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Previous article in issueNext article in issue Introduction: There is a limited documentation about the retreatment of patients failing a recommended NS5A-containing regimen in Italy. Materials & methods: Within the VIRONET-C network, 386 NS5A-failing patients infected with different HCV-genotypes (GT) (GT1a/1b/2a-c/3a-b-g-h/4a-d-n-o-v=93/124/19/112/38) were analyzed. Retreatment of 105 failures was investigated. HCV-resistance-test was performed by Sanger-sequencing. Results: Failures following seven different NS5A-containing regimens were studied: 3D/2D (paritaprevir/ombitasvir ± dasabuvir) ± ribavirin (N = 72/4), daclatasvir/ledipasvir/velpatasvir + sofosbuvir ± ribavirin (N = 105/131/20), grazoprevir/elbasvir ± ribavirin (N = 34), glecaprevir/pibrentasvir (N = 20). Notably, 18.1% of NS5A-failing patients did not show any resistance-associated-substitutions (RAS), while 81.9% showed at least one NS5A-RAS, with multiclass-resistance in 35.5%. NS5A-RAS were observed more frequently in glecaprevir/pibrentasvir failures (GT1a 83.3%: Y93H + Q30H/D or +H58D; GT3a: 83.3% Y93H + A30K/G or +L31I) compared to sofosbuvir/velpatasvir (GT1a 16.6%: Y93H + Q30H, p = 0.08; GT3a 20.0%: Y93H/N + A30K/T, p = 0.03). To date, 105 failures have started a retreatment: sofosbuvir/velpatasvir ± ribavirin (N = 30), sofosbuvir/velpatasvir/voxilaprevir ± ribavirin (N = 67), glecaprevir/pibrentasvir (N = 4), grazoprevir/elbasvir ± sofosbuvir + ribavirin (N = 3), 3D + sofosbuvir + ribavirin (N = 1). The majority of patients were cirrhotic (51.9%) and relapsers (87.5%). The prevalence of NS5A-RASs before retreatment was 80.9%, with multiclass-resistance 29.5%. Among patients completing post-retreatment follow-up, a sustained-viral-response at week 12 (SVR12) was observed in 26/33 (78.8%). SVR4 was documented in 49/56 (87.5%). SVR12 was 76.0% with sofosbuvir/velpatasvir ± ribavirin (N = 25). Differently, SVR12 was 100% with glecaprevir/pibrentasvir for 8/12/16 weeks (N = 3), grazoprevir/elbasvir ± sofosbuvir + ribavirin for 12/24 weeks (N = 3) or 3D + sofosbuvir + ribavirin for 24 weeks (N = 1), despite the presence of NS5A-RASs. Until now, 67 patients started sofosbuvir/velpatasvir/voxilaprevir ± ribavirin recommended-retreatment for 12 weeks. 54/67 (80.6%) showed at least one baseline NS5A-RAS, 23/67 (34.3%) multiple-NS5A-RASs, and 22/67 (32.8%) multiclass-resistance. Of 25 patients with available outcome, 96.0% had SVR4. Only 1 GT1b infected patient was non-responder, without RASs before retreatment. Conclusions: In this real-life setting, NS5A-RASs were frequently detected at failure, and multiclass-resistance was around 30%. Overall, SVR after resistance-test-guided retreatment was >95%, with the exception of the sofosbuvir/velpatasvir retreatment. Our results show how HCV resistance-test at failure may be useful to optimize retreatment strategies.

Objective: To study significant factors associated with the risk of hypertension among obese women, with and without a history of weight cycling (WC). Design: Case–control study. Setting: Obesity Clinic of Chieti University, Italy. Subjects: A group of 258 obese women aged 25–64 y (103 cases with hypertension and 155 controls) were recruited. All obese subjects had the same clinical characteristics, were without a family history for hypertension, were non-smokers, had normal lipidemic profiles and normal glucose tolerance, were not taking any medication and were otherwise healthy. Intervention: In the weight cycling women, the history of WC was established on the basis of at least five weight losses in the previous 5 y due to dieting, with a weight loss of at least 4.5 kg per cycle. A logistic regression model adjusted for confounding variables such as waist-to-hip ratio (WHR) and weight cycling history parameters was used and the odds ratio (OR) with 95% confidence intervals was calculated. Results: The risk of hypertension increases in subjects with larger WHR (OR 7.8; 95% CI 3.4–17.9) and with a positive history for WC (OR 4.1; 95% CI 2.4–6.9). Further, in obese patients with WC, the weight cycling index and the sum of the weight regained are also important risk factors for hypertension. Conclusions: These findings could support the hypothesis that it is the combined exposure of central-type obesity and WC that strongly raises the risk of hypertension. Sponsorship: This work has been financially supported by a grant of Ministero dell’Universita e della Ricerca Scientifica e Tecnologica. European Journal of Clinical Nutrition (2000) 54, 356–360

Internal Medicine lessons were integrated with simulation of clinical cases (Socrates program). The subsequent evaluation of 188 students was conducted with the Procustes program (Computer-Aided Assessment of Patient Problem: CAAPP). An increase in the number of training hours with the Socrates program results in improved examination performance. The data suggest that teaching with a learning program based on simulation of a clinical problem or cases may be a useful tool to integrate with traditional lessons. In addition, assessment with the Procustes program may support the appraisal of clinical knowledge and competence.

The aim of this study was to determine how different scoring methods could influence the results achieved in clinical competence assessment examinations at the end of the medical school curriculum. Fifty-six final-year medical school students were examined using a programme of multimedia computer-based simulated cases (Procuste programme). For generating results, the following scoring methods were applied: (1) the method used for the Internal Medicine official certification examination which includes both weighted and unweighted items; (2) a method with only unweighted items;(3) a method which includes single-item analysis. Each time an absolute pass/fail cut-off standard (#83 60/100) and a relative pass/fail cut-off (mean minus 1 standard deviation) were applied.Taking as a reference the first method, the effect of using different scoring methods on the percentage of student failure was evaluated. Furthermore, correlation studies between the results obtained with these scoring methods and the grades reported by the examinees during the medical school curriculum were performed. It was found that the first method generated a more realistic pass/fail rate compared with the two other methods. Furthermore this method, which has been used for the last 10 years for administering internal medicine examinations, showed better correlation coefficients with the curriculum scores.

Asthma is one of the most common chronic diseases in children and adults. Recent studies have shown that in asthmatic patients treated with inhaled corticosteroids there is a better disease’s control when adding a second drug, than increasing the corticosteroid’s dose. The aim of this study has been to evaluate the effectiveness and tolerance of zafirlukast, a leukotriene receptor antagonist, versus budesonide in clinically steady patients with mild persistent bronchial asthma. We have enrolled 36 subjects non smokers, with mild persistent bronchial asthma and 12 healthy subjects as control group. At the beginning of this study and at the end of the treatment (8 weeks), all patients underwent complete clinical work-up, pulmonary function testing (FEV1, PEF and FVC) and methacholine challenge test. The patients were divided into 3 groups: group A) 20 mg of zafirlukast twice a day; group B) 400 mg of budesonide twice a day; group C) 20 mg of zafirlukast twice a day and 400 mg of budesonide twice a day. Basal FEV1 and PEF presented no significant statistical differences between control subjects and patients of group A, B and C. After eight weeks there were no significant changes for FEV1 and PEF among the three groups. After therapy a strong significant increase of PD20 was documented in group A (p#x003C;0.005), group B (p#x003C;0.001) and group C (p#x003C;0.005), respect to baseline values. The antileukotriene drugs could be taken as an alternative drug, or in association with low-dose inhaled corticosteroids, in patients with mild persistent asthma, both for their clinical effectiveness and their easy ingestion, which is confirmed in compliance studies on inhaled steroids.

We describe the cases of two patients with clinical and radiological findings of the reflex sympathetic dystrophy syndrome (RSDS) in whom the history of a previous genito-urinary inflammation and high levels of ESR lead us to suspect a hidden reactive arthritis. However, instrumental examinations showed a characteristic picture of RSDS without evident signs of arthritis. In both patients we decided a treatment with quinolones because of detection of an ureaplasma urealyticum genito-urinary infection. This brought to complete remission of the joint symptoms in a few days. Our findings suggest that ureaplasma urealyticum can cause and sustain a RSDS picture, maybe with a reactive arthritis-like mechanism, and that an antibiogram-driven antimicrobial treatment can be rapidly effective against this disorder.

The teaching of Clinical Nutrition (CN) is frequently neglected in Medical Schools, though many official institutions strongly recommend its incorporation in their curricula. This work aimed to assess CN knowledge among final-year medical students and final-year dietology diploma students.We compared the performances of final-year Medical School students who did and who did not take the CN course and final-year dietology students in a computer-based multiple choice question examination related to core CN competencies that primary-care physicians and dieticians should know and be able to put into practice. The medical students who did not take the CN course correctly answered significantly fewer questions compared with those who did and the dietology students (both p0.001). There was also a difference in the percentages of who passed the test: students who did not take the course: those 18%; those who did: 77%; dietology students: 76% (p0.001).There are numerous barriers to the incorporation of nutrition in Medical School curricula. The medical school students may have achieved poorer results because dietology students followed nutrition education programs later in their curriculum. Our Medical School has therefore included CN education as part of its internal medicine course since 1998.

The Medical Licensing Examination (MLE) is governed, in Italy, by a law enacted in 1956. An ideal clinical competence assessment tool should effectively, reliably and objectively measure all the components of clinical competence: basic knowledge and clinical skills as history-taking, performing a physical examination, formulating the most likely diagnosis, establishing a management plan, communication and interpersonal relations. Since 1998 first session of the MLE, Chieti University implemented computer-based case simulations and standardized patients in the Multimedia Integrated Pilot Project (MIPP) administration. At the present time, we have examined 370 subjects during five sessions of MLE. This preliminary work shows results regarding the examinees in the first examination session of 1998 and 1999. The two groups of examinees are relatively homogeneous for number, age, gender, length of curriculum and country of University degree. In both groups the curriculum scores (preclinical, clinical and total) and the MIPP final score are reported for all subjects, first ten and last ten examinees. The MIPP final score is moderately correlated with the preclinical, clinical and total curriculum scores. Recently, the Federation of State Medical Boards and the National Board of Medical Examiners, sponsoring organisations of the United States Medical Licensing Examination (USMLE), have been planning the implementation of computer-based testing for the USMLE. It is important to point out that our MIPP-based MLE is not a mere didactic experiment, but a legal certifying examination valid for licensure.

To determine whether an excessive, prolonged and, above all, unusual physical exertion could be associated with episodes of mild hypoglycaemia in non-insulin-dependent diabetes mellitus (NIDDM) patients treated with glibenclamide.11 months of observation with retrospective analysis of patient personal diaries to determine the hypoglycaemic risk.Diabetic Unit-Department of Medicine and Aging-Chieti University School of Medicine.We enrolled 340 NIDDM outpatients adjusted for sex, age, body mass index, alcohol intake and oral treatment regimen with glibenclamide. PATIENTS were tested monthly for circadian blood glucose profiles and glycosylated hemoglobin. Mild hypoglycaemia was defined on the basis of blood glucose values2.8 mmol/l associated with mild autonomic symptoms, without requiring external assistance. Each diabetic patient filled personal diary indicating the therapy regimen and the characteristics of eventual hypoglycaemic episodes occurring during the observation period.21.8% of NIDDM patients experienced one or two episodes of mild hypoglycaemia during the observation period. The analysis of the patients' diaries showed that 60% of the hypoglycaemic episodes was associated with excessive, prolonged and unexpected physical exertions. Within this group, about 70% of the episodes occurred during a holiday ("holiday hypoglycaemia"). After analyzing the socio-demographic and clinical characteristics of the diabetic patients reporting hypoglycaemic events, we found a higher risk for "holiday hypoglycaemia" in patients with a lower educational level, with a sedentary occupation or among the ex-farmers.As resulted in the present study, unexpected physical exertions may represent a relevant cause of mild hypoglycaemia in diabetic patients receiving oral antidiabetic therapy. However, this hypoglycaemic cause may have been underestimated in the literature. Educational programs conducted by general practitioners or diabetologists could be useful for the patients in reducing the number of mild hypoglycaemic episodes.

Until now the different epidemiological studies performed have yielded widely different results in terms of the prevalence of hypertension in obese patients. This is mainly due to methodological errors in blood pressure (BP) measurements, including such false positives as white-coat or cuff hypertension, and more recently, to the different distribution in the study population of obese subjects at risk of hypertension (android obesity type). In 803 obese outpatient women (body mass index range: 28-45) randomly selected and subdivided into younger and older groups, and into android and gynaecoid, the casual BP was measured in the morning with a large size cuff. In addition, in 82 obese outpatients casual BP was measured simultaneously with the large and a standard size cuff. Another group of 94 patients was submitted to 24-h ambulatory blood pressure monitoring (ABPM). The aim was to observed if the use of inappropriate cuffs, or the incidence of white-coat hypertension and the prevalence of obese subjects at risk of hypertension, may contribute considerably to overestimating the prevalence of hypertension in obesity. The hypertension prevalence rate was 37.6% for the entire study group. The prevalence rate was 26.2% in women with gynaecoid type of obesity and 47.1% in android obese subjects. We could conclude that the use of inappropriate cuffs, office or white-coat hypertension and the prevalence of obese subjects at risk of hypertension, may contribute considerably to overestimating the prevalence of hypertension in obesity. The number of hypertensive subjects in younger obese subjects with gynaecoid fat distribution is similar to non-obese subjects who are age-adjusted, but our data confirm that the prevalence of hypertension in android type of obesity is significantly higher than in non-obese subjects.

Percutaneous transluminal coronary angioplasty (PTCA) is an established technique in the management of patients with angina pectoris or acute myocardial infarction. One of the major problems related to PTCA is myocardial ischemia following balloon catheter occlusion of the coronary artery. A new device utilized in an attempt to counteract myocardial ischemia is the perfusion balloon catheter which allows passive transmission of pulsatile blood flow to the distal myocardial bed. Our purpose was to compare immediate results following traditional PTCA and autoperfusion balloon PTCA in two groups randomly assigned to receive one of the two treatments (total patients n. = 158). The results show that coronary angioplasty was successfully performed in 98.87% of patients treated with autoperfusion PTCA and in 97.10% of those treated with conventional PTCA. In the autoperfusion PTCA group we observed a lower incidence (statistically significant) of ST elevation and of minor complications. We conclude that autoperfusion balloon catheter angioplasty may be recommended for its immediate success rate with good patient tolerance and lower incidence of in-hospital complications.

Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) was first described in 1985 by McCarty [1], as an isolated syndrome. Subsequently, a similar picture was reported as a clinical manifestation of different rheumatic diseases of the elderly (mainly polymyalgia rheumatica and spondyloarthropathies) [2] and of malignancies [3]. The association with chondrocalcinosis – but not with gout – was also reported [4]. We here describe for the first time a symmetrical pitting edema resembling RS3PE in a patient suffering from gout. In September 2001 we examined a right-handed 76-year-old Caucasian man with a 4-year history of recurrent attacks of gout, involving mainly the first metatarsophalangeal joints and tarsi, but also his wrist and metacarpophalangeal joints. The arthritis lasted 7–10 days and was treated with rest and, sporadically, with NSAIDs. Allopurinol was taken for short periods only. During the previous month the patient reported a new typical attack involving, initially, the left first metatarsophalangeal joint and then the right one, with a concomitant slightly inflammatory pitting edema, localized on the feet and ankles. This picture lasted a week and then remitted spontaneously without persistent damages. After 3 days the wrist and metacarpophalangeal joints were also involved, and a similar inflammatory pitting edema appeared on the dorsum of the hands, the wrists and the forearms. Fever was also present (38 C) in the evening. After a further 2 weeks the patient was admitted to our department. Physical examination showed persistence of the upper limb involvement. A reduced and painful motion of the wrists and of the second and third metacarpophalangeal joints of the left hand was also found. A mild warm redness was present in these areas. History and examination were negative for skin and mucosal diseases, and for bowel, urogenital and ocular disorders. Family history was negative for the above-mentioned diseases. The only findings of note of our extensive laboratory tests were a high ESR (47 mm/h) and C-reactive protein values (4.4 mg/dl), and high levels of uric acid (8.6 mg/ dl). In particular, the followings were normal or negative: rheumatoid factor, Waaler–Rose reaction, serum glucose, serum calcium, serum phosphate, hemoglobin, iron and ferritin determination, antistreptolysin-O antibodies, immunoglobulins, antinuclear antibodies, and liver and renal function. A large amount of uric acid crystals was found in the urine. Roentgenograms confirmed soft-tissue swelling in the involved areas. Gouty osteolytic areas [5, 6] in the second and third metacarpal heads of the left hand were also seen. Chondrocalcinosis was absent. The administration of a 10-day course of meloxicam (15 mg/daily) led to a complete recovery. To our knowledge, a symmetrical inflammatory pitting edema has not been previously found in gouty patients, so our present report increases the number of rheumatic diseases that may be associated with this kind of picture. It also confirms that inflammatory swelling with pitting edema is a non-specific picture that can typically complicate a large number of rheumatic disorders in old age. Characteristics of our case are the Clin Rheumatol (2003) 22: 506–507 DOI 10.1007/s10067-003-0810-6

Recent studies have documented a relationship between increased morbidity and mortality from cardiovascular diseases and a history of weight cycling (WC) in obese subjects. We performed a cross-sectional analysis in 96 weight-cycling android obese women, matched with 96 non-weight-cycling android obese women by age, body mass index (BMI) and waist-to-hip ratio (WHR), to evaluate any increase in blood pressure (BP) levels in association with WC. The patients were all between 20 and 45 years old, were non-menopausal, did not smoke, did not take any medication, had normal glucose tolerance and were otherwise healthy. A history of WC was established on the basis of at least five weight losses in the previous 5 years due to dieting, with a weight loss of at least 4.5 kg per cycle. We documented higher levels of casual BP in the weight-cycling obese compared with the non-weight-cycling subjects: 147±12/90±8 mmHg versus 125±14/79±8 mmHg (P < 0.001). The women with WC showed a statistically significant positive correlation between BP and age, weight, BMI, waist circumference, WHR, total weight regained and weight cycling index (WCI). However, in a multiple regression model only the WHR and WCI contributed significantly to the BP variability. These findings could support the hypothesis that it is the combined exposure of central-type obesity and WC that strongly raises the prediction of hypertension.

Treatment of mild hypertension with an antihypertensive drug administered by means of a transdermal therapeutic system (TTS) could produce favorable results, when compared with a traditional oral regimen.Using 24-h ambulatory blood pressure (BP) monitoring (ABPM) in mild hypertensive male subjects, to analyze three aspects which have not been completely clarified: a) whether a latency in the antihypertensive effect may be present, recording BP already from the first day of application of the patch, b) the eventual hazardous enhancement of circadian nocturnal fall in BP values in treated mild hypertensive patients and, c) the possible overlapping of antihypertensive effect between the administration of two consecutive patches.In 12 caucasian male outpatients (yrs 55 +/- 3 SEM) with uncomplicated essential mild hypertension, a patch containing placebo was applied for the first week (T 0 period). At the end of the T 0 period, a 5 mg TTS-2 clonidine patch was applied for one week, and, subsequently, a new patch of 5 mg TTS-2 clonidine was kept for another week. ABPM was performed on the last day of the placebo period (T 0) and on the 1st day (T1), the 7th day (T2) and the 14th day (T3) of transdermal clonidine therapy.Both systolic and diastolic BP (24 h mean, day-night-time) decreased on the 1st, 7th and 14th day, when compared with T0. However, no significant differences were documented between the BP levels on the 1st and the 7th day of treatment. The incidence of nocturnal fall in systolic and diastolic BP was evaluated and no significant differences were found, when compared with night-time reference values.When compared with the placebo period, TTS-2 clonidine lowers SBP and DBP within the first 24 hours of application. The antihypertensive effect persists at the end of the first week, as well as after 14 days. The lowest values of systolic-diastolic BP documented were not below the levels reported in normotensive men. Therefore, TTS-2 clonidine seems to act as an antihypertensive agent rather than a hypotensive drug since it normalizes BP without lowering it below physiological levels.