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1.  Preliminary results of a randomized controlled trial carried out with a fixed combination of S-adenosyl-L-methionine and betaine versus amitriptyline in patients with mild depression 
S-adenosyl-L-methionine (SAMe), a safe, endogenous, pleiotropic methyl donor well known for its antidepressant role, has been assumed to have a possible role in increasing plasma levels of compounds known to be able to raise cardiovascular risk. Although the issue is still being debated, betaine (trimethylglycine), a specific methyl donor involved in the homocysteine circuit, may be able to reduce such a risk and/or, by determining a sparing effect on endogenous SAMe, may be able to improve the clinical efficiency of SAMe itself. Indeed, preliminary results have shown clinical improvement determined by an add-on therapy with betaine administered along with SAMe, versus SAMe alone, to patients affected by mild/moderate depression.
To evaluate the safety and antidepressant role played by the association of SAMe plus betaine versus amitriptyline administered in untreated individuals with a recent diagnosis of mild depression.
This small, open-label, randomized, observational study enrolled 64 individuals with a diagnosis of mild depression according to the Zung Self-Rating Depression Scale. After randomization, they were treated with either Laroxyl® (amitriptyline, 75 mg/day) or DDM Metile® (enteric-coated SAMe, 500 mg/day, plus betaine, 250 mg/day) for 12 months. Assessment of clinical scores and tolerability was performed at T=0 and after 3, 6, and 12 months.
After 3 months, both treatments showed a small and not statistically significant improvement. After 6 and 12 months, both treated groups demonstrated a more noticeable improved response, although the group treated with SAMe plus betaine showed better results in terms of score, number of individuals in remission, and side effects. Compliance was overlapping in both treatments.
The association of SAMe plus betaine seems to be a safe and effective tool to counteract mild depression and also when used as monotherapy in subjects with a recent diagnosis.
PMCID: PMC4322882
amitriptyline; betaine; SAMe; moderate depression; methyl donor
2.  Burning feet in polycythemia vera – peripheral sensorimotor axonal neuropathy with erythromelalgia 
Polycythemia vera is a rare myeloproliferative disease. Cutaneous symptoms are uncommon. We report about a 72-year-old female patient with JAK2V617F-positive polycythemia who developed peripheral sensorimotor axonal neuropathy and erythromelalgia. Possible causes and treatment are discussed.
PMCID: PMC4321571
bone marrow diseases; myeloproliferative diseases; JAK2 mutations; burning sensations; peripheral neuropathy
3.  The epidemiological profile of pediatric patients admitted to the general intensive care unit in an Ethiopian university hospital 
In least developing countries, there are few data on children’s critical care. This makes the provision of aid and improvement of outcome difficult.
To describe admission and outcome patterns of children managed in a general intensive care unit at Jimma University Specialized Hospital (JUSH), Ethiopia, over a 5-year period.
A retrospective cross-sectional study design was used. All children from birth to 14 years of age who were admitted to the general ICU of the hospital from 2009–2013 were included. Patient charts and ICU documentation log were reviewed.
A total of 170 children were admitted to the ICU of JUSH over the study period. The greater share was taken by males (54.7%), with a male-to-female ratio of 1.2:1. The overall mortality rate was 40%. The majority of the children were in the age range of 10–14 years (38.8%). Of the total number of patients admitted, 34.7% were trauma cases, 45.8% of whom died. The highest percentage, 69.5%, of trauma patients were admitted for head injuries. Among the trauma cases, burn and polytrauma were the second and third leading causes (15.3%) of admission. Postoperative patients and medical patients accounted for the rest of the admitted cases (28.2% and 27.6% of the cases respectively).
The leading cause of admission and death was trauma. Postoperative and medical causes of admission were also significant. The mortality rate in the ICU was very high, and this could be due to various factors. Further research benchmarking and interventions are highly recommended.
PMCID: PMC4319554
trauma; critical care; pediatric; ICU; ventilation; oxygenation
4.  Association between the ankle–brachial index, intermittent claudication, and physical activity level: what is the influence on the functional capacity of patients with or at high risk of cardiovascular disease? 
Patients with or at high risk of cardiovascular disease have a poor functional capacity; however, the influence of association among intermittent claudication (IC), abnormal ankle–brachial index (ABI), and physical activity level on functional capacity of these patients has not been fully studied.
The primary objective of this study was to investigate the association between the ABI, IC, and physical activity level, and the influence of these variables on the functional capacity of patients with or at high risk of cardiovascular disease seen in a reference cardiology outpatient clinic in Southern Brazil. The secondary objective was to assess the prevalence of peripheral arterial disease (PAD) in this sample of patients.
Patients and methods
This was a prospective cross-sectional study in which 162 consecutive patients were evaluated and classified into three groups according to their ABI: normal ABI (n=104, values between 1.00 and 1.40); borderline PAD (n=23, values between 0.91 and 1.00); and patients with PAD (n=35, ≤0.90). The presence of IC was assessed using the Edinburgh Claudication Questionnaire. The level of physical activity was assessed by the short version of the International Physical Activity Questionnaire (IPAQ) and functional capacity was assessed by the 6-minute walk distance (6MWD).
The prevalence of PAD was 21.6% in the total sample. The 6MWD showed strong correlation with the absence of IC (r=0.785; P<0.001), moderate correlation with age (r=−0.347; P<0.001), and weak correlations with IPAQ scores (r=0.164; P=0.038) and ABI (r=0.216; P=0.006). Age, ABI, and absence of IC were independently associated with the outcome (P=0.001, P=0.001, and P=0.028, respectively).
The current study demonstrates that 6MWD is associated with IPAQ scores, ABI, and absence of IC. Age, ABI and absence of IC were independently associated with functional capacity in patients with or at high risk of cardiovascular disease.
PMCID: PMC4315558
6-minute walk test; cardiology outpatient clinic; IPAQ; peripheral arterial disease
5.  Effects and safety profile of betahistine in patients in the Russian contingent of OSVaLD, an open-label observational study in vestibular vertigo 
We report here data from the >200 patients recruited in Russia to take part in OSVaLD, a 12-week, open-label, post-marketing surveillance study of the response to betahistine 48 mg/day in vertigo of peripheral vestibular origin carried out in a total of 13 countries.
The primary efficacy endpoint was change in the Dizziness Handicap Inventory (DHI; 100-point scale). Changes in Hospital Anxiety and Depression Scale (HADS) and Medical Outcomes Study Short-Form 36, version 2 (SF-36v2®) scores were a priori secondary Outcomes.
Total DHI score improved by 43 points during betahistine treatment. This aggregate improvement was equally distributed across the three domains of the DHI (physical, emotional, and functional; P<0.0001 for main and subscore changes from baseline). Statistically significant improvements versus baseline were also observed in mean HADS scores for anxiety and depression (both P<0.0001), and in the Physical Component Summary and Mental Component Summary scores of the SF-36v2 (both P<0.0001 versus baseline). Only one suspected adverse drug reaction was recorded in the Russian safety population (n=204), indicating that betahistine was well tolerated in those patients.
Betahistine 48 mg/day was associated with clear improvements in well-configured and widely validated measures of health-related quality of life and an encouraging tolerability profile in patients in Russia who took part in OSVaLD.
PMCID: PMC4310344  PMID: 25653552
betahistine; vertigo; dizziness; anxiety; depression; quality of life; Russia
6.  Effects of Bacillus subtilis var. natto products on symptoms caused by blood flow disturbance in female patients with lifestyle diseases 
The fermented soybean product natto is a popular traditional food in Japan and is considered a health supplement. NKCP®, a natto-derived dietary food supplement whose main component is bacillopeptidase F, has antithrombotic, fibrinolytic, and blood pressure-lowering effects. We examined whether daily intake of NKCP® effectively improves subjective symptoms in patients with lifestyle diseases in this cross-over, double-blind study. Fermented soya extract with subtilisin NAT (nattokinase) as the main component was used as an active placebo. A 4-week course of NKCP® significantly decreased the visual analog scale (VAS) score for shoulder stiffness from 42.3 to 32.4 (P=0.009), the VAS score for low back pain from 25.5 to 18.8 (P=0.02), and the VAS score for coldness of the extremities from 33.1 to 25.7 (P=0.002). However, no significant difference was found in the VAS score for headache. After a 4-week course of active placebo, no significant changes in the VAS score were found for any symptoms. The significant improvement in the symptoms secondary to blood flow disturbance was caused by the improvement in blood flow by NKCP®. The use of dietary supplements based on the Japanese traditional food natto helps to relieve subjective symptoms for patients with lifestyle diseases receiving medical care.
PMCID: PMC4310345  PMID: 25653551
bacillopeptidase F; Japanese traditional food; lifestyle disease; subjective symptom; supplement
7.  Systemic inflammatory response syndrome and platelet count ≥250×109 are associated with venous thromboembolic disease 
Prior research has demonstrated that platelet count and inflammation are dominant contributors to hypercoagulability. Our objective is to determine whether elevated platelet count and systemic inflammatory response syndrome (SIRS) have an association with the development of venous thromboembolism (VTE) in hospitalized patients with a high clinical index of suspicion for thromboembolic disease.
We performed a retrospective medical record review of 844 medical and surgical patients with suspected VTE hospitalized from July 2012 to May 2013 who underwent screening by venous duplex and computed tomography pulmonary angiogram. For our purposes, thrombocytosis was arbitrarily defined as platelet count ≥250×109/L.
Venous thromboembolic disease was detected in 229 patients (25.9%). Thrombocytosis was present in 389 patients (44%) and SIRS was present in 203 patients (23%) around the time of imaging. Thrombocytosis and SIRS were positively correlated with VTE (P<0.001). There was no correlation between thrombocytosis and SIRS. Multivariate analysis revealed that SIRS (odds ratio 1.91, 95% confidence interval 1.36–2.68, P<0.001) and thrombocytosis (odds ration 1.67, 95% confidence interval 1.23–2.26, P=0.001) were independently associated with VTE.
Patients at high risk for VTE should be routinely assessed for thrombocytosis (≥250×109/L) and SIRS; if either is present, consideration for empiric anticoagulation should be given while diagnostic imaging is undertaken.
PMCID: PMC4298346  PMID: 25609994
SIRS; thrombocytosis; VTE; platelet count
8.  A review of the pharmacoeconomics of eletriptan for the acute treatment of migraine 
Migraine is a commonly occurring, chronic disorder that can cause significant disability. Eletriptan, a selective serotonin 5-hydroxytryptamine 1 receptor subtype B/D (5-HT1B/1D) agonist, is a clinically effective treatment for moderate to severe migraine. The objective of this literature review was to summarize the available data on the pharmacoeconomics of eletriptan relative to other triptans. Articles meeting the following three criteria were included in the review: 1) contained pharmacoeconomic data on a marketed dose of eletriptan; 2) included data on at least one other comparator triptan; and 3) was in English. A MEDLINE® search yielded a total of eight studies (from the European Union [n=5] and from the USA [n=3]) across multiple regions. Seven of the studies examined the pharmacoeconomics of eletriptan relative to other triptans, and a further study examined the health care costs of eletriptan 40 mg versus sumatriptan 100 mg. Eletriptan 40 mg was among a group of triptans, including rizatriptan 10 mg and almotriptan 12.5 mg, demonstrating the greatest cost-effectiveness. This result held across different definitions of efficacy (2 hours pain-free, sustained pain-free, and sustained pain-free with no adverse events) and also held when cost-effectiveness models accounted for second doses and use of rescue medication, management of adverse events, and productivity loss, in addition to drug acquisition costs. Only limited head-to-head comparator data were available. The majority of pharmacoeconomic studies utilized the same set of efficacy and/or tolerability data, and indirect costs were rarely included despite the fact that the majority of per capita migraine costs are attributable to indirect costs. In summary, although the market is now dominated by generics, eletriptan 40 mg is among the most clinically and cost-effective oral triptans available for the management of acute migraine. Increased effectiveness/efficacy of eletriptan may necessitate a lesser need for other migraine treatments and/or switching to other triptans.
PMCID: PMC4296958  PMID: 25624770
oral triptans; cost-effectiveness; literature search
9.  Clinical determinants of Lyme borreliosis, babesiosis, bartonellosis, anaplasmosis, and ehrlichiosis in an Australian cohort 
Borrelia burgdorferi is the causative agent of Lyme borreliosis. This spirochete, along with Babesia, Bartonella, Anaplasma, Ehrlichia, and the Rickettsia spp. are recognized tick-borne pathogens. In this study, the clinical manifestation of these zoonoses in Australia is described.
The clinical presentation of 500 patients over the course of 5 years was examined. Evidence of multisystem disease and cranial nerve neuropathy was sought. Supportive laboratory evidence of infection was examined.
Patients from every state of Australia presented with a wide range of symptoms of disease covering multiple systems and a large range of time intervals from onset. Among these patients, 296 (59%) were considered to have a clinical diagnosis of Lyme borreliosis and 273 (54% of the 500) tested positive for the disease, the latter not being a subset of the former. In total, 450 (90%) had either clinical evidence for or laboratory proof of borrelial infection, and the great majority of cases featured neurological symptoms involving the cranial nerves, thus mimicking features of the disease found in Europe and Asia, as distinct from North America (where extracutaneous disease is principally an oligoarticular arthritis). Only 83 patients (17%; number [n]=492) reported never leaving Australia. Of the 500 patients, 317 (63%) had clinical or laboratory-supported evidence of coinfection with Babesia or Bartonella spp. Infection with A. phagocytophilum was detected in three individuals, and Ehrlichia chaffeensis was detected in one individual who had never traveled outside Australia. In the cohort, 30 (11%; n=279) had positive rickettsial serology.
The study suggests that there is a considerable presence of borreliosis in Australia, and a highly significant burden of coinfections accompanying borreliosis transmission. The concept sometimes advanced of a “Lyme-like illness” on the continent needs to be re-examined as the clinical interplay between all these infections. Evidence is presented for the first report of endemic anaplasmosis and ehrlichiosis on the continent.
PMCID: PMC4278782  PMID: 25565883
Borrelia; Lyme disease; Babesia; Bartonella; Australia; humans
10.  Lyme borreliosis: a review of data on transmission time after tick attachment 
Lyme borreliosis is increasing rapidly in many parts of the world and is the most commonly occurring vector-borne disease in Europe and the USA. The disease is transmitted by ticks of the genus Ixodes. They require a blood meal at each stage of their life cycle and feed on a wide variety of wild and domestic animals as well as birds and reptiles. Transmission to humans is incidental and can occur during visits to a vector habitat, when host mammals and their associated ticks migrate into the urban environment, or when companion animals bring ticks into areas of human habitation. It is frequently stated that the risk of infection is very low if the tick is removed within 24–48 hours, with some claims that there is no risk if an attached tick is removed within 24 hours or 48 hours. A literature review has determined that in animal models, transmission can occur in <16 hours, and the minimum attachment time for transmission of infection has never been established. Mechanisms for early transmission of spirochetes have been proposed based on their presence in different organs of the tick. Studies have found systemic infection and the presence of spirochetes in the tick salivary glands prior to feeding, which could result in cases of rapid transmission. Also, there is evidence that spirochete transmission times and virulence depend upon the tick and Borrelia species. These factors support anecdotal evidence that Borrelia infection can occur in humans within a short time after tick attachment.
PMCID: PMC4278789  PMID: 25565881
Borrelia burgdorferi sensu lato; disease transmission; tick-borne disease; Lyme disease; tick attachment
11.  Treatment of localized neuropathic pain of different etiologies with the 5% lidocaine medicated plaster – a case series 
To assess the efficacy and safety of the topical 5% lidocaine medicated plaster in the treatment of localized neuropathic pain.
Study design
This was a case series at an Austrian pain clinic, using retrospective analysis.
Patients and methods
Data of 27 patients treated for localized neuropathic pain with the 5% lidocaine medicated plaster were retrospectively analyzed. Assessment included changes in overall pain intensity, in intensity of different pain qualities, and of hyperalgesia and allodynia, and changes in sleep quality.
Patients (17 female, ten male; mean age 53.4±11.4 years) presented mainly with dorsalgia (16 patients) or postoperative/posttraumatic pain (seven patients); one patient suffered from both. The mean overall pain intensity prior to treatment with lidocaine medicated plaster was 8.4±1.2 on the 11-point Likert scale. In the majority of cases, the lidocaine plaster was applied concomitantly with preexisting pain medication (81.5% of the patients). During the 6-month observation period, overall mean pain intensity was reduced by almost 5 points (4.98) to 3.5±2.6. Substantial reductions were also observed for neuralgiform pain (5 points from 7.9±2.6 at baseline) and burning pain (3 points from 5.2±4.1). Sleep quality improved from 4.6±2.6 at baseline to 5.5±1.8. Stratification by pain diagnosis showed marked improvements in overall pain intensity for patients with dorsalgia or postoperative/posttraumatic pain. The lidocaine plaster was well tolerated.
Overall, topical treatment with the 5% lidocaine medicated plaster was associated with effective pain relief and was well tolerated.
PMCID: PMC4278790  PMID: 25565882
localized neuropathic pain; dorsalgia; postoperative/posttraumatic pain; topical analgesic; 5% lidocaine medicated plaster
12.  The spectral analysis of photoplethysmography to evaluate an independent cardiovascular risk factor 
In this study, we evaluate homeostatic markers correlated to autonomic nervous and endothelial functions in a population of coronary artery disease (CAD) patients versus a control group. Since CAD is the highest risk marker for sudden cardiac death, the study objective is to determine whether an independent cardiovascular risk score based on these markers can be used alongside known conventional cardiovascular risk markers to strengthen the understanding of a patient’s vascular state.
Materials and methods
Sixty-five subjects (13 women) with a mean age of 62.9 years (range 40–80 years) who were diagnosed with CAD using coronary angiography (group 1) and seventy-two subjects (29 women) with a mean age of 45.1 years (range 18–85 years) who claimed they were healthy (group 2) were included in the study. These subjects underwent examination with the TM-Oxi and SudoPath systems at IPC Heart Care Centers in Mumbai, India. The TM-Oxi system takes measurements from a blood pressure device and a pulse oximeter. The SudoPath measures galvanic skin response to assess the sudomotor pathway function. Spectral analysis of the photoplethysmograph (PTG) waveform and electrochemical galvanic skin response allow the TM-Oxi and SudoPath systems to calculate several homeostatic markers, such as the PTG index (PTGi), PTG very low frequency index (PTGVLFi), and PTG ratio (PTGr). The focus of this study was to evaluate these markers (PTGi, PTGVLFi, and PTGr) in CAD patients against a control group, and to calculate an independent cardiovascular risk factor score: the PTG cardiovascular disease risk score (PTG CVD), calculated solely from these markers. We compared PTGi, PTGVLFi, PTGr, and PTG CVD scores between the CAD patient group and the healthy control group. Statistical analyses were performed using receiver operating characteristic curves to determine the specificity and sensitivity of the markers to detect CAD at optimal cutoff values for PTGi, PTGVLFi, PTGr, and PTG CVD. In addition, correlation analyses between these markers and conventional autonomic nervous system and endothelial function markers were performed to understand the possible underlying physiological sources of the differences observed in marker values between CAD patients and healthy control patients. Additionally, t-tests were performed between two subgroups of the CAD patient group to determine whether diabetic or coronary artery bypass grafting (CABG) patients have significantly different PTGi marker values.
Each spectral analysis PTG marker yielded a high specificity and sensitivity to detect CAD. Most notably, the PTG CVD score had a sensitivity of 82.5% and specificity of 96.8%, at a cutoff of 2, when used to detect CAD (P=0.0001; area under the receiver operating characteristic curve =0.967). The PTG spectral analysis markers were well-correlated to other autonomic nervous system and endothelial function markers. CAD diabetic patients (n=27) had a lower PTGi value compared with the CAD non-diabetic patients (n=38): and patients that underwent CABG (n=18) had a higher PTGi value compared with the CAD without CABG surgery patients (n=47).
The spectral analysis of the photoplethysmography method is noninvasive, fast, operator-independent, and cost-effective, as only an oximeter and galvanic skin response device are required in order to assess in a single testing the autonomic nervous system and endothelial function. The spectral analysis techniques used on the photoplethysmogram, as outlined in this study, could be useful when used alongside conventional known cardiovascular disease risk markers.
PMCID: PMC4267520  PMID: 25525382
coronary artery disease; PTG spectral analysis; PTGi; PTGVLFi; PTGr; PTG CVD score
13.  Antihypertensive combination therapy in primary care offices: results of a cross-sectional survey in Switzerland 
Most hypertensive patients need more than one substance to reach their target blood pressure (BP). Several clinical studies indicate the high efficacy of antihypertensive combinations, and recent guidelines recommend them in some situations even as initial therapies. In general practice they seem widespread, but only limited data are available on their effectiveness under the conditions of everyday life. The objectives of this survey among Swiss primary care physicians treating hypertensive patients were: to know the frequency of application of different treatment modalities (monotherapies, free individual combinations, single-pill combinations); to see whether there are relationships between prescribed treatment modalities and patient characteristics, especially age, treatment duration, and comorbidities; and to determine the response rate (percentage of patients reaching target BP) of different treatment modalities under the conditions of daily practice.
This cross-sectional, observational survey among 228 randomly chosen Swiss primary care physicians analyzed data for 3,888 consecutive hypertensive patients collected at one single consultation.
In this survey, 31.9% of patients received monotherapy, 41.2% two substances, 20.9% three substances, and 4.7% more than three substances. By combination mode, 34.9% took free individual combinations and 30.0% took fixed-dose single-pill combinations. Combinations were more frequently given to older patients with a long history of hypertension and/or comorbidities. In total, 67.8% of patients achieved their BP target according to their physician’s judgment. When compared, single-pill combinations were associated with a higher percentage of patients achieving target BP than free individual combinations and monotherapies for the total sample and for patients with comorbidity.
Antihypertensive combination therapy was widely used in Swiss primary care practices. The number of prescribed substances depended on age, treatment duration, and type and number of comorbidities. Although the response rate was generally modest under the conditions of daily practice, it was higher for single-pill combinations than for monotherapies and free individual combinations. Further studies are needed to confirm these observations.
PMCID: PMC4267521  PMID: 25525383
hypertension; combination therapy; comorbidity; single-pill combination; fixed-dose combination
14.  Effects and tolerability of betahistine in patients with vestibular vertigo: results from the Romanian contingent of the OSVaLD study 
Background and methods
An efficacy population of 245 patients with vertigo of peripheral vestibular origin was recruited in Romania as part of a 3-month multinational, post-marketing surveillance study of open-label betahistine 48 mg/day (OSVaLD). Endpoints were changes in the Dizziness Handicap Index (primary endpoint), Medical Outcome Study Short-Form 36 (SF-36v2®), and the Hospital Anxiety and Depression Scale.
During treatment, the total Dizziness Handicap Index score improved by 41 points (on a 100-point scale). Statistically significant improvements of 12–14 points were recorded in all three domains of the Dizziness Handicap Index scale (P<0.0001). Betahistine therapy was also accompanied by progressive improvements in mean Hospital Anxiety and Depression anxiety and depression scores (P<0.0001) and significant improvements in both the physical and mental component summary of the SF-36v2 (P<0.0001). Betahistine was well tolerated, with only one suspected adverse drug reaction recorded in the Romanian safety population (n=259).
Betahistine 48 mg/day was associated with improvements in multiple measures of health-related quality of life and had a good tolerability profile in these Romanian patients with recurrent peripheral vestibular vertigo.
PMCID: PMC4260659  PMID: 25506241
betahistine; vertigo; dizziness; anxiety; depression; Romania
15.  Effect of acetylsalicylic acid on thalassemia with pulmonary arterial hypertension 
To compare pulmonary artery systolic pressure (PASP) between thalassemic patients with pulmonary arterial hypertension (PAH) for whom acetylsalicylic acid (ASA) was and was not prescribed after 1 year.
A retrospective cohort study was conducted at the hematological outpatient clinic at Chiang Rai Hospital, Chiang Rai, Thailand. All new cases of thalassemia with PAH from January 2007 to January 2012 were studied at the first month and at 12 months. The patients were classified into two groups. In one group, ASA 81 mg daily was prescribed for 1 year, whereas in another group no ASA was prescribed, due to its contraindications, which included bleeding, gastrointestinal side effects, and thrombocytopenia. PASP, estimated by a Doppler echocardiography, was measured by the same cardiologist. Propensity score adjustment was used to control confounding variables by indication and contraindication. Multivariable regression analysis was used to evaluate the effects of ASA.
Of the 63 thalassemia patients with PAH, there were 47 (74.6%) in the ASA group and 16 (25.4%) in the no ASA group. ASA, as compared with no ASA, did not significantly reduce PASP (adjusted difference −0.95; 95% confidence interval −16.99 to 15.10; P=0.906).
Low-dose ASA may not have a beneficial effect on PASP after 1 year of treatment of PAH in thalassemia.
PMCID: PMC4259867  PMID: 25506240
thalassemia; pulmonary arterial hypertension; acetylsalicylic acid
16.  Analysis of the presence or absence of atrophy of the subgenual and subcallosal cingulate cortices using voxel-based morphometry on MRI is useful to select prescriptions for patients with depressive symptoms 
We objectively evaluated the presence or absence of atrophy of the subgenual anterior cingulate cortex (sgACC) and the subcallosal anterior cingulate cortex (scACC), using new voxel-based morphometry (VBM) software employing Statistical Parametric Mapping software v8 and diffeomorphic anatomic registration through an exponentiated lie algebra. We prepared a database covering young-mature adulthood and investigated the clinical usefulness of the evaluation.
Subjects and methods
One hundred seven patients with major depressive disorder (MDD), 74 patients with bipolar disorder (BD), and 240 healthy control subjects underwent 1.5T magnetic resonance imaging scanning. Using new VBM software and databases covering young-mature adults and the elderly, target volumes of interest were set in the sgACC and scACC, four indicators (severity, extent, ratio, and whole-brain extent) were determined, and the presence or absence of atrophy of the sgACC and scACC was evaluated on the basis of the indicators. In addition, the relationships between the presence or absence of atrophy of the sgACC and scACC and performance of diagnosing MDD and BD and therapeutic drugs were investigated.
It was clarified that the disease is likely to be MDD when atrophy is detected in the sgACC, and likely to be BD when no atrophy is detected in the sgACC but is detected in the scACC. Regarding the relationship with therapeutic drugs, it was clarified that, when atrophy is detected in both the sgACC and the scACC, concomitant administration of mood stabilizers and atypical antipsychotics acting as dopamine-system stabilizers is necessary in many cases.
VBM on magnetic resonance imaging enabled automatic analysis of atrophy in the sgACC and scACC, and findings obtained by this procedure are useful not only for differentiation of MDD and BD patients but also for selection of prescriptions.
PMCID: PMC4259869  PMID: 25506239
major depressive disorder; bipolar disorder; MRI; subgenual anterior cingulate cortex; subcallosal anterior cingulate cortex; voxel-based morphometry
17.  The relationships among sleep efficiency, pulmonary functions, and quality of life in patients with asthma 
Sleep disturbance is commonly observed in patients with asthma, especially in those with poorly controlled asthma. Evaluating sleep quality to achieve good control of asthma is important since nocturnal asthmatic symptoms such as cough, wheezing, and chest tightness may disturb sleep. Actigraphy is an objective, ambulatory monitoring method for tracking a patient’s sleep and wake activities and for assessing sleep quality, as reflected by total sleep time, sleep efficiency, duration of awakening after sleep onset (WASO), and sleep onset latency.
Patients and methods
Fifty patients with asthma were enrolled in this study. Sleep quality was assessed employing wristwatch-type actigraphy (Actiwatch 2). The level of asthma control was assessed by the Asthma Control Questionnaire (ACQ), and asthma-related quality of life was assessed by the Asthma Quality of Life Questionnaire (AQLQ). The parameters for sleep quality were compared using ACQ scores, AQLQ scores, and pulmonary function test results.
The total sleep time was 387.2 minutes, WASO was 55.8 minutes, sleep efficiency was 87.01%, sleep onset latency was 8.17 minutes, and the average ACQ was 0.36. Neither sleep efficiency nor WASO correlated with respiratory functions, ACQ scores, or AQLQ scores.
Sleep-related parameters assessed by actigraphy in well-controlled asthma do not correlate with pulmonary functions, the asthma control level, or daytime quality of life. Sleep quality should be evaluated independently when asthma is well-controlled.
PMCID: PMC4235511  PMID: 25419157
asthma control; respiratory function; sleep efficiency; actigraphy
18.  External nasal dilators: definition, background, and current uses 
Our goal was to revise the literature about external nasal dilators (ENDs) as to their definition, history, and current uses. We reviewed journals in the PubMed and MEDLINE databases. The current uses hereby presented and discussed are physical exercise, nasal congestion and sleep, snoring, pregnancy, cancer, and healthy individuals. Numerous studies have shown that ENDs increase the cross-sectional area of the nasal valve, reducing nasal resistance and transnasal inspiratory pressure and stabilizing the lateral nasal vestibule, avoiding its collapse during final inspiration. These effects also facilitate breathing and are beneficial to patients with nasal obstruction. Furthermore, END use is simple, noninvasive, painless, affordable, and bears minimum risk to the user. Most studies have limited sample size and are mainly focused on physical exercise. In conclusion, ENDs seem useful, so further studies involving potential effects on the performance of physical tests and improvements in sleep quality are necessary, especially in children and teenagers.
PMCID: PMC4234285  PMID: 25419156
external nasal dilator; nasal valve; nasal congestion; nasal resistance
19.  Some mechanisms of the protective effect of ischemic preconditioning on rat liver ischemia-reperfusion injury 
Ischemia-reperfusion (I/R) injury is a multifactorial process that affects graft function after liver transplantation. An understanding of the mechanisms involved in I/R injury is essential for the design of therapeutic strategies to improve the outcome of liver transplantation. The generation of reactive oxygen species subsequent to reoxygenation inflicts tissue damage and initiates a cascade of deleterious cellular responses, leading to inflammation, cell death, and ultimate organ failure. Increasing experimental evidence has suggested that Kupffer cells and T-cells mediate activation of neutrophil inflammatory responses. Activated neutrophils infiltrate the injured liver in parallel with increased expression of adhesion molecules on endothelial cells. The heme oxygenase system is among the most critical of the cytoprotective mechanisms activated during cellular stress, exerting antioxidant and anti-inflammatory functions, modulating the cell cycle, and maintaining the microcirculation. Finally, the activation of toll-like receptors on Kupffer cells may play a fundamental role in exploring new therapeutic strategies based on the concept that hepatic I/R injury represents a case for host “innate” immunity. In the present study, there was a significant decrease in hepatic activity of glycogen in the I/R group as compared with corresponding values in the control group. On the other hand, there was a significant increase in the hepatic activity of glycogen in the I/R-IP (ischemic preconditioning) group as compared with corresponding values in the I/R group.
PMCID: PMC4222984  PMID: 25382983
liver; ischemic preconditioning; reperfusion injury; oxidative stress; nitric oxide; caspase; glycogen
20.  Does the use of Nintendo Wii Sports™ improve arm function and is it acceptable to patients after stroke? Publication of the Protocol of the Trial of Wii™ in Stroke – TWIST 
Many stroke patients experience loss of arm function requiring rehabilitation, which is expensive, repetitive, and does not always translate into “real life.” Nintendo Wii Sports™ (Wii™) may offer task-specific training that is repetitive and motivating. The Trial of Wii™ in Stroke (TWIST) is designed to investigate feasibility, efficacy, and acceptability using Wii™ to improve affected arm function for patients after stroke.
This is a randomized controlled trial (RCT), incorporating a qualitative study and health economics analysis that compares playing Wii™ versus arm exercises in patients receiving standard rehabilitation in a home setting within 6 months of stroke with a motor deficit of less than 5 on the MRC (Medical Research Council) scale (arm). In this study, we expect to randomize 240 participants.
Outcome measures
Primary outcome is change in affected arm function at 6 weeks follow-up in intervention and control group using the Action Research Arm Test. Secondary outcomes include occupational performance using the Canadian Occupational Performance Measure, quality of life using the Stroke Impact Scale, cost effectiveness analysis, and a qualitative study investigating factors that influence use of Wii™ for patients and carers.
TWIST is the first UK RCT assessing the feasibility, cost effectiveness, and acceptability of Wii™ in stroke rehabilitation. The trial has been registered with ISRCTN 06807619 and UK CRN 11030. Results of the study will be published after completion of study in August 2014.
PMCID: PMC4199966  PMID: 25336985
virtual reality; rehabilitation
21.  Omega-3 fatty acid supplementation and cognitive function: are smaller dosages more beneficial? 
As longevity increases, so does the global prevalence of cognitive dysfunction. Numerous lifestyle and/or dietary interventions such as omega-3 fatty acids have been suggested to improve memory. Therefore, this study examined the consistency and strength of the impact of supplementation of omega-3 fatty acids on overall cognitive function using systematic reviews and meta-analytic methods. Of 905 studies retrieved from all searches, 12 randomized controlled trials were included in the meta-analysis. There were differences between studies reporting outcomes for single memory function parameters. Subgroup analysis of doses used (low versus high) indicated that subjects receiving low (<1.73 g/day) doses of omega-3 fatty acids had a significant reduction in cognitive decline rate (−0.07, 95% confidence interval −0.01, −0.02) but there was no evidence for beneficial effects at higher doses (+0.04, 95% confidence interval −0.06, +0.14) compared with the placebo group. This study suggests that omega-3 fatty acids may be beneficial in preventing memory decline at lower doses.
PMCID: PMC4179753  PMID: 25278774
cognitive impairment; Alzheimer’s disease; dietary fatty acids; omega-3; docosahexaenoic acid
22.  Endoscopic alterations in a cohort of hemodialysis patients: a cross-sectional study 
Although the association between chronic kidney disease and dyspepsia is widely known, it remains poorly investigated. Among the types of gastric inflammation that lead to symptoms, erosive antral gastritis is the most common form. A direct correlation between the urea serum levels and the time in hemodialysis with the onset of gastric metaplasia and dyspepsia can be observed. The aim of this study was to report the endoscopic alterations found in hemodialysis patients.
This is a cross-sectional study based on the medical records of 95 patients older than 18 years who were diagnosed with chronic kidney disease. The results of endoscopies performed up to 6 months before the beginning of the study were included.
Among the 95 studied patients, 56.84% were male, 60% were Caucasian, and 71.57% used proton pump inhibitors. The endoscopic alteration most frequently observed was erosive gastritis (77% of the cases); however, the frequency of the alteration that caused the symptoms was irrelevant. The antrum was the most common site of involvement (55.79%).
Patients with chronic kidney disease often show dyspeptic symptoms. Other abnormalities are common but are not correlated with such symptoms. In conclusion, this study identified the endoscopic alterations that are most often observed in hemodialysis patients; erosive and enanthematous gastritis were the most common forms observed.
PMCID: PMC4172199  PMID: 25258556
hemodialysis; chronic kidney disease; dyspepsia
23.  The current status of opioid maintenance treatment in France: a survey of physicians, patients, and out-of-treatment opioid users 
Project Access France was a national survey designed to provide real-world observations on the status of opioid dependence treatment in France.
The views of physicians (n=100), patients (n=130), and out-of-treatment opioid users (n=33) were collected via interviews and questionnaires.
Physicians reported being moderately satisfied with treatment programs in their area (rating 6.9 out of 10). Most physicians (82%) reported being concerned about misuse and diversion of medication-assisted treatment (MAT) medications and 50% identified psychosocial/behavioral counseling as the key change that would most improve patient care. Among patients, the mean number of previous MAT episodes was low (1.5); 78% reported that it was easy to access a doctor to undergo MAT; 14% reported regularly or sometimes using heroin; misuse and diversion were reported in 15% and 39% of patients, respectively; and 57% of patients were not receiving psychosocial help. Out-of-treatment opioid users reported using drugs on a regular basis (42% regularly used heroin) and cited ‘not wanting to give up drugs completely’ as the most frequent reason for staying out of MAT.
This survey highlights a number of positive features of the open-access, GP-based treatment model for opioid dependence in France. Challenges remain with regard to continued misuse/diversion of MAT medications and limited patient access to psychosocial support.
PMCID: PMC4164042  PMID: 25228817
opioid maintenance treatment; medication-assisted treatment; buprenorphine; methadone; buprenorphine–naloxone; France
24.  Burden of disease from atrial fibrillation in adults from seven countries in Latin America 
While some international studies have published epidemiologic overviews of atrial fibrillation (AF) for the Latin America region, detailed data at the national level are lacking. The aim of this study was to estimate the burden of disease and morbidity associated with AF in adults over 40 years of age in Argentina, Brazil, Chile, Colombia, Mexico, Peru, and Venezuela.
National health care system databases for each country in the analysis were used to identify cases of AF during 2010 based on ICD-10 codes. Patient comorbidities and treatment patterns in each country were assessed based on available data and extrapolation from relevant published information where local data were incomplete or unavailable. The prevalence of AF in each country was estimated using country-specific, national census data, and assumptions based on a review of the available literature.
Patients in outpatient or hospital care represented over half of the estimated total cases of AF, of whom around 60% were treated as outpatients. Across the seven countries analyzed, 74.5% of AF cases were adults ≥60 years old. However, with increasing age, the proportion of individuals with AF receiving treatment within the national health care systems decreased overall across all seven countries. The most commonly reported comorbidities associated with AF included arterial hypertension (51%–57%), heart failure (14.5%–30%), diabetes (12%–36.5%), and stroke (3%–12.7%).
This epidemiologic survey quantifies the scale of the challenge posed by AF to the various national health care systems in Latin America. Overall, ambulatory patients in the national health care systems carry a high risk of developing a stroke, yet a significant proportion of these patients do not receive appropriate anticoagulant therapy.
PMCID: PMC4159313  PMID: 25214802
Latin America; stroke; atrial fibrillation; burden of disease; epidemiology; anticoagulation
25.  Prevention and treatment of venous thromboembolism during HRT: current perspectives 
Many large trials in the past 15 years have proven an increased risk of vascular complications in women using oral, mostly non-bioidentical, hormone therapy. The risk of vascular complications depends on the route of administration (oral versus transdermal), age, duration of administration, and type of hormones (bioidentical versus non-bioidentical). Acquired and/or hereditary thrombophilias (eg, factor V Leiden, prothrombin mutation G20210A, and others) lead to a further increase of risk for venous thromboembolism, stroke, or myocardial infarction. Therefore, bioidentical hormone therapy via the transdermal route seems to be the safest opportunity for hormone replacement therapy, although large trials for bioidentical hormone therapy are needed.
PMCID: PMC4155999  PMID: 25210472
hormone replacement therapy; stroke; myocardial infarction; thrombophilia; bioidentical hormone therapy

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