Management of community-acquired pneumonia by trained family general practitioners.

SETTING: Community-acquired pneumonia (CAP) is a respiratory health disease with a high prevalence in the general population. Family general practitioners (GPs) can play an important role in CAP management by reducing unnecessary hospital admissions and, consequently, national health costs. OBJECTIVE: To assess CAP management by trained GPs. DESIGN: A course in CAP management, including a risk classification method based only on clinical criteria, was developed within the framework of an educational programme. GPs who participated in the programme (n = 220) were asked to collect data on their CAP patients. RESULTS: GPs (n = 94, response rate 42.7%) provided information on 370 patients (50% males, aged 18-93 years). The numbers of patients judged to be at low, moderate and high risk were 81%, 13% and 6%, respectively. The admission rate was 19.5%. All home-treated patients had good clinical outcomes. Home treatment was based on quinolones (62%), beta-lactams (23%) and macrolides (15%). The attributable economic mean cost of antibiotic home treatment was euro 96 per episode (standard deviation 71, range 17-445). CONCLUSIONS: The good outcomes suggest that GPs managed their CAP patients well, adhering to the content of the CAP management course. The risk evaluation of patients admitted to hospital, based exclusively on clinical elements, was consistent with more complex classification.

[Cerivastatin. Which lessons for clinical practice?]. / Cerivastatina. Quale lezione per la pratica clinica?

The event of cerivastatin is the starting point for several methodological issues that, in the era of evidence-based medicine, should be the scientific basis of clinical practice. The article goes into three main issues: the production of evidence about efficacy of drugs, their safety profile through the collection of data about adverse drug reactions and the appropriateness of drug prescription.

Clinical evaluation of pancreatitis-associated protein as a serum marker of hepatocellular carcinoma: comparison with alpha-fetoprotein.

This study evaluated the significance of serum pancreatitis-associated protein (PAP) assay, as a marker of hepatocellular carcinoma (HCC), in comparison and combined with alpha-fetoprotein (AFP) assay. Sixty-five patients with HCC, 59 with liver cirrhosis (LC) and 68 asymptomatic controls (C) were studied. PAP and AFP values significantly increased from C to LC and HCC group (p < 0.0001). The area under receiver-operating characteristic (ROC) curve for the two markers was not statistically different. At 100% specificity, ROC analysis gave a cut-off level for AFP of 166 IU/l with 40% sensitivity, and a cut-off level of 240 microg/l for PAP with 23% sensitivity. Diagnostic accuracy of combined AFP and PAP assay was significantly higher than AFP alone. Sensitivity according to tumor size also improved using the combined assay, especially for tumors <5 cm. Stepwise logistic regression indicated that AFP, but not PAP, was associated with an increased risk of developing HCC. These data confirm that PAP production is increased only in some cases of HCC and that the combined PAP and AFP assays do not significantly improve specificity over AFP assay alone. Consequently, PAP assay can only be recommended in cases of justified suspicion of HCC with negative AFP.

[Evidence-based medicine. 2. Research of clinically relevant biomedical information. Gruppo Italiano per la Medicina Basata sulle Evidenze--GIMBE]. / Evidence-based medicine. 2. La ricerca dell'informazione biomedica clinicamente rilevante. Gruppo Italiano per la Medicina Basata sulle Evidenze--GIMBE.

Evidence-based Medicine is a product of the electronic information age and there are several databases useful for practice it--MEDLINE, EMBASE, specialized compendiums of evidence (Cochrane Library, Best Evidence), practice guidelines--most of them free available through Internet, that offers a growing number of health resources. Because searching best evidence is a basic step to practice Evidence-based Medicine, this second review (the first one has been published in the issue of March 1998) has the aim to provide physicians tools and skills for retrieving relevant biomedical information. Therefore, we discuss about strategies for managing information overload, analyze characteristics, usefulness and limits of medical databases and explain how to use MEDLINE in day-to-day clinical practice.

[Evidence-based medicine. 3. Systematic reviews: a tool for clinical practice, permanent education and health policy decisions. Italian Group on Evidence-Based Medicine-GIMBE]. / Evidence-based medicine. 3. Le revisioni sistematiche: uno strumento per la pratica clinica, la formazione permanente e le decisioni di politica sanitaria. Gruppo Italiano per la Medicina Basata sulle Evidenze-GIMBE.

The reviews of research, summarizing a great amount of studies in a manageable format, are invaluable tools for physicians, inundated with enormous amount of biomedical information. However, narrative reviews are often misleading because, mixing together opinions of authors and results of research, the relation between clinical recommendation and evidence is partial and based on a biased citation of primary studies. In contrast to narrative reviews, the systematic reviews assemble, critically appraise, and synthesize the results of primary studies addressing a specific topic. Additionally their authors use strategies for minimizing bias and random error. The science of systematic reviews is now supported by the Cochrane Collaboration, an international network established for "preparing, maintaining and disseminating systematic reviews of the effects of health care". The authors provide tools for searching, critically appraising and using in practice the systematic reviews, which use can help physicians to improve the transfer of research in clinical practice, a task obliged by limitation of financial resources to physicians of any health service.

[Evidence-based medicine. How to use biomedical literature to solve clinical problems. Italian Group on Evidence-Based Medicine-GIMBE]. / Evidence-based medicine. Come usare la letteratura biomedica per risolvere i problemi clinici. Gruppo Italiano per la Medicina Basata sulle Evidenze-GIMBE.

Clinical practice is constantly changing, the rate of changing is accelerating and consequently it may even take years before the results of clinical research will be incorporated in day-to-day practice. So, there is a large gap between what the biomedical literature contains and the care that most of patients receive. The gap is widened by the extensive processing that results of clinical research require before they can be used. Evidence-based medicine is a new approach to health care promoting the collection, interpretation, and integration of valid, important and applicable research-derived evidence. The best available evidence, moderated by patient circumstances and preferences, is applied to improve the quality of clinical judgements. There are many information tools that facilitate the practice of evidence-based medicine. These include users' guides to the medical literature, strategies to improve the yield of MEDLINE searches, standardized formats for abstracts of journal articles and guidelines, new journals, systematic reviews and meta-analyses, resources on-line and software tools bringing high quality information to the point of clinical decision making. However, these tools are poorly spread and physicians lack of necessary skills for their effective utilization. In this article the authors describe guidelines for efficient and effective utilization of biomedical information tools to solve clinical problems and improve the quality and the cost/effectiveness of health care.

Intravenous natural beta-interferon in white patients with chronic hepatitis C who are nonresponders to alpha-interferon.

OBJECTIVES: alpha-Interferons (alpha-IFN) have been shown to be effective in the treatment of chronic viral C hepatitis, but their efficacy remains unsatisfactory. Recently natural beta-interferon (beta-IFN) administered by intravenous infusion has been used successfully. METHODS: To evaluate the efficacy and safety of intravenous beta-IFN administration we treated 20 patients with histologically proven chronic hepatitis C who were nonresponders to at least two previous courses of alpha-IFN treatment. All patients received 6 million units (MU) of natural human fibroblast beta-IFN by drip infusion, 6 times per wk for 8 wk and were followed up for 6 months after suspension of treatment. RESULTS: Five patients (25%) had response at the end of treatment; of these patients only one had sustained response. Patients who responded to therapy had lower, although not significantly, baseline levels of HCV RNA, compared with nonresponders. Whereas mean viral load decreased during therapy, only two patients were HCV RNA negative at the end of treatment, but none were at the end of the follow-up period. Genotype 1 was found in 17 cases, genotype 2 was found in one case, and a combination of genotypes 1b and 2a was found in the remaining two cases. Therapy was well tolerated and beta-IFN administration was neither interrupted nor its dosage reduced due to side effects in any of the patients. CONCLUSIONS: Our study shows that intravenous beta-IFN is well tolerated and that the modest results obtained may depend on the brevity of treatment. Consequently, further studies are needed to define the optimum dose, schedule, and duration of treatment to eradicate HCV infection.

[Evidence-based medicine. 1. The transfer of research results to clinical practice. The Italian Group for Evidence-Based Medicine-GIMBE]. / Evidence-based medicine. 1. Il trasferimento dei risultati della ricerca alla pratica clinica. Gruppo Italiano per la Medicina Basata sulle Evidenze-GIMBE.

Evidence-based Medicine, born officially in November 1992, during last five years is grown everywhere, showing its power to influence virtually all aspects of health care: clinical practice, medical education, patient information and health policy. Because of the raising interest also in Italy for the new paradigm of clinical practice, "Recently Progress in Medicina" launches a series of articles with the aim of giving to physicians tools and skills for searching, critically appraising and implementing in their own decisions the best results of clinical research. For a better explanation of practical aspects of Evidence-based Medicine, the first article discusses about several obstacles existing in transferring correctly and timely the results of research into clinical practice, and about the potential role of Evidence-based Medicine in the evolution of the medical art and the health systems of the third millennium.

Transmission of hepatitis C virus: a study of the main risk factors in a Sicilian population of volunteer blood donors.

BACKGROUND/AIMS: The Hepatitis C virus (HCV) is quite widespread in Sicily, and in the absence of a vaccine, prophylaxis is important. In order to determine the most effective means of prophylaxis, we must first understand the main vectors of transmission. METHODOLOGY: We performed a case control study on 274 consecutive anti-HCV virus positive subjects and compared them with 548 anti-HCV negative subjects, matched for sex and age and selected from voluntary blood donors. The modes of transmission were investigated by means of a detailed questionnaire focused on the common risk factors of HCV contagion. RESULTS: Univariate analysis showed associations between HCV infection and transfusions (OR 23.0), surgery (OR 2.2), family history of chronic liver disease (OR 4.54), and drug addiction (OR 5.74). Multiple logistic regression indicated that transfusions (p < 0.0001), surgery (p < 0.002), family history (p < 0.0001), drug addiction (p < 0.002) and alcohol consumption (p < 0.002) are related to the development of HCV infection. CONCLUSIONS: The modes of transmission of HCV in an endemic area of Sicily do not greatly differ from those in other Italian regions; the subjects at greatest risk were those who had received blood transfusions or underwent surgery, alcoholics, drug abusers and those with a family history of chronic liver disease, who are probably more exposed to contracting the infection by non-conventional ways of transmission.

Comparative responses to three different types of interferon-alpha in patients with chronic hepatitis C.

We investigated the efficacy and tolerability of three different types of interferon-alpha, administered with the same schedule to naive patients with chronic hepatitis C. One hundred and seven patients with histologically proven chronic hepatitis C were enrolled during a period of three years and randomly divided into three groups, to receive (a) leukocyte-interferon-alpha, 6 MU three times a week for 4 months, followed by 3 MU three times a week for 8 months (Group I); (b) recombinant-IFN-alpha-2a, with the same schedule (Group II); and (c) lymphoblastoid-IFN-alpha-N1, with the same schedule (Group III). All patients were followed-up for 6 months to evaluate the long-term response. The 'Complete Response' rates at the end of treatment were: 50%, 46.1% and 41.6%, in Groups I, II and III, respectively; most patients relapsed after the end of therapy, so that the 'sustained responders' were, after 6 months of follow-up, 18.7%, 23.1% and 19.4%, respectively. Analysis of pre-treatment variables showed that age, ALT and gamma GT serum levels, as well as the prevalence of liver cirrhosis, were lower in the 'sustained responder' group. Four patients were eliminated from the study because of severe adverse events: 1, 2 and 1, in Groups I, II and III, respectively. Our results indicate a similar response rate with the three different types of interferon-alpha, although at baseline, age, serum levels of gamma globulins and the number of patients with cirrhosis-possible negative-risk factors, were higher in Group I.

Circulating intercellular adhesion molecule-1 in patients with hepatocellular carcinoma.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is thought to play an important role in cellular immunological reactions. Expression can be induced by inflammatory cytokines in a wide variety of cells, including hepatocytes. OBJECTIVE: To compare the behaviour of ICAM-1 in liver diseases. PATIENTS AND METHODS: We assayed serum ICAM-1 (sICAM-1) in patients with hepatocellular carcinoma-associated liver cirrhosis, and compared them with a group of cirrhotic patients and controls. sICAM-1 values were also correlated with some biochemical parameters of liver function. Moreover, immunohistochemical localization of ICAM-1 was performed on liver tissue sections of patients with hepatocellular carcinoma, liver cirrhosis and a sample of normal liver. RESULTS: sICAM-1 levels were significantly higher in the hepatocellular carcinoma patients than in controls (P < 0.0001) and the cirrhosis group (P < 0.001). sICAM-1 values directly correlated with alanine aminotransferase, total bilirubin, alkaline phosphatase and gamma-glutamyltranspeptidase serum values (P < 0.05), with an inverse correlation with albuminaemia values (P < 0.05). There was no correlation with alpha-fetoprotein values, but sICAM-1 values were higher in hepatocellular carcinoma patients with large tumours (> 3 cm) than in those with small tumours (< 3 cm) (P < 0.04). Immunohistochemical localization of ICAM-1 was negative in normal liver tissue; positive staining for endothelial cells was found in chronic liver disease, while in hepatocellular carcinoma tissues, positive membrane staining was observed in hepatocytes and, to a lesser extent, at the cytoplasmic level. CONCLUSION: These results suggest that high serum levels of sICAM-1 are associated with severe liver disease, such as liver cirrhosis and hepatocellular carcinoma, and that they tend to increase with deteriorating hepatic function and tumour size.

[Levels of scientific evidence and strength of clinical recommendations. From trials to guidelines. The Italian Group on Medicine Based on Evidence--(GIMBE)]. / Livelli di evidenza scientifica e forza delle raccomandazioni cliniche. Dai trials alle linee-guida. Gruppo Italiano per la Medicina Basata sulle Evidenze--(GIMBE).

Evidence-based medicine is a new paradigm of clinical practice that promotes the collection, interpretation and integration of valid, important and applicable to patients research-derived evidence, and it can improve the efficiency and the effectiveness of health care. Nevertheless research often fails to get in clinical practice, also because the traditional tools used by physicians to solve clinical problems are less reliable as the volume/complexity of medical information and biomedical technology have grown exponentially. New tools are emerging to help physicians: the systematic reviews of randomized controlled trials and the clinical practice guidelines that summarize a great volume of medical knowledge to improve health care. Practice guidelines, with a systematic review or meta-analysis pertaining to a definite health problem, summarize the evidence of clinical trials in clinical recommendation. These combine the strength and heterogeneity of the primary studies with magnitude and precision of the treatment effects as it relates to the minimal clinical benefit. The recommendation may suggest therapeutic intervention when the baseline risk is high or otherwise when the baseline risk is low. The Authors discuss principles of evidence-based medicine, measures of treatment effectiveness, systematic reviews and methods used by experts to graduate the strength of clinical recommendations in producing practice guidelines.

Influence of haemodialysis on lipase activity.

Our aim was to determine whether the increase in serum pancreatic lipase values, reported in patients with chronic renal failure maintained on haemodialysis, is the result of haemoconcentration by fluid removal during dialysis, or whether it is due to lipase stimulation by endothelial lipoprotein lipase, induced by the heparin used as an anticoagulant. We therefore compared the increases in serum lipase, when heparin was used, with those observed when this was replaced by the antithrombotic agent, defibrotide, which has no effect on lipoprotein lipase. In addition, in order to determine the effects of haemoconcentration, variations in total protein concentration and haematocrit values were determined on the same samples, both before and after dialysis. The results showed a statistically significant post-dialysis increase in lipase only when heparin was used (p < 0.03). There was also a mean percentage post-dialysis increase of 16.2% in total protein (p < 0.0001) and 15.5% in haematocrit (p < 0.0001), due to fluid removal. No significant correlation in percentage increases was found between lipase vs total protein or haematocrit values. These findings suggest that heparin-induced lipoprotein lipase stimulation is the principal cause of the post-dialysis increase in pancreatic lipase, and that fluid removal during dialysis makes only a minor contribution to this increase.

[Serum variations of 2 markers of fibrogenesis in chronic hepatitis C treated with alpha interferon]. / Variazioni sieriche di due marcatori di fibrogenesi in corso di epatiti croniche C trattate con alfa interferone.

We evaluated variations in serum levels of N-terminal peptide of type III procollagen (PIIIP) and laminin (Lam-P1) in 36 anti-HCV positive patients, confirmed by RIBA II, with chronic hepatitis treated with alpha interferon (IFN) at a dose of 6 million units (MU) three times for week for 6 months, followed by 3 MU three times for week for a further 6 months. We consider responders (R) those patients who after one year of therapy had normalized ALT levels, and non-responders (NR) the remaining subjects. Serum PIIIP and Lam-P1 were determined by RIA on entry to the study and at 12 months. Ten patients underwent a percutaneous liver biopsy also at the end of the therapy for the histological evaluation of the necroinflammatory activity and fibrosis according to the Knodell score system. Overall, at the end of therapy, the mean levels of both markers were lower than at entry to the study, with a statistically significance only for the Lam-P1 values (p < 0.05). When, however, we divided the patients into R (n = 15) and NR (n = 21) subgroups, the mean baseline values of both markers were significantly higher in NR vs controls and after therapy there was a significantly reduction only for PIIIP values (p < 0.01). In the group of R there is a slight, but not significantly reduction of both markers. The comparison of the Knodell's score before and after IFN treatment showed an improvement of the necroinflammatory activity, but not of fibrosis. In conclusion patients R to IFN therapy have lower baseline values of PIIIP and Lam-P1 than NR and therapy with IFN improves the serum values of PIIIP as well as the score of the necroinflammatory activity.

Sex hormones in patients with liver cirrhosis and hepatocellular carcinoma.

Sex hormones have been proposed to play an important role in promoting liver cancer transformation. The aim of our study was to evaluate changes in circulating levels of estradiol (EII), testosterone (T) and the EII/T relationship (ETR) in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) of viral origin compared with a group of healthy controls (C). The study population included 64 patients (41 M) mean age 62.5 years with HCC; 68 patients (41 M) mean age 61.3 years suffering from LC, while the C included 59 subjects (39 M) mean age 60.0 years recruited from voluntary blood donors. EII and T were assayed using the IEMA method; ultrasonography was performed using a Toshiba SSA 240 A scanner with a convex 3.75 MHz probe. Serum EII levels progressively increased from C to LC and HCC with statistically significant values (H=36.9, p<0.0001). Serum values of T progressively decreased from C to LC and HCC but the difference was not significant (H=3.84, p=ns). ETR values differed in the three groups, with a significant difference between C vs LC and HCC (p<0.0001). There was also a significant difference for EII, with values decreasing as the neoplasm dimension increased (p<0.04), and in particular there were differences between HCC <5 cm vs >5 cm (p<0.05). In contrast, ETR progressively increased as the diameter of neoplasm increased, but differences were significant only between <3 cm vs >5 cm (p<0.05). In conclusion, our data confirm that in LC and HCC there is an increase in serum EII levels, which can be important in the genesis of liver carcinoma. Progressive serum reduction in T may be due to increased androgen uptake and progressive accumulation within the neoplastic mass. Further studies are necessary to determine whether subjects with LC and elevated serum levels of estrogens are at higher risk of developing HCC.

[Evidence-based medicine: the emerging of a new model of clinical practice. Italian Group for Evidence-Based Medicine (GIMBE)]. / La medicina basata sulle evidenze: emerge un nuovo modello di pratica clinica. Gruppo Italiano per la Medicina Basata sulle Evidenze (GIMBE).

The introduction of the Diagnosis-Related Groups System to finance Italian hospitals has troubled not only health policy makers but also single physicians, who find themselves in the position of "resource managers" lacking adequate competence to evaluate the effectiveness of medical interventions. Given the limited economic resources and the failure of exclusively managerial-organizational-based solutions, the use of work-related methodologies able to identify and enable diagnostic and therapeutic interventions of documented efficacy for all patients has become a necessity. Evidence-based medicine is an emerging paradigm of clinical practice: promoted by the formulation of specific problems, it is implemented by the collection, interpretation and integration of research-derived evidence. This new model, which facilitates the transfer of progress made in research to clinical practice thanks to the promotion of diagnostic and therapeutic interventions of documented efficacy, can improve the effectiveness and efficiency of health care. The authors review the cultural events that have encouraged the development of this new paradigm of clinical practice, describe its methods, advantages and limits and point out differences from traditional models.

[Factors predicting the response to alpha-interferon therapy in patients with chronic hepatitis C]. / Fattori predittivi di risposta al trattamento con alfa interferone in pazienti con epatopatia cronica anti-HCV positiva.

Objective of the study was to identify predictive factors of response to treatment with interferon in patients with anti-HCV positive chronic liver disease. 92 anti-HCV positive patients, 51 with chronic hepatitis and 41 with active cirrhosis, were treated for 12 months with recombinant alpha 2a interferon at a starting dose of 6 MU TIW/6 months, followed by 3 MU TIW/6 months. Patients were considered responders (RS) when they presented normal serum ALT values both at the end of treatment and after 6 months of follow-up; relapsers (RC) those with normal ALT values at the end of treatment but with increase during the 6 months of follow-up and non-responders (NR) patients who had no beneficial effect on ALT levels during treatment. 21 patients were RS, 11 RC and 60 cases NR. Univariate analysis of pre-treatment factors showed that response to interferon was associated with absence of cirrhosis and lower gamma-GT levels in RS than in RC. Multiple logistic regression of these variables showed that gamma-GT levels and absence of cirrhosis were the only independent factors associated with response to treatment. In conclusion, in our series of patients, only two factors were confirmed useful in predicting response to interferon treatment and it is concluded that they must always be evaluated before starting treatment with interferon which is not without side effects and may not have beneficial effect.