The management of endoscopic retrograde cholangio- pancreatography-related infections risk: results of an italian survey at regional level.

Background and aim: Among the Endoscopic retrograde cholangiopancreatography (ERCP) adverse events, an increasingly arising problem is the transmission of Multi Drug Resistant (MDR) Bacteria through duodenoscopes. The aim of this survey was to evaluate the current clinical practice of management of ERCP associated infections in Emilia-Romagna, Italy. Methods: An online survey was developed including 12 questions on management of ERCP associated infections risk. The survey was proposed to all 12 endoscopy centers in Emilia Romagna that perform at least > 200 ERCPs per year. Results: 11 centers completed the survey (92%). Among all risk factors of ERCP infections, hospitalization in intensive care units, immunosuppressant therapies, and previous MDR infections have achieved a 80 % minimum of concurrence by our respondents. The majority of them did not have a formalized document in their hospital describing categories and risk factors helpful in the detection of patients undergoing ERCP with an high-level infective risk (9/11, 82%). Most centers (8/11, 72%) do not perform screening in patients at risk of ERCP infections. Post procedural monitoring is performed by 6 of 11 centers (55%). Conclusion: Our survey showed that, at least at regional level, there is a lack of procedures and protocols related to the management of patients at risk of ERCP infections.

Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas.

OBJECTIVES: Previously we have shown that 20 days after the tumor cells injection smaller melanomas have been developed in chemically sympathectomized mice in comparison with animals having intact sympathetic nervous system. However, it is known that chemical sympathectomy reduces the sympathetic neurotransmission only temporarily. In the present study, we monitored the survival of the sympathectomized mice with melanoma with an attempt to find out how long the suppressing effect of sympathectomy on the melanoma growth may endure. METHODS: The chemical sympathectomy was performed by intraperitoneal injection of neurotoxin 6-hydroxydopamine in male C57BL/6J mice. Seven days later, the animals were injected subcutaneously with B16-F10 melanoma cells. Then, melanoma development, survival of the tumor-bearing mice and weight of the developed tumor mass were analyzed. RESULTS: Sympathectomy delayed the development of the palpable tumors (18th day vs.14th day) and significantly prolonged the survival of the tumor-bearing mice (median 34 days vs. 29 days). However, the weight of the developed melanoma was significantly increased in the sympathectomized mice in comparison with the animals having intact sympathetic nervous system. CONCLUSIONS: The data of the present study showed that effect of the chemical sympathectomy, performed before the tumor growth induction, persisted even at the time when sympathetic nerves started to regenerate that resulted in a prolonged survival of the mice with melanoma. However, comparing to our previous study, in which we have shown a reduced tumor mass in earlier stages of the tumor growth, specifically 20 days after melanoma cells injection, now we indicate that in later stages of the melanoma progression, the tumor mass was significantly increased in sympathectomized animals. These contra-intuitive findings may indicate that interventions affecting the sympathetic nervous system may exert complex effect on the tumor progression. Based on these data we may suggest that the potential therapeutic interventions affecting the sympathetic signaling in the tumor tissue and its microenvironment should attenuate the sympathetic neurotransmission not only temporarily but till the complete regression of the tumor tissue.

Incidence and initial disease course of inflammatory bowel diseases in 2011 in Europe and Australia: results of the 2011 ECCO-EpiCom inception cohort.

BACKGROUND AND AIMS: The aim of the present study was to validate the IBD (inflammatory bowel diseases) incidence reported in the 2010 ECCO-EpiCom (European Crohn's and Colitis Organization-Epidemiological Committee) inception cohort by including a second independent inception cohort from participating centers in 2011 and an Australian center to investigate whether there is a difference in the incidence of IBD between Eastern and Western European countries and Australia. METHODS: Fourteen centers from 5 Eastern and 9 Western European countries and one center from Australia participated in the ECCO-EpiCom 2011 inception cohort. Patients' data regarding disease type, socio-demographic factors, extraintestinal manifestations and therapy were entered into the Web-based EpiCom database, www.ecco-epicom.eu. RESULTS: A total of 711 adult patients were diagnosed during the inclusion year 2011, 178 (25%) from Eastern, 461 (65%) from Western Europe and 72 (10%) from Australia; 259 (37%) patients were diagnosed with Crohn's disease, 380 (53%) with ulcerative colitis and 72 (10%) with IBD unclassified. The mean annual incidence rate for IBD was 11.3/100,000 in Eastern Europe, 14.0/100,000 in Western Europe and 30.3/100,000 in Australia. Significantly more patients were diagnosed with complicated disease at diagnosis in Eastern Europe compared to Western Europe (43% vs. 27%, p=0.02). CONCLUSION: Incidence rates, disease phenotype and initial treatment characteristics in the 2011 ECCO-EpiCom cohort were not significantly different from that reported in the 2010 cohort.

East-West gradient in the incidence of inflammatory bowel disease in Europe: the ECCO-EpiCom inception cohort.

OBJECTIVE: The incidence of inflammatory bowel disease (IBD) is increasing in Eastern Europe. The reasons for these changes remain unknown. The aim of this study was to investigate whether an East-West gradient in the incidence of IBD in Europe exists. DESIGN: A prospective, uniformly diagnosed, population based inception cohort of IBD patients in 31 centres from 14 Western and eight Eastern European countries covering a total background population of approximately 10.1 million people was created. One-third of the centres had previous experience with inception cohorts. Patients were entered into a low cost, web based epidemiological database, making participation possible regardless of socioeconomic status and prior experience. RESULTS: 1515 patients aged 15 years or older were included, of whom 535 (35%) were diagnosed with Crohn's disease (CD), 813 (54%) with ulcerative colitis (UC) and 167 (11%) with IBD unclassified (IBDU). The overall incidence rate ratios in all Western European centres were 1.9 (95% CI 1.5 to 2.4) for CD and 2.1 (95% CI 1.8 to 2.6) for UC compared with Eastern European centres. The median crude annual incidence rates per 100,000 in 2010 for CD were 6.5 (range 0-10.7) in Western European centres and 3.1 (range 0.4-11.5) in Eastern European centres, for UC 10.8 (range 2.9-31.5) and 4.1 (range 2.4-10.3), respectively, and for IBDU 1.9 (range 0-39.4) and 0 (range 0-1.2), respectively. In Western Europe, 92% of CD, 78% of UC and 74% of IBDU patients had a colonoscopy performed as the diagnostic procedure compared with 90%, 100% and 96%, respectively, in Eastern Europe. 8% of CD and 1% of UC patients in both regions underwent surgery within the first 3 months of the onset of disease. 7% of CD patients and 3% of UC patients from Western Europe received biological treatment as rescue therapy. Of all European CD patients, 20% received only 5-aminosalicylates as induction therapy. CONCLUSIONS: An East-West gradient in IBD incidence exists in Europe. Among this inception cohort--including indolent and aggressive cases--international guidelines for diagnosis and initial treatment are not being followed uniformly by physicians.

Unusual case of oral chronic lymphocytic leukemia presenting as recurrent epistaxis and asymptomatic intraoral swelling.

INTRODUCTION: Usually, oral manifestations of chronic lymphocytic leukemia CLL are related to an advanced stage of a diagnosed disease, and rarely may lead to diagnosis. CLL can also present as bleeding, rarely isolated. We report a rare case of CLL the first symptoms of which were recurrent epistaxis and asymptomatic intraoral swelling. CASE PRESENTATION: A 74-year-old woman consulted for recurrent epistaxis. She presented with a small asymptomatic swelling in the left superior vestibule. Computed tomography revealed a tissular-like mass without invasion of surrounding tissues. The hemogram revealed thrombocytopenia and leukocytosis with 51% of lymphocytes. The immuno-histochemical analysis of the lesion and of the bone marrow allowed diagnosing stage IV CLL. DISCUSSION: CLL may present as unusual symptoms. It should be suspected in elderly patients presenting with atypical clinical signs such as oral swelling or signs of bone marrow involvement.

Post-irradiation malignant fibrous histiocytoma of the larynx: A case report with an unusual metastatic spread pattern.

We report a case of a laryngeal malignant fibrous histiocytoma (MFH) that showed an uncommon clinical behavior. This tumor occurred in a 70-year-old male patient 5 years after radiation treatment for laryngeal squamous cell carcinoma, and unusual metastases were spread unusually to the pleural cavity. The interval between the end of radiotherapy and the onset of MFH can be justified by the development of laryngeal stenosis by fibrotic tissue as a late complication of radiotherapy. Laryngeal fibrosis after radiotherapy probably triggered the MFH. Neither computed tomography nor magnetic resonance imaging differentiate between fibrotic tissue and MFH, and only repeated biopsy was definitive to give us the correct diagnosis.

The AESOP robot system for video-assisted rigid endoscopic laryngosurgery.

Surgeons may occasionally encounter difficulty in visualizing the whole larynx with a direct laryngoscope. In such cases, rigid endoscopic laryngosurgery using a direct laryngoscope is an optimal solution. Multidirectional examination of the larynx using rigid endoscopes during direct laryngoscopy, leads to better control and management of the ventricle, inferior surface of the vocal fold and subglottis, and the anterior commissure. Currently, 0 degrees , 30 degrees , 70 degrees and 120 degrees angled rigid telescopes are used worldwide. Our experience in telescopic endolaryngeal surgery provided us the opportunity to work with AESOP 3000 (automated endoscope system for optimal positioning), coupling a robotic arm to a rigid endolaryngeal telescope. The use of this device allows the surgeon to control the field of view and operate with both hands. A total of 20 patients presenting a laryngeal lesion were randomly selected and included in this study undergoing a robot-assisted procedure. Three of 20 patients presented a difficult laryngeal exposure with direct laryngoscopy due to a rigid, short neck (1 male, 1 female) and prominent teeth (1 male). We used Karl Storz Hopkins II long rigid endoscopes having 0 degrees, 30 degrees and 70 degrees direction of view, a Storz Xenon 300 cold light, a Storz Tricam SL camera, the Kleinsasser direct laryngoscope. The instruments we used are all commercially available for microlaryngeal surgery and included upward curved instruments in case of difficult laryngeal exposure. The operative equipment was the same for all procedures. We evaluated the acquisition of skills in controlling the AESOP 3000, the feasibility of a single surgeon performing procedures with this machine, and any advantages that it might offer to endolaryngeal surgery. The use of robotic devices improves the precision of surgical procedures, offering surgeons a more comfortable working position, particularly for longer procedures, and without an assistant to hold the camera.

Single opioid administration modifies gonadal steroids in both the CNS and plasma of male rats.

While morphine remains one of the most widely used opioids for the treatment of painful conditions, other opioids are also commonly employed. Because of the interactions between opioids and gonadal hormones, in particular opioid-induced hypogonadism, this study investigated the effects of widely used opioids on plasma testosterone and estradiol levels and brain testosterone levels in male rats. Animals were s.c. injected with two concentrations of morphine (5 or 10 mg/kg), fentanyl (0.05 or 0.1 mg/kg), tramadol (10 or 40 mg/kg), buprenorphine (0.05 or 0.1 mg/kg) or saline (0.7 ml/kg). Four or 24 h after treatment, the rats were deeply anesthetized to collect blood samples from the abdominal aorta and to perfuse the brains with saline. Plasma and brain hormone levels were measured by radioimmunoassay. In rats studied 4 h after treatment, all the opioids except tramadol 10 mg/kg decreased plasma testosterone in comparison with saline administration. At the same time, plasma estradiol levels were lower than control in the groups treated with the low doses of morphine, tramadol and buprenorphine, while estradiol remained at control levels in the other groups. Twenty-four hours after treatment, plasma testosterone levels were different (higher) than control in the animals treated with the low doses of morphine, fentanyl and buprenorphine. Estradiol was lower than control in the low dose groups, while the high doses did not produce any changes with respect to control. Four hours after treatment, brain testosterone was drastically decreased in all groups except buprenorphine, in which it remained at control levels. All groups returned to control levels at 24 h after treatment. In conclusion, opioids exert important effects on plasma and CNS sex hormone levels. The different magnitude and time-course of the effects of the different opiates on testosterone and estradiol levels are likely due to their different mechanism of action.

Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain.

OBJECTIVE: The objective of this study was to demonstrate a dose-response effect with 1- and 2-tablet doses of combination hydrocodone 7.5 mg with ibuprofen 200 mg and placebo in patients with moderate to severe postoperative abdominal or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. Previous studies with this combination have demonstrated that the components have an additive analgesic effect as well as efficacy compared with other fixed-dose combination analgesics. METHODS: This randomized, parallel-group, double-blind, single-dose, placebo-controlled study compared 1 tablet of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), 2 tablets of hydrocodone 7.5 mg with ibuprofen 200 mg (n = 60), and placebo (n = 60) in patients with moderate or severe pain after abdominal or gynecologic surgery. Analgesia was evaluated over 8 hours. RESULTS: Mean pain relief (PR) scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.027) and 100 (P = 0.017) minutes and at 2 (P = 0.013), 2.5 (P = 0.012), 3 (P = 0.006), 4 (P = 0.029), 5 (P = 0.002), 6 (P = 0.032), 7 (P = 0.036), and 8 (P = 0.01) hours. Mean pain intensity difference scores were significantly greater for the 2-tablet dose than for the 1-tablet dose at 80 (P = 0.013) and 100 (P = 0.007) minutes and at 2 (P = 0.003), 2.5 (P = 0.002), 3 (P = 0.002), 4 (P = 0.009), 5 (P < 0.001), 6 (P = 0.004), 7 (P = 0.009), and 8 (P = 0.001) hours. Mean total PR scores were significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.01; 0 to 4 hours, P = 0.006; 0 to 6 hours, P = 0.003; 0 to 8 hours, P = 0.003). Mean sum of pain intensity differences was significantly greater for the 2-tablet dose than for the 1-tablet dose for all measured time intervals (0 to 3 hours, P = 0.004; 0 to 4 hours, P < 0.001; 0 to 6 hours, P < 0.001; 0 to 8 hours, P < 0.001). Mean peak PR score and median time-to-remedication were significantly greater for the 2-tablet dose than for the 1-tablet dose (P < 0.029 and P = 0.017, respectively). Both doses were superior to placebo. There were no significant differences in the number of patients experiencing adverse events between the 2-tablet dose (n = 6 [10.0%]), the 1-tablet dose (n = 4 [6.7%]), and placebo (n = 1 11.7%]). Adverse events were not serious, and none of the patients discontinued therapy because of side effects. CONCLUSIONS: This study demonstrated that a 2-tablet dose of hydrocodone with ibuprofen provided significantly more analgesia than a 1-tablet dose (a positive dose-response effect) and that both doses were superior to placebo.

Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone 7.5 mg and ibuprofen 200 mg with that of combination codeine 30 mg and acetaminophen 300 mg for the treatment of chronic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: In this randomized, parallel-group, double-blind, repeated-dose, active-comparator, 4-week, multicenter study, 469 patients were randomly assigned to receive a 1-tablet (n = 156) or 2-tablet (n = 153) dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg (HI1 and HI2, respectively) or a 2-tablet dose of combination codeine 30 mg and acetaminophen 300 mg (CA, n = 160), the active comparator, every 6 to 8 hours as needed for pain. Efficacy was measured through pain relief scores, number of daily doses of study medication, number of daily doses of supplemental analgesics, number of patients who discontinued therapy due to an unsatisfactory analgesic response, and global assessment scores. RESULTS: Of the 469 patients, 255 (54.4%) were female and 214 (45.6%) were male. The mean age was 51.1 years. Types of chronic pain included back (214; 45.6%), arthritic (145; 30.9%), other musculoskeletal (65; 13.9%), cancer (6; 1.3%), diabetic neuropathic (3; 0.6%), postherpetic neuralgic (5; 1.1%), other neurologic (21; 4.5%), and other unclassified chronic pain (10; 2.1%). During the 48 hours prior to the study, 351 (74.8%) patients had been treated with opioid or opioid-nonopioid combination analgesics. The overall mean daily pain relief score was significantly greater in the HI2 group (2.25+/-0.89) than in the HI1 group (1.98+/-0.87) (P = 0.003) or the CA group (1.85+/-0.96) (P < 0.001). The overall mean number of daily doses of study medication was significantly less in the HI2 group (2.94+/-0.99) than in the HI1 group (3.23+/-0.76) (P = 0.036) or the CA group (3.26+/-0.75) (P = 0.014). The overall mean number of daily doses of supplemental analgesics was significantly less in the HI2 group (0.24+/-0.49) than in the HI1 group (0.34+/-0.58) (P = 0.021) or CA group (0.49+/-0.85) (P = 0.010). The number of patients who discontinued treatment due to an unsatisfactory analgesic response was significantly less in the HI2 group (2; 1.3%) than in the CA group (12; 7.5%) (P = 0.008). HI2 was more effective than HI1 and CA as measured by pain relief scores for week 1 (P < 0.001 vs HI1 and CA), week 2 (P < 0.001 vs HI1 and CA), and week 3 (P = 0.008 vs HI1 and P < 0.001 vs CA); daily doses of study medication for week 1 (P = 0.019 vs HI1 and P = 0.011 vs CA); daily doses of supplemental analgesics for week 1 (P = 0.010 vs HI1 and CA); and global assessment scores for week 1 (P = 0.018 vs HI1 and P < 0.001 vs CA), week 2 (P = 0.005 vs HI1 and P < 0.001 vs CA), and week 4 (P = 0.013 vs HI1 and P = 0.023 vs CA). There were no significant differences between HI1 and CA in any efficacy variable. There were no significant differences in the number of patients experiencing adverse events in the HI2 (127; 83%), HI1 (124; 79.5%), and CA (129; 80.6%) groups. However, the mean number of patients who discontinued treatment due to adverse events was significantly greater in the HI2 group (40; 26.1%) than in the HI1 group (23; 14.7%) (P = 0.013). CONCLUSIONS: The results of this study suggest that 2-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be more effective than either 1-tablet doses of this combination or 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg. Moreover, 1-tablet doses of combination hydrocodone 7.5 mg and ibuprofen 200 mg may be as effective as 2-tablet doses of combination codeine 30 mg and acetaminophen 300 mg.

The kinetic and structural characterization of the reaction of nafamostat with bovine pancreatic trypsin.

Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, is active against a number of the serine proteases involved in coagulation. This has been proposed as the basis of its anticoagulant activity. We investigated the reaction of Nafamostat with bovine pancreatic trypsin as a model system. It was shown to act as a time-dependent competitive inhibitor, and the inhibition constants for the binding of Nafamostat to trypsin (i.e., Ki) and the overall inhibition constants (i.e., Ki*) were calculated to be 11.5 microM and 0.4+/-0.14 nM, respectively. The second-order rate constant for the reaction was 4.5+/-0.19x10(5) M(-1)s(-1), and the product released following the acylation step, 6-amidino2-naphthol, showed mixed-type inhibition. The competitive (Kic) and uncompetitive (Kiu) inhibition constants were 14.7 microM and 19.5 microM, respectively. Formation of the acyl-enzyme intermediate was dissected into at least two steps, with rates of 0.9 s(-1) and 195 s(-1). The deacylation step was relatively much slower (3.2+/-0.19x10(-5) s(-1), enabling the mass spectroscopic analysis of the acyl-enzyme intermediate, which confirmed the covalent attachment of 4-guanidinobenzoic acid to trypsin. The product of the deacylation step, 4-guanidinobenzoic acid, showed no inhibition up to a concentration of 200 microM. These data strongly suggest that while Nafamostat is a potent inhibitor of trypsin, it is actually an extremely poor substrate, and that apparent inhibition is due to the competitive formation of a very stable acyl-enzyme intermediate, analogous to some other active site titrants.

Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain.

OBJECTIVE: The objective of this study was to compare the effectiveness of combination hydrocodone and ibuprofen with that of combination oxycodone and acetaminophen in the treatment of moderate to severe postoperative obstetric or gynecologic pain. BACKGROUND: Hydrocodone 7.5 mg with ibuprofen 200 mg is the only approved fixed-dose combination analgesic containing an opioid and ibuprofen. METHODS: This randomized, double-blind, parallel-group, single-dose, active-comparator, placebo-controlled study compared the effects of a 2-tablet dose of hydrocodone 7.5 mg and ibuprofen 200 mg with those of a 2-tablet dose of oxycodone 5 mg and acetaminophen 325 mg and placebo. Analgesia was assessed over 8 hours. RESULTS: Mean pain relief (PR) scores were similar for the hydrocodone with ibuprofen and oxycodone with acetaminophen groups (n = 61 and 59, respectively) at 0.5, 1, 1.5, 2, 2.5, 3, 4, and 7 hours and significantly greater for the hydrocodone with ibuprofen group at 5, 6, and 8 hours (P < or = 0.05). Mean pain intensity difference (PID) scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen at 0.5, 1, 1.5, 2, 2.5, 3, and 4 hours and significantly greater for hydrocodone with ibuprofen at 5, 6, 7, and 8 hours (P < or = 0.05). Total PR scores were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3- and 0- to 4-hour intervals and significantly greater for hydrocodone with ibuprofen for the 0- to 6- and 0- to 8-hour intervals (P < 0.05). The sum of the PID scores was similar for hydrocodone with ibuprofen and oxycodone with acetaminophen for the 0- to 3-, 0- to 4-, 0- to 6-, and 0- to 8-hour intervals. The median estimated time to onset of analgesia, mean peak PR score, median time to remedication, and mean global assessment score were similar for hydrocodone with ibuprofen and oxycodone with acetaminophen. Assay sensitivity was demonstrated by the presence of statistically significant differences between both active treatments and placebo (n = 60). The number of patients experiencing adverse events was similar for each of the 3 groups (11 [18.0%], hydrocodone with ibuprofen; 7 [11.9%], oxycodone with acetaminophen; and 6 [10.0%], placebo). CONCLUSIONS: In this study, a 2-tablet dose of combination hydrocodone 7.5 mg and ibuprofen 200 mg was as effective as a 2-tablet dose of combination oxycodone 5 mg and acetaminophen 325 mg in the treatment of moderate to severe postoperative obstetric or gynecologic pain. Both treatments were superior to placebo. The results of this study suggest that the combination of hydrocodone 7.5 mg and ibuprofen 200 mg may offer prescribers an additional option in combination pain therapy.

The effect of beta-blockers on mental performance on older hypertensive patients.

This double-blind, three-way crossover study measured the influence of beta-blocker treatment on drowsiness and mental test performance in older hypertensive patients and determined if lipophilicity was a determinant of these effects. Twenty-seven hypertensive patients (mean age, 63 +/- 3 years) were studied. Patients received two weeks each of daily treatment with placebo, 100 mg of atenolol, or 150 mg of metoprolol tartrate and were evaluated on the 14th day of each treatment period, after which their next treatment period began. Mental performance was measured using Trails-A maze testing. Drowsiness was measured subjectively using a visual analogue scale, and objectively using critical fusion-frequency threshold testing. Blood pressure control was equivalent and clinically adequate in all subjects. Steady-state levels of metoprolol tartrate (235.7 +/- 46 ng/mL) and atenolol (453.6 +/- 56 ng/nL) achieved were those expected to produce similar beta-blockade. Mental performance as measured by Trials-A testing showed better scores during beta-blocker treatment compared with placebo. Trails-A scores improved as patients went from placebo to metoprolol treatment, but did not change as patients went from placebo to atenolol treatment. Critical fusion-frequency threshold measurements were lower following administration of both drugs than following that of placebo, but subjectively there was no difference in feelings of lethargy between either beta-blocker and placebo. These data show greater improvement in mental testing performance to be associated with metoprolol treatment, but neither produced more lethargy than placebo in elderly patients.