Bone remodelling and integration of two different types of short stem: a dual-energy X-ray - absorptiometry study.

PURPOSE: Different kinds of bone preserving hip stems have been created to assure a more physiological distribution of the strengths on the femur. The aim of this research is to evaluate the density reaction of the periprosthetic bone while changing the conformation of the prosthetic implant on dual-energy X-ray - absorptiometry (DXA). METHODS: This is a prospective, single-centre study assessing bone remodelling changes after implantation of two short hip stems, dividing the patients in two groups according to the implant used: 20 in group A, Metha (B-Braun), and 16 in group B, SMF (Smith and Nephew). All participants had a pre-operative and a post-operative (24 months) DXA evaluating the changes in bone mass density (BMD) occurred in the five Gruen's zones. RESULTS: Compared to the pre-operative value, differences in BMD percentage were statistically significant only in ROI 4 (p < 0.05), with an increase in both groups (9 and 18%, respectively). The average increase in BMD was of 7.3% and 7.2% in the 2 groups. CONCLUSION: According to our study, both stems have proved able to provide good load distribution across the metaphyseal region favouring proper system integration. Nonetheless, is certainly needed to perform other studies with longer follow-up and bigger populations to give strength to these conclusions.

Contamination of revision procedures in patients with adverse tissues reaction to metal on metal implant.

OBJECTIVE: The aim of this study is to evaluate the incidence of infections in MoM total hip replacement revisions and to propose a therapeutic algorithm that can reduce the onset of this complication. Total hip arthroplasty is one of the most successful procedures performed annually in the world. As the population ages, the number of primary arthroplasty procedures performed each year is rising in conjunction with an increasing revision burden. Metal on Metal (MoM) total hip arthroplasties were reintroduced in over the last fifteen years to meet these needs, larger diameters, improved lubrication, better stability, increased ROM and wear properties of the bearing couple. These advantageous features have led to an exponential diffusion of MoM. Since over last decade, it has become evident that hip replacements with MoM bearing have significantly higher revision rates compared to those with Metal on Polyethylene. The common pathway for this failure mode appears to be increased wear or corrosion with excessive release of metal ions and nanoparticles. Complications such as elevated serum metal ion levels, aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) and pseudotumours have all been well documented, but recent studies suggest increased risk of infection with MoM bearing surfaces. PATIENTS AND METHODS: We collect data from a cohort of 44 patients who underwent revision of total hip arthroplasty between 2014 and 2017 for the complication of MoM bearing. Studied by radiological images, blood tests, and intraoperative clinical status, part of the population was treated with one stage revision, while the other was treated with a two-stage revision. RESULTS: Results showed a difference in the occurrence of infections in the two populations. CONCLUSIONS: We consider it appropriate to perform two-stage revision in all case of failure of MoM replacement so as to allow to minimize the likelihood of infection in patients with damaged tissues by ALVAL, pseudotumour, and necrosis that could create an ideal environment for bacterial development.

Low complication rates in Minimally Invasive Plate Osteosynthesis (MIPO) for proximal humeral fractures at 5 years of follow-up.

INTRODUCTION: Purpose of this study was to analyse the medium term follow-up of minimally invasive plate osteosynthesis (MIPO) for proximal humeral fractures in terms of postoperative shoulder function, radiological outcome and complications. METHODS: 76 consecutive patients with unstable proximal humeral fractures were treated using locking plate with a minimally invasive antero-lateral approach in two surgical centers. Constant score and radiographic evaluation of 74 patients were available at mean follow up of 5 years (minimum 4 years). RESULTS: Mean Constant score was 74 (range to 28-100). Results were comparable in the two centers. Younger patients registered significantly higher scores (p < 0.05). 20 patients (27%) developed complications. Subacromial impingement occurred in 16,2% of cases for varus malreduction (6,7%) and for too proximal plate positioning (9,5%). Primary screws perforation (2,7%), secondary perforation due to cut-out (1,4%), avascular necrosis (AVN) of humeral head (1,4%), partial resorption of greater tuberosity (2,7%), secondary displacement of the greater tuberosity (2,7%) and stiffness (2,7%) were observed. DISCUSSION AND CONCLUSIONS: Even at a medium term follow-up, MIPO for proximal humeral fractures ensured good and reproducible results for most common pattern of fractures. Major complications were lower respect to open procedures, because of soft tissue, deltoid muscle and circumflex vessels sparing.

Is there any difference between tapered titanium stems with similar geometry and hydroxyapatite coating?

PURPOSE: Several tapered stems with similar geometry and extensive hydroxyapatite coating have recently been introduced. It is not clear, however, whether they share the same design or whether they exhibit any difference that might affect their clinical performances. In this study, we analysed five tapered stems fully coated with hydroxyapatite to establish whether they exhibit similar geometric features and may therefore be used indifferently when a cementless stem is indicated. METHODS: The length of the stem, the coronal and sagittal diameters, the length of the stem shoulder and the metadiaphyseal angle were measured. The ratio between the proximal and distal coronal diameters of the stem and that between the proximal and distal cross-sectional areas were calculated as a flare index and tapered index, respectively. RESULTS: The proximal coronal diameter ranged between 24.9 and 28 mm in the smaller size and between 34 and 38.4 mm in the largest sizes. The proximal sagittal diameter ranged between 10.2 and 11.8 in the smallest size and between 14.4 and 17.2 in the largest. A significant difference was found between stems of different brands in the flare index, tapered index, length of stem shoulder and metadiaphyseal angle. CONCLUSIONS: Lookalike tapered stems with extensive HA coating actually exhibit significant differences in several geometric features potentially affecting their clinical performances. As a result, these stems should not be used indifferently, but rather they should be selected on the basis of the femoral morphology of the operated patient.

Diurnal preference, mood and the response to morning light in relation to polymorphisms in the human clock gene PER3.

PER3 gene polymorphisms have been associated with differences in human sleep-wake phenotypes, and sensitivity to light. The aims of this study were to assess: i) the frequency of allelic variants at two PER3 polymorphic sites (rs57875989 length polymorphism: PER3 4, PER3 5; rs228697 SNP: PER3 C, PER3 G) in relation to sleep-wake timing; ii) the effect of morning light on behavioural/circadian variables in PER3 4 /PER3 4 and PER3 5 /PER3 5 homozygotes. 786 Caucasian subjects living in Northern Italy donated buccal DNA and completed diurnal preference, sleep quality/timing and sleepiness/mood questionnaires. 19 PER3 4 /PER3 4 and 11 PER3 5 /PER3 5 homozygotes underwent morning light administration, whilst monitoring sleep-wake patterns and the urinary 6-sulphatoxymelatonin (aMT6s) rhythm. No significant relationship was observed between the length polymorphism and diurnal preference. By contrast, a significant association was observed between the PER3 G variant and morningness (OR = 2.10), and between the PER3 G-PER3 4 haplotype and morningness (OR = 2.19), for which a mechanistic hypothesis is suggested. No significant differences were observed in sleep timing/aMT6s rhythms between PER3 5 /PER3 5 and PER3 4 /PER3 4 subjects at baseline. After light administration, PER3 4 /PER3 4 subjects advanced their aMT6s acrophase (p < 0.05), and showed a trend of advanced sleep-wake timing. In conclusion, significant associations were observed between PER3 polymorphic variants/their combinations and both diurnal preference and the response to light.

A comparison of bipolar disorders in children in Italy and the United States.

BACKGROUND: The clinical presentation of bipolar disorders, though clearly recognized in adolescents, remains controversial in younger children and across cultures. The aim of this study was to compare the clinical presentation of bipolar disorders in Italian and American children between ages 5 and 12 years. METHODS: Sixty-seven children from six outpatient programs were enrolled (Italian sample: n=40; American sample: n=28) between January 2010 and June 2011. Children and their parents were interviewed by experienced clinicians using the Washington University in St. Louis Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present, Lifetime Version (WASH-U K-SADS). RESULTS: Italian children scored significantly higher on ratings of "elevated mood" (p=0.002), whereas American children scored significantly higher on ratings of "flight of ideas" (p=0.001) and "productivity" (p=0.001). Rates of comorbidity were different between groups. LIMITATIONS: Data were acquired from several sites in Italy as compared to from a single American site. Medication and educational information were not systematically collected. Furthermore, the sample collected may only reflect characteristics of a less severely ill group of bipolar children. CONCLUSIONS: Our comparison of Italian and American children with early onset bipolar disorders found that the phenotype of bipolar spectrum disorders is largely shared across cultures, although psychiatric comorbidities differed.

Frequency and clinical correlates of bipolar features in acute coronary syndrome patients.

BACKGROUND: Depression and acute coronary syndrome (ACS) are both extremely prevalent diseases. Studies aimed at evaluating whether depression is an independent risk factor for cardiac events provided no definitive results. In most of these studies, depression has been broadly defined with no differentiation between unipolar (MDD) versus bipolar forms (BD). The aim of this study was to evaluate the frequency of DSM-IV BD (bipolar I and bipolar II subtypes, cyclothymia), as well as temperamental or isolated bipolar features in a sample of 171 patients hospitalized for ACS. We also explored whether these psychopathological conditions were associated with some clinical characteristics of ACS. METHODS: Patients with ACS admitted to three neighboring Cardiac Intensive Care Units (CICUs) in a 12-month continuative period of time were eligible for inclusion if they met the criteria for either acute myocardial infarct with or without ST-segment elevation or unstable angina, verified by standard ACS criteria. All patients underwent standardized cardiological and psychopathological evaluations. RESULTS: Of the 171 ACS patients enrolled, 37 patients (21.7%) were found to have a DSM-IV mood disorder. Of these, 20 (11.7%) had bipolar type I or type II or cyclothymia, while 17 (10%) were the cases of MDD. Rapid mood switches ranged from 11% of ACS patients with no mood disorders, to 47% of those with MDD to 55% of those with BD. Linear regression analysis showed that a diagnosis of BD (p=.023), but not that of MDD (p=.721), was associated with a significant younger age at the index episode of ACS. A history of previous coronary events was more frequent in ACS patients with BD than in those with MDD. CONCLUSIONS: Our data indicate that bipolar features and diagnosis are frequent in ACS patients. Bipolar disorder has a negative impact on cardiac symptomatology. Further research in this area is warranted.

Osmophobia in migraine classification: a multicentre study in juvenile patients.

AIMS: This study was planned to investigate the diagnostic utility of osmophobia as criterion for migraine without aura (MO) as proposed in the Appendix (A1.1) of the International Classification of Headache Disorders (ICHD-II, 2004). METHODS: We analysed 1020 patients presenting at 10 Italian juvenile headache centres, 622 affected by migraine (M) and 328 by tension-type headache (TTH); 70 were affected by headache not elsewhere classified (NEC) in ICHD-II. By using a semi-structured questionnaire, the prevalence of osmophobia was 26.9%, significantly higher in M than TTH patients (34.6% vs 14.3%). RESULTS: Osmophobia was correlated with: (i) family history of M and osmophobia; and (ii) other accompanying symptoms of M. By applying these 'new' criteria, we found an agreement with the current criteria for the diagnosis of migraine without aura (MO) in 96.2% of cases; 54.3% of previously unclassifiable patients received a 'new' diagnosis. CONCLUSIONS: In conclusion, this study demonstrates that this new approach, proposed in the Appendix (A1.1), appears easy to apply and should improve the diagnostic standard of ICHD-II in young patients too.

Balance disorders in headache patients: evaluation by computerized static stabilometry.

OBJECTIVES: The aim of the study was to investigate the occurrence of equilibrium disturbances in headache patients, during the interictal period, by computerized static stabilometry. MATERIALS AND METHODS: Sixty-seven patients were studied: 35 with migraine without aura (MwoA), 12 with tension-type headache (TTH) in the episodic form (ETTH) + MwoA, and 20 with only TTH [10 ETTH + 10 chronic (CTTH)]. The stabilometric parameters considered were: statokinesigram length (L) and surface (S) in open (EO) and closed (EC) eyes conditions with/without occlusal bite, EC with head retroflexion (ECR), and optokinetic stimulation (OKN). RESULTS: The alteration of at least one of the stabilometric parameters was observed in 45 patients (67.2%): 21 MwoA, 8 ETTH + MwoA, and 16 TTH (8 ETTH + 8 CTTH). CONCLUSION: In TTH patients (ETTH, CTTH, ETTH + MwoA), the stabilometric findings show a proprioceptive alteration induced by cervicofacial muscle contraction, which was peripheral in origin. In MwoA patients the alterations appear under OKN and support a control impairment in involuntary oculomotility of central origin.

Headache characteristics in obstructive sleep apnea syndrome and insomnia.

OBJECTIVES: To determine headache characteristics in the obstructive sleep apnea syndrome (OSAS) and in insomnia. PATIENTS AND METHODS: Fifty-six OSAS patients and 50 insomnia patients were assessed in the same time period. Patients in both groups underwent an accurate interview to investigate headache occurrence and its characteristics. Results - Headache was reported by 49% of OSAS patients and 48% of insomnia patients. In OSAS patients headache had most frequently a tension-type pattern. Headache occurred on awakening in 74% of OSAS patients, more frequently than in insomnia patients (40%) (chi(2); P < 0.04). The occurrence of morning headache appears to be significantly correlated with nocturnal oxygen desaturation and OSAS severity. CONCLUSION: Headache is a common finding in both OSAS and insomnia patients. Because morning headache seems to be more specific for OSAS than insomnia, and in OSAS its occurrence seems to be associated with disease severity, we hypothesize the involvement of certain pathogenic mechanisms associated with OSAS.

The role of neuroimaging in the diagnosis of headache in childhood and adolescence: a multicentre study.

Following the diagnostic indications of the Guidelines for the diagnosis and therapy of juvenile headache, we present the results of a prospective, multicentre study of headache patients aimed at evaluating the utility of neuroradiologic testing in the diagnosis of headache. A total of 6535 subjects up to age 18 were studied, and 1485 underwent neuroimaging testing based on the indications of the diagnostic Flow-Chart. Abnormal results were observed in 273 (18.5%) subjects. Incidental findings were observed in 138 (9.3%) subjects, not correlated with the headache pathology, whereas alterations that led to the diagnosis of secondary headache were observed in 135 (9.1%) subjects. In conclusion, our data support a greater incidence of positive neuroimaging examinations among patients who underwent testing based on suspicion of a secondary headache pathology when compared with the low percentages observed in study populations.

Different cytokine levels in thrombolysis patients as predictors for clinical outcome.

Thrombolytic therapy not always improves clinical outcome in ischemic stroke patients. This could cause lymphomonocyte accumulation in the infarcted brain area. These produce an excessive amount of proinflammatory cytokines, such as IL-1 beta, IL-6 and TNF-alfa. The aim of our study was to determine ILs levels in fibrinolytic therapy treated patients, compared with healthy controls and to evaluate if the varying levels can predictors of neurological outcome. Eighteen patients underwent thrombolytic treatment with t-PA within 3 h. Plasma levels of IL-1 beta, IL-6, TNF-alfa and IL-10 were determined by ELISA method before and within 24 h after t-PA infusion and compared with controls. Significantly higher levels of IL-1 beta and Il-6 emerged in stroke patients before treatment compared with the control group (P < 0.05 and 0.04, respectively). Slightly higher plasma levels of TNF-alfa and lower plasma levels of IL-10 were also found at base line in stroke patients. After thrombolytic treatment no significant variations were observed in the levels of TNF-alfa and IL-6, whereas a trend toward lower values for IL-1 beta and higher levels for IL-10 was observed. Positive correlations among the values of IL-6, TNF-alfa and National Institute of Health Stroke Scale (NIHSS) at discharges were observed. A similar correlation with modified Rankin scale score at 3 month was found. Pre-treatment cytokine status seems to influence pre-and long-term clinical outcome. Therefore an investigation into the possible predictor of cytokines seem worthy.

Characteristics of migraine in an out-patient population over 60 years of age.

One hundred and sixty-three consecutive patients (129 females and 34 males) over 60 years of age attending the Headache Centre of the University of Perugia in the period January 2000-December 2001 were included in the study. One hundred and fifty-two (93.3%) were affected by a primary headache disorder. According to the 1988 IHS Criteria, their prevailing attacks could be diagnosed as migraine without aura (MwoA) in 57.2% of cases (n = 87) and as migraine with aura (MwA) in 11.8% of cases (n = 18). Attacks both in MwoA and MwA were unilateral and of severe-to-moderate intensity in 45% and 50% of cases. Head pain was referred as pulsating by 56% and 38.9% of MwoA patients MwA patients, respectively. Aggravation with routine daily activities was present in 72.4% and 61.1% in MwoA and MwA patient groups. The most frequent accompanying symptoms were photophobia and phonophobia. Headache attacks were of shorter duration in MwA patients, but in 3.4% of MwoA patients attacks lasted between 2 and 4 h. Of patients affected by MwA, 55% referred, together with the typical attacks, symptoms of aura not followed by headache. A worsening of headache in the last 5 years was reported by 67.8% and 44.4% of MwoA and MwA patients, respectively. Of the patients with MwoA, 86.2% (n = 75), and 83.3% (n = 15) of those with MwA used symptomatic drugs for their attacks. In the majority of cases they took more than one analgesic or non steroidal anti-inflammatory drug. A total of 51.7% of patients with MwoA and 55.5% of patients with MwA were under prophylactic treatment. Preventive drugs included antidepressants, beta-blockers, calcium channel antagonists and antiepileptic drugs. The choice of symptomatic or prophylactic drugs was made, in the majority of cases, on the basis of concomitant diseases.

Event-related potentials in posttraumatic headache.

OBJECTIVES: To assess impairment of cognitive functions occurring in patients with posttraumatic headache as a consequence of a minor cranial trauma in the absence of organic damage involving the central nervous system. BACKGROUND: The term posttraumatic syndrome defines a stereotypic set of symptoms following traumatic brain injury that are subjective and varied. A deficit of cognitive function and impairment of the rapid processes of learning, attention, and short-term memory have frequently been identified. Moreover, headache is the most frequent symptom reported by the patients. Due to the nature of the symptoms, a great limitation in defining the posttraumatic syndrome is represented by the lack of methods and diagnostic tools that allow quantification of the subjective disturbances and evidence of the signs indicative of central nervous system involvement in this pathological condition. METHODS: Twenty-five subjects (16 women, 9 men; mean age, 28 +/- 9 years) were examined between 3 and 6 months after the traumatic event. The P300 event-related potential was recorded by an odd-ball paradigm with an acoustic modality. The patients underwent electroencephalography and brain stem auditory evoked potentials; magnetic resonance imaging was performed to exclude the presence of cerebral lesions. RESULTS: The mean latency of P300 was increased in both central electrodes (Cz and Pz) in patients with posttraumatic syndrome compared with controls (P<.001); assuming the value of mean +/- 2 SD was the cutoff point between normal and abnormal results, the P300 latency results were altered in 13 patients (52%). In the patient group, a significant correlation was demonstrated between Zung Depression Scale score and P3 and N2 wave latencies (r = 0.54, P <.004; r = 0.56, P<.003) and between Zung Anxiety Scale scores and P3 wave latencies (r = 0.46, P<.02). CONCLUSIONS: These data suggest the usefulness of the P300 event-related potential in evaluating cognitive disturbances in patients affected by posttraumatic syndrome. Alteration of cognitive potential in such patients, even in the absence of lesions detectable by neuroimaging, indicate the functional impairment of specific cerebral areas that can occur after a traumatic event.

Light-dependent interaction between Drosophila CRY and the clock protein PER mediated by the carboxy terminus of CRY.

BACKGROUND: The biological clock synchronizes the organism with the environment, responding to changes in light and temperature. Drosophila CRYPTOCHROME (CRY), a putative circadian photoreceptor, has previously been reported to interact with the clock protein TIMELESS (TIM) in a light-dependent manner. Although TIM dimerizes with PERIOD (PER), no association between CRY and PER has previously been revealed, and aspects of the light dependence of the TIM/CRY interaction are still unclear. RESULTS: Behavioral analysis of double mutants of per and cry suggested a genetic interaction between the two loci. To investigate whether this was reflected in a physical interaction, we employed a yeast-two-hybrid system that revealed a dimerization between PER and CRY. This was further supported by a coimmunoprecipitation assay in tissue culture cells. We also show that the light-dependent nuclear interactions of PER and TIM with CRY require the C terminus of CRY and may involve a trans-acting repressor. CONCLUSIONS: This study shows that, as in mammals, Drosophila CRY interacts with PER, and, as in plants, the C terminus of CRY is involved in mediating light responses. A model for the light dependence of CRY is discussed.

Efficient and heritable functional knock-out of an adult phenotype in Drosophila using a GAL4-driven hairpin RNA incorporating a heterologous spacer.

We have developed a modified RNA interference (RNAi) method for generating gene knock-outs in Drosophila melanogaster. We used the sequence of the yellow (y) locus to construct an inverted repeat that will form a double-stranded hairpin structure (y-IR) that is under the control of the upstream activating sequence (UAS) of the yeast transcriptional activator GAL4. Hairpins are extremely difficult to manipulate in Escherichia coli, so our method makes use of a heterologous 330 bp spacer encoding sequences from green fluorescent protein to facilitate the cloning steps. When the UAS-y-IR hairpin is expressed under the control of different promoter-GAL4 fusions, a high frequency of y pigment phenocopies is obtained in adults. Consequently this method for producing gene knock-outs has several advantages over previous methods in that it is applicable to any gene within the fly genome, greatly facilitates cloning of the hairpin, can be used if required with GAL4 drivers to avoid lethality or to induce RNAi in a specific developmental stage and/or tissue, is useful for generating knock-outs of adult phenotypes as reported here and, finally, the system can be manipulated to investigate the trans-acting factors that are involved in the RNAi mechanism.

[Exercise test after acute myocardial infarction: on medical therapy?]. / Test da sforzo nel postinfarto: con terapia?

Given the great relevance of beta-blockers after myocardial infarction, we focused our attention on this therapy, considering also the difficulty of its management: it takes a long time to up titrate as well as to wash out. Other anti-ischemic therapies, i.e. nitroderivatives and calcium-antagonists, are easier to manage and there is less need of precise schedules. Our belief is that predischarge exercise testing should be performed on beta-blocker therapy, since we deem unadvisable to interrupt this treatment in the early phase of the postinfarction clinical course, and the reasons are detailed in the text. After myocardial infarction, beta-blockers may reduce the sensitivity of predischarge exercise testing for the diagnosis of inducible ischemia; however, their interference does not seem to affect negatively the prognostic stratification of the test, also in the "thrombolytic era". This may be true since beta-blockers hide, but also cure, those forms of inducible ischemia of lower clinical importance, and only inducible ischemia occurring in spite of such therapy might be dangerous and should be treated with myocardial revascularization. Patients receiving thrombolytic treatment are a selected minority at lower clinical risk; it is necessary to emphasize that predischarge exercise testing is more frequently positive in these patients, probably because of the presence of residual stenosis of the infarct-related vessel that may often have a trivial relevance. The test has a lower negative predictive value in these patients, mainly for the higher incidence of reinfarction and ischemic events related to plaque instability, events that none of the provocative tests can predict accurately.

[From the great clinical studies to the management of the single patient. Medical therapy in the pre- and post-fibrinolytic era]. / Dai grandi studi clinici alla gestione del singolo paziente. La terapia medica nell'era pre e post-fibrinolitica.

Medical therapy of myocardial infarction has changed over the last 30 years. The "lag phenomenon", i.e. the time lapsing from the appraisal of a new, relevant scientific evidence and its practical adoption, has been variable, and different from one treatment to another. It has been very short for GP IIb/IIIa receptor inhibitors in candidates for urgent coronary angioplasty after myocardial infarction, short for ACE inhibitors, and it has been also short for the decrease in the prescription of calcium channel inhibitors after controversial scientific evidence. This time lapse has been long for beta-blockers, that only now are used quite extensively in Italy: from less than 10% of hospitalized patients during the early '80s, to over 60% nowadays. This evolution of medical therapy has been progressive and continuous, has not been divided into two eras, and thrombolysis seems to have little to do with it. The extensive introduction of thrombolysis has simply divided patients with acute myocardial infarction into two subgroups, very different for clinical characteristics: candidates for this therapy, and "others". Candidates for thrombolysis have a much better prognosis, but for a "paradox effect" they have been studied much more than the others. Now, the bulk of publications concerning patients undergoing thrombolysis carries the risk of spreading the concept that myocardial infarction has changed. We do not think that this corresponds to reality. Probably, the concepts that have guided medical therapy have been very similar and unchanged over the years, and both medical and surgical plus coronary angioplasty therapies are today much more appropriately used than yesterday.

[Guidelines: some considerations on one of the cultural instruments on which the switch in the National Health System can be based]. / Le linee guida: alcune considerazioni su uno degli strumenti culturali su cui si potrebbe fondare la svolta del Sistema Sanitario Nazionale.

In the last few years there has been an explosion of interest in guidelines, reflected in a vivid debate in the international literature. Guidelines for medical practice are not innovative tools, since their history began at least 20 years ago. They are produced with increasing frequency in North America, and similar developments are taking place in Europe. The concept of improving the quality of the services in the National Health System through the production and implementation of valid clinical guidelines has been recognized in Italy by the Ministry of Health, who introduced such a concept in the last reform of the law on the Sanitary Health System. Many international authors deem that clinical guidelines are a way to support effective clinical practice. If this still holds, and we believe it does, then we must ensure that these guidelines are effective. Also for the enthusiast, the entire process from the development to the dissemination, implementation, and evaluation is not an easy task. Guidelines should be written correctly by a multidisciplinary panel of experts, should be peer reviewed and updated. Guidelines should become the common field in which the four major parties of the sanitary "market" (a market far from ideal today) meet: the patient, the doctor, the manager, and the industry involved in medical technology. Guidelines should be disseminated and implemented: simply having evidence available does not necessarily mean that it will be used. Thus, the key question is not so much related to the acceptance of best practice, but the extent to which a guideline is cost-effective. In this review we have tried to discuss such points, taking into consideration all the steps, the discussions, the controversial points, and the unsolved questions which are smoldering under both the potential benefit of practice guidelines (also in the light of appropriateness of medical practice), and all the possible effects on clinical autonomy, health care costs, clinical practice satisfaction, legal implications, and conflicts of interest. It is crucial for medical associations, and indeed for all physicians, to take up this problem and constructively try to play an active part in the process, avoiding the possibility that controversial guidelines be imposed by the regulatory authorities.