Antidepressants and the risk of arrhythmia in elderly affected by a previous cardiovascular disease: a real-life investigation from Italy.

PURPOSE: The study aimed to fill existing knowledge gaps on the safety of antidepressant drugs (ADs) by estimating the risk of hospitalization for arrhythmia associated with use of selective serotonin reuptake inhibitors (SSRIs) and newer atypical ADs (NAAs) among elderly with previous cardiovascular (CV) events. METHODS: The cohort was composed by 199,569 individuals aged ≥ 65 years from five Italian healthcare territorial units who were discharged for cardiovascular outcomes in the years 2008-2010. The 17,277 patients who experienced hospital admission for arrhythmia during follow-up were included as cases. Odds of current ADs use among cases (i.e., 14 days before hospital admission) was compared with (i) odds of current use of 1:5 matched controls (between-patients case-control) and with (ii) odds of previous use during 1:5 matched control periods (within-patient case-crossover). The risk of arrhythmia associated with ADs current use was modelled fitting a conditional logistic regression. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS: Current users of SSRIs and NAAs were at increased risk of arrhythmia with case-control odds ratios (OR) of 1.37 (95% confidence interval, CI 1.18 to 1.58) and 1.41 (1.16 to 1.71) and case-crossover OR of 1.48 (1.20 to 1.81) and 1.72 (1.31 to 2.27). An increased risk of arrhythmia was associated with current use of trazodone (NAA) consistently in case-control and case-crossover designs. CONCLUSIONS: Evidence that current use of SSRIs and NAAs is associated to an increased risk of arrhythmia among elderly with CV disease was consistently supplied by two observational approaches.

Benefit of statins in daily practice? A six-year retrospective observational study.

This observational retrospective study analysed the association of adherence to statins with the achievement of a target total cholesterol level (CL, <200mg/dl), and any association of adherence with the time to first hospital admission for coronary event in hypercholesterolemic patients treated with statins, in one Italian Local Health Authority between 1998 and 2003. The study population consisted of 3516 patients who were prescribed statins and for whom full cholesterol results were available. After three months of treatment, there were significant reductions in CL (p<0.001) in the three treatment groups stratified by adherence (good adherents -24%, poor adherents -22%, and nonadherents -14%). Patients more likely to achieve the target CL were older, male and more adherent to the statins. The risk of first hospitalization was associated positively with increased age and male gender. Patients with co-treatments were more likely to be hospitalized. Surprisingly, better adherence to statin treatment increased the risk of hospitalization.

Protective role of heparin on in vitro functional aortic response in Watanabe heritable hyperlipidemic rabbits.

The effects of prolonged in vivo heparin treatment upon vasomotor responses and content of cholesterol and energy related compounds were studied in isolated thoracic and abdominal aortas from Watanabe heritable hyperlipidemic (WHHL) rabbits. Unfractionated heparin was administered subcutaneously (2 mg/kg twice a day) to 3-month-old WHHL rabbits for a period of 6 months. A group of WHHL rabbits was treated with saline solution and considered as control. Aortic cholesterol infiltration and serum cholesterol were not significantly decreased by the prolonged heparin treatment. In heparin-treated WHHL rabbits, the in vitro aortic endothelium-dependent relaxation produced by acetylcholine or calcimycin (A 23187) was greater than in saline-treated WHHL group. ATP-induced aorta relaxation (endothelium-dependent and endothelium-independent) did not vary significantly in the two groups of WHHL rabbits, even after mechanical removal of endothelium. Also the noradrenaline-induced aorta contraction did not vary between the two groups of WHHL rabbits. No significant variation in energy-related compounds (except for ADP) was found in the aortic arch. These results suggest that heparin produces a protective effect on aortic tissue by acting mainly at endothelial level.

Aortic response to relaxing agents in Watanabe heritable hyperlipidemic (WHHL) rabbits of different age.

Serum and aortic tissue cholesterol levels in parallel with aortic relaxation to endothelium-dependent and independent drugs were determined in Watanabe heritable hyperlipidemic (WHHL) rabbits in comparison with New Zealand (N.Z.) normocholesterolemic rabbits, aged 4-14 months. Serum cholesterol was elevated (626 +/- 99 mg/100 ml) in 4-6-month-old WHHL rabbits and significantly lower in 12-14-month-old animals (344 +/- 51 mg/100 ml). Cholesterol infiltration in thoracic aorta was high in young WHHL compared with N.Z. rabbits (0.88 +/- 0.3 mg/100 mg fresh tissue vs. 0.08 +/- 0.003 mg/100 mg, respectively) and it did not vary with age. In N.Z. rabbits, serum and aortic cholesterol levels were low from 4 to 14 months of age. The aortic relaxation to acetylcholine (0.03-3 microM) on EC50 noradrenaline precontracted rings was similar in 4-6-month-old WHHL and N.Z. rabbits of the same age. In WHHL rabbits, the relaxation to acetylcholine was significantly reduced in 7-11- (-35% at maximum) and in 12-14-month-old rabbits (-40% at maximum). In N.Z. rabbits the response to acetylcholine was not modified in the 3 age groups. The relaxation to ATP (30 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits, but in 12-14-month-old WHHL rabbits the maximal relaxing response was significantly more elevated than in age-matched N.Z. rabbits (50.1 +/- 2.5% vs. 35.1 +/- 3.2%, respectively). The aortic relaxation to NaNO2 (10 microM to 3 mM) was reduced by age both in N.Z. and in WHHL rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cholesterol-supplemented diet in heritable hyperlipidemic Yoshida rats: functional and morphological characterization of thoracic aorta.

In this study we have considered the possibility of inducing vascular damage in Yoshida Pittsburg (YOS) rat, an inbred strain which has endogenous hyperlipidemia without vascular atherosclerotic damage. Cholesterol-enriched diet (4% cholesterol plus 1% cholic acid and 0.5% thiouracil) was administered to YOS rats, in order to induce atherogenesis. The results indicate that, despite significant increase in serum (about 2-fold) and aortic tissue cholesterol (about 6-fold), no morphological damage occurred. A reduction in acetylcholine-mediated relaxation (of about 37%) was observed. No inhibition of ATP- or sodium nitrite-induced relaxation, or of contraction induced by norepinephrine was seen. Serum triglyceride concentration did not vary after administration of a cholesterol-enriched diet. Our results suggest that in heritable hyperlipidemic Yoshida rat, after 2 months of cholesterol-enriched diet, despite increased serum cholesterol levels, no atheromatous plaque developed on the aortic wall. Impaired vascular function and reductions in the response to acetylcholine were related to changed endothelial cell function. Administration of a high cholesterol diet to YOS rat may represent a new model of mixed endogenous and exogenous hyperlipidemia that can resemble many human dislipidemic diseases and therefore may become a useful tool for the study of isolated endothelial dysfunction.

Endothelium-dependent relaxation, cholesterol content and high energy metabolite balance in Watanabe hyperlipemic rabbit aorta.

Functional and metabolic parameters of thoracic aorta from Watanabe heritable hyperlipemic (WHHL) rabbits (aged 11-14 months) were investigated in vitro. The aortic preparations, normally responsive to noradrenaline, showed a diminished response to the endothelium-dependent agent, acetylcholine, in comparison with control preparations from age-matched New Zealand rabbits (maximal relaxation: 33 +/- 4% in WHHL vs. 52 +/- 2% in controls: P less than 0.005). ATP relaxant effect (only partially endothelium-dependent) was unimpaired in WHHL aorta, and it was much higher than in controls (maximal response: 63 +/- 6% vs. 37 +/- 3%, respectively; P less than 0.005). The response to NaNO2, an endothelium-independent relaxant, was unchanged in WHHL aortas. Acetylcholine-induced response was found to be inversely related to the degree of total cholesterol infiltration in aorta (r = -0.62, P less than 0.05). No correlation was observed between either total serum cholesterol or triglycerides and ACh-induced response. Furthermore, the concentration of adenine nucleotides and nucleosides in the aortic tissue of WHHL rabbits was lower than in controls, indicating a loss of energy balance. The results indicate a functional damage induced by genetic hyperlipidemia on endothelium-dependent relaxation and an impairment of energy-rich phosphate metabolism of the aortic wall. The relationship between functional and metabolic parameters is not yet clarified.

Effect of duration of ampullary gallstone obstruction on severity of lesions of acute pancreatitis.

BACKGROUND: This study was done to determine the effects of duration of obstruction on severity of lesions in patients with acute pancreatitis of biliary origin. STUDY DESIGN: This case controlled study used patient data collected prospectively on protocol during a 27-year period in a university teaching hospital. We studied a group of 97 patients with acute pancreatitis, all with an impacted stone at the ampulla of Vater at exploration (Group Ob), and a control group of 49 patients with acute gallstone pancreatitis who experienced spontaneous ampullary disobstruction within 24 hours from the onset of symptoms and who showed a patent ampulla at exploration (Group Cont). Duration of obstruction was defined as the time elapsed between the onset of symptoms and exploration in Group Ob, and from the onset of symptoms until the appearance of signs of ampullary disobstruction in Group Cont. Severity of disease in both groups was determined by the appearance of the pancreas at exploration. Patients in Group Ob were divided into three subgroups according to duration of obstruction: under 24 hours, 25 to 48 hours, and more than 48 hours. RESULTS: The incidence of severe pancreatic lesions was higher in Group Ob than in Group Cont (19.7 percent compared to 6.1 percent, p < .01). Mean duration of obstruction was also significantly longer in Group Ob than in Group Cont (42.4 hours compared to 10.6 hours). In the subgroups of patients whose obstruction lasted under 48 hours, the incidence of severe lesions was low: in the 24 hours or fewer group, severe lesions were observed in 8.1 percent (3 of 37); and in the 25 to 48 hours group, the incidence was 10.6 percent (5 of 47). Neither subgroup differed significantly from Group Cont (6.1 percent, 3 of 49). When duration of obstruction exceeded 48 hours, however, frequency of severe lesions increased significantly to 84.6 percent (11 of 13) (p < .001). CONCLUSIONS: The findings in this study suggest that duration of ampullary obstruction is a major factor determining the severity of pancreatic lesions: severe pancreatic lesions are rare in patients whose obstruction lasts not more than 48 hours. In contrast, pancreatic necrosis develops in nearly all patients with obstruction beyond 48 hours. It may be safe to treat patients conservatively during the first day of the illness. If obstruction is not resolved by the second day, endoscopic retrograde cholangiopancreatography or surgical intervention must be carried out.

Dual effect of ATP and UTP on rat atria: which types of receptors are involved?

The effects of adenine compounds and UTP were examined in electrically driven rat left atria. ATP, ADP, AMP, adenosine and UTP caused a dual inotropic effect: first a rapid decrease in contractility, and second an increase in contractile tension. alpha,beta-Methylene ATP caused an increase in contractile tension only, whereas 2-methylthio-ATP only induced a negative inotropic effect, 1,3-Dipropyl-8-cyclopentylxanthine inhibited the negative effects of ATP and adenosine, whereas 3,7-dimethyl-1-propargylxanthine did not influence the effects of ATP. Suramin but not reactive blue 2 antagonized the positive inotropism induced by ATP and alpha,beta-methylene ATP. Suramin also abolished the positive inotropic effect induced by UTP. These results demonstrate that ATP may induce negative inotropism directly by an action on A1-adenosine receptors and positive inotropism by an action on P2x-purinoceptors. UTP induces a positive inotropic effect mediated by suramin-sensitive receptors.

Phentolamine and hypoxia: modulation of contractility and alpha 1-adrenoceptors in isolated rat atria.

The hypoxia-induced effects on the binding sites and affinity constant of adrenoceptors, in the presence and absence of phentolamine, were determined for atrial membranes of hearts from normal and genetically hyperlipidaemic Yoshida (YOS) rats. Atrial function was also measured during normoxia and hypoxia, in the presence and absence of phentolamine. Hypoxia increased alpha 1-adrenoceptor density in atrial membranes of normal rats (Bmax 10.6 to 26.7 fmoles/mg protein). Phentolamine prevented the increase in the Bmax of alpha 1-adrenoceptors and increased the equilibrium dissociation constant of these receptors (KD 0.17 to 0.53 nmol/l). Beta-adrenoceptors did not change during hypoxia, but the Bmax was slightly increased (26%) in the presence of phentolamine. Thus, the alpha 1/beta ratio increased from 0.40 in normoxia to 1.06 in hypoxia. In normoxic atria from YOS rats, the alpha 1/beta ratio was already elevated (0.86) in comparison to control rats (mainly due to a higher density of alpha 1-adrenoceptors in atrial membranes from YOS rats). This ratio was not modified by hypoxia (0.84), but decreased when phentolamine was present (0.30). Hypoxia reduced the force of contraction and increased diastolic tension of atria of normal rats, while the sinus rate was not significantly modified. Phentolamine abolished the increase in diastolic tension and reduced the negative effect of hypoxia on contractile force. In YOS rat atria, functional parameters were modified by hypoxia in a qualitatively similar way to that of normal rat atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacological characterization of endothelial cell nitric oxide synthase inhibitors in isolated rabbit aorta.

Different receptors mediating the release of endothelium-derived nitric oxide (EDNO) have been identified at endothelial level. In the present study we aimed to characterise, on rabbit aorta by means of pharmacological tools, the generation of EDNO by receptors located on endothelial cell membrane (M3, P2u, P2y) and by direct activation of Ca2+ entry into the endothelial cell. Four vasodilating drugs were tested (acetylcholine, UTP, A23187 and 2-methyl-thio-ATP); they were active only if the endothelial layer was intact, suggesting that they act through endothelial receptors. The effect of different nitric oxide synthase (NOS) inhibitors (0.1 mM: L- and D-NAME, L-NMMA, L-NIO and 7-NI) was investigated on NO-mediated relaxation induced by the relaxants in vessels with intact endothelium. NOS inhibitors differently affected relaxation mediated by the vasoactive drugs in isolated rabbit aorta. Reversibility of the inhibition by using a fixed concentration of L-arginine (0.1 mM) was different depending on the relaxing drug and NOS-inhibitor. The data obtained support the coexistence in aortic vessel of more than one endothelial cell NOS isoform, each provided with different receptor coupling.

P2X-purinoceptors in the heart: actions of ATP and UTP.

Positive inotropic effects of ATP and UTP (1 microM - 1mM) were studied in isolated rat and guinea pig cardiac tissues. The potency order obtained was ATP>UTP in both species, suggesting possible interaction with P2X-purinoceptors. Binding studies using [(3)H]alpha,beta-methylene ATP as marker of P2X-purinoceptors revealed two receptor sites: one high-, the other low-affinity, in atria and ventricles from rat and guinea pig. Both ATP and UTP were found to bind high-affinity sites of [(3)H]alpha,beta-methylene ATP. The effects of various calcium inhibitors such as nifedipine, dantrolene, ryanodine and TMB-8 on positive inotropic effects induced by ATP and UTP were also studied. The results suggest that ATP and UTP may increase inotropism by interaction with P2X-purinoceptors by means of a calcium-dependent mechanism.

Prolonged inhibition of nitric oxide synthesis in Yoshida hyperlipidemic rat: aorta functional and structural properties.

To test whether inhibition of nitric oxide synthesis, associated with high levels of plasmatic lipids, can induce atherosclerotic lesions and phenotypic changes in smooth muscle cell composition in the aortic wall of an atherosclerotic-resistant species such as the rat, an inbred strain of hyperlipidemic Pittsburgh Yoshida rat was subjected to prolonged treatment (2 months) with the nitric oxide-synthase inhibitor L omega-nitro-arginine-methyl ester or with L-arginine. The two types of in vivo treatments were not able to modify in vitro aortic endothelium-mediated relaxation induced by acetylcholine or calcium-ionophore A-23187, the endothelium-independent sodium nitrite relaxation and the contractile response to serotonin. Histology and lipid infiltration of vascular specimens showed that L omega-nitro-arginine-methyl ester in vivo treatment did not induce any significant change in the aortic wall. Monoclonal antibodies to myosin isoforms and immunofluorescence procedures revealed the presence of an immature smooth muscle cell subpopulation in aortic specimens from saline-treated Pittsburgh Yoshida rats, whose expansion has been related in other species to atherogenesis. This peculiar cell phenotype disappeared in our animal model after prolonged L omega-nitro-arginine-methyl ester treatment. These data indicate that, despite interference with endothelium-mediated nitric oxide synthesis, atherosclerosis does not develop in this animal model and furnish for the first time a biological justification for atherogenesis resistance of rat, i.e., the lack of activation of an immature aortic smooth muscle cell population which in atherosclerosis-prone species is involved in lesion formation.

Effects of N omega-nitro-L-arginine methyl ester on benzodiazepine binding in some limbic areas of hyperlipidaemic rats.

Quantitative autoradiography techniques were used to evaluate the chronic effects of the potent nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, on the binding pattern of [3H]flunitrazepam (benzodiazepine agonist) in some behaviorally key limbic areas of the genetic hyperlipidaemic Pittsburg Yoshida rat. Administration of this potent synthase inhibitor was capable of supplying higher and moderately higher binding levels in the basolateral amygdala nucleus (+52%) and in the oriens-pyramidalis CA1 hippocampus layer (+38%), respectively. When we tested for the binding changes in the presence of GABA (principal benzodiazepine modulator) we noticed that a physiological concentration (20 microM) of this inhibitory neurotransmitter was sufficient to induce notable changes in other limbic areas. In fact, lower binding values (-65%) were reported for the bed nucleus of stria terminalis whereas moderately higher values (+38%) were obtained for the radiatum-lacunosum molecular CA1 hippocampus layer. From the saturation studies, it was possible to observe that the major receptor variations provoked by the potent synthase inhibitor were not only due to changes in the total number of binding sites because there were variations, as in the case of the basolateral amygdala nucleus, that were instead due to differences in the affinity binding state. These results provide evidences of a GABAergic-nitric oxide synthase inhibitor interaction that might also be involved in the regulation of convulsive, anxiolytic, and aggressive behaviors that are modulated at the benzodiazepine site.

Purine- and nucleotide-mediated relaxation of rabbit thoracic aorta: common and different sites of action.

The mechanisms of the relaxant effect of purines and pyrimidines in New Zealand rabbit isolated aorta were investigated at endothelial and smooth muscle cell levels. Endothelium-mediated relaxation by ATP was only partially inhibited by the P2-purinoceptor antagonist suramin (0.1 mM). The pyrimidine UTP produced vasodilation by acting at the endothelial level and relaxation was not antagonized by suramin (0.1 mM). This effect was not mediated by P2 purinoceptors, indicating that UTP, like ATP to a certain extent, produces relaxation via an endothelium nucleotide (N) pyrimidinoceptor. ATP, ADP, AMP, adenosine, 5'-N-ethylcarboxamidoadenosine (NECA) and inosine were all active as relaxants on smooth muscle. The NECA relaxant effect was not antagonized by P1-purinoceptor antagonists 3,7-dimethyl-1-propargylxanthine (50 microM) or 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (5 microM), excluding a P1-mediated effect. P2-related activity was excluded because adenosine-mediated relaxation was not antagonized by suramin (0.1 mM). UTP was ineffective as a relaxant at smooth muscle level, thus excluding the presence of muscular nucleotide (N) pyrimidinoceptor and suggesting a P3 purinoceptor. The rank order of potency of this muscle purinoceptor was NECA > adenosine > ATP approximately equal to ADP approximately equal to AMP approximately equal to inosine.

Utilisation Pattern of Nonspecific Nonsteroidal Anti-Inflammatory Drugs and COX-2 Inhibitors in a Local Health Service Unit in Northeast Italy.

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed widely in Italy. They include nonspecific NSAIDs (NS-NSAIDs) and the newly marketed cyclo-oxygenase (COX)-2 specific inhibitors (COXIBs) celecoxib and rofecoxib. The objective of this study was to describe the prescribing patterns for NS-NSAIDs and COXIBs in a local Italian area, analysing an administrative database. PATIENTS AND METHODS: We extracted from the database information on subjects who had received at least one reimbursed prescription of an NSAID during the period between 1 January 2001 and 31 December 2001, including age, sex, patient identification code, Anatomical Therapeutic Chemical (ATC) classification system code, strength, formulation, number of packs prescribed, prescription date, and prescription of gastroprotective agents (GPAs) on the same day as the prescription of the NSAID. On the basis of the type of NSAID received, we divided the patients into five cohorts: oral NS-NSAIDs only during the observed year, injectable NS-NSAIDs only, celecoxib only, rofecoxib only, and a combination. For descriptive purposes, we defined three age groups: <40 years, 40-64 years, and >64 years. The duration of exposure to NSAID therapy was calculated using the most commonly prescribed dose for the different drugs. Subjects receiving >/=30 doses per year were defined as "regular users". Analyses included mean age, mean duration of exposure, percentage of regular users, and percentage of GPAs co-prescribed in the different cohorts. RESULTS: NSAIDs were prescribed to 62 059 subjects from a resident population of 365 321 inhabitants; 43.8% received oral NS-NSAIDs only, 22.6% injectable NS-NSAIDs only, 7.2% celecoxib only, 5.2% rofecoxib only, and 22% different regimens of different types of NSAIDs. The mean duration of treatment increased with age in all cohorts; the mean age was 56 years in the NS-NSAID cohort, 61 years in the celecoxib cohort, and 62 years in the rofecoxib cohort (p = 0.01, COXIBs vs NS-NSAIDs). The mean duration of therapy was 11.4 days/year for injectable NS-NSAIDs, 43.8 days/year for rofecoxib, 50.5 days/year for oral NS-NSAIDs, and 53.7 days/year for celecoxib. Fifty-four percent of subjects in the oral NS-NSAID cohort were regular users versus 64% in the rofecoxib and 70% in the celecoxib groups (p = 0.001, COXIBs vs NS-NSAIDs). Co-prescription with GPAs was 9.5% for NS-NSAIDs, 8.4% for rofecoxib, and 7.7% for celecoxib. CONCLUSIONS: Analysis of an administrative database in Italy showed a trend suggesting that COXIBs are prescribed to an older population and for a longer period of time than NS-NSAIDs, and that their use is less frequently associated with GPAs.

Does seawater acidification affect survival, growth and shell integrity in bivalve juveniles?

Anthropogenic emissions of carbon dioxide are leading to decreases in pH and changes in the carbonate chemistry of seawater. Ocean acidification may negatively affect the ability of marine organisms to produce calcareous structures while also influencing their physiological responses and growth. The aim of this study was to evaluate the effects of reduced pH on the survival, growth and shell integrity of juveniles of two marine bivalves from the Northern Adriatic sea: the Mediterranean mussel Mytilus galloprovincialis and the striped venus clam Chamelea gallina. An outdoor flow-through plant was set up and two pH levels (natural seawater pH as a control, pH 7.4 as the treatment) were tested in long-term experiments. Mortality was low throughout the first experiment for both mussels and clams, but a significant increase, which was sensibly higher in clams, was observed at the end of the experiment (6 months). Significant decreases in the live weight (-26%) and, surprisingly, in the shell length (-5%) were observed in treated clams, but not in mussels. In the controls of both species, no shell damage was ever recorded; in the treated mussels and clams, damage proceeded via different modes and to different extents. The severity of shell injuries was maximal in the mussels after just 3 months of exposure to a reduced pH, whereas it progressively increased in clams until the end of the experiment. In shells of both species, the damaged area increased throughout the experiment, peaking at 35% in mussels and 11% in clams. The shell thickness of the treated and control animals significantly decreased after 3 months in clams and after 6 months in mussels. In the second experiment (3 months), only juvenile mussels were exposed to a reduced pH. After 3 months, the mussels at a natural pH level or pH 7.4 did not differ in their survival, shell length or live weight. Conversely, shell damage was clearly visible in the treated mussels from the 1st month onward. Monitoring the chemistry of seawater carbonates always showed aragonite undersaturation at 7.4 pH, whereas calcite undersaturation occurred in only 37% of the measurements. The present study highlighted the contrasting effects of acidification in two bivalve species living in the same region, although not exactly in the same habitat.

Analysis and improvement of organizational models for the management of patients with type 2 diabetes mellitus: a case study in north-east Italy.

PURPOSE: The study aimed to establish whether the organization for the management of type 2 diabetes mellitus at 9 diabetic units (DUs), in 5 neighboring local health authorities (LHAs), was able to (a) comply with the organizational model prescribed by specific regional standards; (b) ensure adequate clinical management of diabetic patients; (c) assess whether the relationship between primary care physicians (PCPs) and diabetologists (SDs) was instrumental to the needs of patients; (d) optimize specialist treatment at the DUs; (e) optimize drug management; and (f) check whether organizational changes led to variations in clinical results. METHODS: This 6-stage study analyzed procedures, precoded actions, and recordable processes. Stage (1) Defining clinical and organizational endpoints; (2) Drafting flowcharts to describe the actions and work procedures implemented within each LHA; (3) Comparing the flowcharts with the data obtained from related literature; (4) Establishing a protocol shared with PCPs for the management and treatment of patients with type 2 diabetes; (5) Changing the procedures at the DUs; and (6) Evaluating the results. The data were assessed before and after establishing a shared protocol for SDs and PCPs (year 2009 vs 2011). RESULTS: The study shows inconsistencies in the organization of work in the 5 LHAs; however, collaboration with PCPs has guaranteed: (a) unchanged hemoglobin A1C values before and after applying the protocol; (b) a percentage increase in the number of patients with type 2 diabetes who were identified thanks to these protocols; (c) an increase in the use of biguanides compared to the preprotocol period; and (d) no change in the number of patients hospitalized because of acute complications from type 2 diabetes mellitus. CONCLUSIONS: This study confirms how adequate collaboration between SDs and PCPs keeps the risk of complications stable. Nevertheless, shared protocols and clearly defined roles are required.

Resource consumption and costs of treating pain in patients affected by cancer in a district of northeast Italy.

WHO declared that pain is a relevant problem in public health and that opioids are the gold standard therapy for the treatment of moderate to severe pain. The present retrospective, epidemiological, observational study is aimed to evaluate resource consumption therapy in patients treated with opioids and died with a diagnosis of cancer in Treviso, a district in northeast Italy. For the monetisation of resource consumed, the Italian National Health Service perspective was adopted. For each patient, resource monetized were drugs (opioids, NSAIDs and adjuvants), hospitalizations with cancer diagnosis, diagnostic examinations and laboratory tests. All databases were linked in order to obtain patient profile of resource consumption. A total of 935 patients were included in the study. The incident opioid prescribed were for 60% morphine, 37% fentanyl, and 2.5% buprenorphine. The average length of treatment with opioids was 105+/-73 days. Of the patients included in the study, 79% received an anti-inflammatory drug (traditional NSAIDs and/or COX2 inhibitors), while 21% of patients treated with opioids never had an anti-inflammatory reimbursed prescription during the observation period. The average length of anti-inflammatory treatment was 133+/-83 days. For the vast majority of prescribed anti-inflammatory drugs, the received daily dose (RDD) was widely greater then the defined daily dose (DDD) before and during treatment with opioids, while for opioids the RDD was in line with the revised DDD for fentanyl, and less than the DDD for morphine and buprenorphine. The total daily cost per patient before the first prescription of opioids was euro 11.36 while after the first prescription of opioids, it increased to euro 21.12. This study confirms the under utilization of opioids in Italy both in terms of dosages and length of therapy.