Unanswered clinical questions in the management of cardiometabolic risk in the elderly: a statement of the Spanish society of internal medicine.

BACKGROUND Despite the progressive increase in life expectancy and the relationship between aging with multi-morbidities and the increased use of healthcare resources, current clinical practice guidelines (CPG) on cardiometabolic risk cannot be adequately applied to elderly subjects with multiple chronic conditions. Its management frequently becomes complicated by both, an excessive use of medications that may lead to overtreatment, drug interactions and increased toxicity, and errors in dosage and non-compliance. Concerned by this gap, the Spanish Society of Internal Medicine created a group of independent experts on cardiometabolic risk who discussed what they considered to be unanswered questions in the management of elderly patients. DISCUSSION Current guidelines do not specifically address the problem of elderly with multiple chronic conditions. For this reason, the combined use of the limited available evidence, clinical experience and common sense, could all help us to address this unmet need. In very old people, life expectancy and functionality are the most important factors for guiding potential treatments. Their higher propensity to develop serious adverse events and their shorter lifespan could prevent them from obtaining the potential benefits of the interventions administered. SUMMARY In this document, experts on cardiometabolic risk factors have established a number of consensual recommendations that have taken into account international guidelines and clinical experience, and have also considered the more effective use of healthcare resources. This document is intended to provide general recommendations for clinicians and to promote the effective use of procedures and medications.

Study protocol for a pragmatic randomised controlled trial in general practice investigating the effectiveness of acupuncture against migraine.

BACKGROUND Migraine is a chronic neurologic disease that can severely affect the patient's quality of life. Although in recent years many randomised studies have been carried out to investigate the effectiveness of acupuncture as a treatment for migraine, it remains a controversial issue. Our aim is to determine whether acupuncture, applied under real conditions of clinical practice in the area of primary healthcare, is more effective than conventional treatment. METHODS/DESIGN The design consists of a pragmatic multi-centre, three-armed randomised controlled trial, complemented with an economic evaluation of the results achieved, comparing the effectiveness of verum acupuncture with sham acupuncture, and with a control group receiving normal care only. Patients eligible for inclusion will be those presenting in general practice with migraine and for whom their General Practitioner (GP) is considering referral for acupuncture. Sampling will be by consecutive selection, and by randomised allocation to the three branches of the study, in a centralised way following a 1:1:1 distribution (verum acupuncture; sham acupuncture; conventional treatment). Secondly, one patient in three will be randomly selected from each of the acupuncture (verum or sham) groups for a brain perfusion study (by single photon emission tomography). The treatment with verum acupuncture will consist of 8 treatment sessions, once a week, at points selected individually by the acupuncturist. The sham acupuncture group will receive 8 sessions, one per week, with treatment being applied at non-acupuncture points in the dorsal and lumbar regions, using the minimal puncture technique. The control group will be given conventional treatment, as will the other two groups. DISCUSSION This trial will contribute to available evidence on acupuncture for the treatment of migraine. The primary endpoint is the difference in the number of days with migraine among the three groups, between the baseline period (the 4 weeks prior to the start of treatment) and the period from weeks 9 to 12. As a secondary aspect, we shall record the index of laterality and the percentage of change in the mean count per pixel in each region of interest measured by the brain perfusion tomography, performed on a subsample of the patients within the real and sham acupuncture groups. TRIAL REGISTRATION Current Controlled Trials ISRCTN98703707.

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.

Discriminating irritable bowel syndrome from inflammatory bowel disease: what is the role of biomarkers in daily practice?

Background and Aims: Discriminating irritable bowel syndrome (IBS) from inflammatorybowel disease (IBD) can be a clinical challenge as symptoms can overlap. We and othershave recently shown that fecal calprotectin (FC) is more accurate for discriminating IBSfrom IBD compared to C-reactive protein (CRP) and blood leukocytes. Data on the biomarkersused in daily gastroenterological practice are lacking. We therefore aimed to assess whichbiomarkers are used by gastroenterologists in their daily practice for discriminating IBSfrom IBD.Methods: A questionnaire was sent to all board certified gastroenterologists inSwitzerland focusing on demographic informations, number of IBS patients treated in thetime period from May 2009 to April 2010, and the specific biomarkers evaluated fordiscriminating IBS from IBD.Results: Response rate was 57% (153/270). Mean physician'sage was 50±9years, mean duration of gastroenterologic practice 14±8years, 52% of themwere working in private practice and 48% in hospitals. Thirty-nine percent had taken careof more than 100 IBS patients in the last 12 months, 37% had seen 41-100 and 24% hadseen 1-40 IBS patients. Gastroenterologists in private practice more frequently took care ofat least 40 IBS patients in a year compared to hospital-based gastroenterologists (P<0.001).The following biomarkers were determined for discriminating IBS from IBD: CRP 100%,FC 79%, hematogram (red blood cells and leukocytes) 70%, iron status (ferritin, transferrinsaturation) 59%, erythrocyte sedimentation rate 2.7%, protein electrophoresis 0.7%, andalpha-1 antitrypsin clearance 0.7%. There was a trend for using FC more often in privatepractice than in hospital (P = 0.08). Twenty-four percent of gastroenterologists had usedFC in the workup of more than 70% of patients classified as IBS, 22% had used FC in 30-70% of IBS patients, 39% in less than 30%, and 15% had never used FC for the work-upof suspected IBS. Eighty-nine percent of gastroenterologists considered FC to be superiorto CRP for discriminating IBS from IBD, 87% thought that patient's compliance for fecalsampling is high, and 51% judged the fee of USD 60 for a FC test as appropriate.Conclusions:FC is widely used in clinical practice to discriminate IBS from IBD. In accordance with thescientific evidence, the majority of gastroenterologists consider FC to be more accurate thanCRP for discriminating IBS from IBD. Gastroenterologists in private practice take care ofsignificantly more IBS patients than colleagues in hospital.

Clinical results of enzyme replacement therapy in Fabry disease: a comprehensive review of literature.

Enzyme replacement therapy (ERT) has been used to treat Fabry disease - a progressive lysosomal storage disorder - since 2001. Two preparations of the enzyme alpha-galactosidase A are available in Europe: agalsidase alpha, produced in a human cell line, and agalsidase beta, produced in Chinese hamster ovary cells. To review critically the published evidence for the clinical efficacy of these two enzyme preparations. A systematic literature search was undertaken to identify open or randomised controlled trials published on Fabry disease since 2001. Eleven trials fulfilled the criteria for inclusion in this review, of a total of 586 references on Fabry disease. To date, no direct comparisons exists between the two available enzyme preparations. Significant clinical benefits compared with placebo, however, have been demonstrated with ERT, with positive effects on the heart, kidneys, nervous system and quality of life. The quality of most of these publications was less than optimal. Further prospective studies are required to confirm the long-term clinical benefits of ERT. More studies are also needed on the effects of ERT in women and on the use of ERT early in the course of Fabry disease, to prevent organ damage. Large national and international outcomes databases will also be invaluable in evaluating treatment effects and safety.

Predicting clinical scores from magnetic resonance scans in Alzheimer's disease.

Machine learning and pattern recognition methods have been used to diagnose Alzheimer's disease (AD) and mild cognitive impairment (MCI) from individual MRI scans. Another application of such methods is to predict clinical scores from individual scans. Using relevance vector regression (RVR), we predicted individuals' performances on established tests from their MRI T1 weighted image in two independent data sets. From Mayo Clinic, 73 probable AD patients and 91 cognitively normal (CN) controls completed the Mini-Mental State Examination (MMSE), Dementia Rating Scale (DRS), and Auditory Verbal Learning Test (AVLT) within 3months of their scan. Baseline MRI's from the Alzheimer's disease Neuroimaging Initiative (ADNI) comprised the other data set; 113 AD, 351 MCI, and 122 CN subjects completed the MMSE and Alzheimer's Disease Assessment Scale-Cognitive subtest (ADAS-cog) and 39 AD, 92 MCI, and 32 CN ADNI subjects completed MMSE, ADAS-cog, and AVLT. Predicted and actual clinical scores were highly correlated for the MMSE, DRS, and ADAS-cog tests (P<0.0001). Training with one data set and testing with another demonstrated stability between data sets. DRS, MMSE, and ADAS-Cog correlated better than AVLT with whole brain grey matter changes associated with AD. This result underscores their utility for screening and tracking disease. RVR offers a novel way to measure interactions between structural changes and neuropsychological tests beyond that of univariate methods. In clinical practice, we envision using RVR to aid in diagnosis and predict clinical outcome.

Clinical indicators for the initiation of endotracheal suction in children: An integrative review.

BACKGROUND: Critical decisions and interpretation of observations by the nurse caring for the paediatric intensive care (PIC) patient can have dramatic and potential adverse impact on the clinical stability of the patient. A common PIC procedure is endotracheal tube (ETT) suction, however there is inconsistent evidence regarding the clinical indicators to guide and support nursing action. Justification for performing this procedure is not clearly defined within the literature. Further, a review of the literature has failed to establish clear standards for determining if the procedure is warranted, especially for paediatric patients. OBJECTIVE: The objective of the review is to identify current clinical indicators used in practice to determine why ETT suction should be performed. METHOD: An integrative review using a systematic approach to summarise the empirical and theoretical evidence within the literature as it relates to clinical practice was used. RESULTS: Consensus of opinion indicates that ETT suctioning should only be performed when clinically indicated. There is no general consensus regarding which clinical indicators should be measured and used to guide the decision to perform ETT suctioning. CONCLUSION: Research is required to identify the clinical indicators that could be used to design a valid and clinically appropriate tool to use to assist in the decision making process to perform ETT suction.

European French-speaking study from the GEMO group on bone metastases management: a special focus on external beam radiotherapy practice survey.

This study seeks to perform a survey of patterns of practice among the different physicians involved in the bone metastases management, with special focus on external beam radiotherapy (EBRT).A questionnaire about bone metastases based on clinical cases and supplemented with general questions, including medical therapies, EBRT and metabolic radiotherapy strategies, surgery, and supportive care approaches, was sent to 4,706 French-speaking physicians in Belgium, France, Luxemburg, and Switzerland.Overall, 644 questionnaires were analyzed. Twenty-eight percent concerned the radiotherapy approach and were judged adequate to respond to the part dedicated to EBRT. Sixty-nine percent of physicians used a total dose irradiation of 30 Gy delivered in ten fractions. A large majority (75%) used two opposed fields prescribed at mid-depth (30%), or with non-equally weighted fields (45%). Seventy percent irradiated also above and below the concerned vertebra. A dosimetry planning treatment was done in 85% and high-energy megavoltage photons were used in 42%. Moreover, 54% physicians used short course radiotherapy in routine.Radiotherapy remains the mainstay of treatment of bone metastases, but there is substantial heterogeneity in clinical practice. Guidelines and treatment protocols are required to improve the treatment quality.

Official Positions for FRAX® clinical regarding international differences from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®.

Osteoporosis is a serious worldwide epidemic. Increased risk of fractures is the hallmark of the disease and is associated with increased morbidity, mortality and economic burden. FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors, femoral neck BMD, country specific mortality and fracture data and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator at the time paper was accepted for publication. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available. In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians. In order to provide additional guidance to clinicians, a FRAX® International Task Force was formed to address specific questions raised by physicians in countries without FRAX® calculators and seeking to integrate FRAX® into their clinical practice. The main questions that the task force tried to answer were the following: The Task Force members conducted appropriate literature reviews and developed preliminary statements that were discussed and graded by a panel of experts at the ISCD-IOF joint conference. The statements approved by the panel of experts are discussed in the current paper.

European society of hypertension position paper on ambulatory blood pressure monitoring.

Ambulatory blood pressure monitoring (ABPM) is being used increasingly in both clinical practice and hypertension research. Although there are many guidelines that emphasize the indications for ABPM, there is no comprehensive guideline dealing with all aspects of the technique. It was agreed at a consensus meeting on ABPM in Milan in 2011 that the 34 attendees should prepare a comprehensive position paper on the scientific evidence for ABPM.This position paper considers the historical background, the advantages and limitations of ABPM, the threshold levels for practice, and the cost-effectiveness of the technique. It examines the need for selecting an appropriate device, the accuracy of devices, the additional information and indices that ABPM devices may provide, and the software requirements.At a practical level, the paper details the requirements for using ABPM in clinical practice, editing considerations, the number of measurements required, and the circumstances, such as obesity and arrhythmias, when particular care needs to be taken when using ABPM.The clinical indications for ABPM, among which white-coat phenomena, masked hypertension, and nocturnal hypertension appear to be prominent, are outlined in detail along with special considerations that apply in certain clinical circumstances, such as childhood, the elderly and pregnancy, and in cardiovascular illness, examples being stroke and chronic renal disease, and the place of home measurement of blood pressure in relation to ABPM is appraised.The role of ABPM in research circumstances, such as pharmacological trials and in the prediction of outcome in epidemiological studies is examined and finally the implementation of ABPM in practice is considered in relation to the issue of reimbursement in different countries, the provision of the technique by primary care practices, hospital clinics and pharmacies, and the growing role of registries of ABPM in many countries.

Expertises croisées dans la dégénérescence maculaire liée à l'âge. Focus sur la physiopathologie, l'angiogenèse, les données pharmacologiques et cliniques [Review and expert opinion in age related macular degeneration. Focus on the pathophysiology, angiogenesis and pharmacological and clinical data].

Age related macular degeneration (AMD) is a pathological aging of the macula, brought about by the interaction of genetic and environmental factors. It induces geographic atrophy of the retina and/or choroidal neovascularization. In the latter, abnormal vessels develop from the choriocapillaris, with the involvement of VEGF (vascular endothelial growth factor). The VEGF family includes several factors, including VEGF-A, B, C, D, F and PlGF (placental growth factor). Their biological properties and their affinities to the VEGFR1, VEGFR2 and VEGFR3 receptors found on endothelial cells differ. Exudative AMD involves mainly VEGF-A and VEGF-R2. Anti-VEGF agents used in ophthalmology (ranibizumab, bevacizumab and aflibercept) are designed to primarily target this pathway. In vitro, all have sufficient affinity to their ligands. Their therapeutic efficacy must therefore be judged based on clinical criteria. In clinical practice, the minimum number of injections required for a satisfactory result appears to be comparable with all the three. The few available studies on therapeutic substitutions of anti-VEGF compounds suggest that some patients may benefit from substituting the anti-VEGF in cases of an unsatisfactory response to an initial molecule. Although local side effects, including increased risk of geographic atrophy, and systemic effects, including vascular accidents, have been suggested, these risks remain low, specially compared to the benefits of the treatment. Differences in safety between anti-VEGF are theoretically possible but unproven.

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

The non-invasive evaluation of myocardial ischemia is a priority in cardiology. The preferred initial non-invasive test is exercise ECG, because of its high accessibility and its low cost. Stress radionuclide myocardial perfusion imaging or stress echocardiography are now routinely performed, and new non-invasive techniques such as perfusion-MRI, dobutamine stress-MRI or 82rubidium perfusion PET have recently gained acceptance in clinical practice. In the same time, an increasing attention has been accorded to the concept of myocardial viability in the decisional processes in case of ischemic heart failure. In this indication, MRI with late enhancement after intravenous injection of gadolinium and 18F-FDG PET showed an excellent diagnostic accuracy. This article will present these new imaging modalities and their accepted indications.

Impact of prolonged antihypertensive duration of action on predicted clinical outcomes in imperfectly adherent patients: comparison of aliskiren, irbesartan and ramipril.

Background: Most patients miss occasional doses of antihypertensives. The use of 'forgiving' drugs (i.e. drugs with duration of action longer than the 24-h dosing interval) may allow an adequate blood pressure (BP) reduction to be maintained despite missed doses. Aim:To quantify the effects of adherence level and duration of action on estimated mean systolic BP (SBP) reduction and cardiovascular disease (CVD) risk. Method:For 1250 patients, we simulated 256-day dosing histories with realistically distributed drug holidays based on a study of electronically monitored dosing records. Adherence was set to the desired level by altering the proportion of doses missed. Mean office SBP-lowering effect (aliskiren 300 mg, -14.1 mmHg; irbesartan 300 mg, -13.3; ramipril 10 mg, -10.1 mmHg) and the rate of SBP increase after stopping treatment (off-rate; aliskiren, 1.0 mmHg/day; irbesartan, 3.6 mmHg/day; ramipril, 4.0 mmHg/day) were taken from the results of a randomised, double-blind trial. SBP was averaged over time and patient to estimate mean reductions in SBP and 10-year CVD risk (Framingham risk equation, baseline absolute 10-year CVD risk: 27%). Results:Predicted reductions in SBP and CVD risk with aliskiren were larger and less affected by imperfect adherence than the reductions with irbesartan or ramipril. For aliskiren, reducing adherence from 90% to 60% led to a predicted rise in SBP of 1.0 mmHg and three additional CVD events per 1000 treated patients; larger predicted differences were observed for irbesartan (2.5 mmHg; 7.5 events/1000 treated patients) and ramipril (2.2 mmHg; 6.7 events/1000 treated patients). Conclusion:To offset the effects of imperfect adherence, a common challenge with antihypertensives, for better BP management it may be prudent to prescribe 'forgiving' drugs.

Computer-generated reminders delivered on paper to healthcare professionals; effects on professional practice and health care outcomes.

BACKGROUND: Clinical practice does not always reflect best practice and evidence, partly because of unconscious acts of omission, information overload, or inaccessible information. Reminders may help clinicians overcome these problems by prompting the doctor to recall information that they already know or would be expected to know and by providing information or guidance in a more accessible and relevant format, at a particularly appropriate time. OBJECTIVES: To evaluate the effects of reminders automatically generated through a computerized system and delivered on paper to healthcare professionals on processes of care (related to healthcare professionals' practice) and outcomes of care (related to patients' health condition). SEARCH METHODS: For this update the EPOC Trials Search Co-ordinator searched the following databases between June 11-19, 2012: The Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Library (Economics, Methods, and Health Technology Assessment sections), Issue 6, 2012; MEDLINE, OVID (1946- ), Daily Update, and In-process; EMBASE, Ovid (1947- ); CINAHL, EbscoHost (1980- ); EPOC Specialised Register, Reference Manager, and INSPEC, Engineering Village. The authors reviewed reference lists of related reviews and studies.  SELECTION CRITERIA: We included individual or cluster-randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) that evaluated the impact of computer-generated reminders delivered on paper to healthcare professionals on processes and/or outcomes of care. DATA COLLECTION AND ANALYSIS: Review authors working in pairs independently screened studies for eligibility and abstracted data. We contacted authors to obtain important missing information for studies that were published within the last 10 years. For each study, we extracted the primary outcome when it was defined or calculated the median effect size across all reported outcomes. We then calculated the median absolute improvement and interquartile range (IQR) in process adherence across included studies using the primary outcome or median outcome as representative outcome. MAIN RESULTS: In the 32 included studies, computer-generated reminders delivered on paper to healthcare professionals achieved moderate improvement in professional practices, with a median improvement of processes of care of 7.0% (IQR: 3.9% to 16.4%). Implementing reminders alone improved care by 11.2% (IQR 6.5% to 19.6%) compared with usual care, while implementing reminders in addition to another intervention improved care by 4.0% only (IQR 3.0% to 6.0%) compared with the other intervention. The quality of evidence for these comparisons was rated as moderate according to the GRADE approach. Two reminder features were associated with larger effect sizes: providing space on the reminder for provider to enter a response (median 13.7% versus 4.3% for no response, P value = 0.01) and providing an explanation of the content or advice on the reminder (median 12.0% versus 4.2% for no explanation, P value = 0.02). Median improvement in processes of care also differed according to the behaviour the reminder targeted: for instance, reminders to vaccinate improved processes of care by 13.1% (IQR 12.2% to 20.7%) compared with other targeted behaviours. In the only study that had sufficient power to detect a clinically significant effect on outcomes of care, reminders were not associated with significant improvements. AUTHORS' CONCLUSIONS: There is moderate quality evidence that computer-generated reminders delivered on paper to healthcare professionals achieve moderate improvement in process of care. Two characteristics emerged as significant predictors of improvement: providing space on the reminder for a response from the clinician and providing an explanation of the reminder's content or advice. The heterogeneity of the reminder interventions included in this review also suggests that reminders can improve care in various settings under various conditions.

FRAX(®) Bone Mineral Density Task Force of the 2010 Joint International Society for Clinical Densitometry International Osteoporosis Foundation Position Development Conference.

FRAX(®) is a fracture risk assessment algorithm developed by the World Health Organization in cooperation with other medical organizations and societies. Using easily available clinical information and femoral neck bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA), when available, FRAX(®) is used to predict the 10-year probability of hip fracture and major osteoporotic fracture. These values may be included in country specific guidelines to aid clinicians in determining when fracture risk is sufficiently high that the patient is likely to benefit from pharmacological therapy to reduce that risk. Since the introduction of FRAX(®) into clinical practice, many practical clinical questions have arisen regarding its use. To address such questions, the International Society for Clinical Densitometry (ISCD) and International Osteoporosis Foundations (IOF) assigned task forces to review the best available medical evidence and make recommendations for optimal use of FRAX(®) in clinical practice. Questions were identified and divided into three general categories. A task force was assigned to investigating the medical evidence in each category and developing clinically useful recommendations. The BMD Task Force addressed issues that included the potential use of skeletal sites other than the femoral neck, the use of technologies other than DXA, and the deletion or addition of clinical data for FRAX(®) input. The evidence and recommendations were presented to a panel of experts at the ISCD-IOF FRAX(®) Position Development Conference, resulting in the development of ISCD-IOF Official Positions addressing FRAX(®)-related issues.