Are sales representatives and the sale strategies of pharmaceutical companies getting too aggressive towards physicians?
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Biomedical subjects
Publications and source records attributed to A Bianco.
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BACKGROUND: Frail patients with non-Hodgkin's lymphoma (NHL) are generally excluded from clinical trials and not even treated. The aim of this study was to evaluate the efficacy and tolerability of vinorelbine and prednisone in frail elderly patients with NHL. PATIENTS AND METHODS: Thirty consecutive frail elderly patients were entered in a phase II study with vinorelbine 25 mg/m2 i.v. on days 1 and 8 and oral prednisone 30 mg total dose on days 1-8 for six cycles. Criteria of frailty were age > or =80 years, or age > or =70 years and three or more comorbidities of grade 3 or at least one comorbidity of grade 4 according to the Cumulative Illness Rating Scale (CIRS), or not self-sufficient or the presence of one or more geriatric syndromes. RESULTS: Of 30 evaluable patients, three (10.0%) achieved a complete response (CR), nine (30.0%) showed a partial response (PR), while 10 presented with stable disease and eight with progressive disease. The median duration of CR was 29 months (range 5-36 months), and the median duration of PR was 1 month (range 1-22 months). Three patients had grade 3 neutropenia and one had grade 4. One grade 4 neurotoxicity was observed. Three patients died because of heart failure within 28 days of therapy, and one patient died after 4 days because of rapid progression. The median overall survival was only 10 months. CONCLUSION: Vinorelbine and prednisone is a relatively non-toxic combination with modest activity in frail patients with NHL. If initial aggressive chemotherapy has been excluded, this combination could be tried to obtain a temporary palliation.
The study explores the awareness of technical terms used in evidence-based medicine (EBM) and manner of treating patients with migraine among a random sample of 500 general practitioners (GPs). A mailed questionnaire included questions on GPs' demographics and practice characteristics; awareness of EBM; sources of information about migraine and EBM; and patient's treatment behaviour. Only 27.2% of GPs agreed that clinical trials are needed to evaluate the efficacy of treatments and this awareness was higher in those who learned about migraine from scientific journals or continuing education courses and who attended courses on EBM. For two-thirds of GPs, disability is equivalent to illness diagnosis, and this behaviour was more prevalent in those who agreed that clinical trials are needed to evaluate the efficacy of preventive or curative treatments of migraine and that the clinical approach to migraine required an evaluation of clinical effectiveness, in those who treated a lower number of headache patients, who were older, and in those who did not use guidelines. The majority (93.1%) of GPs indicated that it is important to integrate clinical practice and the best available evidence, and this behaviour was significantly more frequent in those who agreed that the clinical approach to migraine required a clinical effectiveness evaluation, that clinical trials are needed to evaluate the efficacy of preventive or curative treatments of migraine, and in those who attended courses on EBM. Training and continuing educational programmes on EBM and guidelines on treatments of headache for GPs are strongly needed.
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We analyze the infrared and Raman spectra (both experimentally and with the aid of quantum chemical calculations) of a series of polyenals which provide us with the fortunate case of a set of polyene chains with one of the end groups consisting of a C=O group which not only does take part in the conjugation but also pulls electrons from the chain making the whole system highly polar, thus affecting the vibrational transition moments. In the following we show, for the first time, that it is possible to derive experimental phonon dispersion curves and these prove to be different for each chain length. We support our experimental findings with Density Functional Theory quantum chemical calculations which reproduce with sufficient accuracy the IR and Raman spectral pattern and at the same time help in disentangling the assignment of the fine structure observed in the experimental spectra.
The purpose of this study was to determine the extent of inappropriate admissions and days of stay in acute beds of patients who were admitted to hospital after attending the emergency department for urgent medical attention in Italy. The medical records of all adult patients (aged 16 years and over) on one randomly preselected day during the period January-December 2001 were reviewed. The retrospective application was made using the Appropriateness Evaluation Protocol list of criteria. Overall, 28.4 and 75.7% of hospital admissions and days of stay, respectively, were judged to be inappropriate. Results of the multiple logistic regression analysis indicated that inappropriate admission was significantly more likely in patients who lived closer to hospital, in younger patients, in patients from lower socio-economic classes, and in patients who did not receive diagnostic procedures in the emergency department. The proportion of patients whose admission was considered inappropriate was significantly lower in medical specialties wards. The number of inappropriate hospitalisation days was significantly higher in younger patients, in those admitted inappropriately, and in patients sampled close to discharge (during the final-third of his/her stay). The number of inappropriate hospitalisation days was significantly lower in patients admitted to surgical and traumatology/orthopaedics and medical specialties wards. Our findings indicate the need for specific interventions to reduce the prevalence of inappropriate hospital use and to modify physicians' attitudes and behaviours.
The occurrence of iridoid glycosides in a number of Cymbalaria spp. collected in Italy is shown and chemosystematic implications are discussed.
The purpose of this study was to determine the extent of non-urgent visits and the effect of different characteristics on such visits to one public hospital emergency department located in Catanzaro, Italy. Of 581 patients aged 15 years and older who were registered for care in the emergency department, 40 were excluded from the study as they were too ill or distressed. The survey questionnaire included questions about the patients' demographic and socio-economic characteristics, distance from home to hospital, usual health status and health status at the time of presentation to the emergency department. Of the 541 patients who agreed to participate, 19.6% of patients, according to the judgement of two observers, had non-urgent conditions. The results of the multiple logistic regression analysis showed that among all variables tested, age and sex were significant predisposing factors for utilization of the emergency department for non-urgent visits. Indeed, the odds of presenting for non-urgent care were significantly higher if patients were younger and female. Moreover, the odds of requiring non-urgent care were significantly higher in patients who present to the emergency department without medical referral and in patients who present with problems of longer duration. The most frequent reason given by patients for their visit to the emergency department was that they felt their problem was an emergency. Further investigations are necessary to evaluate the use of primary care since closer co-operation within the healthcare organization system may provide a more responsive service.
Clinical manifestations of pulmonary tuberculosis (TB) may depend on a complex interaction between the host and the pathogen. Clinical outcomes of pulmonary tuberculosis are variable, ranging from asymptomatic lifelong infection to parenchymal lung destruction, resulting in cavitary lesions. To investigate the hypothesis that local cellular immune response may affect presentation and outcome in tuberculosis, we performed bronchoalveolar lavage (BAL) in lung segments affected by cavitary and non-cavitary tuberculosis. We then correlated the type of cellular response at the level of the involved lung segments with clinical evolution in terms of cavity formation. We found alveolar lymphocytosis in patients with both cavitary and non-cavitary pulmonary tuberculosis, with increased CD4+ lymphocytes in patients with non-cavitary pulmonary tuberculosis. A predominant Th1 immune response has been observed in non-cavitary patients, while cavitary involved segments exhibit the presence of Th2 lymphocyte subsets. These data, while confirming the importance of Th1-type CD4+ cells and IFN-gamma in effective cellular immunity in active pulmonary tuberculosis, also suggest that the presence of Th2 lymphocytes may contribute to tissue necrosis phenomena associated with cavitary evolution of pulmonary tuberculosis. Our observations indicate the importance of the type of local immune response at the site of disease in the development of different clinical characteristics and outcome in pulmonary tuberculosis.
BACKGROUND: The colonic ischemic necrosis is one of the most serious complication in the surgical reconstruction of abdominal aorta aneurysm (AAA) due to surgical inappropriate binding of the inferior mesenteric artery (IMA). METHODS: A retrospective analyzed of a group of 118 infrarenal AAA surgically treated is presented. RESULTS: The most common cause of ischemic colitis (75% of cases) is the surgical binding of an opened IMA or its failed reimplantation. CONCLUSIONS: In this paper according to their personal experience and the literature data, the authors outline a diagnostic behaviour to select the patients needing the reimplantation of IMA; they suggest to complete the pre operative information with an instrumental evaluation during the surgical treatment.
The diverticular disease is rarely located in the small intestine (0.1-1.4%). The most important feature is due to the lack of a typical symptomatology which may appear only on the occasion of the complications it may incur (perforation, haemorrhage and so on). It isn't also infrequent that the surgeon may observe intestinal diverticula accidentally, on the occasion of laparotomies carried out in emergency or for other pathologies. The literature on intestinal diverticula is reviewed and personal experience in a clinical case presenting as acute abdomen is described.
This study describes the extent of inappropriate day-hospital assistance and the effect of different variables on such inappropriateness. A random sample of patients admitted to pediatric and adult day-hospital care during the period Janurary--December 2000 in three hospitals located in the area of Catanzaro, Italy were reviewed. Assessment of appropriateness was made for the first access and for each of the following accesses in day-hospital. A total of 826 patients were reviewed. Overall, 23.8% of the first access in day-hospital care was judged to be inappropriate and 49.7% of the sample showed at least one inappropriate access for day-hospital care with a mean of 1.4 inappropriate accesses. Multiple logistic regression analysis indicated that the inappropriateness of the first access significantly increased with relation to lower distance from hospital to patient's home; admission to general medicine wards; first access from Monday to Thursday; lower number of patient's diagnostic procedures and medical examinations in the first access. Stepwise multiple linear regression analysis showed that the number of inappropriate accesses was significantly higher for general medicine and surgery and trauma/orthopedics wards; in patients who the first access was inappropriate; in those who received a lower number of diagnostic procedures and medical examinations; in patients who showed a higher length of care in day-hospital. The findings suggest the need for standardized diagnostic and therapeutic guidelines for day-hospital care.
Cytotoxic T-lymphocyte (CTL) responses directed to different human immunodeficiency virus (HIV) epitopes vary in their protective efficacy. In particular, HIV-infected cells are much more sensitive to lysis by anti-Gag/p17(77-85)/HLA-A2 than to that by anti-polymerase/RT(476-484)/HLA-A2 CTL, because of a higher density of p17(77-85) complexes. This report describes multiple processing steps favoring the generation of p17(77-85) complexes: (i) the exact COOH-terminal cleavage of epitopes by cellular proteases occurred faster and more frequently for p17(77-85) than for RT(476-484), and (ii) the binding efficiency of the transporter associated with antigen processing was greater for p17(77-85) precursors than for the RT(476-484) epitope. Surprisingly, these peptides, which differed markedly in their antigenicity, displayed qualitatively and quantitatively similar immunogenicity, suggesting differences in the mechanisms governing these phenomena. Here, we discuss the mechanisms responsible for such differences.
Peptidomimetics of the major histocompatibility complex (MHC) class I-restricted ovalbumin-derived T cell epitope SIINFEKL were generated by replacing parts of the peptide backbone by a poly-N-acylated amine (PAA) backbone with aromatic, heteroaromatic, and pseudoaromatic side chains that branch off of the main chain at the amine nitrogen. The structure of the PAAs was designed to position this side chain in the central epitope anchor pocket of the MHC molecule. A number of biologically active PAAs were found that induced cytolysis by the mouse cytotoxic T cell clone 4G3. Competition experiments with independent peptides that are known to bind to the restricting MHC molecule H-2K(b) suggest that the PAAs are bound by the MHC molecules at the same site as conventional peptide epitopes. The PAAs were active also in vivo and induced primary cytotoxic T cell responses in mice.
First and foremost among the many factors that influence epitope presentation are the degradation of Ag, which results in peptide liberation, and the presence of HLA class I molecules able to present the peptides to T lymphocytes. To define the regions of HIV-1 Nef that can provide multiple T cell epitopes, we analyzed the Nef sequence and determined that there are 73 peptides containing 81 HLA-binding motifs. We tested the binding of these peptides to six common HLA molecules (HLA-A2, -A3, -A24, -B7, -B8, and -B35), and we showed that most of them were efficient binders (54% of motifs), especially peptides associating with HLA-A3, -B7/35, and -B8 molecules. Nef peptides most frequently recognized by T cells of HIV-1-infected individuals were 90-97, 135-143, 71-81, 77-85, 90-100, 73-82, and 128-137. The frequency of T cell recognition was not directly related to the strength of peptide-HLA binding. The generation of Nef epitopes is crucial; therefore, we investigated the digestion by the 20S proteasome of a large peptide, Nef(66-100). This fragment was efficiently cleaved, and NH(2)-terminally extended precursors of epitope 71-81 were recognized by T cells of an HIV-1-infected individual. These results suggest that a high frequency of T cell recognition may depend on proteasome cleavage.
The structure of the 19-amino acid peptide epitope, corresponding to the 141-159 sequence of capsid viral protein VP1 of foot-and-mouth disease virus (FMDV), bound to three different resins, namely, polystyrene-MBHA, PEGA, and POEPOP, has been determined by high-resolution magic angle spinning (HRMAS) NMR spectroscopy. A combination of homonuclear and heteronuclear bidimensional experiments was used for the complete peptide resonance assignment and the qualitative characterization of the peptide folding. The influence of the chemicophysical nature of the different polymers on the secondary structure of the covalently attached FMDV peptide was studied in detail. In the case of polystyrene-MBHA and polyacrylamide-PEGA resins, the analysis of the 2D spectra was hampered by missing signals and extensive overlaps, and only a propensity toward a peptide secondary structure could be derived from the assigned NOE correlations. When the FMDV peptide was linked to the polyoxyethylene-based POEPOP resin, it was found to adopt in dimethylformamide a helical conformation encompassing the C-terminal domain from residues 152 to 159. This conformation is very close to that of the free peptide previously analyzed in 2,2,2-trifluoroethanol. Our study clearly demonstrates that a regular helical structure can be adopted by a resin-bound bioactive peptide. Moreover, a change in the folding was observed when the same peptide-POEPOP conjugate was swollen in aqueous solution, displaying the same conformational features as the free peptide in water. The possibility of studying solid-supported ordered secondary structures by the HRMAS NMR technique in a wide range of solvents can be extended either to other biologically relevant peptides and proteins or to new synthetic oligomers.