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.

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.

Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT).

The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.

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.

Oxidative stress and APO E polymorphisms in Alzheimer's disease and in mild cognitive impairment.

A number of evidences indicates oxidative stress as a relevant pathogenic factor in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Considering its recognized major genetic risk factors in AD, apolipoprotein (APO E) has been investigated in several experimental settings regarding its role in the process of reactive oxygen species (ROS) generation. The aim of this work has been to evaluate possible relationships between APO E genotype and plasma levels of selected oxidative stress markers in both AD and MCI patients. APO E genotypes were determined using restriction enzyme analysis. Plasma levels of oxidative markers, advanced oxidation protein products, iron-reducing ability of plasma and, in MCI, activity of superoxide dismutases were evaluated using spectrophotometric analysis. We found, compared to controls, increased levels of oxidized proteins and decreased values of plasma-reducing capacity in both AD patients (p < 0.0001) and MCI patients (p < 0.001); the difference between AD and MCI patients was significant only for plasma-reducing capacity (p < 0.0001), the former showing the lowest values. Superoxide dismutase activity was reduced, although not at statistical level, in MCI compared with that in controls. E4 allele was statistically associated (p < 0.05) with AD patients. When comparing different APO E genotype subgroups, no difference was present, as far as advanced oxidation protein products and iron-reducing ability of plasma levels were concerned, between E4 and non-E4 carriers, in both AD and MCI; on the contrary, E4 carriers MCI patients showed significantly decreased (p < 0.05) superoxide dismutase activity with respect to non-E4 carriers. This study, in confirming the occurrence of oxidative stress in AD and MCI patients, shows how it can be related, at least for superoxide dismutase activity in MCI, to APO E4 allele risk factor.

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.

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.

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.

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.

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.

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.

The role of vascular factors in late-onset sporadic Alzheimer's disease. Genetic and molecular aspects.

Alzheimer's disease (AD) is a late-onset progressive neurodegenerative disorder which results in the irreversible loss of cortical neurons, particularly in the associative neocortex and hippocampus. AD is the most common form of dementia in the elderly. Apart from the neuronal loss, the pathological hallmarks are extracellular senile plaques, containing the peptide beta-amyloid (Abeta), and neurofibrillary tangles. The Abeta cascade hypothesis remains the main pathogenetic model, as suggested by familiar AD, mainly associated to mutation in amyloid precursor protein and presenilin genes. The remaining 95% of AD patients are mostly sporadic late-onset cases, with a complex aetiology due to interactions between environmental conditions and genetic features of the individual. A relationship between genetic and acquired vascular factors and AD has been hypothesized. Many vascular risk factors for AD, such as atherosclerosis, stroke and cardiac disease in the aging individual, could result in cerebrovascular dysfunction and trigger AD pathology. A major vascular susceptibility factor gene is the apolipoprotein E gene, found to be associated with sporadic late-onset AD cases. Another interesting vascular susceptibility gene is angiotensin converting enzyme. Other possible genes include VLDL-R, LRP, NOS3, CST3, OLR1, MTHFR, PON1 and VEGF, but many of the related studies have shown conflicting results. In this paper, we review the role of molecular vascular abnormalities and of the "vascular risk" genes supposed to be involved in the pathogenesis of AD, in an attempt to provide a comprehensive picture of what is known about the mechanisms underlying the role of vascular factors in late-onset sporadic AD.

CSF phosporylated TAU protein levels correlate with cerebral glucose metabolism assessed with PET in Alzheimer's disease.

One major goal of drug development would be the establishment of biomarkers as objective indicators of normal biological and pathogenetic processes, or pharmacological response to a therapeutic intervention. A potential approach is to investigate proteins in CSF linked to key neuropathological features of Alzheimer's disease (AD). Recently CSF phosphorylated-Tau (p-Tau) levels have been reported to reflect neurofibrillary changes within the brain of patients with AD, however the use of serial CSF investigations in order to monitor the disease progression is not applicable. PET with FDG reveals characteristic patterns in AD patients, however so far no correlation between in vivo metabolic information and pathological features has been reported. In the present study, we tested whether CSF Tau levels correlate with metabolic rate for glucose consumption in a cohort of 28 AD patients. We found a statistically significative correlation between both CSF total and p-TAU protein and relative metabolic indexes obtained from 18FDG-PET scans in parietal, temporal and occipital lobes bilaterally. These results indicate the existence of a correlation between impairment of cerebral metabolism, estimated throughout FDG-PET, and CSF Tau protein levels.

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.

Feasibility, limits and problems of clinical studies in Intensive Care Unit.

In critical care medicine there is still a paucity of evidence on how to manage most of the clinical problems commonly encountered in critically ill patients. Randomized controlled trials (RCTs) are the most powerful instruments to evaluate the efficacy of a therapeutic intervention and to generate evidence for clinical practice. Unfortunately, the design and conduct of RCTs in our field are particularly complicated, because of some intrinsic and structural problems (e.g. lack of reliable nosography, concomitant use of different therapies, problems in the definition of end-points besides mortality) that will be discussed in this review. Further challenges are represented by the lack of tradition of large ICU networks, difficulties in linking or integrating physiologic and therapeutic objectives in designing clinical protocols, scarcity of independent or non-profit funds. A particularly stimulating opportunity of development is represented also by the relationship of critical care to EBM. Because of the above problems, metanalyses could be less informative than in other areas of medicine, as they are based on few trials which are often contradictory and of unsatisfactory quality. Few suggestions are formulated which could help looking forwards.

[Angiotensin converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in microalbuminuric patients with one or more cardiovascular risk factors. Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes randomized trial (LIRICO).]. / ACE-inibizione, antagonismo recettoriale e terapia combinata in soggetti microalbuminurici con fattori di rischio cardiovascolare. Protocollo dello studio randomizzato multicentrico ''Long-term impact of RAS inhibition on cardiorenal outcomes-LIRICO".

Angiotensin converting enzyme inhibitors (ACE-i) and angiotensin II receptor blockers (ARB) are considered to be equally effective for patients with diabetic kidney disease, while only ACE-i have been shown to determine a significant reduction in the risk of all-cause mortality, predominantly cardiovascular, in these patients. Studies on the cardio-renal efficacy of combined therapy with ACE-i and ARB are not available or not conclusive, in a population with cardiovascular risk with micro- or macroalbuminuria. In this paper, we present the protocol of a randomized controlled clinical trial that will address the question. The LIRICO (Long-term Impact of RAS Inhibition on Cardiorenal Outcomes) study will evaluate the comparative efficacy for cardiovascular and renal outcomes of combined therapy with ACE-i and ARB versus monotherapy with ACE-i or ARB in micro/macroalbuminuric individuals at cardio-renal risk. The study will enrol 2100 patients allocated to monotherapy with ACE-i, ARB or combined treatment with ACE-i + ARB. The LIRICO study is a randomized comparative trial, with PROBE (Prospective Randomized Open Blinded End-Point) design. The study has been approved and funded by the Agenzia Italiana del Farmaco (AIFA) within the 2005 funding plan for independent research on drugs. Availability of funding for this study provides, for the first time in our Country, an opportunity to organize a collaborative national network of nephrology, internal medicine and diabetology outpatient clinics to develop a large multicentre trial collaboration. The results of this trial will establish the optimal therapy for micro/macroalbuminuric individuals with cardiovascular and renal risk.

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.

Principios de epidemiología del medicamento

Publicación estructurada en 12 capítulos: \"Estudios de utilización de medicamentos y de farmacovigilancia\", \"Utilización de medicamentos, fármacos esenciales y políticas de salud en países desarrollados y subdesarrollados\", \"Promoción del uso racional de los medicamentos y preparación de guías farmacológicas\", \"Métodos aplicados en estudios descriptivos de utilización de medicamentos\", \"Mecanismos de producción y diagnóstico clínico de los efectos indeseables producidos por medicamentos\", ...