European Journal of Internal Medicine - Articles in Press

Plasma metalloproteinase-9 and restrictive filling pattern as major predictors of outcome in patients with ischemic cardiomyopathy - Corrected Proof

2012-05-18

Abstract: Objective: Assessment of plasma matrix metalloproteinase-9 (MMP-9) and Doppler markers of increased left ventricular (LV) filling pressure may be added to risk stratify patients with ischemic cardiomyopathy (IC). Therefore, we aimed at investigating the value of plasma MMP-9 and restrictive filling pattern (RFP) in IC patients.Methods: Eighty-eight consecutive patients hospitalized for heart failure (LV ejection fraction≤40%) due to IC were enrolled. A complete M-mode and two-dimensional echo-Doppler examination were performed. Patients were defined as having RFP if they had a mitral E wave deceleration time<150ms. Plasma MMP-9 and N-terminal protype-B natriuretic peptide levels were assessed at the time of the index echocardiogram. The end point was all-cause mortality or hospitalization for worsening HF. Follow-up period was 25±17months.Results: Median value of MMP-9 was 714ng/ml. On univariate analysis, a number of measurements predicted the composite end point: NYHA class>2, RFP, MMP-9>60.5ng/ml, LV ejection fraction<27%, anemia, pulmonary pressure≥35mmHg, N-terminal protype-B natriuretic peptide>1742pg/ml, and glomerular filtration rate<60ml/min/1.73m2. Independent variables of outcome were anemia (HR=1.9, p=0.031), and the combination of plasma MMP-9 and RFP (HR=3.2, p=0.004). On Kaplan–Meier survival curves, patients with elevated MMP-9 levels and RFP had the lowest event-free survival rate (log-rank: 29.0, p<0.0001). The net reclassification improvement showed a significant increase in the prediction model when elevated MMP-9 and RFP were added to the base model that included clinical, biochemical and echocardiographic parameters (p<0.0001).Conclusion: MMP-9 levels and RFP have an incremental predictive value to risk classify IC patients.

Ischemia-modified albumin in patients with hyperthyroidism and hypothyroidism - Corrected Proof

Shao-gang Ma, Liu-xue Yang, Feng Bai, Wei Xu, Bing Hong — 2012-05-17

Abstract: Background: The relationship between ischemia-modified albumin (IMA) and thyroid dysfunction remains uncertain. This study aimed to investigate the influence of overt hypothyroidism (Oho), overt hyperthyroidism (Ohe), and their treatments on serum IMA levels.Methods: A total of 35 untreated patients with Ohe, 35 untreated patients with Oho, and 35 control subjects were enrolled in the study. C-reactive protein (CRP), homocysteine (Hcy), IMA, and lipid profiles were measured and evaluated before and after treatment.Results: CRP, Hcy, and IMA levels and lipid profiles were higher in patients with Oho than in euthyroid or Ohe subjects (p<0.05). Basal IMA levels were reduced after treatments in all patients (p<0.05). In Ohe patients, serum IMA levels were positively correlated with free triiodothyronine (r=0.424, p=0.011) and free thyroxine (r=0.567, p<0.001) levels. In Oho patients, serum IMA levels were inversely correlated with free triiodothyronine (r=−0.555, p=0.001) and free thyroxine (r=−0.457, p=0.006) but positively correlated with anti-thyroid peroxidase antibody, C-reactive protein, and homocysteine levels (p<0.05). Linear regression analyses showed that free triiodothyronine was the most important factor affecting serum IMA levels in Ohe (β=0.694, p=0.019) and in Oho (β=−0.512, p=0.025).Conclusions: IMA levels are increased in patients with thyroid dysfunction, particularly in overt hypothyroidism. Thyroid dysfunction has a significant impact on the oxidative stress status.

Resistant hypertension in visceral obesity - Corrected Proof

Michał Holecki, Jan Duława, Jerzy Chudek — 2012-05-17

Abstract: Background: Visceral obesity increases the risk of arterial hypertension (78% of cases of hypertension in men and 65% of cases in women). The aim of the study is to assess the role of visceral obesity in causing resistant hypertension (RH).Methods: The survey was performed on 5065 hypertensive patients with visceral obesity. BP control was analyzed on the basis of office and home BP measurements. Patients reporting non-compliance were excluded from the study.Results: The percentage of RH after excluding undertreated patients (receiving less than 3 drugs or on at least 3-drug regimen without diuretic and without reaching target BP goal) was 13.9%. RH was more frequent only in obese with BMI≥35 and <40kg/m2 (16.2%) and in morbidly obese individuals (26.5%). Patients with BMI≥35 and <40kg/m2 and with morbid obesity were receiving three-drug therapy more frequently than patients with visceral obesity and BMI<30kg/m2. A multiple regression analysis revealed that obesity was associated with RH independent from longer than 5-year period of antihypertensive therapy, diabetes, smoking cigarettes, cardiovascular disease and heart failure. The analysis of home BP measurement revealed that in 11.1% of patients RH was in fact “white coat” hypertension.Conclusions: Undertreatment, underuse of diuretics in multidrug regimens, and the “white-coat” effect are the most common reasons for over-diagnosing resistant hypertension in patients with visceral obesity. Obesity is an independent risk factor for the occurrence of RH.

Kayser–Fleischer ring in Wilson's disease: A cohort study - Corrected Proof

M. Fenu, M. Liggi, E. Demelia, O. Sorbello, A. Civolani, L. Demelia — 2012-05-16

Abstract: Aims: To evaluate Wilson's disease (WD) features in Sardinian patients with Kayser–Fleischer (KF) ring and to evaluate correlations between modifications in KF and anti-copper therapy and systemic WD evolution.Patients and methods: Sixty-seven WD patients (35m/32 f; mean age 41years) were retrospectively studied. At diagnosis and during follow up comprehensive ophthalmologic and neurologic examinations, brain RMN and ECD SPECT, detailed objective laboratory studies and hepatic histological examination were performed on all patients for analysis. All patients were given anti-copper therapy with d-Penicillamine in mono-therapy or in combination with Zinc Salts.Results: At diagnosis, KF was observed in 27% of patients with equal distribution in all age groups. Significant correlations between KF at diagnosis, neuro-psychiatric manifestations and pathologic features in brain RMN and in brain ECD SPECT were found at diagnosis. During follow up, a decrease in, or regression of KF was seen in 14% of patients. Anti-copper therapy leads to KF regression and prevents the appearance of KF. No significant correlations were observed between KF regression and clinical neurological or neuro-imaging improvement nor between KF modifications and clinical hepatic improvement.Conclusions: Our study highlights the peculiar features of Sardinian WD patients: low representation of KF, its equal distribution in all age groups, significant correlation between KF at diagnosis and clinical neurological manifestations, pathologic brain RMN and brain ECD-SPECT are highlighted by our study. Anti-copper therapy induces KF regression and prevents its onset. Therefore, KF ring does appear to be a predictive factor in the neurological and hepatic evolution of WD.

Haptoglobin genotype and cardiovascular outcomes in diabetes mellitus — natural history of the disease and the effect of vitamin E treatment. Meta-analysis of the medical literature - Corrected Proof

Moshe Vardi, Shany Blum, Andrew P. Levy — 2012-05-16

Abstract: Background: Diabetes mellitus carries a high risk for vascular events. Diabetics with different haptoglobin (Hp) types may carry different risk profiles, and may respond differently to vitamin E treatment. We aim to summarize the evidence about cardiovascular risk in diabetic patients, according to their Hp type, and the effect of vitamin E treatment on these sub-groups.Methods: We searched MEDLINE and on-going trials' databases until February 2011; gray literature; reference lists of identified articles; and experts. Two investigators screened and selected studies that prospectively followed cardiovascular outcomes in diabetic patients with different Hp types (natural history analysis), and randomized controlled trials reporting the effect of vitamin E on cardiovascular outcomes in diabetics, in which Hp typing was performed (interventional analysis).Results: Five and three studies, comprising 1829 and 2110 patients, were eligible for the natural history and the interventional analyses, respectively. The percentage of diabetic patients experiencing non-fatal MI, stroke, or cardiovascular death was significantly higher in the Hp 2–2 population (odds ratio (OR) 2.03 (95% confidence interval (CI) 1.46 to 2.81)). In patients with Hp 2–2 genotype, the OR for a combined endpoint was 0.66 in favor of the vitamin E treated group (95% CI 0.48 to 0.9). This effect was not shown in other Hp types.Conclusion: Hp type 2–2 carries a high risk of cardiovascular events in diabetic patients. A pharmacogenomic approach towards treatment of diabetic patients with vitamin E may be warranted.

Acupuncture's benefits spring from a rational approach - Corrected Proof

Adrian White, Mike Cummings — 2012-05-14

Pandolfi champions a rational approach to modern clinical medicine in his piece entitled the ‘Autumn of Acupuncture’ . We dispute his argument that we should ignore evidence of acupuncture's efficacy because prescientific explanations for acupuncture are implausible.

Antiplatelet treatment in primary and secondary stroke prevention in women - Corrected Proof

2012-05-14

Abstract: Stroke is a leading cause of death worldwide and the first cause of disability in the Western world. Over the last 20years, antiplatelet agents have reduced overall stroke rates in primary and secondary prevention in men. However, this has not been the case for women.In this narrative review, the most widely used antiplatelet therapies for primary and secondary prevention in stroke, excluding cardioembolic stroke, will be outlined.First, the largest randomised controlled trials will be analysed as well as the enrolment percentages of women. Second, analyses on sex-interaction effects in each study will be examined. Moreover, the Authors will discuss the need to develop targeted antiplatelet therapies specifically for women.Based on current results, the most randomised clinical trials and meta-analyses on antiplatelet agents in cerebrovascular disease have not performed sub-analyses on sex-related differences and this is mainly because women were underrepresented. Despite this, antiplatelet agents are considered to be equally effective for both sexes in primary and secondary stroke prevention. Finally, aspirin is the most widely studied antiplatelet in women and has been shown to provide greater benefit for women as primary prevention of ischemic stroke without a significant increased risk in haemorrhage.

Effectiveness of varenicline for smoking cessation at 2 urban academic health centers - Corrected Proof

2012-05-07

Abstract: Background: Smoking is a major cause of morbidity in lower socioeconomic groups. In randomized trials, varenicline improves long term quit rates, but effectiveness in a clinic setting is unknown.Methods: We conducted a retrospective cohort study of adults who received a prescription for varenicline or nicotine replacement therapy (NRT) at two inner city health centers in 2008–9. Primary outcome was smoking status at 52weeks. Secondary outcomes included follow up visits, behavioral counseling, and side effects. Multivariable Poisson regression was used to compare quit rates with varenicline and NRT adjusted for covariates.Key results: A total of 371 patients received a prescription for varenicline (46%) or NRT (54%). The mean age was 43years, 58% were female, 44% white, 29% African American and 12% Hispanic. Mental illness, alcohol and drug abuse were common. Within one year, 247 (67%) had follow-up, and 26 (10.5%) maintained abstinence through week 52, 10.2% with varenicline and 10.8% with NRT (p=1.0). Loss to follow-up was 37% for varenicline, 31% for NRT (p=0.20). Including lost patients as smokers, the adjusted quit rates for varenicline and NRT were similar (6.5% vs. 7.6%, p=0.69). Only 69/371 (19%) received behavioral counseling. Counseled patients were more likely to maintain abstinence (13% vs. 7.8%, p=0.04). Side effects were more common with varenicline than NRT (6.5% vs. 2.5%, p=0.07).Conclusion: In an inner city clinic, abstinence rates were lower than those in clinical trials and did not differ between varenicline and NRT.

Mean platelet volume and β-thromboglobulin levels in familial mediterranean fever: Effect of colchicine use? - Corrected Proof

2012-05-07

Abstract: Background: Many studies have shown that subclinical inflammation persisted during remission period of Familial Mediterranean Fever (FMF) patients but long term effects of subclinical inflammation in these patients aren't clearly known. Besides, a few of the recent studies revealed that risk of atherosclerosis had increased in FMF patients. β-Thromboglobulin (β-TG) is considered as a sensitive marker of platelet activation. In this study Mean Platelet Volume (MPV) and β-TG levels were evaluated in FMF patients.Methods: Following the Local Ethics Committee's consent, 25 FMF patients were included in the study. Twenty eight age and sex matched healthy volunteers were recruited as a control group. Lipid profile, inflammatory parameters, hemogram, β-TG, MPV were assessed. Statistical analysis was performed with SPSS for Windows 16.00.Results: Group I consisted of 25 FMF cases (16 females, 9 males; mean age: 35.72±12.34years), Group II consisted of 28 cases (22 females, 6 males; mean age 31.78±10.31years). There was no statistically significant difference between the groups in terms of age and gender distribution, smoking status, total cholesterol, triglyceride, LDL and MPV (p>0.05). HDL levels were found to be statistically lower in Group I (p:0.04). Median β-TG levels was significantly higher in Group II than Group I (129.50 (range:372.00) ng/mL versus 104.00 (range:212.80) ng/mL respectively; p:0.03).Conclusion: In this study MPV and β-TG were evaluated for FMF cases and healthy controls, β-TG levels were found significantly lower among patients; we hypothesized that this difference may have resulted from the effect of colchicine use on platelet functions.

Anemia—prevalence and risk factors in pregnancy - Corrected Proof

Gabriela Bencaiova, Tilo Burkhardt, Christian Breymann — 2012-05-07

Abstract: Background: To assess the prevalence of decreased iron stores and anemia in pregnant women. To determine whether the risk factors: socio-demographic background, age, BMI, and parity are associated with abnormal hemoglobin concentrations and/or abnormal iron status.Methods: A longitudinal study was carried out at the Department of Obstetrics, University Hospital of Zurich to establish the risk factors and prevalence of the decreased iron stores and anemia in early pregnancy. In order to determine the hematological parameters and ferritin levels, venous blood samples of 470 singleton pregnancies between 16 and 20 pregnancy weeks were collected. According to hemoglobin and iron status, the patients were divided into four groups: patients with iron deficiency anemia, patients with decreased iron stores, patients with anemia for other reasons and normal patients. The determinants socio-demographic background, age, BMI and parity were explored using multiple logistic regression analysis.Results: The prevalence of decreased iron stores (ferritin<20μg/l) was observed in 31.8% of subjects (149/470) and anemia (Hb<110g/l) in 18.5% (87/470). The prevalence of iron deficiency anemia was higher among women coming from former Yugoslavia and developing countries (p=0.004 and p=0.012). In patients coming from developing countries, a significant increase of anemia for other reasons was observed (p=0.027) and in patients older than 30years, a significant increase of decreased iron stores (p=0.018).Conclusions: In our study population with low parity, the prevalence of abnormal hemoglobin and abnormal iron status was 50.2% (236/470), and socio-demographic background was the most important risk factor of anemia.

Doctor–patient relationship: A resource to improve respiratory diseases management - Corrected Proof

2012-05-03

Abstract: Background: Many respiratory diseases are chronic conditions that are strongly linked with the patient-physician relationship, disease perception and therapy adherence. The aim of the present study was to evaluate patient's viewpoint about the different aspects involved in their respiratory diseases.Methods: This is a prospective observational survey. 46 Italian medical centres were involved and equally distributed. The interviews were carried out and were performed by means of a questionnaire which consisted of 32 questions regarding lung disease, modality of access to medical facilities, therapy and level of medical assistance.Results: 1116 patients were enrolled and the most important respiratory symptoms referred were: dyspnoea (69%), chronic phlegm (28%), cough (13%). During programmed visits 98.3% and 98.8% of interviewed patients knew were aware of asthma and COPD respectively, percentage that dropped, during emergency accesses, to 1.7% and 1.1% knew to have asthma and COPD respectively. Primarily were prescribed 1.67 spirometry/patient/year while only the 2% of patients referred to have performed a blood gas analysis. The 18% of patients spontaneously discontinued the therapy, considering it too complex. The average time that patients identified as being used by the doctor to perform the visit was of 22 minutes, with an high mean medical assistance satisfaction score.Discussion: There has been little research examining what factors may influence patient acceptance and participation of chronic respiratory diseases. Our national survey demonstrated that a good patient-physician relationship represents one of the first points in the successful management of respiratory diseases.

Thrombotic biomarkers and left ventricle characteristics as short-term predictors of thrombotic events in patients hospitalized for acute decompensated heart failure - Corrected Proof

2012-05-01

Abstract: Background: Hospitalized acute decompensated heart failure (ADHF) patients have high risk of thromboembolic events (TE). The aim of this study is to determine the short-term prognostic value of TE for different thrombotic biomarkers (fibrinogen; D-dimer; tissue plasminogen activator antigen, t-PA; and plasminogen-activator inhibitor type 1 antigen, PAI-1) and left ventricle echocardiographic characteristics (diastolic diameter, LVDD; ejection fraction, LVEF) in admitted ADHF patients.Methods and results: We included 140 patients with ADHF in NYHA classes III–IV (October 2009 to November 2011). Subjects with anticoagulant drugs, arrhythmias, or thrombosis were excluded. Biochemical and echocardiographic data were obtained within 12h after admission and all patients were given enoxaparin 40mg/day. Throughout hospitalization (median, 11days), 14 subjects (10.0%) with ADHF received a TE diagnosis. Pulmonary embolism (PE, 5.0%), deep-vein thrombosis (DVT, 7.1%), or a combination of these were confirmed in 3, 6 and 4 patients respectively. Cardioembolic stroke was diagnosed in 1 subject (0.7%) associated with left ventricular intracavitary thrombus developed after admission. The following determinations most strongly predicted the short-term risk of TE: fibrinogen>500mg/dL (Odds Ratio [OR] 6.19; p=.0019), D-dimer>600ng/dL (OR 7.84; p=.0009), t-PA>10ng/dL (OR 7.22; p=.0007), PAI-1>30ng/dL (OR 8.70; p 50mm (OR 5.67; p=.0039), and LVEF<30% (OR 5.48; p=.0163).Conclusions: Elevated levels of fibrinogen, D-dimer, t-PA and PAI-1 antigens as well as a dilated left ventricle with poor systolic function determined at admission are associated with a significantly high short-term risk of TE.

Necrotizing pneumonia with Staphylococcus aureus carrying Panton–Valentine leukocidin genes: An underestimated gravity? - Corrected Proof

Xavier Roux, Bruno Soullié, Fabrice Camou, Christophe Rapp, Jean Louis Koeck — 2012-04-30

Panton–Valentine leukocidin (PVL) associated staphylococcal pneumonia is a distinct clinical entity affecting mainly healthy children and young adults, usually associated with a high mortality rate. Its physiopathology is quite well-known and its clinical specifications were recently described. The PVL-producing S. aureus causes rapidly progressive, haemorrhagic, necrotizing pneumonia. The PVL associated pneumonia is sometimes preceded by an influenza infection, which seems to be a risk factor of this pathology. The factors predicting mortality were studied among PVL associated staphylococcal pneumonia when the diagnosis was done . However, the initial severity can be underestimated with the usual evaluation tools used in emergency room, mainly due to the low age of patients.

Current practice of chronic hepatitis B treatment in Southern Italy - Corrected Proof

2012-04-26

Abstract: Background: Treatment choice for chronic HBV infection is a continuously evolving issue, with a wide range of options. We aimed to evaluate the current practice of HBV therapies in the real world in Southern Italy.Methods: A prospective study enrolling over a six month period (February–July 2010) all consecutive HBsAg positive subjects, never previously treated, referred to 16 liver units in two Southern Italy regions (Calabria and Sicily).Results: Out of 247 subjects evaluated, 116 (46.9%) had HBV-DNA undetectable or lower than 2000UI/ml. There were 108 (43.7%) inactive carriers, 103 (41.7%) chronic hepatitis, and 36 (14.6%) liver cirrhosis. Antiviral treatment was planned in 94 (38.0%) patients (26 cases with Interferon or Pegylated Interferon and 68 with nucleos(t)ides analogues). As many as 49.5% of subjects with chronic hepatitis did not receive antiviral treatment.Discussion: The majority of chronic HBsAg carrier referring centres for evaluation were not considered suitable for antiviral treatment. Nucleos(t)ides analogues are the preferred first choice for therapy. A long-lasting period of observation may be needed to make appropriate therapeutic decisions in several cases.

The association of Raynaud's syndrome with cisplatin-based chemotherapy — A meta-analysis - Corrected Proof

Melvin Mohokum, Peter Hartmann, Peter Schlattmann — 2012-04-23

Abstract: Background: Vasospastic disorders of the digital circulation such as the Raynaud's syndrome (RS) are known side-effects of treatment of cisplatin-based chemotherapy. The prevalence of RS in patients during treatment with cisplatin-based chemotherapy is not well-defined.Objective: The objective of this paper was to assess the prevalence of RS in patients receiving cisplatin-based chemotherapy — a meta-analysis of published data was performed.Material and methods: The PubMed database of the National Library of Medicine and ISI Web of Knowledge was used for studies dealing with RS and patients receiving cisplatin-based chemotherapy. The studies provided sufficient data to estimate the prevalence of RS in patients receiving cisplatin-based chemotherapy. A forest plot was determined by the revealed prevalences. Statistical analysis was based on methods for a random effects meta-analysis and a finite mixture model for proportions. Publication bias was investigated with the linear regression test (Egger's method). A meta-regression was conducted by the year of publication and latitude.Results: 24 eligible studies, contributing data on 2749 subjects, were included in this meta-analysis. For RS in patients receiving cisplatin-based chemotherapy a pooled prevalence of 24% and 95% CI (0.175, 0.313) was obtained. A mixture model analysis found four latent classes. Statistically, publication bias was not present (p-value 0.74). The meta-regression indicated that the odds ratio increased when the latitude increased, too (p-value 0.011).Conclusion: Despite some heterogeneity there is a possible indication of an association between RS and patients receiving cisplatin-based chemotherapy.

The coexistence of heart failure predicts short term mortality, but not disability, in patients with acute ischemic stroke treated with thrombolysis: The Florence area Registry - Corrected Proof

2012-04-20

Abstract: Background: Thrombolysis in ischemic stroke reduces disability but not mortality. Our aim was to evaluate the predictivity of heart failure (HF) diagnosis on 90-day mortality and disability in stroke patients undergoing thrombolysis.Material and methods: Hospital records of all consecutive stroke patients treated with thrombolysis at our University Hospital were reviewed. Clinical assessment for HF and echocardiogram were available for all patients according to the thrombolysis institutional protocol. History of HF, LVEF <40%, or BOSTON score ≥5 were tested as predictors.Results: Of 130 patients (age 66±14years, 64.6% males, baseline NIHSS 15.6±8.8), 17 (13.1%) had a history of HF, 16 (12.7%) a BOSTON score ≥5, 13 (10.9%) a LVEF <40% and 24 (19.0%) met clinical criteria for HF diagnosis. Ninety-day mortality and incidence of disability were 16.1% and 36.1%, respectively. After adjustment for age, sex, baseline stroke severity and pre-stroke disability, LVEF <40% and clinical diagnosis of HF were predictors of 90-day mortality, (p=0.007 and p=0.037, respectively).Conclusion: Clinical diagnosis of HF predicts mortality, but not disability, in acute stroke patients undergoing thrombolysis. Unlike anamnestic record of HF, clinical evaluation of cardiac function, with estimation of LVEF, predicts mortality.

Anaemia in the elderly: An aetiologic profile of a prospective cohort of 95 hospitalised patients - Corrected Proof

Inessa Petrosyan, Gilles Blaison, Emmanuel Andrès, Laure Federici — 2012-04-16

Abstract: Background and objectives: Anaemia is a significant problem in the elderly, and the cause of anaemia in approximately one third of the general population is unidentified. To date, only a few studies have focused on hospitalised patients.Patients and methods: We prospectively included anaemic patients (according to OMS criteria) aged 65years and older who were hospitalised in the internal medicine department. The typical clinical data were collected, and a standardised set of biological tests, including cupraemia was performed.Results: Of 360 total patients, 191 (53%) patients were anaemic; however, 96 patients were excluded because their data were incomplete. Of the remaining 95 patients that were included, 45 were men (47.4%) and 50 were women (52.6%); the mean patient age was 79.7years (66–101years). At least one cause of anaemia was diagnosed in 87 of the 95 (91.6%) patients, and anaemia was multifactorial in 44 of the 95 (46.3%) cases. The five most prominent causes of anaemia were inflammation (62.1%), iron deficiency (30.5%), folic acid deficiency (21%), chronic renal failure (17.9%) and cobalamin deficiency (11.6%). Microcytosis was present in only 27.5% of the patients who had an iron deficiency, and macrocytosis was present in only 7.4% of the patients who had a folic acid and/or cobalamin deficiency. The cause of anaemia could not be identified for 8 of the patients. The cupraemia was normal in all the patients.Conclusion: A predefined protocol for older hospitalised patients was ability to identify the aetiology of anaemia in 91.6% of the cases; strikingly, anaemia was frequently caused by more than one factor (43.5%). Diagnostic orientation based on the mean corpuscular volume does not appear to correlate with mean cellular volume profile. Finally, anaemia caused by an unknown aetiology is rare and copper deficiency was not documented in any case.

Pacing of the interventricular septum versus the right ventricular apex: A prospective, randomized study - Corrected Proof

2012-04-13

Abstract: Background: Left ventricular (LV) function may be impaired by right ventricular (RV) apical pacing. The interventricular septum is an alternative pacing site, but randomized data are limited. Our aim was to compare ejection fraction (EF) resulting from pacing the interventricular septum versus the RV apex.Methods: RV lead implantation was randomized to the apex or the mid-septum. LVEF and RVEF were determined at baseline and after 1 and 4years by radionuclide angiography.Results: We enrolled 59 patients, of whom 28 were randomized to the apical group and 31 to the septal group, with follow-up available in 47 patients at 1year and 33 patients at 4years. LVEF in the apical and in the septal groups was 55±8% vs. 46±15% (p=0.021) at 1year and 53±12% vs. 47±15% (p=0.20) at 4years. Echocardiography confirmed a mid-septal lead position in only 54% of patients in the septal group, with an anterior position in the remaining patients. In the septal group, LVEF decreased significantly in patients with an anterior RV lead (−10.0±7.7%, p=0.003 at 1year and −8.0±9.5%, p=0.035 at 4years), but not in patients who had a mid-septal lead. Left intraventricular dyssynchrony was significantly increased in case of an anterior RV lead. RVEF was not significantly impaired by RV pacing, regardless of RV lead position.Conclusions: Pacing at the RV septum confers no advantage in terms of ventricular function compared to the apex. Furthermore, inadvertent placement of the RV lead in an anterior position instead of the mid-septum results in reduced LV function.

Readmissions to medical wards: Analysis of demographic and socio-medical factors - Corrected Proof

Naiel Bisharat, Chovav Handler, Naama Schwartz — 2012-04-05

Abstract: Background: Unplanned readmissions affect occupancy rates in medical wards and these have been constantly increasing in Israel. We examined the frequency and risk factors affecting the likelihood of 30-day emergency medical readmissions.Methods: We compared the clinical, epidemiological, and socioeconomic characteristics of readmitted patients during 2009 to a control group matched by age, sex, and primary medical diagnosis.Results: Rate of unplanned readmissions within 30days was 12.2%. The mean time to readmission was 12.8days. The mean length of hospital stay at index admission was 4.4 and 3.8days for the study and control groups, respectively, and 4.99days in the second admission (study group only). By simple univariate logistic regression, living in a nursing home, chronic kidney disease, ischemic heart disease, previous cerebrovascular accident, number of chronic medications, length of hospital stay at index admission, and hospitalization in the previous year prior to index admission were significantly associated with risk of readmission. In multivariate logistic regression model, only living in a nursing home (OR=2.94, 95%CI=1.15–7.48), presence of chronic kidney disease (OR=1.62, 95%CI=1.06–2.46), length of index admission ≥3days (OR=1.53, 95%CI=1.07–2.2), and hospitalization in the previous year (OR=3.33, 95%CI=2.34–4.74) were found to be significantly associated with likelihood of readmission.Conclusion: Risk factors affecting 30-days readmission at our medical centre are similar to previous observations, and yet, some are perhaps unique to our region.

The effects of electrode misplacement on clinicians’ interpretation of the standard 12-lead electrocardiogram - Corrected Proof

R.R. Bond, D.D. Finlay, C.D. Nugent, C. Breen, D. Guldenring, M.J. Daly — 2012-04-05

Abstract: Introduction: This study investigates how a particular incorrect electrode configuration affects the 12-lead Electrocardiogram (ECG).Methods: A correct and an incorrect 12-lead ECG were extracted from a 192-lead BSPM. This was done for 232 BSPMs yielding 464 12-lead ECGs. The particular incorrect ECG involved displacing electrodes V1 and V2 in the second intercostal space whilst also offsetting the remaining electrodes. These ECGs were examined in two stages: (a) analysis of the effects of electrode misplacement on signal morphology and (b) analysis of how often the incorrect electrode configuration changed the diagnosis of two clinicians in a random sample of 75 patients.Results: According to the Root Mean Square Error (RMSE) of the difference between PQRST intervals in the correct and incorrect ECGs, lead V2 is the most affected lead (mean: 185μV±82μV), followed by lead V4 (mean: 114μV±59μV) and lead V1 (mean: 100μV±47μV). It was found that if the incorrect electrode configuration is applied, there is a 17% to a 24% chance the diagnostic interpretation will be different. Quantified using Similarity Coefficient (SC) leads V1 and V2 were found to be more alike when misplaced in the second intercostal space. The average SC between these leads when correctly placed was 0.08 (±0.65), however when incorrectly placed, the average SC was 0.43 (±0.3).Conclusion: There is a reasonable chance this particular incorrect electrode configuration will change the diagnosis of the 12-lead ECG. This highlights the importance of developing algorithms to detect electrode misplacement along with better education regarding ECG acquisition.

Predictors of survival within 2years of inpatient rehabilitation among older adults - Corrected Proof

F. Nicosia, F. Bonometti, M.K. Ghisla, S. Cossi, G. Romanelli, A. Marengoni — 2012-04-04

Abstract: Background: Restoring functional independence in elderly people with disabilities is one of the main purposes of a geriatric rehabilitation unit. However, the rehabilitation period may also represent a useful circumstance to identify predictors of long-term health outcomes. The aim of this study was to evaluate a broad spectrum of characteristics in geriatric patients admitted to a rehabilitation unit in order to identify possible predictors of long-term survival.Methods: This cross-sectional and prospective study was carried out in an Evaluation and Rehabilitation unit in Northern Italy. 243 persons aged 65 or older were enrolled over a period of 12months (2007–8) and followed for 2years. Possible predictors of survival were identified among a large spectrum of demographic, clinical (Charlson Index, lab data), nutritional (Mini-Nutritional Short-Form, bio-impedance analysis), and respiratory (spirometry) features. Logistic regression models were used to evaluate the association between patients' characteristics and survival.Results: 189 (86.3%) participants were alive after 2years of follow-up. Younger age, better functional status at discharge, a lower Charlson Index score, higher hemoglobin and albumin values at discharge, lower basal fasting glucose, creatinine, TNF-α levels, and extra-cellular water, as well as higher cholesterol, vital capacity (VC), and inspiratory capacity were significantly associated with survival. In the multivariate model, higher VC (OR=6.2; 95%CI=1.6–24.6) and albumin (OR=3.7; 95%CI=1.2–11.8) were associated with survival, whereas the Charlson Index and male gender showed an inverse correlation (OR=0.77; 95%CI=0.60–0.99 and OR=0.23; 95%CI=0.10–0.95, respectively).Conclusion: VC was identified as one of the best predictors of survival along with higher albumin and lower Charlson Index score within 2years of inpatient rehabilitation among older adults.

High value, cost-conscious care: An international imperative - Corrected Proof

Virginia L. Hood, Steven E. Weinberger — 2012-03-30

Abstract: Health care costs in the United States are the highest in the world, and are continuing to rise at a level that is unsustainable. However, although this problem is more acute in the United States than elsewhere in the world, it is a challenge for all nations to control the costs of health care. The high cost of health care in the U.S. is not accompanied by a higher quality of care, but rather is related in large measure to health system “waste” that does not benefit patients but adds to cost. Representing approximately 30% of dollars spent on health care, this waste includes a significant amount of money spent on overuse and misuse of diagnostic testing, including screening tests. The American College of Physicians, the largest specialty society for physicians in the U.S., representing internal medicine and all of its subspecialties, has embarked upon a High Value, Cost-Conscious Care initiative, aimed at identifying areas of overuse and misuse of care, and leading to development of guidelines, educational materials, and other resources targeted to health care providers, trainees, and the general public. It is incumbent upon physicians, non-physician health care professionals, patients, and other health care stakeholders to address the issue of reducing care that is not appropriate, both to improve the overall quality of care and to reduce the associated unsustainable financial burden to society.

Historical study of acute hepatitis B in subjects with or without hepatitis C infection - Corrected Proof

2012-03-30

Abstract: Background: The epidemiological pattern of hepatitis B virus infection in Italy has greatly changed over the past decades. The aim of the study was to evaluate during time the epidemiological features of acute hepatitis B cases referred to an Infectious Disease Unit in North-East of Italy between 1978 and 1995.Patients and methods: Stored sera of 183 cases were tested for HBV markers, HBV genotypes, anti-Delta and anti-HCV.Results: Anti-HBcIgM was positive in all cases. Mean age increased from 30.2years in 1978 to 37.5 in 1995 (P<0.01). Significant increase was observed in proportion of cases reporting intravenous drug use from 11.5% to 29.6% (P<0.03). Chronicity rate was as low as 1.1%. Mean days of hospitalization significantly decreased. HBV genotype determination showed that majority of cases was infected by genotype D, but its prevalence decreased from 88.2% in 1978 to 75.0% in 1995. Delta coinfection was present in 8.2%. The prevalence of HCV in patients with acute HBV was 35.0%; it fluctuated from 26.2% to 44.2%, mostly related (53.1%) to intravenous drug use. Dual infection did not lead to a more severe course of disease.Conclusions: From this retrospective study, remarkable fluctuations in the prevalence of dual HBV–HCV infection before the implementation of HBV vaccination were observed. Presence of anti-HCV did not affect the course of acute HBV.

The use of non-invasive ventilation during acute respiratory failure due to pneumonia - Corrected Proof

Miquel Ferrer, Roberto Cosentini, Stefano Nava — 2012-03-29

Abstract: The use of non-invasive ventilation in patients with community-acquired pneumonia is controversial since this is associated with high rates of treatment failure, compared with other causes of severe acute respiratory failure. The populations of patients with community-acquired pneumonia who have demonstrated better response to non-invasive ventilation are those with previous cardiac or respiratory disease, particularly chronic obstructive pulmonary disease. By contrast, the use of non-invasive ventilation in patients with community-acquired pneumonia without these pre-existing diseases should be very cautious and under strict monitoring conditions, since there are increasing evidences that the unnecessary delay in intubation of those patients who fail treatment with non-invasive ventilation is associated with lower survival.Pulmonary complications of immunosuppressed patients are associated with high rates of intubation and mortality. The use of non-invasive ventilation in these patients may decrease the need for intubation and improve the poor outcome associated with these complications.Continuous positive airway pressure has been used to treat acute respiratory failure in several conditions characterised by alveolar collapse. While this is extremely useful in patients with acute cardiogenic pulmonary oedema, the efficacy in pneumonia seems limited to immunosuppressed patients with pulmonary complications. Conversely, there are no sufficient evidences on the efficacy of continuous positive airway pressure in immunocompetent patients with pneumonia and severe acute respiratory failure.

Diabetic gastrointestinal autonomic neuropathy: Current status and new achievements for everyday clinical practice - Corrected Proof

A. Gatopoulou, N. Papanas, E. Maltezos — 2012-03-29

Abstract: Gastrointestinal symptoms occur frequently among patients with diabetes mellitus and are associated with considerable morbidity. Diabetic gastrointestinal autonomic neuropathy represents a complex disorder with multifactorial pathogenesis, which is still not well understood. It appears to involve a spectrum of metabolic and cellular changes that affect gastrointestinal motor and sensory control. It may affect any organ in the digestive system. Clinical manifestations are often underestimated, and therefore autonomic neuropathy should be suspected in all diabetic patients with unexplained gastrointestinal symptoms. Advances in technology have now enabled assessment of gastrointestinal motor function. Moreover, novel pharmacological approaches, along with endoscopic and surgical treatment options, contribute to improved outcomes. This review summarises the progress achieved in diabetic gastrointestinal autonomic neuropathy during the last years, focusing on clinical issues of practical importance to the everyday clinician.

Geriatric assessment and chronic kidney disease in the oldest old: The Octabaix study - Corrected Proof

2012-03-29

Abstract: Background: The prevalence of chronic kidney disease (CKD) in older people is increasing.We determine the proportion of CKD in a sample of 321, 85-year-old community-dwelling subjects, and assess the association of socio-demographic data, global geriatric assessment data and comorbidity with CKD according to the estimated glomerular filtration rate (eGFR) of subjects.Methods: Serum creatinine, eGFR (derived in ml/min/1.73m2 using the Modification of Diet in Renal Disease formula), socio-demographic variables, the Barthel Index (BI), the Spanish version of the Mini-Mental State Examination (MEC), the Mini Nutritional Assessment (MNA), the Charlson Index, the Gait Rating Scale, social risk, quality of life and prevalent chronic diseases were collected.Results: CKD prevalence was 56.7% for eGFR<60ml/min/1.73m2, 19.9% for eGFR<45ml/min/1.73m2 and 6.6% for GFR<30ml/min/1.73m2. Multiple logistic regression analysis showed that a prior diagnosis of hypertension was associated with an eGFR<60ml/min/1.73m2 (p<0.008, OR 2.134, 95% CI 1.216–3.744). A diagnosis of heart failure (p<0.001, OR 3.610, 95% CI 1.677–7.771) and a poor score on the quality of life measure (p<0.008, OR 0.9660, 95% CI 0.966–0.995) were associated with an eGFR<45ml/min/1.73m2.Conclusions: More than half of the oldest old in this study had an eGFR<60ml/min/1.73m2. A history of hypertension was associated with CKD. The group of patients with an eGFR<45ml/min/1.73m2 was associated with a diagnosis of heart failure and a worse quality of life.

Intensive versus conventional glucose control in critically ill patients: A meta-analysis of randomized controlled trials - Corrected Proof

Yan Ling, Xiaomu Li, Xin Gao — 2012-03-26

Abstract: Background: Critically ill patients commonly develop hyperglycemia. It remains unclear, however, to what extent correcting hyperglycemia will benefit these patients. We performed this meta-analysis to evaluate the benefits and risks of intensive glucose control versus conventional glucose control in critically ill adult patients.Methods: A systematic literature search of MEDLINE, PubMed, and Cochrane databases (until June 2011) was conducted using specific search terms. Randomized controlled trials that compared intensive glucose control with a target glucose goal <6.1mmol/l (110mg/dl) to conventional glucose control in adult intensive care patients were included. The random-effect model was used to estimate the pooled risk ratio of the two treatment arms.Results: Twenty two studies that randomized 13,978 participants were included in the meta-analysis. Overall, intensive glucose control did not reduce the short-term mortality (RR=1.02, 95% CI: 0.95–1.10, p=0.51), 90day or 180day mortality (RR=1.06, 95% CI: 0.99–1.13, p=0.08), sepsis (RR=0.96, 95% CI: 0.83–1.12, p=0.59) or new need for dialysis (RR=0.96, 95% CI: 0.83–1.11, p=0.57). The incidence of hypoglycemia was significantly higher in intensive glucose control group compared with conventional glucose control group (RR=5.01, 95% CI: 3.45–7.28, p<0.00001).Conclusions: This meta-analysis found that intensive glucose control in critically ill adults did not reduce mortality but is associated with a significantly increased risk of hypoglycemia.

Metabolic syndrome and vascular risk estimation in a Mediterranean non-diabetic population without cardiovascular disease - Corrected Proof

2012-03-26

Abstract: Aims: Vascular risk equations are tools used to help prevent cardiovascular events. Our aim was to compare the REGICOR and SCORE equations in a general population and in persons with the metabolic syndrome (MS) according to the criteria of the International Diabetes Federation.Methods and results: We calculated the cardiovascular risk with both equations in a random sample of 838 non-diabetic persons aged 40–65years without a history of cardiovascular disease, of whom 251 had the MS. Of the 838 persons, 3.6% had a high risk according to SCORE and 1.5% according to REGICOR, and of these, 53.3% and 61.5%, respectively, had the MS. The mean risk was greater in the persons with the MS than those without (REGICOR 4.6% vs. 2.6% and SCORE 1.7% vs. 1%; p<0.01 for each). In comparison with the group without the MS, the percentage of persons with the MS who had a high risk was greater with both scales: REGICOR (3.2% vs. 0.8%, p=0.027) and SCORE (6.4% vs. 2.4%, p=0.004). The agreement (kappa index) classifying the subjects with a high risk, was 0.453 in the overall sample and 0.391 in the subgroup with the MS.Conclusions: The percentage of persons classified as having a high cardiovascular risk differed between REGICOR and SCORE. Using these scales only a small percentage of non-diabetic persons with the MS have a high risk. The presence of the MS multiplies the percentage of non-diabetic persons with a high vascular risk two-fold with SCORE and four-fold with REGICOR.

Pleural fluid C-reactive protein contributes to the diagnosis and assessment of severity of parapneumonic effusions - Corrected Proof

2012-03-26

Abstract: Background and aims: Prompt identification of parapneumonic effusions has immediate therapeutic benefits. We aimed to assess whether C-reactive protein (CRP) and routine biochemistries in pleural fluid are accurate markers of parapneumonic effusions, and to evaluate their properties as indicators for drainage (complicated parapneumonic effusion).Methods: A retrospective review of 340 non-purulent parapneumonic effusions and 1,659 non-parapneumonic exudates from a single center was performed and the discriminative properties of pleural fluid routine biochemistries and, when available, CRP were evaluated. CRP, along with classical fluid parameters, was also applied to classify patients as having complicated or uncomplicated parapneumonic effusions. ROC analysis established the threshold of CRP for discriminating between groups.Results: Pleural fluids with neutrophilic predominance and CRP levels >45mg/dL were most likely to be parapneumonic in origin (likelihood ratio=7.7). When attempting to differentiate non-purulent complicated from uncomplicated effusions, a CRP >100mg/L had the same performance characteristics (area under the curve=0.81) as the widely accepted biochemistries pH and glucose. Combinations of CRP with pH or glucose resulted in incrementally discriminating values, pertaining to either sensitivity (75–80%) or specificity (97%), for complicated effusions.Conclusion: Pleural fluid CRP may be a useful adjunctive test in pleural effusions, both as a marker of parapneumonics and, particularly, as a differentiator between complicated and uncomplicated effusions.

Five-year survival and prognostic factors in a cohort of hospitalized nonagenarians - Corrected Proof

2012-03-21

Abstract: Background: The number of hospitalized nonagenarians is increasing. Only a few studies have evaluated long-term predictors of survival in these patients. The aim of this study was to determine the 5-year outcome of a cohort of hospitalized nonagenarians, and to identify predictors of long-term survival.Methods: In 124 consecutive medical hospitalized patients older than 89years, and followed up during 5years, the following variables were prospectively recorded: sociodemographic characteristics, main diagnoses, Charlson comorbidity index, Barthel index, Lawton–Brody test, Mini-Mental State Examination, Short Portable Mental Status Questionnaire of Pfeiffer, Mini Nutritional Assessment, albumin levels, and the 5-year survival.Results: Out of the 124 patients, 109 died (87.9%) during the follow-up. The probability of being alive at 1, 3 and 5years was 45%, 22% and 12%, respectively. A worse 5-year survival was significantly related to the diagnoses of pneumonia (p=0.037), heart failure (p=0.045), higher Charlson index (p=0.026), poorer functional status measured by the Barthel index (p=0.003), and the Lawton–Brody test (p=0.007), cognitive impairment measured by the Pfeiffer test (p=0.011), and lower levels of albumin (p=0.028). In the multivariate analysis, the Charlson index (p<0.001), and the Barthel index (p=0.003) were independently related to 5-year survival. These two variables were also 5-year survival prognostic factors in the subgroup of discharged patients. A prognostic index using these two variables was created: PI=(0.2×Charlson index+0.6×Barthel index)×0.92.Conclusions: In hospitalized nonagenarian patients, poor scores in the Barthel Index and a higher comorbidity evaluated by the Charlson index are independently related to 5-year survival.

Non-every day statin administration — A literature review - Corrected Proof

Avishay Elis, Michael Lishner — 2012-03-19

Abstract: Background: Statins are the treatment of choice for lowering LDL-C levels and reducing cardiovascular events. They have a remarkable safety profile, although some patients do not tolerate them. The aim of the study was to summarize the existing data on non-every day statin administration regimens.Methods: We searched the MEDLINE databases to identify articles on non-every day statin administration, published between 1990 and January 2010. All publications regardless of methodology, design, size, or language were included. Data extracted included study design, duration and aims, type of statin, therapeutic regimen, patient characteristics, effectiveness, tolerability, and costs.Results: The 21 retrieved articles were characterized by small sample size, short follow up period, and a preponderance of males and “primary” prevention cases. Several lacked randomization or a control group. The heterogeneity of the study groups, medications, doses, design and aims precluded a pooled or meta-analysis. The most reported and effective regimens were atorvastatin and rosuvastatin on alternate days. These regimens, with or without other lipid lowering agents, were well tolerated even among subjects with previous statin intolerance, and produced meaningful cost savings. Nevertheless, the effectiveness of these regimens on cardiovascular events was not clarified.Conclusions: Atorvastatin or rosuvastatin on alternate days might be considered for patients who are intolerant to statin therapy. Further studies are needed to evaluate the effect of these regimens on cardiovascular events.

Association of ALOX5AP haplotypes with susceptibility to coronary artery disease in a Chinese Han population - Corrected Proof

2012-03-16

Abstract: Background: The 5-lipoxygenase activating protein (FLAP), encoded by the activating 5-lipoxygenase (ALOX5AP) gene, is a crucial mediator of the biosynthesis of leukotrienes, which have been implicated in atherosclerosis. This study investigates whether ALOX5AP polymorphisms are associated with coronary artery disease (CAD) in a Chinese Han population.Methods: The promoter, exons, splice site region and 3′-untranslated region of the ALOX5AP gene were sequenced in 48 subjects. Three polymorphic sites (−1340T/G, +8733T/C, +20616G/C) found through sequencing were evaluated in 656 patients with angiographically proven CAD and 678 controls with normal coronary angiograms using a polymerase chain reaction and restriction fragment length polymorphism assay. Allelic, genotypic linkage disequilibrium and haplotypic association testing were performed using SHEsis and LDA software. Binary logistic regression was used to control for the presence of vascular risk factors.Results: Seven single nucleotide polymorphisms (SNPs) were found through screening. No significant differences in allele carriers and genotype frequencies of the ALOX5AP polymorphisms were observed between the two groups. However, when the results of the three SNPs were combined, there was a significant association between two of the haplotypes and the risk of CAD. The haplotype GCG had a significantly greater frequency in patients than in controls (P<0.001, OR=1.728, 95%CI=1.375–2.171), and the frequency of haplotype TCG was higher in controls (P<0.001, OR=0.623, 95%CI=0.519–0.748).Conclusion: The data indicate that ALOX5AP gene variation is a genetic factor associated with interindividual differences in CAD risk.

The metalloproteinase system and vitamin D deficiency - Corrected Proof

Eda Demir Onal — 2012-03-05

I read with great interest the article by Isik et al. . They found that the serum transforming growth factor beta 1 (TGF-β1) levels were significantly higher in patients with severe vitamin D deficiency. They speculated that severe vitamin D deficiency may contribute to bone marrow fibrosis, and increased systemic TGF-β1 levels may be an early indicator of bone marrow fibrosis in patients with severe vitamin D deficiency. I think that measurement of serum matrix metalloproteinases (MMPs) as well as TGF-β1 could have been an original contribution to study design.

Vitamin D status in normocalcaemic primary hyperparathyroidism - Corrected Proof

Oscar M.P. Jolobe — 2012-03-05

The evaluation of vitamin D status in primary hyperparathyroidism (PHPT) should, for the sake of completeness, also include a comment on the role of documentation of vitamin D status in the characterisation of normocalcaemic hyperparathyroidism, the latter now recognised as a distinct phenotype in its own right . For this diagnosis to be valid vitamin D(25OHD) status has to be evaluated so as to rule out hypovitaminosis D as the underlying cause of elevation in serum parathyroid hormone (PTH). Other causes of secondary hyperparathyroidism, such as renal insufficiency, also have to be ruled out, all this in the context of total serum calcium which falls within the normal range when corrected for serum albumin. In a study which utilised those criteria 37 patients aged 32–78 were identified, 29 of whom were postmenopausal women, and only 2 of whom were male. In spite of normocalcaemia 14% of those patients had a history of kidney stones, and 57% had osteoporosis . On median follow up of 3years seven of those patients subsequently became hypercalcaemic . Diagnostic criteria for normocalcaemic PHPT were further refined in a workshop which specified that patients with this diagnosis should also have normal levels of ionised calcium , a recommendation supported by the observation that patients with primary hyperparathyroidism may have raised levels of ionised serum calcium even when total serum calcium and serum albumin levels are normal . Although, according to one view, “many patients once thought to have normocalcaemic PHPT (primary hyperparathyroidism) are instead patients with the more usual hypercalcaemic PHPT who have coexisting vitamin D deficiency, which lowers their serum calcium levels into the reference range” , correction of coexisting vitamin D deficiency does not necessarily generate an increase in serum calcium to the hypercalcaemic range. The absence of post-treatment increase in serum calcium was exemplified by two patients with normocalcaemic PHPT in whom pretreatment serum 25-hydroxy vitamin D levels amounted to 9ng/ml, and 11ng/ml, respectively (reference range 11–55ng/ml), and in whom vitamin D replacement therapy resulted in an increase in serum vitamin D levels to 21ng/ml in each instance . What is also uncertain is whether, in the event of coexistence of raised PTH levels, hypovitaminosis D, and normocalcaemia, a therapeutic trial of vitamin D repletion can achieve a diagnostic separation between normocalcaemic PHPT and secondary hyperparathyroidism. In theory, a sustained increase in PTH concentration (as was the case in two normocalcaemic patients who participated in the therapeutic trial of vitamin D repletion) , validates the diagnosis of normocalcaemic PHPT. An alternative view, however, is that, in that context, a sustained increase in PTH concentration is merely indicative of refractory secondary hyperparathyroidism . The complex interplay between serum calcium intact PTH, 25OH vitamin D levels and age in PHPT and in normal subjects has now been defined in a four-dimensional nomogram which is intended to facilitate definitive diagnosis of atypical presentations such as normocalcaemic PHPT . Even though this nomogram relies on total rather than on ionised serum calcium, the fact that it is vitamin D-based bears testimony to the crucial relevance of vitamin D status in the evaluation of all subtypes of PHPT .

The role of lung ultrasound in the diagnosis and follow-up of community-acquired pneumonia - Corrected Proof

Angelika Reissig, Andrea Gramegna, Stefano Aliberti — 2012-02-23

Abstract: CAP may be diagnosed and followed up by lung sonography (LUS), a technique that shows excellent sensitivity and specificity that is at least comparable with that of chest X-ray in two planes. LUS may be performed with any abdomen-sonography device. Therefore, LUS is a readily available diagnostic tool that does not involve radiation exposure and has wide applications especially in situations where X-ray is not available and/or not applicable. An X-ray or CT of the chest should be performed in cases of negative lung sonography and if other differential diagnoses or complications are suspected.

Vitamin D and gestational diabetes: A systematic review and meta-analysis - Corrected Proof

Y.H.M. Poel, P. Hummel, P. Lips, F. Stam, T. van der Ploeg, S. Simsek — 2012-02-22

Abstract: Background: Conflicting results currently exists on the association between vitamin D and glucose metabolism. The role of maternal vitamin D status in gestational diabetes mellitus (GDM) is not clear. This meta-analysis aimed to examine this role in women with GDM compared with normal glucose tolerance (NGT).Methods: We performed a systematic review and meta-analysis by searching MEDLINE database, the Cochrane library and Uptodate® Online for English-language literature up to September 2011. Summary odds ratios were calculated using a random-effects model meta-analysis.Results: Seven observational studies were eligible for the meta-analysis, including 2146 participants of whom 433 were diagnosed with GDM. Four studies reported a high incidence of vitamin D deficiency in pregnant women (>50%). Overall vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD)<50nmol/l) in pregnancy was significantly related to the incidence of GDM with an odds ratio of 1.61 (95% CI 1.19–2.17; p=0.002). Serum 25OHD was significant lower in participants with GDM than in those with NGT (−5.33nmol/l (95% CI −9.73 to −0.93; p=0.018).Conclusions: This meta-analysis indicates a significant inverse relation of serum 25OHD and the incidence of GDM. However, it remains unclear whether this association is causal due to the observational study design of the studies. Clinical trials are needed to examine whether vitamin D supplementation will improve glycemic control in women with GDM.

25 hydroxyvitamin D levels in patients undergoing coronary artery catheterization - Corrected Proof

2012-02-21

Abstract: Introduction: A growing body of evidence suggests that vitamin D deficiency is associated with increased cardiovascular morbidity and mortality. The present study assessed the association between low serum 25-hydroxyvitamin D (25(OH)D) and coronary artery disease status defined by coronary catheterization findings.Methods: An observational study of 101 consecutive patients admitted to Assaf Harofeh Medical Center during 2009, and scheduled to undergo coronary catheterization was undertaken. Blood was collected for parathyroid hormone, 25(OH)D and high sensitivity C reactive protein (hsCRP). 25(OH)D deficiency was defined as <20ng/ml. Patients were divided into two groups: patients with normal or non-significant coronary artery disease and patients with a significant coronary artery disease as found during cardiac catheterization. Logistic regression model was used to compare pathological coronary catheterization findings, including 25(OH)D levels dichotomized to low (serum 25(OH)D levels<20ng/ml) vs. high (serum 25(OH)D levels≥20ng/ml) and other confounders.Results: Patients with pathological coronary catheterization had 25(OH)D deficiency (75% vs 55.1%, p=0.036). Pathological coronary catheterization was more prevalent among patients with 25(OH)D deficiency (Odds ratio (OR) 2.44, 95% confidence interval (CI) 1.05–5.68, p=0.038). This difference was more pronounced after controlling for sex, age, BMI, ethnicity and present smoking (OR 2.92, 95% CI 1.01–8.46, p=0.016).Conclusions: 25(OH)D deficiency is significantly associated with pathological cardiac catheterization findings. This association is strengthened further by controlling for other cardiovascular disease risk factors.

Predictive model of readmission to internal medicine wards - Corrected Proof

2012-02-15

Abstract: Objective: Prevention of readmission to hospital is considered an outstanding example of a cost-effective practice. Our aim was to derive and validate a clinically useful index to quantify the risk of readmission among patients discharged from Internal Medicine departments.Methods: We analysed hospital Basic Minimum Data Sets (BMDS) recorded between 2006 and 2008 to determine patterns of rehospitalization. Multivariate statistical analysis of routinely collected data was used to develop an algorithm (‘SEMI INDEX’) to identify patients predicted to have the highest risk of readmission in the 30days following discharge. The algorithm was developed by using data from admissions in 2006–2007, for four age subgroups. Coefficients for the most powerful and statistically significant variables were applied against episodes recorded in 2008 to validate the findings of the algorithm developed from the first sample.Results: Of the 999,089 internal medicine admissions in Spain during 2006–2007, 12.4% were rehospitalized within 30days. The key factors that predicted subsequent admission included male sex, length of stay, comorbidity of the patient, and some clinical conditions. There were small but relevant differences among the different age subgroups.Conclusions: Readmissions to Internal Medicine departments are prevalent (12.4%). The SEMI INDEX can be used to assess accurately the risk of readmission within 30days after discharge.

D-dimer levels in assessing severity and clinical outcome in patients with community-acquired pneumonia. A secondary analysis of a randomised clinical trial - Corrected Proof

2011-11-21

Abstract: Background: D-dimer levels are in several studies elevated in patients with CAP. In this study we assess the use of D-dimer levels and its association with severity assessment and clinical outcome in patients hospitalised with community-acquired pneumonia.Methods: In a subset of randomised trial patients with community-acquired pneumonia serial D-dimer levels was analysed. CURB-65 scores were calculated at admission.Results: A total of 147 patients were included. D-dimer levels at admission were higher in patients with severe CAP (2166±1258 versus1630±1197μg/l, p=0.03), with clinical failure at day 30 (2228±1512 versus 1594±1078μg/l, p=0.02) and with early failure (2499±1817μg/l versus 1669±1121μg/l, p=0.01). Non-survivors had higher D-dimer levels (3025±2105 versus 1680±1128μg/l, p=0.05). None of the 16 patients with D-dimer levels<500μg/l died. In multivariate analysis D-dimer levels were not associated with clinical outcome. D-dimer levels have poor accuracy for predicting clinical outcome at day 30 (AUC 0.62, 95% CI 0.51–0.73) or 30day mortality (AUC 0.71 (95% CI 0.51–0.91)). Addition of D-dimer levels to CURB-65 did not increase accuracy. No differences were observed in serial D-dimer levels between patients with clinical success or failure at day 30.Conclusion: D-dimer levels are elevated in patients with CAP. Significantly higher D-dimer levels are found in patients with clinical failure and with severe CAP. D-dimer levels as single biomarker or as addition to the CURB-65 have no added value for predicting clinical outcome or mortality. D-dimer levels<500μg/l may identify candidates at low risk for complications.

Can we use severity assessment tools to increase outpatient management of community-acquired pneumonia? - Corrected Proof

James D. Chalmers, Julia Rutherford — 2011-11-04

Abstract: Outpatient management of community-acquired pneumonia (CAP) has several potential advantages, including significant cost-savings, a reduction in hospital-acquired infections and increased patient satisfaction. Despite the benefits, it is often difficult to identify which patients may be managed in the community without compromising patient safety. CAP severity scores, such as the pneumonia severity index (PSI) and the British Thoracic Society CURB65/CRB65 scores are designed to identify groups of patients at low risk of mortality who may be suitable for outpatient care.This review discusses the strengths and weaknesses of severity scores for use in determining site of care for patients with pneumonia.Use of the PSI in emergency departments has been shown to increase the proportion of patients treated in the community without increasing patient mortality or hospital readmissions. The CURB65 and CRB65 scores are less complex alternatives to the PSI that have been shown to perform similarly for prediction of 30-day mortality.All 3 scores identify populations at low risk of mortality who may be eligible for outpatient care. Nevertheless, a number of factors not included in severity scores may prevent discharge of these patients, including social factors, co-morbidities and severity markers not captured by severity scores. The limitations of severity scores are discussed along with recent attempts to improve predictive tools, with the development of new biomarkers and alternative scoring systems.

Hypovitaminosis D: Don't forget dementia - Corrected Proof

Cédric Annweiler, Olivier Beauchet — 2011-09-01

Recently, Makariou et al. reported the results of an interesting literature review in which the “novel roles of vitamin D in disease” were studied. Based on a non-systematic method, the authors did an admirable effort to list the recently described links between vitamin D and several predefined outcomes including mortality, immunity and cardiovascular diseases. The key messages were that the vitamin D concentration decreases with the advance in age, and is associated with dysimmune diseases as well as with metabolic syndrome, hypertension, diabetes and stroke . The involvement of vitamin D in immune function and vascular health seems of particular importance in older adults since both these mechanisms are involved not only in the clinical complications cited by Makariou et al., but also in brain aging and cognitive decline , which is one of the main issue of aging.

Corrected Proof

2011-08-17

Reprint of: Diagnosis of Cushing's syndrome - Corrected Proof

J.W.F. Elte — 2011-08-16

The diagnosis of Cushing's syndrome (CS), including pituitary-dependent CS (Cushing's disease), adrenal CS (adenoma, carcinoma, hyperplasia), ectopic and iatrogenic CS, is easy as long as it presents in its classical and full-blown form. A description can be found in every textbook and the diagnosis is usually made “at first sight”. Specific clinical signs and symptoms include moon face, purple striae, central obesity, growth retardation in children, decreased libido, menstrual changes, hirsutism, hypertension, ecchymoses, depression, weakness, dorsal fat pad (buffalo hump), edema, abnormal glucose tolerance and osteopenia . However, CS is rare (0.1–1.2 per 100,000) and many of the individual symptoms and signs are rather non-specific . There are subgroups of patients in whom the prevalence of CS is higher, such as those with diabetes mellitus type 2 and obesity , but even then the diagnosis is made in a small minority .

Reprint of: Thiazolidinediones for the treatment of type 2 diabetes - Corrected Proof

J.W.F. Elte, J.F. Blicklé — 2011-08-16

Abstract: Thiazolidinediones (TZD), or glitazones, represent a new generation of antidiabetic drugs that have recently been introduced in Europe. They improve insulin resistance, one of the key anomalies involved in the pathogenesis of type 2 diabetes mellitus, by activating the nuclear peroxoxisome proliferator activated receptor-γ (PPAR-γ), leading to crucial metabolic alterations in adipose tissue. Rosiglitazone and pioglitazone have been shown to be active as monotherapy, in combination therapy with metformin or sulfonylureas, and even in triple therapy. They are generally well tolerated but can induce fluid retention. Cardiac failure is a contraindication for the use of TZDs, as is the concomitant administration of insulin. Aside from their effect on glycemic control, TZDs act on several cardiovascular risk factors and may protect pancreatic β cells from apoptosis. The cardiovascular protective effect of TZDs has recently been demonstrated with the results of the PROactive study, and long-term preservation of β-cell function is currently under further investigation.

Reprint of: Proposal for a multidisciplinary approach to the patient with morbid obesity: The St. Franciscus Hospital Morbid Obesity Program - Corrected Proof

2011-08-16

Abstract: Morbid obesity is a serious disease as it is accompanied by substantial co-morbidity and mortality. The prevalence is increasing to an alarming extent, in Europe as well as in the United States. In the past few decades, bariatric surgery has developed and gained importance. It currently represents the only long-lasting therapy for this group of patients, resulting in an efficient reduction in body weight and obesity-related medical conditions, mostly cardiovascular in nature. The importance of a standardized protocol, the use of selection criteria, and a multidisciplinary approach have been stressed but not yet described in detail. Therefore, in this article, the multidisciplinary approach and the treatment protocol that have been applied in our hospital for more than 20 years are set out in a detailed manner. The application of a strict protocol may help to select and follow-up motivated patients and to organize multidisciplinary research activities.

Reprint of: Peripheral arterial disease: A growing problem for the internist - Corrected Proof

2011-08-16

Abstract: The atherothrombotic conditions, coronary artery disease, cerebrovascular disease and peripheral arterial disease (PAD), together account for almost one-half of all deaths in Europe each year; however, perception of the specific risks associated with PAD is generally poor compared with its related conditions. PAD is not just a localised disease — it has serious systemic effects, and affected individuals have a higher risk of serious cardiovascular sequelae or death within 1 year of diagnosis compared with those with coronary artery or cerebrovascular disease. PAD, which currently affects approximately 16% of the general population aged over 55 years, is increasing because of the population aging and the continuing rise in cardiovascular risk factors. The management of PAD is a multi-disciplinary approach, and while this can have its advantages, it can also mean that responsibility for patient care is unclear. Globally, almost one-third of all patients with PAD are under internist care. Internists are ideally placed to identify patients at risk of PAD and initiate prompt risk factor management because of their role in the continued care of elderly patients and those with diabetes, hypertension, dyslipidaemia, and chronic renal disease. Multi-disciplinary guidelines for the clinical management of PAD, based on consensus among international specialists in a number of fields, have been developed to create an informed, unified and proactive approach to the treatment of PAD. They stress the continuity of care, the use of office-based ankle–brachial index testing to aid early diagnosis, and prompt and aggressive risk factor management.

Reprint of: The history of the (Young) AEMI(E) and the EFIM - Corrected Proof

Ugo E.F. Carcassi, Jan Willem F. Elte, Christopher Davidson — 2011-08-16

Abstract: The European Federation of Internal Medicine (EFIM) was formed in 1996 through a merger between the Association Européenne de Médicine Interne (d' Ensemble) (AEMI(E)) and the Forum of Presidents of National Societies of Internal Medicine (IM). It arose as a result of ideas from Carcassi (Rome/Cagliari) and Merino (Alicante) to transform the largely French-speaking and rather elitist AEMI into a more easily accessible and English-speaking federation of national societies. The founding meeting of the General Assembly of the EFIM took place in May 1996 in Paris. Since then, the EFIM has initiated many activities, some of them originating from the time of the AEMI(E).

Reprint of: Bone metastasis of a follicular thyroid carcinoma originated in a toxic multinodular goiter - Corrected Proof

T.S. Schmitt, J.W.F. Elte, A.P. Rietveld, H.C.T. van Zaanen, M. Castro Cabezas — 2011-08-16

Follicular thyroid carcinoma is the second most common thyroid malignancy, accounting for 5–15% of such tumours . Because physical examination does not differentiate between benign and malignant nodules, laboratory and cytological evaluation are usually warranted . When evaluating a thyroid nodule measuring serum thyrotropin (TSH) level is one of the first steps taken. If the serum TSH level is normal or elevated, the patient should undergo fine needle aspiration (FNA). However, if the serum TSH level is subnormal, a radionuclide thyroid scan may be performed prior to FNA in order to determine whether the nodule is hyper-, iso-, or non-functioning . Thyroid cancer generally presents as a single, cold thyroid nodule on a radionuclide scan. Thyroid cancer manifesting as a hot nodule is much less frequent, with a prevalence of 4–11% . It is unusual for this neoplasm to present early in its course as a single metastasis in the spine . We report a case of follicular thyroid carcinoma presenting as a spine metastasis which originated in a toxic multinodular goiter.

Reprint of: Detrimental action of thiazolidinediones on bone (rebuttal) - Corrected Proof

J.W.F. Elte, J.F. Blicklé — 2011-08-16

Dr. Mascitelli and colleagues raise an important problem. At the time our review was written and accepted, data on bone problems were not known to us. In Table 2 of our article, we adapted a table from Ovalle and Ovalle–Bérumen (our reference 62). “Less bone turnover” was included as a potentially beneficial effect, but we agree that this is highly questionable.

Reprint of: Differential diagnosis by laboratory medicine: a quick reference for physicians - Corrected Proof

J.W.F. Elte — 2011-08-16

This reference book is divided into four parts: Introduction to laboratory medicine; biochemical/laboratory parameters in biological materials; biochemical/laboratory findings in clinical units and conditions; and medicaments: interfering factors and reference ranges. In addition, it has a number of appendices that include SI conversion factors, cluster of differentiation (CD) molecules, and sampling rules, together with an extensive list of frequently used synonyms and an index.