Equity in the recovery of elective and oncological surgery volumes after the COVID-19 lockdown: a multicentre cohort study in Italy.

BACKGROUND: The COVID-19 pandemic has had, and still has, a profound impact on national health systems, altering trajectories of care and exacerbating existing inequalities in health. Postponement of surgeries and cancellation of elective surgical procedures have been reported worldwide. In Italy, the lock-down measures following the COVID-19 pandemic caused cancellations of surgical procedures and important backlogs; little is known about potential social inequalities in the recovery process that occurred during the post-lockdown period. This study aims at evaluating whether all population social strata benefited equally from the surgical volumes' recovery in four large Italian regions. METHODS: This multicentre cohort study covers a population of approximately 11 million people. To assess if social inequalities exist in the recovery of eight indicators of elective and oncological surgery, we estimated Risk Ratios (RR) through Poisson models, comparing the incidence proportions of events recorded during COVID-19 (2020-21) with those in pre-pandemic years (2018-19) for each pandemic period and educational level. RESULTS: Compared to 2018-19, volumes of elective surgery showed a U-shape with the most significant drops during the second wave or the vaccination phase. The recovery was socially unequal. At the end of 2021, incidence proportions among highly educated people generally exceeded the expected ones; RRs were 1.31 (95%CI 1.21-1.42), 1.24 (95%CI 1.17-1.23), 1.17 (95%CI 1.08-1.26) for knee and hip replacement and prostatic surgery, respectively. Among low educated patients, RR remained always < 1. Oncological surgery indicators showed a similar social gradient. Whereas volumes were preserved among the highly educated, the low educated were still lagging behind at the end of 2021. CONCLUSIONS: Surgical procedures generally returned to pre-pandemic levels but the low educated experienced the slowest recovery. An equity-oriented appraisal of trends in healthcare provision should be included in pandemic preparedness plans, to ensure that social inequalities are promptly recognised and tackled.

Examining potential Long COVID effects through utilization of healthcare resources: a retrospective, population-based, matched cohort study comparing individuals with and without prior SARS-CoV-2 infection.

BACKGROUND: A significant proportion of individuals reports persistent clinical manifestations following SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) acute infection. Nevertheless, knowledge of the burden of this condition-often referred to as 'Long COVID'-on the health care system remains limited. This study aimed to evaluate healthcare utilization potentially related to Long COVID. METHODS: Population-based, retrospective, multi-center cohort study that analyzed hospital admissions and utilization of outpatient visits and diagnostic tests between adults aged 40 years and older recovered from SARS-CoV-2 infection occurred between February 2020 and December 2021 and matched unexposed individuals during a 6-month observation period. Healthcare utilization was analyzed by considering the setting of care for acute SARS-CoV-2 infection [non-hospitalized, hospitalized and intensive care unit (ICU)-admitted] as a proxy for the severity of acute infection and epidemic phases characterized by different SARS-CoV-2 variants. Data were retrieved from regional health administrative databases of three Italian Regions. RESULTS: The final cohort consisted of 307 994 previously SARS-CoV-2 infected matched with 307 994 uninfected individuals. Among exposed individuals, 92.2% were not hospitalized during the acute infection, 7.3% were hospitalized in a non-ICU ward and 0.5% were admitted to ICU. Individuals previously infected with SARS-CoV-2 (vs. unexposed), especially those hospitalized or admitted to ICU, reported higher utilization of outpatient visits (range of pooled Incidence Rate Ratios across phases; non-hospitalized: 1.11-1.33, hospitalized: 1.93-2.19, ICU-admitted: 3.01-3.40), diagnostic tests (non-hospitalized: 1.35-1.84, hospitalized: 2.86-3.43, ICU-admitted: 4.72-7.03) and hospitalizations (non-hospitalized: 1.00-1.52, hospitalized: 1.87-2.36, ICU-admitted: 4.69-5.38). CONCLUSIONS: This study found that SARS-CoV-2 infection was associated with increased use of health care in the 6 months following infection, and association was mainly driven by acute infection severity.

Indirect impact of the COVID-19 pandemic and its containment measures on social inequalities in hospital utilisation in Italy.

BACKGROUND: The pandemic may undermine the equity of access to and utilisation of health services for conditions other than COVID-19. The objective of the study is to evaluate the indirect impact of COVID-19 and lockdown measures on sociodemographic inequalities in healthcare utilisation in seven Italian areas. METHODS: In this multicentre retrospective study, we evaluated whether COVID-19 modified the association between educational level or deprivation and indicators of hospital utilisation and quality of care. We also assessed variations in gradients by sex and age class. We estimated age-standardised rates and prevalence and their relative per cent changes comparing pandemic (2020) and pre-pandemic (2018-2019) periods, and the Relative Index of Inequalities (RIIs) fitting multivariable Poisson models with an interaction between socioeconomic position and period. RESULTS: Compared with 2018-2019, hospital utilisation and, to a lesser extent, timeliness of procedures indicators fell during the first months of 2020. Larger declines were registered among women, the elderly and the low educated resulting in a shrinkage (or widening if RII <1) of the educational gradients for most of the indicators. Timeliness of procedures indicators did not show any educational gradient neither before nor during the pandemic. Inequalities by deprivation were nuanced and did not substantially change in 2020. CONCLUSIONS: The socially patterned reduction of hospital utilisation may lead to a potential exacerbation of health inequalities among groups who were already vulnerable before the pandemic. The healthcare service can contribute to contrast health disparities worsened by COVID-19 through more efficient communication and locally appropriate interventions.

Indirect impact of Covid-19 on hospital care pathways in Italy.

Earlier in 2020, seven Italian regions, which cover 62% of the Italian population, set up the Mimico-19 network to monitor the side effects of the restrictive measures against Covid-19 on volumes and quality of care. To this aim, we retrospectively analysed hospital discharges data, computing twelve indicators of volume and performance in three clinical areas: cardiology, oncology, and orthopaedics. Weekly indicators for the period January-July 2020 were compared with the corresponding average for 2018-2019; comparisons were performed within 3 sub-periods: pre-lockdown, lockdown, and post-lockdown. The weekly trend of hospitalisations for ST-segment elevation myocardial infarction (STEMI) showed a 40% reduction, but the proportion of STEMI patients with a primary PTCA did not significantly change from previous years. Malignant neoplasms surgery volumes differed substantially by site, with a limited reduction for lung cancer (< 20%) and greater declines (30-40%) for breast and prostate cancers. The percentage of timely surgery for femoral neck in the elderly remained constantly higher than the previous 2 years whereas hip and knee replacements fell dramatically. Hospitalisations have generally decreased, but the capacity of a timely and effective response in time-dependent pathways of care was not jeopardized throughout the period. General trends did not show important differences across regions, regardless of the different burden of Covid-19. Preventive and primary care services should adopt a pro-active approach, moving towards the identification of at-risk conditions that were neglected during the pandemic and timely addressing patients to the secondary care system.

Cost per care of the first year of direct antiviral agents in the Liguria Region: a multicenter analysis.

AIMS: Despite the remarkable efficacy shown in clinical practice, concerns have been raised about the costs associated with direct antiviral agent (DAA) therapy. This article presents the real-life costs for DAA treatment sustained by the Italian National Health Service in the Liguria Region (Northern Italy). METHODS: A retrospective analysis of the cost per care sustained for DAA treatment, relating to the period from January 1 to December 31, 2015 in five centers in Liguria was performed. All patients undergoing DAA-based treatments for hepatitis C virus (HCV) infection were enrolled. On-treatment costs included: HCV treatment, laboratory test, outpatient services, attended visits, drugs used for the management of adverse events (erythropoietin, albumin or red blood cell packs) and inpatient service admissions. RESULTS: In total, 327 patients were enrolled. No difference in terms of sustained virologic response (SVR) rate among different treatments was reported. The majority (85.0%) of patients did not report any side effects and only 15 (4.6%) required hospital admission. Forty-two patients (12.8%) required high-cost drugs for the management of adverse events. The overall cost sustained was €14,744,433. DAA±ribavirin (RBV) accounted for the wide majority of this cost (98.9%; €14,585,123). Genotype (GT) 1, the most commonly treated GT, was associated with an average cost of €43,445 per patient. Detailed analysis of the costs for GT 1 showed the treatment based on ritonavir boosted paritaprevir/ombitasvir + dasabuvir±RBV with an average cost of €24,978 (RBV+) and €25,448 (RBV-) per patient was the most cost-effective. The average cost per SVR was €48,184. Once again, the ritonavir boosted paritaprevir/ombitasvir + dasabuvir regimen was associated with the lowest cost/SVR (€25,448/SVR [GT 1b] and similar results for other GTs). CONCLUSION: Antiviral regimen is the major contributor to costs in the treatment of HCV infection. Appropriate regimen selection could result in a major cost saving, which can be reinvested to allow more patients to be treated.

Influence of EGFR mutational status on metastatic behavior in non squamous non small cell lung cancer.

Epidermal Growth Factor Receptor (EGFR) mutated Non Small Cell Lung Cancers (NSCLCs) are a molecularly subgroup of patients with peculiar clinic-pathological characteristics. Previous studies have suggested a possible interaction between oncogene status and metastatic behavior in non squamous NSCLCs with conflicting results. The aim of this study was to compare the different metastatic patterns, at baseline and during the course of the disease, in a cohort of 137 Caucasian patients with non-squamous NSCLC according to the EGFR mutational status and survival differences according to the different metastatic behavior. We observed unique metastatic distributions between EGFR-mutated and EGFR wild type non-squamous NSCLCs. These data support the hypothesis that tumor bio-molecular characteristics and genotype may influence the metastatic process in NSCLC and might help the development of enrichment strategies for tumor genotyping in these tumors, especially in the presence of limited tissue availability.

Efficacy, safety and cost per responder of biologics in the treatment of non-radiographic axial spondyloarthritis.

Anti-tumour necrosis factor (TNF) agents are recommended as second-line therapy for patients with axial spondyloarthropathies. This analysis reviewed data on studies investigating the efficacy and tolerability of anti-TNF agents in patients with non-radiographic axial spondyloarthritis (nr-axSpA) who had failed first-line non-steroidal anti-inflammatory (NSAID) treatment. Efficacy data from RCTs were used to calculate the number needed to treat (NNT) for individual anti-TNFs and then the cost per responder was determined to provide an indication of the value of each therapy. A systematic literature review and analysis of search results over the period January 2008 to September 2014 identified four randomised placebo-controlled trials that were included in the analysis. Adalimumab, etanercept and certolizumab pegol were all effective and well tolerated in patients with nr-axSpA. A patient was more likely to reach ASAS20 or ASAS40 when treated with etanercept or adalimumab, the NNT was lowest for adalimumab, and the risk of adverse events was higher with certolizumab pegol 200 mg every 2 weeks. The cost per responder (NNT) was lowest for adalimumab, followed closely by certolizumab 400 mg every 4 weeks, intermediate for certolizumab 200 mg every 2 weeks and highest for etanercept. Although all anti-TNF agents were associated with clinical improvement in patients with nr-axSpA, adalimumab presented a better cost per responder than etanercept and certolizumab pegol.

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.

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.

Celecoxib for the prevention of nonmuscle invasive bladder cancer: results from a matched control study.

OBJECTIVES: New targets and approaches are under investigation for the treatment of nonmuscle invasive bladder cancer (NMIBC). Preclinical data suggest cyclooxygenase-2 (COX-2) as a promising target. Celecoxib, a COX-2 selective inhibitor, inhibits tumor development and enhances survival, both in vitro and in vivo models of bladder cancer. Therefore, we conducted a pilot study of celecoxib to prevent recurrence in patients with intermediate risk NMIBC. METHODS: Treatment with celecoxib was administered orally for 12 months and compared with a contemporary series of patients treated with intravesical mitomycin C (MMC), given weekly for 4 weeks and then monthly for 11 months. Primary endpoints were time to first recurrence and adverse events. RESULTS: From 2003 through 2006, 58 patients were treated with celecoxib and compared with 66 patients receiving MMC. After a median follow up of 75 months, 49 patients were disease free, including 23 (34.85%) in the MMC group and 26 (44.8%) in the celecoxib group. Median disease-free interval was 67 months [95% confidence interval (CI) 35.8 to NA] versus 41 months (95% CI 27.1-67.1; log-rank p = 0.25) for patients treated with MMC and celecoxib, respectively. In the multivariate analysis, treatment was not found to be an independent predictor for recurrence [hazard ratio (HR) 0.76, 95% CI 0.47-1.22, p = 0.25). Overall, 45 AEs were recorded in 35/124 patients. There were no differences between the two groups. CONCLUSIONS: Our data support a clinical benefit of celecoxib and encourage future trials in which COX-2 inhibitors may be tested in selected patients with NMIBC.

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.

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.

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.

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.

Analysis of oncological outcomes and renal function after laparoendoscopic single-site (LESS) partial nephrectomy: a multi-institutional outcome analysis.

OBJECTIVE: To report on a large multi-institutional series of laparoendoscopic single-site (LESS) partial nephrectomy (PN) and analyse renal function and short-term oncological outcomes. MATERIAL AND METHODS: We conducted a retrospective analysis of consecutive cases of LESS-PN performed between November 2007 and March 2012 at 11 participating institutions. Demographic data and data on the main peri-operative outcomes and complications were gathered and analysed. Kidney function was evaluated by measuring serum creatinine concentration and estimated glomerular filtration rate (eGFR). Chronic kidney disease was defined in stages for each patient according to the National Kidney Foundation, Kidney Disease Outcomes Quality Initiative. RESULTS: A total of 190 cases were included in this analysis. The mean renal tumour size was 2.6 cm, and the mean PADUA score was 7.2. The median operating time was 170 min with a median estimated blood loss of 150 mL. A clampless technique was used in 70 cases (36.8%) and the median warm ischaemia time (WIT) was 16.5 min. PADUA score independently predicted the length of WIT (low vs high score: odds ratio 5.11, CI 1.50-17.41, P = 0.009; intermediate vs high score: odds ratio 5.13, CI 1.56-16.88, P = 0.007). The overall postoperative complication rate was 14.7%. Where a clamping technique was used, a significant increase in serum creatinine concentration and a significant decrease in eGFR were observed postoperatively and at 6 months. On multivariate analysis PADUA score was the only predicting factor. Overall survival rates were 99, 97 and 88% at 12-, 24- and 36-month follow-up, respectively, while disease-free survival rates were 98% at 12-month and 97% at 24- and 36-month follow-up. CONCLUSION: The study showed that LESS-PN is effective in terms of renal function preservation and oncological control at short- and intermediate-term follow-up.

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.