, and argue against vasospasm being the sole cause of the delayed ischaemic complications. Cerebral autoregulation-a mechanism that maintains stability of cerebral blood flow in response to changes in cerebral perfusion pressure-has been reported to fail after SAH, often before vasospasm becomes apparent. Failure of autoregulation, therefore, has been implicated in development of delayed cerebral ischaemia. In this Review, we summarize current knowledge about the clinical effect of disturbed cerebral autoregulation following aneurysmal SAH, with emphasis on development of delayed cerebral ischaemia and clinical outcome, and provide a critical assessment of studies of cerebral autoregulation in SAH with respect to the method of blood-flow measurement. Better understanding of cerebral autoregulation following SAH could reveal mechanisms of blood-flow regulation that could be therapeutically targeted to improve patient outcome.