Association Between CSF Beta-Amyloid and Apathy in Early-Stage Alzheimer Disease.

AIM: The apathetic syndrome is a common clinical feature in patients with Alzheimer diseases (AD), from preclinical phases to late stages of dementia, and it is strongly related to major disease outcomes. Unfortunately, no specific pharmacological treatments for apathy have been accomplished so far. Translational evidences have previously shown that a link between apathy and hallmarks of AD-related pathophysiology, that is, ß-amyloid (Aß) plaques and neurofibrillary tangles, exists. However, only few studies investigated the association between core biomarkers of AD and apathy scores, finding conflicting results. METHODS: Thirty-seven patients were identified as having AD dementia according to National Institute on Aging-Alzheimer Association 2011 criteria. All participants underwent an extensive diagnostic workup including cerebrospinal fluid (CSF) assessment to measure the concentrations of Aß42, t-tau, and pTau181. To follow, they were stratified as: apathy absence, apathy mild, and apathy severe according to the Neuro Psychiatric Inventory-apathy item scores. We investigated for potential associations between apathy scores and CSF biomarkers concentrations as well as for differences in terms of clinical and CSF biomarkers data across the 3 apathy groups. RESULTS: The CSF Aß42 concentrations were negatively correlated with apathy scores. In addition, patients with severe apathy had significantly lower Aß42 levels compared to nonapathetic ones. CONCLUSION: Based on our results, we encourage further studies to untangle the potential association between the complex pathophysiological dynamics of AD and apathy which may represent an innovative reliable clinical outcome measure to use in clinical trials, investigating treatments with either a symptomatic or a disease-modifying effect.

Recommendations of the Sleep Study Group of the Italian Dementia Research Association (SINDem) on clinical assessment and management of sleep disorders in individuals with mild cognitive impairment and dementia: a clinical review.

Clinical assessment and management of sleep disturbances in patients with mild cognitive impairment and dementia has important clinical and social implications. Poor sleep results in an increased risk of morbidities and mortality in demented patients and is a source of stress for caregivers. Sleep disturbances show high prevalence in mild cognitive impairment and dementia patients and they are often associated one to another in the same patient. A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of individuals with cognitive decline. The Sleep Study Group of the Italian Dementia Research Association (SINDem) reviewed evidence from original research articles, meta-analyses and systematic reviews published up to December 2013. The evidence was classified in quality levels (I, II, III) and strength of recommendations (A, B, C, D, E). Where there was a lack of evidence, but clear consensus, good practice points were provided. These recommendations may not be appropriate for all circumstances and should therefore be adopted only after a patient's individual characteristics have been carefully evaluated.

Qualitative evaluation of the Rey-Osterrieth Complex Figure Test in patients with progressive supranuclear palsy.

Objective: In early stages of disease, the differential diagnosis between Parkinson's Disease (PD) and atypical parkinsonism, such as Progressive Supranuclear Palsy (PSP), could be challenging. Growing attention has recently been dedicated to investigating neuropsychological markers of degenerative parkinsonism. The Rey-Osterrieth Complex Figure Test (ROCFT) copy score was hypothesized able to differentiate PSP from PD. However, ROCFT is a drawing test requiring multiple cognitive abilities and it is still unknown which of them assumes an important role in PSP performance. Using a qualitative scoring system, we investigated which cognitive abilities underpin the PSP performance at the ROCFT copy trial. Moreover, we evaluated usefulness of the BQSS scores in discriminating PSP from PD. Methods: Thirty PSP-Richardson's Syndrome (PSP-RS) patients, 30 PD patients, and 30 healthy control (HC) comparable for age, education, and gender were enrolled. All subjects underwent a neuropsychological evaluation; ROCFT copy were evaluated with the 36-Point Score and with the Boston Qualitative Scoring System (BQSS). Results: PSP-RS patients performed worse in ROCFT 36-Point Score and in several BQSS scores compared to other groups. Most suitable scores discriminating PSP-RS from PD were "Perseveration" and "Vertical Expansion" of BQSS. A logistic regression model considering "Perseveration" and "Vertical Expansion" showed a diagnostic accuracy of 83,3% for PSP-RS condition. Conclusion: our findings showed that "Perseveration" and "Vertical Expansion" BQSS scores were useful in discriminating PSP-RS from PD. "Perseveration" and "Vertical Expansion" BQSS scores might be included in the cognitive evaluation along with quantitative scores when PSP diagnosis is considered.

Impact of early access to a palliative/supportive care intervention on pain management in patients with cancer.

BACKGROUND: No study has so far addressed whether differences do exist in the management of cancer pain between patients receiving usual care by primary specialists and those receiving early palliative/supportive intervention. PATIENTS AND METHODS: A multicentre cross-sectional study in 32 Italian Hospitals has included 1450 patients, receiving analgesic therapy for cancer pain: 602 with access to primary specialist alone (standard care, SC) and 848 with early access to a palliative/supportive care (ePSC) team, concomitant with primary oncology care. RESULTS: Statistically significant differences in the analgesic drug administration according to care model have been evident: non-opioids were more frequently used in SC (9.5% versus 2%; P<0.001), while strong opioids in ePSC group (80% versus 63%; P<0.001). The number of patients with severe pain was lower in ePSC compared with SC group (31% versus 17%; P<0.001). Results of multivariate analysis have shown that ePSC integrated with primary oncologic care (relative risk 0.69; 95% confidence interval 0.48-0.99; P=0.045) was an independent factor associated with a 31% reduced risk of suffering from severe pain. CONCLUSIONS: An ePSC team provides the most effective standard of analgesic therapy for cancer pain. A randomized clinical trial is needed to confirm these findings.

Unrecognised ventricular dysfunction in COPD.

While both chronic congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) impose a substantial disease burden and share aetiological and epidemiological associations, they have largely been studied separately. The aim of our study was to assess the prevalence and the prognostic implications of the coexistence of left ventricular dysfunction in COPD patients and airway obstruction in CHF patients. We used a prospective cohort study including stable ≥ 60-yr-old patients with echocardiographically confirmed CHF (n=201) and stable ≥ 60-yr-old patients with clinically and spirometry-confirmed COPD (n=218). All CHF patients underwent routine spirometry, and all COPD patients underwent routine echocardiographic assessment and B-type natriuretic peptide (BNP) measurement. Patients were followed for 2 yrs. The prevalence of airway obstruction among CHF patients was 37.3% and the prevalence of ventricular dysfunction among COPD patients was 17%. The presence of ventricular dysfunction in patients with COPD tended to increase the risk of mortality during follow-up (hazard ratio 2.34, 95% CI 0.99-5.54; p=0.053). The presence of airway obstruction in patients with CHF did not influence survival. CHF and COPD frequently coexist, and ventricular dysfunction worsens survival in patients with COPD. Considering the high prevalence and the prognostic implications of ventricular dysfunction, routine assessment with either BNP or echocardiogram should be considered in COPD patients.

APOE and Alzheimer disease: a major gene with semi-dominant inheritance.

Apolipoprotein E (APOE) dependent lifetime risks (LTRs) for Alzheimer Disease (AD) are currently not accurately known and odds ratios alone are insufficient to assess these risks. We calculated AD LTR in 7351 cases and 10 132 controls from Caucasian ancestry using Rochester (USA) incidence data. At the age of 85 the LTR of AD without reference to APOE genotype was 11% in males and 14% in females. At the same age, this risk ranged from 51% for APOE44 male carriers to 60% for APOE44 female carriers, and from 23% for APOE34 male carriers to 30% for APOE34 female carriers, consistent with semi-dominant inheritance of a moderately penetrant gene. Using PAQUID (France) incidence data, estimates were globally similar except that at age 85 the LTRs reached 68 and 35% for APOE 44 and APOE 34 female carriers, respectively. These risks are more similar to those of major genes in Mendelian diseases, such as BRCA1 in breast cancer, than those of low-risk common alleles identified by recent GWAS in complex diseases. In addition, stratification of our data by age groups clearly demonstrates that APOE4 is a risk factor not only for late-onset but for early-onset AD as well. Together, these results urge a reappraisal of the impact of APOE in Alzheimer disease.

Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients.

BACKGROUND/AIMS: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. METHODS: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer's disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson's disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. RESULTS: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer's disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson's disease dementia. CONCLUSION: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.

Impact of setting of care on pain management in patients with cancer: a multicentre cross-sectional study.

BACKGROUND: No study has so far addressed whether differences do exist in the management of cancer-related pain in patients admitted to oncology and non-oncology settings. PATIENTS AND METHODS: A multicentre cross-sectional study in 48 Italian hospitals has enrolled 819 patients receiving analgesic therapy for cancer-related pain. Demographics and clinical and analgesic therapy information have been prospectively collected by standardized forms. Adequacy of pain management has been evaluated by the Pain Management Index (PMI). RESULTS: Differences in the analgesic drug administration according to settings of care have been evident, non-opioids more frequently being administered in non-oncology units (19.6% versus 7.0%; P < 0.0001), while strong opioids are more frequently used in the oncology units (69.5% versus 51.9%; P < 0.0001). The number of patients receiving inadequate therapy (PMI < 0) has lowered in oncology compared with non-oncology units (11.3% versus 18.8%; P = 0.0024). Results of multiple logistic regression analysis have shown that the admission to non-oncology setting [odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.15-2.67; P = 0.0096] and the absence of metastatic disease (OR = 1.60, 95% CI = 1.04-2.44; P = 0.0317) were independent factors associated with an increased risk of receiving an inadequate analgesic therapy. CONCLUSION: Oncology wards provide the most adequate standard of analgesic therapy for cancer-related pain.

Sleep disturbances in elderly subjects: an epidemiological survey in an Italian district.

OBJECTIVES: Disturbed sleep is common in elderly people and has been related to comorbidities. The aim of this study was to evaluate the prevalence of sleep problems and their relationship with chronic disease in an elderly population. MATERIALS AND METHODS: The whole population of subjects aged more than 65 years, in the municipality of Vecchiano, Pisa was considered as eligible and underwent a clinical interview and a questionnaire about insomnia, sleepiness, snoring and sleep apnea. A model of logistic regression was applied to the data. RESULTS: The participation rate was 60.3% (1427 subjects). Insomnia was observed in 44.2% of our population, while sleepiness in 31.3%, snoring in 47.2% and sleep apnea in 9.0%. The most common diseases associated with sleep symptoms were depression, cognitive decline and diabetes. CONCLUSIONS: Our results confirm that sleep problems are very common in elderly subjects and closely related to medical and psychiatric illnesses.

N-3 polyunsaturated fatty acids in heart failure: mechanisms and recent clinical evidence.

Over the past 20 years, there has been significant progress in our knowledge of the pathophysiology of heart failure (HF) with consequent considerable development of both pharmacological and non pharmacological approaches. Despite improved therapeutic strategies, HF still remains burdensome in terms of mortality, quality of life, and hospitalization costs. A new and promising medical treatment to improve survival in HF patients stems from the recent results of the Italian study, Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Heart Failure (GISSI-HF). GISSI-HF was a randomized, large scale, double-blind, placebo-controlled trial showing that n-3 PUFA (850-882 mg/d) reduced mortality and admission to the hospital for cardiovascular reasons in patients with chronic heart failure (HF) who were already receiving recommended therapies. The clinical benefit observed in GISSI-HF seemed to be mediated prominently by the antiarrhythmic effects of n-3 PUFA, though an effect on mechanisms related to HF progression cannot be excluded. This article presents the results of GISSI-HF study and reviews the previous clinical evidence on n-3 PUFA and risk of heart failure and discusses in depth the potential mechanisms through which n-3 PUFA treatment can improve clinical outcome in HF patients.

Persistent platelet activation in patients with type 2 diabetes treated with low doses of aspirin.

BACKGROUND: The percentage of diabetic patients who do not benefit from the protective effect of aspirin is larger than in other populations at cardiovascular risk. OBJECTIVE: We compared the ability of aspirin to suppress TxA2 and platelet activation in vivo, in type-2 diabetics vs. high-risk non-diabetic patients. METHODS: Urinary 11-dehydro-TXB2, plasma sCD40 L, and sP-selectin were measured, together with indices of low-grade inflammation, glycemic control, and lipid profile, in 82 patients with type-2 diabetes and 39 without diabetes, treated with low doses of aspirin. RESULTS: Urinary 11-dehydro-TxB2, plasma sCD40L and sP-selectin were significantly higher in diabetics than in controls: [38.9 (27.8-63.3) vs. 28.5 (22.5-43.9) ng mmol(-1) of creatinine, P = 0.02], [1.06 (0.42-3.06) vs. 0.35 (0.22-0.95) ng mL(-1); P = 0.0001], [37.0 (16.8-85.6) vs. 20.0 (11.2-35.6) ng mL(-1), P = 0.0001], respectively. The proportion of individuals with diabetes increased across quartiles of 11-dehydro-TxB2, sCD40L, and sP-selectin, with the highest quartiles of 11-dehydro-TxB2, sCD40L and sP-selectin, including 66%, 93.3%, and 93.3% of individuals with diabetes. Markers of platelet activation positively correlated with indices of glycemic control but not with markers of low-grade inflammation. CONCLUSIONS: Platelet dysfunction associated with insufficient glycemic control, may mediate persistent platelet activation under aspirin treatment.

Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial.

Microalbuminuria is a strong, consistent and independent risk factor for cardiovascular and renal disease in patients with diabetes and/or hypertension and in the general population. Several randomized trials have shown the efficacy of inhibiting the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) to prevent cardiovascular events and the progression of kidney disease. These 2 classes of drugs are equally effective for renal outcomes in patients with diabetic nephropathy, but only ACEIs have been found to significantly impact the risk of all-cause mortality, predominantly cardiovascular, in patients with diabetic nephropathy. Studies on the cardiorenal efficacy of combined therapy with ACEIs and ARBs in individuals with microalbuminuria or macroalbuminuria and other cardiovascular risk factors have been inconclusive. The Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) study aims to address existing questions in this setting. This is a phase III, randomized, comparative, pragmatic trial with prospective randomized open blinded endpoint (PROBE) design. It will evaluate the comparative efficacy of combined therapy with ACEIs and ARBs versus monotherapy with either ACEIs or ARBs in improving cardiovascular and renal outcomes in microalbuminuric or macroalbuminuric individuals at cardiorenal risk. The study will enroll 2,100 patients, selected in a network of internal medicine, diabetology or nephrology outpatient clinics. Patients will be randomly allocated to ACEIs, ARBs or their combination. The study has been approved and funded by the Agenzia Italiana del Farmaco (A.I.F.A.) within the 2005 funding plan for independent research on drugs.

No evidence for allelic association of serotonin 2A receptor and transporter gene polymorphisms with depression in Alzheimer disease.

Patients with Alzheimer disease (AD) often exhibit psychiatric symptoms associated with cognitive impairment. The serotoninergic system may be involved in the development of depressive symptoms in AD patients, as suggested by the evidence that antidepressant drugs having the serotonin transporter as their target are effectively used to treat depressive AD patients. The aim of this study was to investigate the role of serotonin in depression, searching for association of two serotoninergic polymorphisms (T102C of serotonin receptor 5-HT2A and serotonin transporter linked polymorphic region -5-HTTLPR- of SLC6A4 gene) with depressive symptoms and considering their possible interactions with Apolipoprotein E (ApoE) and between themselves, in a sample of 208 sporadic AD patients and 116 normal controls from Italy. 5-HTTLPR and T102C are not associated with AD when separately analysed. However, we found out an interaction between the two polymorphisms in L/L and C/C genotype carriers increasing the risk for the disease (p=0.015, OR=8.048; 95% CI: 1.497-43.262). No association of the polymorphisms was detected with depression linked to AD. No interaction between 5-HTTLPR and T102C was detected in depressive AD subjects, even after stratification according to the presence of ApoE4 allele. These results suggest that the serotoninergic system may be not involved in the pathogenesis of depressive symptoms in AD patients, and it may be involved in other aspects of disease pathophysiology like cognitive symptoms and psychosis.

Early enteral immunonutrition vs. parenteral nutrition in critically ill patients without severe sepsis: a randomized clinical trial.

OBJECTIVES: We compared early parenteral nutrition (PN) and early enteral immunonutrition (iEN) in critically ill patients, distinguishing those with and without severe sepsis or septic shock (SS) on admission to intensive care units (ICUs). DESIGN AND SETTING: Multicenter, randomized, unblinded clinical trial in 33 Italian general ICUs. PATIENTS AND PARTICIPANTS: The study included 326 patients, 287 of whom did not have SS on ICU admission. Eligibility criteria excluded the two tails in the spectrum of critical conditions, i.e., patients either too well or too ill. Of the patients recruited 160 were randomized to iEN (142 without SS) and 166 to PN (145 without SS). INTERVENTIONS: Patients were randomized to two arms: early iEN or early PN. MEASUREMENTS AND RESULTS: Primary endpoint was 28-day mortality for all patients and the occurrence of SS during ICU stay for patients admitted without such condition. While 28-day mortality did not differ between iEN and PN (15.6% vs. 15.1%), patients without SS who received iEN had fewer episodes of severe sepsis or septic shock (4.9% vs. 13.1%). ICU length of stay was 4 days shorter in patients given iEN. CONCLUSIONS: Compared to parenteral nutrition iEN appears to be beneficial in critical patients without severe sepsis or septic shock. Parenteral nutrition in these patients should be abandoned, at least when enteral nutrition can be administered, even at an initial low caloric content.

Alcohol consumption and the risk of breast cancer in women.

The relationship between breast cancer and alcoholic beverage consumption was investigated in a case-control study of 437 women with breast cancer and 437 age-matched controls admitted to the hospital for acute conditions apparently unrelated to alcohol consumption. Compared to the relative risks (RR) for women who had never drunk alcohol, the RR for those reporting 1-3 and more than 3 alcoholic drinks per day were 1.24 and 1.93, respectively. A similar positive trend in risk with increasing daily consumption was evident for wine alone, and the point estimates were above unity for beer and spirits. Allowance for all identified potential confounding factors (including the major risk factors for breast cancer and a few selected dietary items) did not appreciably change any of the alcohol-related estimates. The RR, however, were higher at younger ages and did not rise with increasing duration of use. Nonetheless, the findings of the present study and their similarity with those of another case-control study conducted in northeastern Italy indicate that the association between alcoholic beverage consumption and breast cancer in this population is probably real, though not necessarily causal.

Age at first birth and the risk of epithelial ovarian cancer.

The relationships between age at first birth, parity, and the risk of ovarian cancer were evaluated in a case-control study of 272 women with histologically confirmed epithelial ovarian cancer and 544 age-matched controls with a spectrum of acute conditions unrelated to any of the established or potential risk factors for ovarian cancer. Late age at first birth was associated with increased risk: Compared to women who first had a child before the age of 22 years, the relative risks (RR) for those who first gave birth at ages 22-24, 25-27, and 28 or more were 2.7, 3.2, and 4.0, respectively. Nulliparous women showed increased RR (3.9) comparable to the RR among women who first bore a child at age 25 or more, regardless of the number of births. The elevated risk associated with later age at first birth was not accounted for by low parity. The risk of ovarian cancer, as expected, increased with decreasing parity: RR estimates for women having 5 or more, 3 or 4, and 1 or 2 children and for nulliparae were 1.0, 1.7, 1.9, and 2.6, respectively. However, the inverse association between parity and ovarian cancer could be accounted for largely by the importance of age at first birth, because when adjustment was made for that variable, the RR for 3 or 4 and 1 or 2 children decreased to 1.3 and 1.2, respectively. Thus the results of the present study show a strong independent effect of age at first birth on the risk of epithelial ovarian cancer, whereas the association with parity can be explained largely or totally in terms of a high correlation between total parity and age at first birth. The pattern of ovarian cancer risk that emerges from this study, therefore, is similar to the epidemiology of breast cancer. General evidence on this issue from various other studies, however, is rather controversial, and similar analysis of other data-sets would be useful.

Risk factors for endometrial cancer at different ages.

The importance of the major risk factors for endometrial cancer in women of different ages was evaluated with the use of data from a hospital-based case-control study conducted in Milan, Italy, on 283 women with endometrial cancer and 566 age-matched controls. Current weight was related strongly to the risk of endometrial cancer both in younger (premenopausal) and in older women (with risk estimates for the heaviest categories of 20.3 and 7.7, respectively), thus confirming that obesity is the major cause of endometrial cancer in Northern Italy. Endometrial cancer risk appeared to be approximately proportional to the second power of body mass index. Early menarche and nulliparity were associated with an increased risk of endometrial cancer in premenopausal women, the point estimate for nulliparity rising to 35.1 (with lower confidence limit of 10.2) after adjustment for marital status. However, no association with these factors was evident in postmenopausal women. Combination oral contraceptives were used by 2 cases and 19 controls only [relative risk (RR) = 0.2, with 95% confidence interval = 0.1-0.8]. The use of noncontraceptive estrogens was associated with an elevated risk, which was greater in perimenopausal women (RR = 5.1 for greater than 2 yr of use), and decreased progressively with increasing time after menopause. Late menopause was also related to endometrial cancer. However, the risk estimates for late menopause apparently were more elevated in older women (greater than or equal to 65 yr) than in perimenopausal women. Most of the risk factors identified (excluding late menopause) apparently act on one of the later stages of the process of carcinogenesis, because the excess risk drops after cessation of exposure.

Benign breast disease and consumption of beverages containing methylxanthines.

The relationship between methylxanthine (Mx) consumption and benign breast disease was evaluated in a case-control study of 288 women with histologically confirmed benign breast lumps (203 dysplastic lesions and 85 benign tumors) and 2 groups of control women--285 patients in the hospital for acute conditions apparently unrelated to the consumption of Mx-containing beverages and 291 outpatients. The relative risk estimates of dysplastic breast lesions (fibrocystic disease), with allowance for all identified potential distorting factors, for women who drank 1-2 or 3 or more cups of coffee per day were 4.1 and 6.4, respectively, when the hospital controls were the comparison group and 2.0 and 3.7, respectively, when the outpatient controls were the comparison group. The relationship was even stronger when the total consumption of Mx-containing beverages (coffee plus tea) was considered and increased with increasing duration of use. The association was not explained by any of the major risk factors for fibrocystic breast diseases or by differences in general characteristics or other lifestyle habits between cases and controls. Mx consumption was not related to the risk of benign breast tumors (fibroadenomas). These findings support the hypothesis that Mx consumption is related to the risk of dysplastic lesions of the breast.

Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial infarction in high-risk ischemic situations. Main results of the GUARDIAN trial. Guard during ischemia against necrosis (GUARDIAN) Investigators.

BACKGROUND: The transmembrane sodium/hydrogen exchanger maintains myocardial cell pH integrity during myocardial ischemia but paradoxically may precipitate cell necrosis. The development of cariporide, a potent and specific inhibitor of the exchanger, prompted this investigation of the potential of the drug to prevent myocardial cell necrosis. METHODS AND RESULTS: A total of 11 590 patients with unstable angina or non-ST-elevation myocardial infarction (MI) or undergoing high-risk percutaneous or surgical revascularization were randomized to receive placebo or 1 of 3 doses of cariporide for the period of risk. The trial failed to document benefit of cariporide over placebo on the primary end point of death or MI assessed after 36 days. Doses of 20 and 80 mg every 8 hours had no effect, whereas a dose of 120 mg was associated with a 10% risk reduction (98% CI 5.5% to 23.4%, P=0.12). With this dose, benefit was limited to patients undergoing bypass surgery (risk reduction 25%, 95% CI 3.1% to 41.5%, P=0.03) and was maintained after 6 months. No effect was seen on mortality. The rate of Q-wave MI was reduced by 32% across all entry diagnostic groups (2.6% versus 1.8%, P=0.03), but the rate of non-Q-wave MI was reduced only in patients undergoing surgery (7.1% versus 3.8%, P=0.005). There were no increases in clinically serious adverse events. CONCLUSIONS: No significant benefit of cariporide could be demonstrated across a wide range of clinical situations of risk. The trial documented safety of the drug and suggested that a high degree of inhibition of the exchanger could prevent cell necrosis in settings of ischemia-reperfusion.

Antiemetic activity of high doses of metoclopramide combined with methylprednisolone versus metoclopramide alone in cisplatin-treated cancer patients: a randomized double-blind trial of the Italian Oncology Group for Clinical Research.

We designed a multicenter, double-blind randomized study to determine the safety and antiemetic effectiveness of intravenous (IV) methylprednisolone (P) combined with high-dose IV metoclopramide (MTC) v MTC alone in 200 untreated cancer patients receiving cisplatin chemotherapy. One hundred eighty-five patients were evaluable for treatment efficacy. MTC plus P was significantly superior to MTC alone in reducing the number and length of vomiting episodes (P = .001 and P = .0008, respectively) and the maximal intensity of nausea (P = .0124 with a score system; P = .0155 with a linear analogue scale) and length of nausea (P = .0056). The subgroup with a major incidence of nausea and vomiting was women, especially young women, outpatients, and those treated with higher doses of cisplatin. Side effects were low and equally distributed between the two treatment groups. We conclude that MTC plus P has greater antiemetic activity than MTC alone in patients receiving cisplatin chemotherapy.