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Non-pharmacological interventions are increasingly being acknowledged as valuable options to overcome or reduce functional problems in patients with Parkinson’s disease. In the last decades, Nordic Walking was employed and investigated by rehabilitation specialists. Clinical trials on the effect of Nordic Walking on motor and non-motor Parkinson’s disease symptoms are few, small, and heterogeneous for inclusion criteria and intervention protocols. As a result, Nordic Walking training cannot be recommended as a standard rehabilitative tool in Parkinson’s disease patients. This randomized controlled single-blind trial recruited Parkinson’s disease patients at a Hoehn and Yahr stage between 2 and 3 assigned to a Nordic Walking vs. Walking group. Subjects were extensively assessed for motor and non-motor symptoms at baseline and after 8 weeks of intervention period. To study the effects of intervention on the overall sample, paired-sample t test and Wilcoxon signed rank test were used, while differences between groups were estimated with general linear models repeated-measure and Mann–Whitney U test. Among 32 patients who ended the study period, improvements were observed in the following assessments: global motor outcome (p 0.001), dynamic and static balance ability (p 0.005; p 0.002), global non-motor symptoms outcome (p 0.003), fatigue (p 0.016), anxiety (p 0.043), and quality of life (p 0.003). The treatment group (Nordic Walking) failed to show any difference compared to the control group (Walking) in all considered outcomes. Nordic Walking was not superior compared to Walking in the studied population. Moderate intensity outdoor group activities like Nordic Walking and Walking seem to improve motor and non-motor symptoms parameters in patients with Parkinson’s disease.

Background: Multiple myeloma (MM) is a common hematological disorder, often complicated by venous thromboembolism, especially during treatment with immunomodulatory drugs. Acetylsalicylic acid (ASA) has been extensively used as thromboprophylaxis but its rationale is unclear and the efficacy versus low-molecular weight heparins (LMWH) is still matter of debate. European and American guidelines suggest different approaches and the optimal antithrombotic strategy is yet to be established. Methods: We conducted an exploratory metanalysis and a systematic review on studies comparing ASA versus other interventions for thromboprophylaxis (no intervention or LMWH) in patients with MM. Results: Ten studies were included (2 randomized controlled trials, 6 longitudinal and 2 retrospective studies) with 1,964 participants (1,257 treated with ASA, 640 with LMWH and 67 with no thromboprophylaxis). Patients treated with ASA had a significantly lower risk of VTE compared to no intervention (OR=0.20; 95%CI: 0.07-0.61, p=0.005; I 2 =41%). The use of ASA was associated with a higher VTE risk compared to LMWH in longitudinal studies (OR=2.60; 95%CI: 1.08-6.25; p=0.03; I 2 =0%), however no differences have been showed in randomized controlled trials. Conclusions: ASA demonstrated a good efficacy compared to no intervention; data are insufficient to confirm superiority of LMWH over ASA as thromboprophylaxis in MM patients. Large and well powered trials are warranted. © 2017 Elsevier Inc.

Non-pharmacological interventions are increasingly being acknowledged as valuable options to overcome or reduce functional problems in patients with Parkinson's disease. In the last decades, Nordic Walking was employed and investigated by rehabilitation specialists. Clinical trials on the effect of Nordic Walking on motor and non-motor Parkinson's disease symptoms are few, small, and heterogeneous for inclusion criteria and intervention protocols. As a result, Nordic Walking training cannot be recommended as a standard rehabilitative tool in Parkinson's disease patients.This randomized controlled single-blind trial recruited Parkinson's disease patients at a Hoehn and Yahr stage between 2 and 3 assigned to a Nordic Walking vs. Walking group. Subjects were extensively assessed for motor and non-motor symptoms at baseline and after 8 weeks of intervention period. To study the effects of intervention on the overall sample, paired-sample t test and Wilcoxon signed rank test were used, while differences between groups were estimated with general linear models repeated-measure and Mann-Whitney U test.Among 32 patients who ended the study period, improvements were observed in the following assessments: global motor outcome (p 0.001), dynamic and static balance ability (p 0.005; p 0.002), global non-motor symptoms outcome (p 0.003), fatigue (p 0.016), anxiety (p 0.043), and quality of life (p 0.003). The treatment group (Nordic Walking) failed to show any difference compared to the control group (Walking) in all considered outcomes.Nordic Walking was not superior compared to Walking in the studied population. Moderate intensity outdoor group activities like Nordic Walking and Walking seem to improve motor and non-motor symptoms parameters in patients with Parkinson's disease.

Background Atrial fibrillation is highly prevalent among the elderly population, which is also frequently prone to thromboembolic complications. Anticoagulant prophylaxis is underused in the elderly due to fear of bleeding, which tends to be more frequent and severe within this group. Randomized controlled trials and several observational studies have shown the comparative effectiveness of direct oral anticoagulant (DOAC) against vitamin K antagonists (VKA), and their superior safety, at least in terms of intracranial bleeding. However, for patients aged 85 or older, there is still insufficient literature, leaving unanswered the question of which prophylaxis to use. Purpose The aim of the study is to compare the incidence of established outcomes and to investigate the net clinical benefit between DOAC and VKA in patients aged ≥85 years. Methods A cohort of 553 outpatients from the real world began treatment using DOACs at our clinic. The prospective follow-up on average lasted 1.97 years. Main endpoints were stroke and systemic thromboembolism, major hemorrhage, myocardial infarction and mortality for all causes. A sample of the 160 patients aged ≥85 years was compared with the remaining younger ones and with a second cohort of 298 outpatients aged ≥85 years. Retrospectively analyzed, with follow-ups at our center, who started VKAs; the average time was 2.03 years. The “net clinical benefit” of DOACs against VKAs was calculated as the difference between thromboembolic events with VKAs and with DOACs, minus the difference (weighted by 1.5) between spontaneous intracranial bleeding with DOACs and VKAs. Results In terms of thromboembolic events, DOACs and VKAs (2.43% p-y vs. 1.82% p-y, p=0.975) have shown comparable efficacy in a higher risk sample (CHA2DS2-VASc score: 5.2 vs. 4.5; p Conclusions DOACs are as effective in very old patients with atrial fibrillation compared to very old patients receiving VKAs, but they are associated with increased major bleeding. The same is true when compared with younger DOACs users. TTR, representing quality achieved by the anticoagulation with a VKA, can influence the comparison with DOACs. Considering ischemic strokes and spontaneous intracranial hemorrhages, there is however a net benefit for DOACs use in specific categories of elderly patients.

Background Due to the fear of increased risk of bleeding, anticoagulation treatment is underutilized in the prevention of stroke in elderly patients with non-valvular atrial fibrillation (NVAF). Although direct oral anticoagulants (DOAC) are safer than VKA, still little is known about the risk factors associated with bleeding in elderly patients treated with DOAC. Furthermore, it is still uncertain whether the risk scores that are currently used can serve to effectively identify higher bleeding risk in elderly subjects. Purpose The aim of this study was to identify predictors of bleeding in a cohort of elderly people affected by NVAF treated with DOAC, and to evaluate the accuracy of risk scores for bleeding used at present. Methods Data on outpatients aged ≥75 years, naïve for DOAC therapy, who started therapy with Dabigatran, Rivaroxaban, Apixaban or Edoxaban for the prevention of thromboembolism during FANV were analyzed. HASBLED, ATRIA, OBRI and ORBIT scores were calculated for each patient. Patients had follow-up for 12 months during which deaths, therapy discontinuation and adverse events such as thromboembolism and bleeding were reported. Potential predictors of bleeding and the predictive value of each bleeding score were tested using univariate Cox regression; testing accuracy was evaluated using ROC curves. Results A total of 291 patients (52.9% female, mean age 82.85±5.18 years) had a median follow-up time of 11 (10–12) months. The incidence rate of major bleeding was 4.7 per 100 patient-years, the rate of intracranial bleeding was 0.4 per 100 patient-years. Patients who had major bleeding were more often affected by heart failure (63.6% vs 25%; p=0.009) and thrombocytopenia (36.4% vs 7.4%; p=0,009). However in the multivariate analysis only heart failure remained statistically associated with major bleeding (HR 3.83, 95% CI 1.06–13.85; p=0.041). None of tested bleeding risk scores was able to predict major bleeding in our cohort. HASBLED and ORBIT scores were able to predict major and non-major clinically relevant bleeding (HR 1.32; 95% CI 1.01–1.71; p=0.042 and HR 1.20; 95% CI 1.00- 1.43; p=0.046); only the ORBIT score was found to be statistically significant, but with weak discriminatory power at ROC curves (AUC 0.59; 95% CI 0.51–0.68; p=0.041). Conclusions In our cohort of elderly patients aged 75 or older, anticoagulated for NVAF, heart failure history was the only effective predictor of major bleeding risk during DOAC treatment. None of the bleeding risk scores used currently have demonstrated a good discriminatory power in our cohort. As predictive factors of bleedings in DOAC-treated patients may not be the same as those for VKA-treated patients and those in elderly may also be differ in younger people, it calls for more investigation on the topic.

Background Lemierre syndrome is a potentially life-threatening condition occurring in otherwise healthy children and adolescents with head/neck bacterial infections (usually tonsillitis due to anaerobe bacteria). Peculiar complications are neck vein thromboses contiguous to the site of infection and multiple septic embolization. Arterial thrombosis and cardiac complications have been described as possible clinical manifestations of Lemierre syndrome: however, in light of the rarity of this condition (one case/1,000,000 person-years), no comprehensive analysis has ever been conducted. Purpose To describe the frequency and the patterns of acute cardiac and arterial complications in patients with Lemierre syndrome. Methods We identified 715 cases of Lemierre syndrome (years 2000–2016) and retrieved complete individual patient-level data. Study outcomes assessed on admission or during hospitalization were: i) objectively diagnosed ischemia or arterial infarction/thrombosis, arterial stenosis due to inflammatory process, and septic aneurysms; ii) new objectively diagnosed cardiac complications; iii) all-cause death. Results Of the 715 patients with Lemierre syndrome, 56 (7.6%, 95% confidence interval [CI]: 6.1%–10.0%) experienced cardiac or arterial complications. Median age was 19 (interquartile range [IQR]: 16–25) years and 35 (62.5%) were men. Intracranial ischemia or infarction was found in 23 patients, corresponding to 3.2% of the whole study population. Carotid artery thrombosis, stenosis, or septic aneurysm occurred in 28 (3.9% of total), pericardial disease in 11 (1.5% of total), and infective endocarditis in 5 (0.7% of total) (Figure). A total of 32 (57.1%) patients developed these complications during the course of hospitalization after a median of 6 (IQR: 3–12 days) days from admission. A total of 37 (66.1%) patients received anticoagulation. Fatality rate was 10.7% (95% CI: 5.0%–21.4%; n=6). Cardiac and arterial complications. Conclusions An unexpectedly high proportion of patients with Lemierre syndrome developed acute cardiac or arterial complications. In this group, the fatality rate was substantial. Our observation that most of the cardiovascular events occurred during the course of hospitalization may have implications for the development of diagnostic and management strategies. It remains unclear whether antithrombotic therapies may influence prognosis.

Consequences of warfarin suspension after major bleeding in very elderly patients with non valvular atrial fibrillation

Lemierre syndrome usually affects otherwise healthy adolescents or young adults and occurs at an overall rate of 1 to 10 cases per million person-years with an estimated fatality rate of 4 to 9%. Diagnostic criteria remain debated and include acute neck/head bacterial infection (often tonsillitis caused by anaerobes at high potential for sepsis and vascular invasion, notably Fusobacterium necrophorum) complicated by local vein thrombosis, usually involving the internal jugular vein, and systemic septic embolism. Medical treatment is based on antibiotic therapy with anaerobic coverage, anticoagulant drugs and supportive care in case of sepsis. Surgical procedures can be required, including drainage of the abscesses, tissue debridement and jugular vein ligation. Evidence for clinical management is extremely poor in the absence of any adequately sized study with clinical outcomes. In this article, we illustrate two cases of Lemierre syndrome not caused by Fusobacterium necrophorum and provide a clinically oriented discussion on the main issues on epidemiology, pathophysiology and management strategies of this disorder. Finally, we summarize the study protocol of a proposed systematic review and individual patient data meta-analysis of the literature. Our ongoing work aims to investigate the risk of new thromboembolic events, major bleeding or death in patients diagnosed with Lemierre syndrome, and to better elucidate the role of anticoagulant therapy in this setting. This effort represents the starting point for an evidence-based treatment of Lemierre syndrome built on multinational interdisciplinary collaborative studies. ispartof: HAMOSTASEOLOGIE vol:39 issue:1 pages:76-86 ispartof: location:Germany status: published

Oral anticoagulation (OAC) is given for ischemic stroke prevention in patients with nonvalvular atrial fibrillation. OAC's most serious complications are major bleeding and, in particular, hemorrhagic stroke. Together with vitamin K antagonists (VKAs), direct oral anticoagulants (DOAC) are now available which have a more rapid onset/offset of action and more predictable anticoagulant effect. The advent of DOAC has given to the clinician an opportunity to tailor OAC therapy in order to maximize advantages and minimize complications.This review covers data published in literature regarding the risk of hemorrhagic stroke in patients taking OAC. Bleeding risk assessment is discussed and different bleeding risk factors are presented. The paper will also review clinical studies comparing DOAC against standard anticoagulation, in regard to the risk of hemorrhagic stroke.Bleeding assessment is mandatory in order to select patients at high hemorrhagic risk who will benefit the most from close monitoring. Blood pressure, alcohol intake, concomitant medication and comorbidities should be constantly evaluated and treated accordingly. During VKA therapy, adherence and intensity of anticoagulation must be strictly monitored. DOAC are associated with lower risk of hemorrhagic stroke than VKA. However, periodic hepatic and renal checks as well as careful evaluation of time adherence are necessary to reduce the risk of bleeding.

The direct oral anticoagulants (DOACs) have been compared with parenteral anticoagulants and vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE) in several robust studies. DOACs have shown similar efficacy in preventing recurrent VTE and significant reductions in critical site (intracranial) bleeding, fatal bleeding, major and nonmajor bleeding. Warfarin and other VKAs are not dead as treatment modalities for VTE. A better way to describe the current situation is to use a boxing expression, “down but not out.” VKAs and parenteral anticoagulants still have a role to play in the management of VTE in several clinical settings. In indications where DOACs can be used, VKAs should not, as the safety profile of VKAs is considerably worse than DOACs. Hence, guidelines are now recommending DOACs in preference to VKAs. In this article, we consider where DOACs are indicated, where there is growing evidence for use, where we have little evidence for use, and finally where there is no evidence for use and where they, thus, should not be used. We have included recommendations and examples of our own practice which may not be applicable to all settings. © Thieme Medical Publishers333 Seventh Avenue, New York, NY 10001, USA.

Essentials Anticoagulation in the elderly is still a challenge and suspension of warfarin is common. This is an observational study reporting reasons and consequences of warfarin suspension. Vascular disease, age, time in therapeutic range, and bleedings are associated with suspension. After suspension for bleeding or frailty, patients remain at high-risk of death or complications. SummaryBackground Anticoagulation in elderly patients with non-valvular atrial fibrillation (NVAF) is still a challenge, and discontinuation of warfarin is common. The aim of this study was to analyze the aspects related to warfarin discontinuation in a real-world population. Methods This was an observational cohort study on very elderly NVAF patients naive to warfarin therapy (VENPAF). The included subjects were aged at least 80 years, and started using warfarin after a diagnosis of NVAF. Warfarin discontinuation was assessed, and the reason reported for discontinuation, the person who decided to stop treatment, subsequent antithrombotic therapy and mortality, ischemic and bleeding events were collected. Results Over a period of 5 years, warfarin was discontinued in 148 of 798 patients. Despite similar CHA2DS2-VASc scores, the frequencies of thromboembolic and major bleeding events were significantly higher (P = 0.01 and P = 0.001, respectively) and the time in therapeutic range (TTR) was significantly lower (P < 0.001) in patients who discontinued warfarin. Independent risk factors for warfarin discontinuation were vascular disease (hazard ratio [HR] 2.5, P < 0.001), age ≥ 85 years (HR 1.4, P = 0.04), TTR < 60% (HR 1.8, P = 0.001), and bleeding events (HR 2.3, P < 0.001). The main reasons for warfarin discontinuation were physician-perceived frailty or low life-expectancy (45.9%), bleeding complications (19.6%), and sinus rhythm restoration (16.9%). Event and death rates were very high, especially in frail patients and in those with bleeding complications. Conclusions Warfarin discontinuation is frequent in very elderly patients, and is associated with increased risks of death and adverse events. Identification of elderly patients who are at high risk of bleeding and the poor quality of anticoagulation during warfarin are still unsolved clinical problems.

The purpose of the study is to evaluate whether donepezil (D) plasma concentrations and activity of CYP2D6 and CYP3A4 are associated with the therapeutic response of patients with mild to moderate Alzheimer's disease (AD).This study comprised 54 patients affected by probable AD in therapy with D 10 mg/daily for at least 3 months. Plasma concentrations of D and its three main metabolites (6DD, 5DD, DNox) were assayed with a novel high performance liquid chromatography (HPLC) technique. Cognitive progression was assessed at baseline and at 9 months of follow-up with the mini mental state examination (MMSE). The activities of the two cytochromes involved in D metabolism-CYP2D6 and CYP3A4-were evaluated according to their metabolic ratios in plasma or urine, after test doses of probe drugs (dextromethorphan and omeprazole).A significant correlation was found between plasma levels of D and variations in MMSE scores after 9 months of therapy (r (2) = 0.14; p = 0.006). Neither the concentrations of D metabolites nor the metabolic ratios of CYP2D6 and CYP3A4 showed any correlations with cognitive variations. Low CYP2D6 activity and advanced age were associated with high D concentrations. Patients who were treated with CYP2D6 and P-glycoprotein (P-gp) inhibitors also had higher D plasma levels (mean difference = 19.6 ng/mL; p = 0.01) than those who were not.D plasma concentrations, but not cytochrome phenotyping, are associated with cognitive outcomes in AD patients.

Background In humans, donepezil (D) is metabolized to 5-O-desmethyl-donepezil (5DD), 6-O-desmethyl-donepezil (6DD), and donepezil-N-oxide (DNox). Although 6DD and DNox are pharmacologically active, the activity of 5DD is unknown. At present, no routine methods are available to detect D and its 3 metabolites simultaneously. In this study, a novel high-performance liquid chromatography method was developed and applied to a population of patients with Alzheimer disease on stable treatment with the drug. Methods Liquid-liquid extraction from plasma was accomplished by means of a solvent mixture of n-hexane/dichloromethane/ethylacetate (45:40:15) after sample alkalinization. Disopyramide was the internal standard. After evaporation, the residue was reconstituted in 200 μL of mobile phase (acetonitrile 85%:1% acetic acid 15%) and 50 μL was injected into the high-performance liquid chromatography column (X-Terra, RP8; flow: 1 mL/min). Photometric and fluorimetric detectors were used in tandem, to maximize the sensitivity of fluorescent compounds (D, 5DD, and DNox) and also to reveal nonfluorescent compounds (6DD and internal standard). Results The method was linear in the 10-100 ng/mL concentration range. Imprecision (coefficient of variation) varied between 3.2% and 12.6% and inaccuracy (% mean absolute error) between 1.3% and 13.3%, depending on the compound, concentration, and detection mode. The quantitation limits were 0.1-0.3 ng/mL for fluorescent compounds and 1.2-4.3 ng/mL for photometric compounds. D, 5DD, 6DD, and DNox through concentrations were measured in 54 patients with Alzheimer disease on treatment with D (10 mg q.d.). No interfering peaks by endogenous compounds or coadministered drugs were noted. Plasma concentrations were quite variable among patients (D: 10-106 ng/mL; 5DD: 0.07-2.8 ng/mL; 6DD: 1.2-36 ng/mL; DNox: 0.5-45.4 ng/mL). Of note, in 6 patients, the plasma concentrations of the 2 active metabolites (6DD and DNox) were higher than those of the parent drug. Conclusions The above method proved to be suitable for therapeutic drug monitoring and may be useful in ascertaining the real contribution of metabolites to the therapeutic effects of donepezil.

Objective To determine whether the incidence of atrial fibrillation (AF) is static or rising in the UK. Design Among the cohort of all individuals aged ≥45 years in the UK Clinical Practice Research Datalink (CPRD) (linked to hospital discharges) we identified incident non-valvular AF cases between 2001 and 2013. Overall and annual AF incidence rates were calculated and standardised to the UK population. Results The cohort of 2.23 million individuals included 91 707 patients with incident AF. The overall standardised AF incidence rate was 6.7 (95% CI 6.7 to 6.8) per 1000 person-years, increasing exponentially with age and higher in men of all ages. There was a small increase in the standardised incidence of AF in the last decade from 5.9 (5.8 to 6.1)/1000 person-years in 2001 to 6.9 (6.8 to 7.1)/1000 person-years in 2013, mostly attributable to subjects aged >80 years with a non-primary hospital discharge diagnosis of AF. Standardised incidence rates of AF among white patients was 8.1 (8.1 to 8.2)/1000 person-years, compared with 5.4 (4.6 to 6.3) for Asians and 4.6 (4.0 to 5.3) for black patients. AF diagnosis was first made in general practice in 39% of incident AF. Conclusions The incidence of AF in the UK has increased gradually in the last decade, with more than 200 000 first-ever non-valvular AF cases expected in 2015. This increase is only partly due to population ageing, though the principal increase has been in the elderly hospitalised for a reason other than AF.

Atrial fibrillation is a common condition in the elderly, and the incidence of thromboembolic events secondary to atrial fibrillation increases with age. Antithrombotic therapy effectively prevents stroke and systemic embolism but also exposes patients to the risk of bleeding. Because the risk of bleeding also increases with age, clinicians tend to withhold anticoagulation in the elderly. Anticoagulation is particularly complex in the frail elderly patient, who presents additional risk factors affecting both efficacy and safety of thromboembolic prevention. The main clinical trials rarely include frail elderly patients and, consequently, the guidelines do not provide guidance for their management. In the absence of clear indications for this class of patients, we identified some areas that should be taken into account both before starting and when discontinuing anticoagulation: comorbidities, polypharmacotherapy, adherence, cognitive impairment, mobility and monitoring barriers, nutritional status and swallowing disorders, risk of falls, and reduced life expectancy. We also suggest a multidimensional algorithm covering both a standard ischemic and bleeding risk assessment and an additional anticoagulation-focused frailty assessment. This is of particular relevance given the recent introduction of the oral direct inhibitors, as they are likely to widen the treatment options for the frail elderly. Depending on which aspect of frailty is present, anticoagulation can now be tailored accordingly.

summaryPrimary prevention is the key to managing a significant proportion of the burden of venous thromboembolism (VTE), defined as deep venous thrombosis (DVT) or pulmonary embolism (PE). This is because VTE may lead to sudden death or are often misdiagnosed and therefore treatment is not feasible. Primary prevention usually commences in hospital as VTE following hospitalisation adds to the significant disease burden worldwide. Numerous medical, surgical and other risk factors have been recognised and studied as indications for prophylaxis. The risk of VTE continues following admission to hospital with a medical or surgical condition, usually long after discharge and therefore prolonged primary prophylaxis is often recommended. Clinical and observational studies in surgical patients show this risk extends for months and perhaps more than one year, for medical patients the risk extends for at least several weeks. For the specific groups of patients at higher risk of developing VTE primary prevention, either pharmaceutical or mechanical, is recommended. The aim of this review is to describe the population at risk, the main related risk factors and the approach to thromboprophylaxis in different populations.

Cardiovascular disease (CVD) includes a number of conditions such as myocardial infarction, coronary heart disease, stroke, and venous thromboembolism. CVD is a leading health problem worldwide and a major cause of mortality, morbidity, and disability; it is also associated with high healthcare costs. The incidence of CVD is predicted to increase in the forthcoming years, and thus it is crucial that physicians are aware of the benefits and limitations of the available therapies to ensure patients receive optimized treatment. Current clinical practice guidelines provide recommendations on the use of anticoagulants and antiplatelets for both the prevention and treatment of CVD. Aspirin is the most studied antiplatelet agent in this context. The benefits of aspirin are well documented and supported by data from robust clinical trials for CVD conditions, such as acute coronary syndrome and stroke prevention in patients with atrial fibrillation. However, the clinical benefits of aspirin are less clear for other conditions, namely for primary prevention of venous thromboembolism after major orthopaedic surgery, particularly in comparison with newer drugs such as the direct oral anticoagulants. This article provides an outline of the current guidelines and a critical assessment of the efficacy and safety data supporting the recommendations for the use of aspirin in the treatment and prevention of venous thromboembolism and other cardiovascular disorders.

Morgagni-Stewart-Morel syndrome is defined as the presence of hyperostosis frontalis interna, variably associated with metabolic, endocrine, and neuropsychiatric disorders. The possible cause-effect relationship of these associations remains uncertain.A 75-year-old woman presented with severe frontal headache and a history of psychotic disorders. On instrumental examination she was found to have extensive frontal hyperostosis and cortical atrophy. These findings, associated to the metabolic and neuropsychiatric pattern of the patient, are consistent with a high penetrance of Morgagni-Stewart-Morel syndrome.In this clinical case seminar, we summarize the current understanding of the association between hyperostosis frontalis interna and Morgagni-Stewart-Morel, based on a MEDLINE search (case reports, original articles, and reviews published between 1928 and 2011) on this topic. Possible pathophysiological mechanisms underlying both the headache and the hyperostosis frontalis interna are discussed.A case of full penetrance of Morgagni-Stewart-Morel syndrome is reported, presenting many of the clinical features described in the literature. Metabolic and endocrine dysfunctions should be interpreted not only as isolated components of the syndrome, but also as the reason behind its pathogenesis. Endocrine or nutritional disorders may have led to an altered bone metabolism with frontal bone apposition. On the other hand, the severity of our patient's neurological and psychiatric symptoms correlates well with the severity of her hyperostosis frontalis interna and the cortical atrophy.

Asymptomatic deep vein thrombosis (DVT) and pulmonary embolism are leading causes of morbidity following the hospitalization of elderly people. The diagnosis of DVT is supported by the D-dimer laboratory assay. The concentration of D-dimer increases in patients with DVT, but may be high in other conditions too (i.e. cancer, infections and inflammation). Old age coincides with a physiological increase in D-dimer values, and that is why D-dimer assay in the elderly is characteristically highly sensitive but scarcely specific. The aim of our study was to explore the reliability of different D-dimer cutoffs for the diagnosis of asymptomatic DVT in a population of bedridden hospitalized elderly patients. We studied 199 patients who were a mean 86.3 ± 6.7 years old. All participants underwent lower limb Doppler ultrasound (DUS) and D-dimer venous blood sampling on admission. In our cohort, the usual cutoff proved highly sensitive (100%), but its specificity was very poor (20.1%). To find a higher cutoff that could improve the method's specificity, we analyzed our data using a receiver operating characteristic curve analysis. The resulting D-dimer cutoff of 492 μg/l enabled us to retain the same sensitivity while improving the test's specificity to 39.1%, with a consequent improvement in its positive predictive value and accuracy. In addition to improving the method's reliability, this result may be helpful in clinical practice, in both medical wards and nursing homes. By adopting a cutoff of 492 μg/l, clinicians could significantly increase the proportion of older patients in whom DVT can be safely ruled out, reducing referrals for DUS and administration of heparin, with consequent clinical, practical and economic advantages.

Background: To assess the influence of body mass index (BMI) on the progression of dementia. Methods: Sixty elderly outpatients with untreated dementia followed for 12 months. All patients underwent clinical, cognitive, functional, and nutritional assessment at the baseline and after 12 months. Patients were divided into 2 groups by baseline BMI (< or ≥25 kg/m2). Results: Participants with a baseline BMI ≥25 kg/m2 had significantly higher Mini-Mental State Examination (MMSE) scores (21 ± 5.1 vs 15.9 ± 5.5; P < .001), while clinical dementia rating (CDR) and multidimensional prognostic index (MPI) scores were similar in the 2 groups. After 12 months, the MMSE score decreased significantly in both groups compared to the baseline, while the CDR and MPI scores increased significantly for patients with a baseline BMI 2. Conclusion: A BMI cutoff of 25 kg/m2 could be useful for identifying frail patients with dementia who will experience a more rapid global impairment, which could be assessed adequately using multidimensional evaluation tools.

Long-term treatment with vitamin K inhibitors (VKA) for stroke prevention is recommended in most patients with atrial fibrillation (AF) [1]. An exception to this rule are patients without clinical risk factors for stroke as those with a CHADS2 score = 0 [1]. To evaluate the rate of low risk patients with AF treated with VKA, we assessed the CHADS2 score of patients referred to our anticoagulation clinic. The presence of congestive heart failure, hypertension, age [75, diabetes, and previous stroke/TIA was ascertained by reviewing hospital records and directly interviewing each patient. Congestive heart failure was defined as a recent (\90 days) hospital admission for impaired left ventricular systolic function at transthoracic echocardiography (ejection fraction less than 50%). Hypertension was defined as a systolic blood pressure higher than 160 mmHg on two consecutive occasions or the use of antihypertensive drugs. Diabetes was defined according to the American Diabetes Association criteria [2]. Cerebral ischemia was a previous sudden neurological defect confirmed by cerebral imaging. From January 2004 to October 2008, 609 consecutive AF patients were considered. One-hundred and nine were excluded as data were incomplete (n = 51), an elective cardioversion was programmed (n = 32) or mitral valve disease was associated (n = 7). Remaining 19 patients refused to participate in the study. Of the 500 included patients, 96 (19.2%) had a CHADS2 score of 0. Sixty-eight were males and 28 females, with a mean age (±SD) of 65 ± 8.5 years. The reasons why they were prescribed VKA are shown in Table 1: most of them simply followed the recommendations of their physician (81.2%) without further specifications. Few reported gastrointestinal problems or aspirin intolerance, or had a family history positive for cerebral ischemia. A large proportion (62.8%) of these patients with CHADS2 score = 0 was referred to our Anticoagulation Clinic by a specialist (cardiologist or internist), and 20% by their general practitioner. Our actual major bleeding rate among CHADS2 0 patients reached 1.78 pts%/year (7 events). Bleeding was classified as major when fatal, intracranial (documented by imaging), ocular causing loss of sight, to major articulations, retroperitoneal, gastro-intestinal, when surgery was required or hemoglobin was reduced of 2 g/dl or more and/ or were requested more than two blood units for transfusion [3]. Among these, we had a rate of 0.51 pts%/year of intracranial bleeding (2 events). These data show that VKA are often prescribed in young patient with AF and no risk factors for stroke. Ischemic stroke is the most severe consequence of AF and the calculated risk is 4.5% per year [4]. However, the risk is different among AF patients varying between 1–2 and 12–18% a year according to the presence of risk factors [5]. In the last 20 years, many different risk stratification models have been proposed to identify AF patients at low, moderate and high risk of stroke. CHADS2 is a simple and widely used score that identifies low-risk patients (score = 0) in whom long-term aspirin therapy at a dose of S. Granziera G. Nante (&) E. Manzato Department of Medical and Surgical Sciences, Geriatric Clinic, Giustinianeo Hospital, University of Padova, via Giustiniani, 35128 Padua, Italy e-mail: giovanni.nante@sanita.padova.it

Commentary on: Schulman S, Kakkar AK, Goldhaber SZ, et al. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis. Circulation 2014;129:764–72.[OpenUrl][1][Abstract/FREE Full Text][2] Until recently, an initial course of parenteral anticoagulation followed by vitamin K antagonist (VKA) was the standard of care for the treatment of venous thromboembolism (VTE). In the past few years, direct oral anticoagulants (DOAC) have been found to be non-inferior to VKA.1–3 The RE-COVER study found dabigatran to be non-inferior to warfarin, with a reduced risk for clinically relevant bleeding.4 In order to confirm these findings, the RE-COVER II trial was performed and the results of both studies pooled. Almost identical to the RE-COVER study, RE-COVER II was a randomised, double-blind, double-dummy trial. It enrolled 2589 patients with acute, proximal deep vein thrombosis (DVT) or pulmonary embolism. Exclusion criteria included haemodynamic instability, thrombolytic therapy, recent unstable cardiovascular disease, high bleeding … [1]: {openurl}?query=rft.jtitle%253DCirculation%26rft_id%253Dinfo%253Adoi%252F10.1161%252FCIRCULATIONAHA.113.004450%26rft_id%253Dinfo%253Apmid%252F24344086%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=circulationaha&resid=129/7/764&atom=%2Febmed%2F19%2F5%2F180.atom