Design of pharmaceutical products to meet future patient needs requires modification of current development paradigms and business models.

Drugs represent the most common intervention strategy for managing acute and chronic medical conditions. In light of demographic change and the increasing age of patients, the classic model of drug research and development by the pharmaceutical industry and drug prescription by physicians is reaching its limits. Different stakeholders, e.g. industry, regulatory authorities, health insurance systems, physicians etc., have at least partially differing interests regarding the process of healthcare provision. The primary responsibility for the correct handling of medication and adherence to treatment schedules lies with the recipient of a drug-based therapy, i.e. the patient. It is thus necessary to interactively involve elderly patients, as well as the other stakeholders, in the development of medication and medication application devices, and in clinical trials. This approach will provide the basis for developing a strategy that better meets patients' needs, thus resulting in improved adherence to treatment schedules and better therapeutic outcomes.

Intra-session test-retest reliability of pelvic floor muscle electromyography during running.

INTRODUCTION AND HYPOTHESIS: The prevalence of female stress urinary incontinence is high, and young adults are also affected, including athletes, especially those involved in "high-impact" sports. To date there have been almost no studies testing pelvic floor muscle (PFM) activity during dynamic functional whole body movements. The aim of this study was the description and reliability test of PFM activity and time variables during running. METHODS: A prospective cross-sectional study including ten healthy female subjects was designed with the focus on the intra-session test-retest reliability of PFM activity and time variables during running derived from electromyography (EMG) and accelerometry. RESULTS: Thirteen variables were identified based on ten steps of each subject: Six EMG variables showed good reliability (ICC 0.906-0.942) and seven time variables did not show good reliability (ICC 0.113-0.731). Time variables (e.g. time difference between heel strike and maximal acceleration of vaginal accelerator) showed low reliability. However, relevant PFM EMG variables during running (e.g., pre-activation, minimal and maximal activity) could be identified and showed good reliability. CONCLUSION: Further adaptations regarding measurement methods should be tested to gain better control of the kinetics and kinematics of the EMG probe and accelerometers. To our knowledge this is the first study to test the reliability of PFM activity and time variables during dynamic functional whole body movements. More knowledge of PFM activity and time variables may help to provide a deeper insight into physical strain with high force impacts and important functional reflexive contraction patterns of PFM to maintain or to restore continence.

Influence of the timing of ultrasound application on the penetration of corticosteroids.

BACKGROUND: The application of ultrasound to enhance the transdermal transport of drugs is often referred to as 'sonophoresis'. In physiotherapy sonophoresis is applied to the skin through two different procedures: (1) the pre-treatment procedure where the skin is treated with ultrasound irradiation prior to the drug application and (2) a simultaneous treatment mode, where the skin is treated with ultrasound during the application of the pharmacologic substance. The aim of this study was to compare the bioavailability of halcinonide in the stratum corneum comparing the ultrasound pre-treatment vs. the simultaneous treatment method. METHODS: The effect of pre and simultaneous ultrasound treatment (1 MHz, 1 W/cm(2)) was evaluated on the halcinonide blanching response using tristimulus colorimetry 2 h after the initial application. RESULTS: Within the evaluation period, only the ultrasound pre-treatment method resulted in a significant blanching response. CONCLUSION: Timing of the ultrasound application seems to influence the availability and percutaneous penetration process and should be taken into account when estimating the ultrasound enhancing effect.

Continuous versus intermittent stochastic resonance whole body vibration and its effect on pelvic floor muscle activity.

AIMS: To determine the optimal stochastic whole body vibration (SR-WBV) load modality regarding pelvic floor muscle (PFM) activity in order to complete the SR-WBV training methodology for future PFM training with SR-WBV. METHODS: The continuous and the intermittent SR-WBV modalities were tested by means of electromyography in two independent groups (27 women 8 weeks to 1-year postpartum and 23 women nulliparae or >1-year postpartum) with self-reported stress urinary incontinence. The change in the PFM activity within a single set and over three sets were calculated for both SR-WBV modalities together (time effect) and for both SR-WBV modalities separately (modality-time interaction). RESULTS: There was no statistically significant or clinically relevant change in PFM activity over time or PFM fatigue in either SR-WBV modality within one or three sets and no difference between the modalities or the groups. CONCLUSIONS: The lack of change in PFM activity could be due to a no more than moderate to submaximal PFM activity during SR-WBV, the maintenance of reflexive PFM activity despite PFM fatigue or a compensation of slow red PFM fiber fatigue by an increase of innervation frequency and motor unit recruitment of the fast white fibers. As there is no SR-WBV modality dependent difference regarding PFM activity, the continuous modality is recommended in clinical practice as it is easier to apply and less time consuming.

Scapular positioning and movement in unimpaired shoulders, shoulder impingement syndrome, and glenohumeral instability.

The purpose of this manuscript is to review the knowledge of scapular positioning at rest and scapular movement in different anatomic planes in asymptomatic subjects and patients with shoulder impingement syndrome (SIS) and glenohumeral shoulder instability. We reviewed the literature for all biomechanical and kinematic studies using keywords for impingement syndrome, shoulder instability, and scapular movement published in peer reviewed journal. Based on the predefined inclusion and exclusion criteria, 30 articles were selected for inclusion in the review. The literature is inconsistent regarding the scapular resting position. At rest, the scapula is positioned approximately horizontal, 35° of internal rotation and 10° anterior tilt. During shoulder elevation, most researchers agree that the scapula tilts posteriorly and rotates both upward and externally. It appears that during shoulder elevation, patients with SIS demonstrate a decreased upward scapular rotation, a decreased posterior tilt, and a decrease in external rotation. In patients with glenohumeral shoulder instability, a decreased scapular upward rotation and increased internal rotation is seen. This literature overview provides clinicians with insight into scapular kinematics in unimpaired shoulders and shoulders with impingement syndrome and instability.

Prosthetic gait of unilateral lower-limb amputees with current and novel prostheses: A pilot study.

BACKGROUND: Novel lower-limb prostheses aim to improve the quality of locomotion of individuals with an amputation. This study evaluates the biomechanics of a novel bionic foot during walking. METHODS: Able-bodied individuals (n = 7) and individuals with a transfemoral (n = 6) or transtibial amputation (n = 6) were included. Able-bodied individuals conducted one experimental trial, whereas individuals with transtibial and transfemoral amputations conducted a familiarization (with current prosthesis) and two experimental trials using a passive and bionic prosthesis. Each trial consisted of 3 bouts of 2 min of treadmill walking at different speeds. Biomechanical data were gathered using a force platform and motion capture system and analysed using Statistical Parametric Mapping and (non)-parametric tests. FINDINGS: Conventional prosthetic feet alter gait patterns and induce locomotion difficulties. While walking at a normal speed with the passive prosthesis, transtibial amputees display reduced maximum heel forces, increased ankle and trunk angular velocities at midstance, and increased knee angle during stance and swing phases on their effected side (P ≤ 0.026). Improved lower-limb kinematics was demonstrated during slow and normal speed walking with the bionic prosthesis; however, dynamic trunk stability was negatively impacted during this condition. The bionic prosthesis did not benefit transfemoral amputees at any walking speed. INTERPRETATION: Transtibial amputees can better approximate typical movement patterns at slow and normal walking speeds using the novel bionic prosthesis; however the same benefit was not observed in transfemoral amputees.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.

Does manual mobilization influence motion coupling patterns in the atlanto-axial joint?

BACKGROUND: A restricted number of publications have reported on the analysis of coupling patterns in the atlanto-axial joint using an in vitro set-up applying pure moments of forces. The aim of this study is to analyze segmental motion coupling patterns during cervical manual mobilization. METHODS: The position and attitudes of sensors mounted on the atlas and axis were traced in nine embalmed and one fresh human spinal specimen using an electromagnetic tracking system. Segmental bony reference points were registered using a 3D-digitizing stylus for the definition of bone embedded coordinate systems. Segmental motion coupling was recorded for the atlanto-axial joints during manual mobilization through the full range of axial rotation and lateral bending. RESULTS: Coupled motions were described by the direction of the associated motion and by cross-correlation analysis. The results confirm the contra-lateral coupling pattern of axial rotation with lateral bending at C1-C2 observed in previous studies. The cross-correlation analysis offered a more objective interpretation of the coupling pattern for the analysis of the more irregular coupling patterns during lateral bending. Inter-individual differences in coupling patterns were observed. INTERPRETATIONS: The presented method provides possibilities for the study of coupled motion during manual diagnostic and therapeutic practice. Practitioners should be aware of the segmental 3D-aspects of manually induced so called planar mobilizations and their possible influence on motion coupling. Motion coupling patterns may be related to specimen specific anatomy.

Glenohumeral joint kinematics related to minor anterior instability of the shoulder at the end of the late preparatory phase of throwing.

OBJECTIVE: The first aim of this study was an approach to quantify the 3D kinematics of the glenohumeral joint referred to the joint surfaces. The method was used to study the glenohumeral patho-arthrokinematics related to minor anterior instability at the end of the late preparatory phase of throwing. STUDY DESIGN: Using a finite helical axis approach, arthrokinematics focused on: (i) the rotations and shift of the humeral head on the glenoid cavity, and (ii) the migration of contact of the articular surfaces. BACKGROUND: Controversy still exists whether the clinical syndrome called 'minor anterior glenohumeral instability' can be validly termed as an instability. METHODS: Helical CT-data of discrete shoulder positions were three-dimensionally reconstructed. Based on humeral and scapular sets of skeletal landmarks, rotation matrices and translation vectors were estimated and processed in glenohumeral finite helical axes. The finite helical axis parameters of rotation, shift and direction were related to a co-ordinate system embedded on the glenoid, whereas the position of the finite helical axis was related to the articulating surface of the humeral head. RESULTS: From 90 degrees abduction and 90 degrees external rotation to full cocking (90 degrees abduction with full external rotation and horizontal extension), the humeral head in the normal shoulders did not externally/internally rotate on the glenoid. In contrast, a large external rotation component was found in the minor unstable shoulders. The geometrical centre of the humeral head of the normal shoulders translated into a posteriorized position on the glenoid, whereas in minor anterior instability it translated centrally on the glenoid. CONCLUSIONS: Compared with in vitro biomechanical research which states that towards full cocking the anterior part of the inferior glenohumeral ligament limits anterior translation and external rotation of the humeral head on the glenoid, the results suggest in minor anterior instability a dysfunction of the anterior part of the inferior glenohumeral ligament. RELEVANCE: The results indicate that the so-called 'minor anterior glenohumeral instability syndrome' can validly be stated as an instability problem. The results also indicate that the glenohumeral joint does not move consistently as a ball-and-socket joint, meaning that the concave-convex rules for glenohumeral joint mobilization need 'evidence-based' adjustments.

[Validity of the tympanic infrared thermometer in geriatric inpatients]. / De validiteit van de tympane infrarood thermometer bij gehospitaliseerde, geriatrische patiënten.

The purpose of this study was to assess the agreement between rectal temperature and infrared emission detection (IRED). The specificity and sensitivity, the positive predictive value and the negative predictive value were calculated. It was a prospective, observational and unblinded study. Thermoscan-pro-1 was used to collect pairs of data in 41 patients, all hospitalised on an acute geriatric ward during a 4-month period. 41% of the patients were febrile. The 'bias' between rectal and tympanic measurement (left ear) was -0.64 degree C (d) and the standard deviation 0.58 degree C (s). The '95% Confidence Interval' for the bias was -0.82 degree C and -0.46 degree C. The '95% limits of agreement' between the rectal measurement and the tympanic measurement (left ear) was -1.78 degrees C and 0.50 degree C. Regression analysis taught us that bias was increasing with increasing temperature. If we take into account one measurement with the IRED ear thermometry, the sensitivity was 41%, the specificity 83%. The positive predictive value was 64% en the negative predictive value 67%. We can conclude that the IRED ear thermometry is not a valuable alternative for the rectal, digital thermometry in the elderly, frail and febrile hospital inpatients.

[Surgery in the 4th age. The opinion of the geriatrician]. / Heelkunde in de vierde leeftijd. De mening van de geriater.

Mortality and morbidity of surgery in the very old patient is much less than generally accepted. Age on his own is never a good reason to refuse surgical intervention. Good assessment after extended interrogation of patient and family, clinical examination and eventually technical procedures will reveal a number of other diseases. The higher the number of other diseases the higher will be the risk of the operation. More attention is needed for the quality of life after the operation. The fact that the patient will remain independent for the activities of daily living is for the very old patient more important than his 5-year survival. I am wondering why the number of female who come to operation is relatively lower than the men. A possible explanation is the fact that to many very old people receive to much nursing care and not enough real medical care.

In vivo measurement of the 3D kinematics of the temporomandibular joint using miniaturized electromagnetic trackers: technical report.

OBJECTIVE: The aim of this study was to evaluate the use of miniaturized electromagnetic trackers (1 × 0.5 × 0.5 cm) fixed on teeth of the maxilla and mandible to analyse in vivo the 3D kinematics of the temporomandibular joint (TMJ). A third sensor was fixed to the forehead, and a fourth sensor was used as a stylus pointer to detect several anatomical landmarks in order to embed a local frame on the cranium. Temporomandibular opening/closing, chewing, laterotrusion and protrusion were examined. RESULTS: The prime objective within this study was to rigidly attach electromagnetic minisensors on teeth. The key for a successful affixation was the kevlar interface. The distances between the two mandibular affixed sensors and between the two maxillar affixed sensors were overall smaller than 0.033 cm for position and 0.2° for attitude throughout the temporomandibular motions. The relative motions between a forehead sensor and the maxilla affixed sensor are too big to suggest a forehead sensor as an alternative for a maxilla affixed sensor. CONCLUSION: The technique using miniaturized electromagnetic trackers furthers on the methods using electromagnetic trackers on external appliances. The method allows full range of motion of the TMJ and does not disturb normal TMJ function.

Guidance synthesis. Medical research for and with older people in Europe: proposed ethical guidance for good clinical practice: ethical considerations.

INTRODUCTION: In Europe the population is ageing rapidly. Older people are taking many medicinal products daily and these may not necessarily be suitable for them. Publications show that older patients are underrepresented in clinical trials, especially those over 75 years, with multiple co-morbidities, concomitant treatments and/or frailty. This document provides a summary of recommendations on ethical aspects of clinical trials with older people, who may in some cases be considered a vulnerable patient population. The EFGCP's Geriatric Medicine Working Party (GMWP) has developed this guidance to promote such research and to support health care professionals in their efforts. ETHICAL, SCOPE AND CONTEXT: The definition of a geriatric patient is reviewed. Frail and vulnerable patients, who are a minority of geriatric patients, should be included whenever it is relevant. The legal context is described. THE PROCESS OF INFORMED CONSENT: All adults should be presumed capable of consent, unless proven otherwise; informed consent must be sought for all older people who are able to consent. A simple, short and easy-to-understand information sheet and consent form will contribute to improving the readability and understanding of the older participant. A participant guide and the use of a simple tool to ensure decision making capacity, are recommended. Whenever older people are unable to consent, their assent should be sought systematically using adequate information, in addition to seeking the consent of their legal or authorised representative as appropriate. ETHICS COMMITTEES: Research ethics committees need internal and/or external geriatric expertise to balance the benefits and risks of research in older people and to appreciate and recognise their autonomy. DESIGN AND ANALYSES: Design and Analyses should be adapted to the objectives with appropriate outcomes and are not different from other clinical trials. CONCLUSIONS: The absence of proper recruitment or insufficient presence of older patients in clinical development plans for new medicinal products is detrimental; there is a need to improve evidence-based knowledge, understanding and management of their conditions and treatment. The aim of this guidance is to facilitate clinical research for and with the older patient population. The long version of the guidance will be available on the EFGCP's website: www.efgcp.be/.

Promoting access to innovation for frail old persons. IAGG (International Association of Gerontology and Geriatrics), WHO (World Health Organization) and SFGG (Société Française de Gériatrie et de Gérontologie) Workshop--Athens January 20-21, 2012.

UNLABELLED: Frailty tends to be considered as a major risk for adverse outcomes in older persons, but some important aspects remain matter of debate. OBJECTIVES: The purpose of this paper is to present expert's positions on the main aspects of the frailty syndrome in the older persons. PARTICIPANTS: Workshop organized by International Association of Gerontology and Geriatrics (IAGG), World Health Organization (WHO) and Société Française de Gériatrie et de Gérontologie (SFGG). RESULTS: Frailty is widely recognized as an important risk factor for adverse health outcomes in older persons. This can be of particular value in evaluating non-disabled older persons with chronic diseases but today no operational definition has been established. Nutritional status, mobility, activity, strength, endurance, cognition, and mood have been proposed as markers of frailty. Another approach calculates a multidimensional score ranging from "very fit" to "severely frail", but it is difficult to apply into the medical practice. Frailty appears to be secondary to multiple conditions using multiple pathways leading to a vulnerability to a stressor. Biological (inflammation, loss of hormones), clinical (sarcopenia, osteoporosis etc.), as well as social factors (isolation, financial situation) are involved in the vulnerability process. In clinical practice, detection of frailty is of major interest in oncology because of the high prevalence of cancer in older persons and the bad tolerance of the drug therapies. Presence of frailty should also be taken into account in the definition of the cardiovascular risks in the older population. The experts of the workshop have listed the points reached an agreement and those must to be a priority for improving understanding and use of frailty syndrome in practice. CONCLUSION: Frailty in older adults is a syndrome corresponding to a vulnerability to a stressor. Diagnostic tools have been developed but none can integrate at the same time the large spectrum of factors and the simplicity asked by the clinical practice. An agreement with an international common definition is necessary to develop screening and to reduce the morbidity in older persons.

IAGG workshop: health promotion program on prevention of late onset dementia.

IAGG, WHO, and SFGG organized a international workshop on Health promotion programs on prevention of late on-set dementia. Thirty world specialists coming from Europe, North America, Asia, South America, Africa and Australia, shared their experience on methods and results of large epidemiological interventions to reduce incidents of dementia or delay its on-set. Chaired by Laura FRATIGLIONI, an expert in Epidemiological studies on dementia issues, the workshop gave opportunity for discussions and controversies about the state-of-the-art. Based on different national and international trials (ADAPT, MAPT, FINGER, GUDIAGE, GEM etc) the questions remained opened for different aspects of methodology, the choice of domain or multi domain intervention, the choice and the definition of the target populations, the best age of candidates, the issues related to the discrepancy between late effects, and interventions' duration. We are please to publish in the Journal, the presentations presented to this workshop. These publications will complete previously task force published in the journal in the last two years on methodological issues for Alzheimer's trials including end point, biomarkers, and the experience of past therapeutic trials.

The primary care physician and Alzheimer's disease: an international position paper.

This paper aims to define the role of the primary care physician (PCP) in the management of Alzheimer's disease (AD) and to propose a model for a work plan. The proposals in this position paper stem from a collaborative work of experts involved in the care of AD patients. It combines evidence from a literature review and expert's opinions who met in Paris, France, on July 2009 during the International Association of Geriatrics and Gerontology (IAGG) World Congress. The PCP's intervention appears essential at many levels: detection of the onset of dementia, diagnostic management, treatment and follow-up. The key role of the PCP in the management of AD, as care providers and care planners, is consolidated by the family caregiver's confidence in their skills. In primary care practice the first step is to identify dementia. The group proposes a "case finding" strategy, in target situations in which dementia should be detected to allow, secondarily, a diagnosis of AD, in certain cases. We propose that the PCP identifies 'typical' cases. In typical cases, among older subjects, the diagnosis of "probable AD" can be done by the PCP and then confirm by the specialist. While under-diagnosis of AD exists, so does under-disclosure. Disclosure to patient and family should be done by both specialist and PCP. Then, the PCP has a central role in management of the disease with the general objectives to detect, prevent and treat, when possible, the complications of the disease (falls, malnutrition, behavioural and psychological symptoms of dementia). The PCP needs to give basic information to the caregiver on respite care and home support services in order to prevent crisis situations such as unplanned institutionalisation and "emergency" hospital admission. Finally, therapeutic research must be integrated in the daily practice of PCP. It is a matter of patients' right to benefit from access to innovation and clinical research whatever his age or diseases, while of course fully respecting the rules and protective measures that are in force.