Bortezomib-based therapy in non-transplant multiple myeloma patients: a retrospective cohort study from the FABIO project.

INTRODUCTION: Randomized clinical trials showed that bortezomib, in addition to conventional chemotherapy, improves survival and disease progression in multiple myeloma (MM) patients not eligible for stem cell transplantation. The aim of this retrospective population-based cohort study is the evaluation of both clinical and economic profile of bortezomib-based versus conventional chemotherapy in daily clinical practice. METHODS: Healthcare utilization databases of six Italian regions were used to identify adult patients with non-transplant MM, who started a first-line therapy with bortezomib-based or conventional chemotherapy. Patients were matched by propensity score and were followed from treatment start until death, lost to follow-up or study end-point. Overall survival (OS) and restricted mean survival time (RMST) were estimated using the Kaplan-Meier method. Association between first-line treatment and risk of death was estimated by a conditional Cox proportional regression model. Average mean cumulative costs were estimated and compared between groups. RESULTS: In the period 2010-2016, 3509 non-transplant MM patients met the inclusion criteria, of which 1157 treated with bortezomib-based therapy were matched to 1826 treated with conventional chemotherapy. Median OS and RMST were 33.9 and 27.9 months, and 42.9 and 38.4 months, respectively, in the two treatment arms. Overall, these values corresponded to a HR of death of 0.79 (95% CI 0.71-0.89) over a time horizon of 84 months. Average cumulative cost were 83,839 € and 54,499 €, respectively, corresponding to an incremental cost-effectiveness ratio of 54,333 € per year of life gained, a cost coherent with the willingness-to-pay thresholds frequently adopted from Western countries. CONCLUSIONS: These data suggested that, in a large cohort of non-transplant MM patients treated outside the experimental setting, first-line treatment with bortezomib-based therapy was associated with a favourable effectiveness and cost-effectiveness profile.

Cardiovascular Risk After Adjuvant Trastuzumab in Early Breast Cancer: An Italian Population-Based Cohort Study.

BACKGROUND: Although trastuzumab (T) represents the standard of care for the adjuvant treatment of HER2-positive early-stage breast cancer, contrasting results are available about the cardiac toxicity associated to its use. We conducted a multiregional population-based cohort investigation aimed to assess both the short- and long-term cardiovascular (CV) outcomes in women with early breast cancer treated with T-based or standard adjuvant chemotherapy (CT). MATERIALS AND METHODS: We used health care use databases of six Italian regions, overall accounting for 42% of the Italian population. The study cohort was made by all women surgically treated for breast cancer who started a first-line adjuvant T-based or CT treatment. Patients treated with T were 1:2 matched to those treated with CT based on date of treatment start, age, and presence of CV risk factors. Short- and long-term CV outcomes (heart failure and cardiomyopathy) were measured, respectively, after 1 year and at the end of follow-up. RESULTS: Among 28,599 women who met the inclusion criteria, 6,208 T users were matched to 12,416 CT users. After a mean follow-up of 5.88 years, short- and long-term cumulative CV risk were 0.8% and 2.6% in patients treated with T and 0.2% and 2.8% in those treated with CT, respectively. Adjusted hazard ratios were 4.6 (95% confidence interval [CI], 2.6-8.0) for short-term and 1.2 (95% CI, 0.9-1.6) for long-term CV risk. DISCUSSION: In our large real-world investigation, T-associated cardiotoxicity was limited to the treatment period. The addition of T to adjuvant CT did not result in long-term worsening of CV events. IMPLICATIONS FOR PRACTICE: Adjuvant trastuzumab-based chemotherapy represents the backbone therapy in patients with HER2-positive early breast cancer. Although well tolerated, cardiovascular events can manifest during or after therapy because of treatment-related toxicities. In this wide multicenter and unselected cohort, long-term symptomatic cardiotoxicity was low and limited to the treatment period. The findings suggest that developing tools that would be adequately able to predict cardiac toxicity at an early stage remains an important area in which additional research efforts are needed.

Effectiveness and Costs Associated to Adding Cetuximab or Bevacizumab to Chemotherapy as Initial Treatment in Metastatic Colorectal Cancer: Results from the Observational FABIO Project.

Evidence available on the effectiveness and costs of biological therapies for the initial treatment of metastatic colorectal cancer (mCRC) is scarce and contrasting. We conducted a population-based cohort investigation for assessing overall survival and costs associated with their use in a real-world setting. Healthcare utilization databases were used to select patients newly diagnosed with mCRC between 2010 and 2016. Those initially treated with biological therapy (bevacizumab or cetuximab) added to chemotherapy were propensity-score-matched to those treated with standard chemotherapy alone, and were followed up to June 30th, 2018. Kaplan-Meier survival estimates, restricted mean survival time (RMST) and cumulative costs were compared between the two treatment arms. The study cohort included 1896 mCRC patients treated with biological therapy matched to 5678 patients treated with chemotherapy alone. Median overall survival was 21.8 and 20.2 months, respectively. After 84 months of follow-up, RMSTs were 30.9 and 31.9 months (p = 0.193), indicating no differences between the average survival time between treatment arms. Patients treated with biological therapy were associated with higher costs. Cumulative per capita costs were €59,663 and €44,399, respectively. In our study, first-line biological therapy did not improve long-term overall survival and was associated with higher costs as compared to standard chemotherapy.

Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial.

BACKGROUND: Strongyloides stercoralis infection is a neglected condition that places people who are immunocompromised at risk of hyperinfection and death. Ivermectin is the drug of choice for the treatment of S stercoralis infection, but there is no definitive evidence on the optimal dose. This trial aimed to assess whether multiple doses of ivermectin were superior to a single dose for the treatment of non-disseminated strongyloidiasis. METHODS: Our study was designed as a multicentre, open-label, phase 3, randomised controlled superiority trial. Participants were enrolled in four centres in Italy, three in Spain, and two in the UK, and recruiting sites were predominantly hospitals. Eligible patients were older than 5 years, weighed more than 15 kg, were residents in an area not endemic for S stercoralis, and either were positive for S stercoralis in faecal tests and on serology (any titre) or had a positive serological test with high titres, irrespective of the result of faecal tests. Patients were randomly assigned (1:1) using a computer-generated, blinded allocation sequence (with randomly mixed block sizes of six, eight, and ten participants) to receive either one dose of ivermectin 200 µg/kg or four doses of ivermectin 200 µg/kg (given on days 1, 2, 15, and 16). The primary endpoint was the proportion of participants with clearance of S stercoralis infection at 12 months, which was assessed in all randomly assigned participants who were not lost to follow-up (modified full-analysis set) and in participants in the modified full-analysis set who did not deviate from the assigned treatment regimen (per-protocol set). All participants were included in the safety analysis. The trial was registered with ClinicalTrials.gov, NCT01570504, and is now closed for recruitment. FINDINGS: Of the 351 patients assessed for eligibility, 309 recruited between March 26, 2013, and May 3, 2017, were randomly assigned to one dose (n=155) or four doses (n=154) of ivermectin. At 12 months in the modified full-analysis set, 86% (95% CI 79 to 91; 102 of 118 participants) had responded to treatment in the single-dose group compared with 85% (77 to 90; 96 of 113 participants) in the four-dose group (risk difference 1·48%, 95% CI -7·55 to 10·52; p=0·75); similar results were observed in the per-protocol set. Adverse events were generally of mild intensity and more frequent in the multiple-dose than in the single-dose group. The trial was terminated early due to futility. INTERPRETATION: Multiple doses of ivermectin did not show higher efficacy and was tolerated less than a single dose. A single dose should therefore be preferred for the treatment of non-disseminated strongyloidiasis. FUNDING: There was no funding source for this study.

Persistence of Central Venous Oxygen Desaturation During Early Sepsis Is Associated With Higher Mortality: A Retrospective Analysis of the ALBIOS Trial.

BACKGROUND: Relevance of low (< 70%) central venous oxygen saturation (Scvo2) during early sepsis has been recently questioned by three negative trials (Protocol-Based Care for Early Septic Shock, Australasian Resuscitation in Sepsis Evaluation, and Protocolized Management in Sepsis) on early goal-directed therapy; however, subjects included in those trials had Scvo2 at enrollment as high as 71 ± 13%, 73 ± 11%, and 70 ± 12%. Here we assess the association between Scvo2 < 70% at 6 h and 90-day mortality in subjects enrolled in the Albumin Italian Outcome Sepsis (ALBIOS) trial, focusing on those with initial Scvo2 < 70%. METHODS: Regardless of treatment assignment (to receive albumin or not), all subjects enrolled in the ALBIOS trial received early goal-directed therapy aiming for Scvo2 ≥ 70% at 6 h. Using multivariable logistic regression analyses, we tested the association between Scvo2 < 70% at 6 h and 90-day mortality in those with initial Scvo2 < 70% (n = 514) or ≥ 70% (n = 961). RESULTS: Scvo2 < 70% at 6 h was independently associated with higher 90-day mortality in subjects with initial Scvo2 < 70% (OR, 1.84; 95% CI, 1.19-2.85; P = .007) but not in those with initial Scvo2 ≥ 70% (OR, 1.25; 95% CI, 0.79-1.95; P = .357). Scvo2 < 70% at enrollment and at 6 h was associated with history and/or signs of cardiac dysfunction but not with greater severity of disease or more aggressive resuscitation (required per protocol). CONCLUSIONS: In the ALBIOS trial, persistence of low Scvo2 was associated with higher 90-day mortality, possibly because it reflected underlying cardiac dysfunction. Subjects with Scvo2 < 70% may benefit most from individually tailored interventions aimed at normalizing the balance between systemic oxygen delivery and consumption. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT00707122; URL: www.clinicaltrials.gov.

Sequential N-Terminal Pro-B-Type Natriuretic Peptide and High-Sensitivity Cardiac Troponin Measurements During Albumin Replacement in Patients With Severe Sepsis or Septic Shock.

OBJECTIVES: Myocardial dysfunction is a frequent complication in patients with severe sepsis and can worsen the prognosis. We investigated whether circulating biomarkers related to myocardial function and injury predicted outcome and were associated with albumin replacement. DESIGN: A multicenter, randomized clinical trial about albumin replacement in severe sepsis or septic shock (the Albumin Italian Outcome Sepsis trial). SETTING: Forty ICUs in Italy. PATIENTS: Nine hundred and ninety-five patients with severe sepsis or septic shock. INTERVENTIONS: Randomization to albumin and crystalloid solutions or crystalloid solutions alone. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of N- terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T were measured 1, 2, and 7 days after enrollment. We tested the relationship of single marker measurements or changes over time with clinical events, organ dysfunctions, albumin replacement, and ICU or 90-day mortality in the overall population and after stratification by shock. N-terminal pro-B-type natriuretic peptide levels were abnormal in 97.4% of the patients and high-sensitivity cardiac troponin T in 84.5%, with higher concentrations in those with shock. After extensive adjustments, N-terminal pro-B-type natriuretic peptide concentrations predicted ICU or 90-day mortality, better than high-sensitivity cardiac troponin T. Early changes in N-terminal pro-B-type natriuretic peptide or high-sensitivity cardiac troponin T concentrations were independently associated with subsequent mortality in patients with shock. Patients given albumin had significantly higher N-terminal pro-B-type natriuretic peptide levels; in addition, early rise in N-terminal pro-B-type natriuretic peptide was associated with a better outcome in this subgroup. CONCLUSIONS: Circulating N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin T are frequently elevated in severe sepsis or septic shock and have relevant prognostic value, which may be important in monitoring the clinical efficacy of supporting therapy.

Randomized Trial of Low-Dose Morphine Versus Weak Opioids in Moderate Cancer Pain.

PURPOSE: The WHO guidelines on cancer pain management recommend a sequential three-step analgesic ladder. However, conclusive data are lacking as to whether moderate pain should be treated with either step II weak opioids or low-dose step III strong opioids. PATIENTS AND METHODS: In a multicenter, 28-day, open-label randomized controlled study, adults with moderate cancer pain were assigned to receive either a weak opioid or low-dose morphine. The primary outcome was the number of responder patients, defined as patients with a 20% reduction in pain intensity on the numerical rating scale. RESULTS: A total of 240 patients with cancer (118 in the low-dose morphine and 122 in the weak-opioid group) were included in the study. The primary outcome occurred in 88.2% of the low-dose morphine and in 57.7% of the weak-opioid group (odds risk, 6.18; 95% CI, 3.12 to 12.24; P < .001). The percentage of responder patients was higher in the low-dose morphine group, as early as at 1 week. Clinically meaningful (≥ 30%) and highly meaningful (≥ 50%) pain reduction from baseline was significantly higher in the low-dose morphine group (P < .001). A change in the assigned treatment occurred more frequently in the weak-opioid group, because of inadequate analgesia. The general condition of patients, which was based on the Edmonton Symptom Assessment System overall symptom score, was better in the morphine group. Adverse effects were similar in both groups. CONCLUSION: In patients with cancer and moderate pain, low-dose morphine reduced pain intensity significantly compared with weak opioids, with a similarly good tolerability and an earlier effect.

Patient's adherence on pharmacological therapy for benign prostatic hyperplasia (BPH)-associated lower urinary tract symptoms (LUTS) is different: is combination therapy better than monotherapy?

BACKGROUND: Recent studies showed that the non-adherence to the pharmacological therapy of patients affected by BPH-associated LUTS increased the risk of clinical progression of BPH. We examined the patients adherence to pharmacological therapy and its clinical consequences in men with BPH-associated LUTS looking at the differences between drug classes comparing mono vs combination therapy. METHODS: A retrospective, population-based cohort study, using prescription administrative database and hospital discharge codes from a total of 1.5 million Italian men. Patients ≥ 40 years, administered alpha-blockers (AB) and 5alpha-reductase inhibitors (5ARIs), alone or in combination (CT), for BPH-associated LUTS were analyzed. The 1-year and long term adherence together with the analyses of hospitalization rates for BPH and BPH-related surgery were examined using multivariable Cox proportional hazards regression model and Pearson chi square test. RESULTS: Patients exposed to at least 6 months of therapy had a 1-year overall adherence of 29 % (monotherapy AB 35 %, monotherapy 5ARI 18 %, CT 9 %). Patient adherence progressively declined to 15 %, 8 % and 3 % for AB, 5ARI, and CT, respectively at the fifth year of follow up. Patients on CT had a higher discontinuation rate along all the follow-up compared to those under monotherapy with ABs or 5ARIs (all p < 0.0001). Moreover, CT was associated with a reduced risk of hospitalization for BPH-related surgery (HR 0.94; p < 0.0001) compared to AB monotherapy. CONCLUSIONS: Adherence to pharmacological therapy of BPH-associated LUTS is low and varies depending on drugs class. Patients under CT have a higher likelihood of discontinuing treatment for a number of reasons that should be better investigated. Our study suggests that new strategies aiming to increase patient's adherence to the prescribed treatment are necessary in order to prevent BPH progression.

Current Pharmacological Treatment for Male LUTS due to BPH: Dutasteride or Finasteride?

Benign prostatic hyperplasia (BPH) is a potentially progressive disease which is commonly associated with bothersome lower urinary tract symptoms (LUTS) and might result in complications, such as acute urinary retention and BPH-related surgery. In the current medical therapy scenario for LUTS attributed to BPH, only one class of drugs, 5-α reductase inhibitors (5ARIs), has been found to be effective in reducing the risk of disease progression. The two 5ARIs that are currently available include finasteride and dutasteride. These two drugs have different pharmacokinetic and pharmacodynamic properties. Greater suppression of dehydrotestosterone is achieved by dutasteride (>90% dutasteride vs 70% finasteride) which theoretically should correlate with greater efficacy in alleviating urinary symptoms. Unfortunately, this hypothesis has not yet been clinically demonstrated. The pertinent literature is scarce and heterogeneous and produces low scientific levels of evidence. The present review article aims to evaluate the comparative head-to-head studies in order to evaluate if the hypothetical clinical differences between dutasteride and finasteride do exist. Pharmacological treatment with either drug results in similar symptom improvements; however dutasteride seems to have a better profile in reducing the risk of prostate surgery and acute urinary retention (AUR). More studies are necessary to better evaluate both the clinical and pharmacoeconomic profile of the two 5ARIs.

On the hypothetical universal use of statins in primary prevention: an observational analysis on low-risk patients and economic consequences of a potential wide prescription rate.

PURPOSE: Recent guidelines expand indications for statins. However, research on practical economic feasibility and cost-effectiveness in low-risk people is lacking. We aimed to describe the incidence of cardiovascular events (CVE), their total direct costs and the hypothetical effects of wide provision of statins on those rates and expenditures. METHODS: We conducted a population-based cohort study using administrative data among low risk individuals. Estimators of effects of statins were taken from Cholesterol Treatment trialist metaanalysis and from Heart Protection Study trial. Two statin prices were used for analyses: National Italian Health System (€ 0.36) and the International Drug Price Indicator (€ 0.021). RESULTS: Overall, 920,067 persons at low risk were identified and 14,849 CVE were registered (incidence rate 27.3 per 10,000 person-years). Direct costs for hospitalizations for CVE were 143 M €. Universal provision of statins would result in a significant decrease in CVE rates, from 27.3 to 17.5 per 10,000 person-years (PY) (95% confidence interval (CI): 15.8-19.4). Universal prescription of simvastatin 20 mg would cost 802 M €. Otherwise, provision of simvastatin at International Drug Price Indicator's prices would be both clinically effective and cost saving in men older than age 44 (observed expenditures 120 M €, expected 97.4 M €) but not in women (observed expenditures 22.7 M €, expected 36.5 M €). CONCLUSIONS: Among a low-risk population, hypothetical universal provision of low-cost simvastatin to men over 44 years could be both clinically effective and a cost-saving strategy.

Identification of subgroups of early breast cancer patients at high risk of nonadherence to adjuvant hormone therapy: results of an Italian survey.

BACKGROUND: Adherence to adjuvant endocrine therapy (HT) is suboptimal among breast cancer patients. A high rate of nonadherence might explain differences in survival between clinical trial and clinical practice. Tailored interventions aimed at improving adherence can only be implemented if subgroups of patients at higher risk of poor adherence are identified. Because no data are available for Italy, we undertook a large survey on adherence among women taking adjuvant HT for breast cancer. PATIENTS AND METHODS: Patients were recruited from 10 cancer clinics in central Italy. All patients taking HT for at least 1 year were invited, during one of their follow-up visit, to fill a confidential questionnaire. The association of sociodemographic and clinical characteristics of participants with adherence was assessed using logistic regression. The RECPAM method was used to evaluate interactions among variables and to identify subgroups of patients at different risk of nonadherence. RESULTS: A total of 939 patients joined the study and 18.6% of them were classified as nonadherers. Among possible predictors, only age, working status, and switching from tamoxifen to an aromatase inhibitor were predictive of nonadherence in multivariate analysis. RECPAM analysis led to the identification of 4 classes of patients with a different likelihood of nonadherence to therapy, the lowest being observed in retired women with a low level of education, the highest in the group of unmarried, employed women, or housewives. CONCLUSION: The identification of these subgroups of "real life" patients with a high prevalence of nonadherers might be functional in designing intervention studies aimed at improving adherence.

Drug adherence and clinical outcomes for patients under pharmacological therapy for lower urinary tract symptoms related to benign prostatic hyperplasia: population-based cohort study.

BACKGROUND: Little is known about drug adherence in men treated for lower urinary tract symptoms (LUTS). Benign prostatic hyperplasia (BPH) is one of the causes of LUTS. OBJECTIVE: To examine adherence to pharmacological therapy and its clinical value in men with LUTS. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study using an administrative prescription database and hospital discharge codes for 1.5 million men aged ≥40 yr treated with alpha blockers (ABs) and 5-alpha reductase inhibitors (5ARIs) alone or in combination (CT). INTERVENTIONS: Therapy with ABs and/or 5ARIs. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The 1-yr and long-term adherence; hospitalization rates for BPH and BPH surgery. Multivariate Cox proportional hazards regression model, propensity score matching, and sensitivity analyses. RESULTS AND LIMITATIONS: The 1-yr adherence was 29% in patients exposed to at least 6-mo therapy. Patients on CT had a higher discontinuation rate in the first 2 yr compared to those on monotherapy (p<0.0001). Overall hospitalization rates for BPH and BPH surgery were 9.04 and 12.6 per 1000 patient-years, respectively. A lower risk of hospitalization was observed for 5ARI compared to AB therapy (hazard ratio [HR] 0.46 and 0.23; p<0.0001). CT was associated with a reduced risk of hospitalization for BPH surgery (HR 0.94; p<0.0001) compared to AB. Discontinuation of drug treatment was an independent risk factor for hospitalization for BPH and BPH surgery (HR 1.65 and 2.80; p<0.0001) regardless of therapeutic group. Limitations include the paucity of clinical measures and the absence of patient-reported outcomes. CONCLUSIONS: Adherence to pharmacological therapy for BPH is low and could affect clinical outcomes. Long-term 5ARI and CT use was associated with an independent reduced risk of hospitalization for BPH surgery. Our findings suggest the need for new strategies to increase patient adherence to prescribed treatment and more appropriate prescribing by physicians. PATIENT SUMMARY: Our research shows that adherence to prescribed pharmacological therapy is crucial in the management of patients suffering from lower urinary tract symptoms. Moreover, pharmacological therapy can prevent disease progression.

Circulating presepsin (soluble CD14 subtype) as a marker of host response in patients with severe sepsis or septic shock: data from the multicenter, randomized ALBIOS trial.

PURPOSE: Presepsin is a soluble fragment of the cluster-of-differentiation marker protein 14 (CD14) involved in pathogen recognition by innate immunity. We evaluated the relation between its circulating concentration, host response, appropriateness of antibiotic therapy, and mortality in patients with severe sepsis. METHODS: Plasma presepsin was measured 1, 2, and 7 days after enrollment of 997 patients with severe sepsis or septic shock in the multicenter Albumin Italian Outcome Sepsis (ALBIOS) trial. They were randomized to albumin or crystalloids. We tested with univariate and adjusted models the association of single measurements of presepsin or changes over time with clinical events, organ dysfunctions, appropriateness of antibiotic therapy, and ICU or 90-day mortality. RESULTS: Presepsin concentration at baseline (946 [492-1,887] ng/L) increased with the SOFA score, the number of prevalent organ dysfunctions or failures, and the incidence of new failures of the respiratory, coagulation, liver, and kidney systems. The concentration decreased in ICU over 7 days in patients with negative blood cultures, and in those with positive blood cultures and appropriate antibiotic therapy; it increased with inappropriate antibiotic therapy (p = 0.0009). Baseline presepsin was independently associated with, and correctly reclassified, the risk of ICU and 90-day mortality. Increasing concentrations of presepsin from day 1 to day 2 predicted higher ICU and 90-day mortality (adjusted p < 0.0001 and 0.01, respectively). Albumin had no effect on presepsin concentration. CONCLUSIONS: Presepsin is an early predictor of host response and mortality in septic patients. Changes in concentrations over time seem to reflect the appropriateness of antibiotic therapy.

Albumin replacement in patients with severe sepsis or septic shock.

BACKGROUND: Although previous studies have suggested the potential advantages of albumin administration in patients with severe sepsis, its efficacy has not been fully established. METHODS: In this multicenter, open-label trial, we randomly assigned 1818 patients with severe sepsis, in 100 intensive care units (ICUs), to receive either 20% albumin and crystalloid solution or crystalloid solution alone. In the albumin group, the target serum albumin concentration was 30 g per liter or more until discharge from the ICU or 28 days after randomization. The primary outcome was death from any cause at 28 days. Secondary outcomes were death from any cause at 90 days, the number of patients with organ dysfunction and the degree of dysfunction, and length of stay in the ICU and the hospital. RESULTS: During the first 7 days, patients in the albumin group, as compared with those in the crystalloid group, had a higher mean arterial pressure (P=0.03) and lower net fluid balance (P<0.001). The total daily amount of administered fluid did not differ significantly between the two groups (P=0.10). At 28 days, 285 of 895 patients (31.8%) in the albumin group and 288 of 900 (32.0%) in the crystalloid group had died (relative risk in the albumin group, 1.00; 95% confidence interval [CI], 0.87 to 1.14; P=0.94). At 90 days, 365 of 888 patients (41.1%) in the albumin group and 389 of 893 (43.6%) in the crystalloid group had died (relative risk, 0.94; 95% CI, 0.85 to 1.05; P=0.29). No significant differences in other secondary outcomes were observed between the two groups. CONCLUSIONS: In patients with severe sepsis, albumin replacement in addition to crystalloids, as compared with crystalloids alone, did not improve the rate of survival at 28 and 90 days. (Funded by the Italian Medicines Agency; ALBIOS ClinicalTrials.gov number, NCT00707122.).

Presepsin (soluble CD14 subtype) and procalcitonin levels for mortality prediction in sepsis: data from the Albumin Italian Outcome Sepsis trial.

INTRODUCTION: Sepsis, a leading cause of death in critically ill patients, is the result of complex interactions between the infecting microorganisms and the host responses that influence clinical outcomes. We evaluated the prognostic value of presepsin (sCD14-ST), a novel biomarker of bacterial infection, and compared it with procalcitonin (PCT). METHODS: This is a retrospective, case-control study of a multicenter, randomized clinical trial enrolling patients with severe sepsis or septic shock in ICUs in Italy. We selected 50 survivors and 50 non-survivors at ICU discharge, matched for age, sex and time from sepsis diagnosis to enrollment. Plasma samples were collected 1, 2 and 7 days after enrollment to assay presepsin and PCT. Outcome was assessed 28 and 90 days after enrollment. RESULTS: Early presepsin (day 1) was higher in decedents (2,269 pg/ml, median (Q1 to Q3), 1,171 to 4,300 pg/ml) than in survivors (1,184 pg/ml (median, 875 to 2,113); P = 0.002), whereas PCT was not different (18.5 µg/L (median 3.4 to 45.2) and 10.8 µg/L (2.7 to 41.9); P = 0.31). The evolution of presepsin levels over time was significantly different in survivors compared to decedents (P for time-survival interaction = 0.03), whereas PCT decreased similarly in the two groups (P = 0.13). Presepsin was the only variable independently associated with ICU and 28-day mortality in Cox models adjusted for clinical characteristics. It showed better prognostic accuracy than PCT in the range of Sequential Organ Failure Assessment score (area under the curve (AUC) from 0.64 to 0.75 vs. AUC 0.53 to 0.65). CONCLUSIONS: In this multicenter clinical trial, we provide the first evidence that presepsin measurements may have useful prognostic information for patients with severe sepsis or septic shock. These preliminary findings suggest that presepsin may be of clinical importance for early risk stratification.

Actual medical management of lower urinary tract symptoms related to benign prostatic hyperplasia: temporal trends of prescription and hospitalization rates over 5 years in a large population of Italian men.

PURPOSE: The purpose of the study is to estimate the trends in drug prescriptions and the hospitalization rates for lower urinary tract symptoms/benign prostatic hyperplasia (LUTS/BPH) in real-life clinical practice, using information deriving from administrative databases of the Italian health care system. METHODS: Prescription data on approximately 1,500,000 men over 40 were examined, and prescribed boxes of alpha-blockers (ABs) and/or 5 alpha reductase inhibitors (5ARI) were calculated for 5 consecutive years, from 2004 to 2008. Annual use prevalence and incidence rates for each drug class and for the combination therapy (CT) were calculated according to age for the entire study period. Hospitalization rates for reasons related to LUTS/BPH were also evaluated for the same time period. RESULTS: The overall distribution of drugs for LUTS/BPH, in terms of number of boxes prescribed, increased by 43 %. This increase was accounted for by both classes of drugs although it was greater for 5ARI than for AB (+49 vs +41 %). The prevalence of CT showed a substantial increase to almost 25 % in patients aged ≥75. Hospitalization rate for BPH/LUTS-related reasons decreased during the study period (8 and 3 % per year for non-surgical and surgical reasons, respectively). CONCLUSIONS: The prevalence of the use of drugs prescribed for LUTS/BPH has steadily increased. An increase in terms of prescribed boxes was observed for both classes of drugs, even though the increase was greater for 5ARIs. The reduction in the hospitalization rates needs additional researches.

Is pain reporting to health care professionals age-related? A cross sectional multicenter study in a hospital setting.

BACKGROUND: Failure to report pain by older patients is usually considered a major obstacle to receive adequate pain management. OBJECTIVES: To compare the frequency of reporting pain to health care professionals (HCPs) among older (≥ 65 yrs) and younger adults (< 65 yrs) and to evaluate whether age and setting of care influence pain reporting to HCPs. RESULTS: Overall, 3285 patients (54.7 ≥ 65 yrs) were interviewed. Despite analgesic therapy, 2821 patients had pain. Among these, 1178 patients (41.8%) had severe pain. The frequency of patients not reporting pain to HCPs is significantly lower among older vs. younger adults (18.1 vs. 23.6%; p < 0.001). Multiple multilevel logistic regression, however, shows that nonreporting pain is not age-related, but is associated with: nonmalignant pain (OR = 1.53; 95% CI: 1.00 - 2.35; p = 0.05), a short hospitalization (OR = 1.58; 95% CI: 1.20 - 2.07; p = 0.001), admission to a hospital without a 'pain-free hospital' project (OR = 2.00; 95% CI: 1.18 - 3.39; p = 0.011). CONCLUSIONS: The results suggest that failure to report pain does not appear to be associated with the age of the patient in itself, but with type of pain and clinical context. Both patients and physicians should be encouraged to actively address pain management. Further research is needed.

[ProMoFIA_Oncologic: monitoring project of the innovative oncology drugs in Abruzzo]. / ProMoFIA_Oncologici: Progetto di Monitoraggio dei Farmaci Oncologici Innovativi in Abruzzo.

INTRODUCTION: The unmet therapeutic needs lead to accelerated registration of new oncology drugs, even with incomplete information of the benefit-risk ratio. METHODS: In Italy the Onco-AIFA Register was established to monitor oncology drugs when used according to authorized indications and to assure their appropriate use in clinical practice. In the Abruzzo region, an observational longitudinal study (ProMoFIA_Oncologici) was performed to evaluate in standard clinical practice all patients treated with these new oncology drugs for any indication. RESULTS: During the period 2008-2011, 3435 patients were observed: in 62.2% of patients, the use of these drugs was eligible also for the Onco-AIFA Register; in 22.7% it was in-label but not monitored in the Onco-AIFA; in 15.1% the use was off-label. DISCUSSION: The study findings showed a widespread use of the new oncology drugs beyond the Onco-AIFA indications, as well as their off-label use.