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Flaminia Coluzzi,1 Francesca Bifulco,2 Arturo Cuomo,2 Mario Dauri,3 Claudio Leonardi,4 Rita Maria Melotti,5 Silvia Natoli,3 Patrizia Romualdi,6 Gennaro Savoia,7 Antonio Corcione8 1Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anaesthesia, Intensive Care and Pain Medicine, Sapienza University of Rome, Polo Pontino, Latina, 2National Cancer Institute “G Pascale” Foundation, Unit of Anaesthesia, Intensive Care and Pain Medicine, Naples, 3Department of Clinical Science and Translational Medicine, Tor Vergata University of Rome, 4Addiction Disease Department, Local Health Unit (ASL) Rome 2, Rome, 5Department of Medical and Surgical Sciences, 6Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Bologna, 7Department Anesthesia, Fatebenefratelli Hospital, Naples, 8Unit of Anaesthesia and Intensive Care, Dei Colli Hospital, V. Monaldi, Naples, Italy Abstract: The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone. Keywords: opioids, postoperative pain, addiction, abusers, buprenorphine, methadone

Boaz Gedaliahu Samolsky Dekel,1–3 Marco Palma,4 Maria Cristina Sorella,1–3 Alberto Gori,3 Alessio Vasarri,3 Rita Maria Melotti1–3 1Department of Medicine and Surgery Sciences, University of Bologna, 2Department of Emergency-Urgency, Bologna’s University Teaching Hospital, Policlinic S. Orsola-Malpighi, 3University of Bologna, Post Graduate School of Anaesthesia and Intensive Care, 4Collegio Superiore, Istituto di Studi Superiori – ISS, University of Bologna, Bologna, Italy Objectives: Variable prevalence and treatment of breakthrough pain (BTP) in different clinical contexts are partially due to the lack of reliable/validated diagnostic tools with prognostic capability. We report the statistical basis and performance analysis of a novel BTP scoring system based on the naïve Bayes classifier (NBC) approach and an 11-item IQ-BTP validated questionnaire. This system aims at classifying potential BTP presence in three likelihood classes: “High,” “Intermediate,” and “Low.”Methods: Out of a training set of n=120 mixed chronic pain patients, predictors associated with the BTP likelihood variables (Pearson’s χ2 and/or Fisher’s exact test) were employed for the NBC planning. Adjusting the binary classification to a three–likelihood classes case enabled the building of a scoring algorithm and to retrieve the score of each predictor’s answer options and the Patient’s Global Score (PGS). The latter medians were used to establish the NBC thresholds, needed to evaluate the scoring system performance (leave-one-out cross-validation).Results: Medians of PGS in the “High,” “Intermediate,” and “Low” likelihood classes were 3.44, 1.53, and −2.84, respectively. Leading predictors for the model (based on score differences) were flair frequency (∆S=1.31), duration (∆S=5.25), and predictability (∆S=1.17). Percentages of correct classification were 63.6% for the “High” and of 100.0% for either the “Intermediate” and “Low” likelihood classes; overall accuracy of the scoring system was 90.9%.Conclusion: The NBC-based BTP scoring system showed satisfactory performance in classifying potential BTP in three likelihood classes. The reliability, flexibility, and simplicity of this statistical approach may have significant relevance for BTP epidemiology and management. These results need further impact studies to generalize our findings. Keywords: naïve Bayes classifier, breakthrough pain, multiclass scoring-system

Introduction: Occipital neuralgia (ON) is a disabling cephalalgia form with demanding diagnostic workflow. We report the description and reliability analyses of the occipital nerves-applied strain (ONAS) test for occipital neuralgia (ON) early-stage diagnosis in cephalalgia patients., Methods: In a retrospective and observational study, we evaluated, among n = 163 consecutive cephalalgia patients, the sensitivity, specificity, and prior probability [positive (PPV) and negative (NPV) predictive values] of the ONAS test against two reference tests (occipital nerve anesthetic block and the painDETECT questionnaire). Multinomial logistic regression (MLR) and χ 2 analyses verified the ONAS test outcome's dependence upon independent variables (gender, age, pain site, block test, and painDETECT outcomes). We assessed inter-rater agreement with Cohen's kappa statistic., Results: ONAS test showed sensitivity and specificity of 81 and 18%, respectively, against the painDETECT and of 94 and 46%, respectively, against the block test. PPV was > 70% against both tests, while NPV was 81% against the block test and 26% against the painDETECT. Interrater agreement Cohen's kappa was excellent. Significant association (χ 2 analyses) and relationship (MLR) were found only between ONAS test and pain site but not with the other independent predictors., Conclusions: The ONAS test showed satisfactory reliability among cephalalgia patients; thus, it might be considered a valuable early stage tool for ON diagnosis in these patients., (© 2023. The Author(s).)

Background: Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team., Material and Methods: An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript., Conclusion: Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies., (© 2022. The Author(s).)

Background: Differential diagnosis of low back pain (LBP) is complex and a prominent issue at all health-care levels; guidance may come from patients' history cues and clinical examination signs. Human and animal studies report that diagnosis of lumbar radicular pain (LRP) may come from evaluating subjective responses of injured lumbar nerves to a strain applied at the buttock. The Buttock Applied Strain (BUAS-test) test may guide the differential diagnosis of LBP. Following an ex-adiuvantibus criterion, clinical improvement of LRP, diagnosed with the BUAS-test and congruently treated, may support this test diagnostic ability., Methods: Among 258 LRP patients, who, upon first visit (V1), tested positive on the BUAS-test (with/without positive Straight Leg Raising Test, SLRT), the effect of gabapentin prescription on painDETECT (PD) questionnaire and Brief Pain Inventory (BPI) outcomes was quantified in the follow-up visit (V2). To support BUAS-test diagnostic ability, we hypothesized that, at V2, >50% of the sample would present negative PD outcome, significant ( t -test) and ⩾2 points V2-V1 differences for each of the BPI-item's score. We used multinomial logistic regression (MLR) and χ 2 analyses to evaluate the PD-V2 outcomes' dependence upon independent variables., Results: Of the sample, 77% reported a negative PD-V2 outcome. V2-V1 differences of all BPI items were significant and >2 points. PD-V2 outcomes showed significant associations with SLRT-V1 and PD-V1, respectively, but not with gender, age group or pain site. MLR showed a significant relationship between SLRT-V1 and PD-V2 outcomes., Conclusion: Among LRP patients, diagnosed by the BUAS-test and treated with gabapentin, all prespecified endpoints were reached. These results may be considered a piece of ex-adiuvantibus evidence for the BUAS-test ability to diagnose LRP. While positive BUAS-test implies potential LRP, the co-presence with positive SLRT may imply a severer LRP condition. Further prospective research, in different settings and direct clinical measures, is needed., Competing Interests: Conflict of interest: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The British Pain Society 2021.)

Background: Hyperhomocysteinemia (HHcy) is considered as an independent risk factor for several diseases, such as cardiovascular, neurological and autoimmune conditions. Atherothrombotic events, as a result of endothelial dysfunction and increased inflammation, are the main mechanisms involved in vascular damage. This review article reports clinical evidence on the relationship between the concentration of plasmatic homocysteine (Hcy) and acute brain injury (ABI) in neurocritical care patients., Materials and Methods: a systematic search of articles in the PubMed and EMBASE databases was conducted, of which only complete studies, published in English in peer-reviewed journals, were included., Results: A total of 33 articles, which can be divided into the following 3 subchapters, are present: homocysteine and acute ischemic stroke (AIS); homocysteine and traumatic brain injury (TBI); homocysteine and intracranial hemorrhage (ICH)/subarachnoid hemorrhage (SAH). This confirms that HHcy is an independent risk factor for ABI and a marker of poor prognosis in the case of stroke, ICH, SAH and TBI., Conclusions: Several studies elucidate that Hcy levels influence the patient's prognosis in ABI and, in some cases, the risk of recurrence. Hcy appears as biochemical marker that can be used by neuro-intensivists as an indicator for risk stratification. Moreover, a nutraceutical approach, including folic acid, the vitamins B6 and B12, reduces the risk of thrombosis, cardiovascular and neurological dysfunction in patients with severe HHcy that were admitted for neurocritical care.

Introduction: The literature lacks formally validated and reliable tools for the diagnosis of breakthrough cancer pain (BTcP). The Italian Questionnaire for BTcP diagnosis (IQ-BTP) is an 11-item questionnaire aimed at detecting potential-BTP and classifying it into three likelihood classes: high, intermediate, and low., Methods: A multicenter, prospective, and observational study was designed to validate the IQ-BTP. In three consecutive visits with each cancer patient, the demographic and clinical details of the patient, the Brief Pain Inventory (BPI) scores, IQ-BTP outcomes, and clinicians' autonomous BTcP diagnosis (gold standard) and the agreement of this diagnosis with IQ-BTP outcomes were recorded. The assessed domains for IQ-BTP validation were: Validity, including content and face validity, construct validity (hypothesis testing, and cross-cultural validity\measurement invariance), and criterion validity; Reliability (internal consistency, reliability, and measurement error); Interpretability, and Responsiveness., Results: Seven palliative and pain management facilities in Italy recruited 280 patients, yielding 753 evaluations. Using the IQ-BTP, the rate of potential-BTcP was 27.2%, of which its likely presence was high in 52.7% of patients, intermediate in 38.5, and low in 8.8%. The BPI item scores differed significantly between the two IQ-BTP classes (no-BTcP and potential-BTcP classes). The correlation of the latter class with BPI items was significant but low. The IQ-BTcP showed two principal components, accounting for 66.6% of the variance. Cronbach's α was 0.71. The agreement rate between the gold standard and IQ-BTP outcomes was 82%. Cohen's [Formula: see text] was 0.535. The IQ-BTP showed sensitivity and specificity of 69 and 86%, respectively., Conclusions: The IQ-BTP extensive formal validation showed satisfactory psychometric and validity properties. Its content, face, construct, and criterion validities and its reliability, interpretability, and responsiveness were shown. Its use enabled potential-BTcP to be identified and differentiated into three likelihood classes with direct therapeutic and epidemiological implications. The latter may be confirmed in future studies., (© 2021. The Author(s).)

This study aimed to investigate DNA methylation levels in patients undergoing major breast surgery under opioid-based general anesthesia. Blood samples were collected from eleven enrolled patients, before, during and after anesthesia. PBMC were isolated and global DNA methylation levels as well as DNA methyltransferase (DNMT) and cytokine gene expression were assessed. DNA methylation levels significantly declined by 26%, reversing the direction after the end of surgery. Likewise, DNMT1a mRNA expression was significantly reduced at all time points, with lowest level of -68%. DNMT3a and DNMT3b decreased by 65 and 71%, respectively. Inflammatory cytokines IL6 and TNFα mRNA levels showed a trend for increased expression at early time-points to end with a significant decrease at 48 h after surgery. This exploratory study revealed for the first time intraoperative global DNA hypomethylation in patients undergoing major breast surgery under general anesthesia with fentanyl. The alterations of global DNA methylation here observed seem to be in agreement with DNMTs gene expression changes. Furthermore, based on perioperative variations of IL6 and TNFα gene expression, we hypothesize that DNA hypomethylation may occur as a response to surgical stress rather than to opiate exposure ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Caputi, Carboni, Rullo, Alessandrini, Balzani, Melotti, Romualdi, Candeletti and Fanelli.)

The synergic combination of D-dimer (as proxy of thrombotic/vascular injury) and static compliance (as proxy of parenchymal injury) in predicting mortality in COVID-19-ARDS has not been systematically evaluated. The objective is to determine whether the combination of elevated D-dimer and low static compliance can predict mortality in patients with COVID-19-ARDS. A "training sample" (March-June 2020) and a "testing sample" (September 2020-January 2021) of adult patients invasively ventilated for COVID-19-ARDS were collected in nine hospitals. D-dimer and compliance in the first 24 h were recorded. Study outcome was all-cause mortality at 28-days. Cut-offs for D-dimer and compliance were identified by receiver operating characteristic curve analysis. Mutually exclusive groups were selected using classification tree analysis with chi-square automatic interaction detection. Time to death in the resulting groups was estimated with Cox regression adjusted for SOFA, sex, age, PaO 2 /FiO 2 ratio, and sample (training/testing). "Training" and "testing" samples amounted to 347 and 296 patients, respectively. Three groups were identified: D-dimer ≤ 1880 ng/mL (LD); D-dimer > 1880 ng/mL and compliance > 41 mL/cmH 2 O (LD-HC); D-dimer > 1880 ng/mL and compliance ≤ 41 mL/cmH 2 O (HD-LC). 28-days mortality progressively increased in the three groups (from 24% to 35% and 57% (training) and from 27% to 39% and 60% (testing), respectively; p < 0.01). Adjusted mortality was significantly higher in HD-LC group compared with LD (HR = 0.479, p < 0.001) and HD-HC (HR = 0.542, p < 0.01); no difference was found between LD and HD-HC. In conclusion, combination of high D-dimer and low static compliance identifies a clinical phenotype with high mortality in COVID-19-ARDS.

Background: Patients undergoing elective primary total hip replacement and spinal anesthesia may encounter significant hemodynamic instability Objective: The study is aimed at observing the haemodynamic modifications after spinal anaesthesia during total hip replacement in patients managed to "preload independence" with goal directed fluid therapy (GDFT) and monitored non-invasively with Clearsight., Methods: Thirty patients, aged 50-80 years, with an American Society of Anaesthesiologists' (ASA) score II-III, undergoing elective primary total hip replacement and spinal anaesthesia were enrolled. Patients were monitored with the EV1000 platform and the Clearsight finger-cuff and managed with a goal directed fluid therapy., Results: The 79% of the population showed preload independence at baseline. After spinal, the 93% did not show a significant mean arterial pressure reduction. In our population, 79% reported a decrease >10% of the stroke volume during surgery, while 66% in the Recovery Room. Patients showed an improvement in mean arterial pressure, systemic vascular resistances indexed (SVRI), stroke volume (SV) and stroke volume indexed (SVI) at spinal resolution compared to baseline., Conclusions: Our cohort population showed hemodynamic stability throughout the study period, with increased SV and decreased SVRI at spinal resolution compared to basal values. Further randomized prospective studies are advocated in the same setting.

Purpose: A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice., Methods: Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use., Results: Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients' cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy., Conclusion: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments). Paolo MancaPatents, Royalties, Other Intellectual Property: Patent for a method for the identification of gene panels optimal for TMB estimation (Inst)Grazia ArmentoConsulting or Advisory Role: Novartis Travel, Accommodations, Expenses: TevaBruno VincenziSpeakers' Bureau: PharmaMarPaolo MarchettiHonoraria: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eisai, Incyte, Merck Sharp & Dohme, Novartis, Pierre Fabre, Pfizer, Roche Consulting or Advisory Role: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche Research Funding: AstraZeneca (Inst), Bristol Myers Squibb (Inst), Incyte (Inst), Eli Lilly (Inst), Merck Serono (Inst), Merck Sharp & Dohme (Inst), Novartis (Inst), NanoString Technologies (Inst), Pierre Fabre (Inst), Pfizer (Inst), Roche (Inst), Takeda (Inst) Travel, Accommodations, Expenses: Boehringer Ingelheim, Bristol Myers Squibb, Incyte, Merck Sharp & Dohme, RocheAugusto CaraceniConsulting or Advisory Role: Angelini Pharma, Shionogi Molteni, Kyowa Hakko KirinRocco Domenico MediatiSpeakers' Bureau: Angelini Pharma, Kyowa Hakko KirinRenato VellucciTravel, Accommodations, Expenses: Grünenthal GroupSilvia NatoliConsulting or Advisory Role: Grünenthal Italia, Sandoz, Angelini Pharma Speakers' Bureau: Mylan Travel, Accommodations, Expenses: AMS Group, SandozGiuseppe AzzarelloConsulting or Advisory Role: MerckVittorio GuardamagnaConsulting or Advisory Role: Istituto GentiliStefano MorosoConsulting or Advisory Role: Novartis, Janssen-CilagGiuseppe ToniniConsulting or Advisory Role: Novartis, Molteni Farmaceutici, Roche, Pierre Fabre, Italfarmaco Research Funding: PharmaMar (Inst), Novartis (Inst) No other potential conflicts of interest were reported., (© 2020 by American Society of Clinical Oncology.)

Background: Low-back pain (LBP) pathophysiological conditions include nociceptive back pain, somatic referred pain, radicular pain (RP), and radiculopathy. Differential diagnosis is challenging; guidance may come from patients' thorough clinical history and physical examination and, particularly for lumbar RP, from the evaluation of subjective responses of injured lumbar nerves to a strain applied at the buttock (buttock applied strain [BUAS] test)., Methods: In a sample of 395 consecutive patients with LBP, sensitivity, specificity, and prior probability (positive predictive values [PPVs] and negative predictive values [NPVs]) of the BUAS test were evaluated against 2 reference tests: the straight leg raising test (SLRT) and the painDETECT (PD) questionnaire. Multinomial logistic regression (MLR) and χ 2 analyses were used to evaluate the BUAS test outcomes' dependence upon independent variables (gender, age group, pain localization, SLRT outcomes, and PD outcomes). Cohen's kappa statistic was used to assess inter-rater agreement., Results: Compared with the PD questionnaire, the BUAS test showed a sensitivity of 92%, specificity of 100%, PPV of 100%, and NPV of 82%; compared with the SLRT, the BUAS test showed a sensitivity of 82%, NPV of 82%, specificity of 40%, and PPV of 40%. Inter-rater agreement of Cohen's kappa was 0.911. Significant associations were found between BUAS test outcomes and pain localization, SLRT outcomes, and PD outcomes, but not with the predictors gender or age group. MLR showed significant congruent relationships between BUAS test and PD outcomes., Conclusion: Among patients with LBP, the BUAS test showed satisfactory sensitivity, specificity, prior probability, and inter-rater reliability; thus, it may be considered a useful adjunctive tool to diagnose RP in patients with LBP. For more generalized results, more research, in clinical settings other than pain clinics, is needed., (© 2020 World Institute of Pain.)

Background: A proper antalgic treatment is based on the use of titrated drugs to provide adequate relief and a good tolerability profile. Therapies have a variable effectiveness among subjects depending on medical and genetic conditions. CYP2D6 variations determine a different clinical response to most analgesic drugs commonly used in daily clinical practice by influencing the drugs' pharmacokinetics. This study was a monocentric clinical trial exploring the CYP2D6 variants in 100 patients with a diagnosis of chronic pain., Methods: DNA was extracted to evaluate the genotype and to classify patients as normal-fast (gNMs-F), normal-slow (gNMs-S), ultrarapid (gUMs), intermediate (gIMs), and poor metabolizers (gPMs) using the Activity Score (AS). Information on therapies and general side effects experienced by patients was collected. Nongenetic co-factors were evaluated to examine the discrepancy between metabolic profile predicted from genotype (gPh) and metabolic profile (phenocopying)., Results: The distribution of our data underlined the prevalence of the gNMs-F (67%), whereas gNMs-S were 24%, gIMs 6%, gPMs 3%, and no gUMs were found, resulting in 33% of patients with reduced metabolic activity. In the analyzed population sample, 86% and 56% of patients, respectively, took at least one or two drugs inhibiting in vitro activity of the CYP2D6 enzyme., Conclusions: Over one-third of the enrolled patients showed altered CYP2D6 enzymatic metabolic activity, with a risk of phenocopying potentially due to polypharmacology., Trial Registration: ClinicalTrials.gov ID: NCT03411759., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Assessment of opioid-induced constipation (OIC) prevalence and relationship with demographic, clinical, and drug predictors in our daily practice., Design: Observational and retrospective study., Setting: Chronic pain (CP) center of Bologna's Teaching Hospital, Italy., Subjects: Mixed consecutive CP opioid-user outpatients (n = 128)., Main Outcome Measure(s): OIC was assessed with the Bowel Function Index (BFI) in three consecutive visits. Absolute difference and Student's t-test were used to compare BFI scores. Predictors (opioid compound and type, morphine-equivalent daily-dose [MEDD], and laxatives) were retrieved from the patients' charts. BFI and predictors relationships were checked by multinomial logistic regression (MLR); independent predictors of BFI scores were assessed with χ 2 analysis., Results: Of the 384 evaluations, 85 percent were on strong opioids with a MEDD range of 11-50 mg per day in the majority (60 percent) and 64 percent showed moderate constipation; 42 percent did not use laxatives while 24 percent used macrogol with significant decrease in the BFI. MLR showed that oxycodone was associated with a risk for moderate constipation. Lactulose and glycerin suppositories were associated with severe constipation. Non-opioid users and cancer patients were associated with normal bowel function and severe constipation, respectively., Conclusions: OIC was found in almost all evaluations of weak or strong opioidusers (97 percent); moderate to severe OIC was found in 72 percent of the evaluations. Cancer patients were associated with severe constipation. Macrogol was superior to other laxatives. In our experience, macrogol relieved constipation in those on the combination of oxycodone and naloxone and in those on fentanyl patches. Lactulose and glycerol suppositories were associated with severe constipation.

Background: Multiple studies demonstrate substantial utilization of acute hospital care and, potentially excessive, intensive medical and surgical treatments at the end-of-life., Aim: To evaluate the relationship between the use of home and facility-based hospice palliative care for patients dying with cancer and service utilization at the end of life., Design: Retrospective, population-level study using administrative databases. The effect of palliative care was analyzed between coarsened exact matched cohorts and evaluated through a conditional logistic regression model., Setting/participants: The study was conducted on the cohort of 34,357 patients, resident in Emilia-Romagna Region, Italy, admitted to hospital with a diagnosis of metastatic or poor-prognosis cancer during the 6 months before death between January 2013 and December 2015., Results: Patients who received palliative care experienced significantly lower rates of all indicators of aggressive care such as hospital admission (odds ratio (OR) = 0.05, 95% confidence interval (CI): 0.04-0.06), emergency department visits (OR = 0.23, 95% CI: 0.21-0.25), intensive care unit stays (OR = 0.29, 95% CI: 0.26-0.32), major operating room procedures (OR = 0.22, 95% CI: 0.21-0.24), and lower in-hospital death (OR = 0.11, 95% CI: 0.10-0.11). This cohort had significantly higher rates of opiate prescriptions (OR = 1.27, 95% CI: 1.21-1.33) ( p < 0.01 for all comparisons)., Conclusion: Use of palliative care at the end of life for cancer patients is associated with a reduction of the use of high-cost, intensive services. Future research is necessary to evaluate the impact of increasing use of palliative care services on other health outcomes. Administrative databases linked at the patient level are a useful data source for assessment of care at the end of life.

Background: The aim of this study was to identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP). Methods: Cancer patients with a diagnosis of BTP were enrolled. Demographic and clinical characteristics, as well as background pain and BTP characteristics were collected. Multivariate analyses were conducted to assess the correlation between BTP characteristics and the variables examined. Results: Data of 4016 patients were analysed. Average daily number of BTP episodes was 2.4, mean intensity was 7.5, and a mean duration was 43.3 min. A short onset BTP was observed in 68.9% of patients. In 30.5% of patients BTP was predictable. There were 86.0% of participants who reported a marked interference of BTP with their daily activities. Furthermore, 86.8% of patients were receiving opioids for the management of BTP. The average time to meaningful pain relief was 16.5 min and 70.9% of patients were satisfied with their BTP medications. Age, head and neck cancer, Karnofsky, background pain intensity, predictable and fast onset BTP were independently associated with the number of BTP episodes. BTP pain intensity was independently associated with background pain intensity, fast onset BTP, and Karnofsky. Neuropathic pain mechanism was independently associated with unpredictable BTP. Variables independently associated with a longer duration of BTP were age, place of visit, cancer diagnosis, disease-oriented therapy, background pain intensity and mechanism, and unpredictable BTP. Age, Karnofsky, background pain intensity, fast onset, and long duration of BTP were independently associated with interference with daily activity. Conclusions: BTP has a variable presentation depending on interdependent relationships among its different characteristics.

Damage control resuscitation may lead to postoperative intra-abdominal hypertension or abdominal compartment syndrome. These conditions may result in a vicious, self-perpetuating cycle leading to severe physiologic derangements and multiorgan failure unless interrupted by abdominal (surgical or other) decompression. Further, in some clinical situations, the abdomen cannot be closed due to the visceral edema, the inability to control the compelling source of infection or the necessity to re-explore (as a "planned second-look" laparotomy) or complete previously initiated damage control procedures or in cases of abdominal wall disruption. The open abdomen in trauma and non-trauma patients has been proposed to be effective in preventing or treating deranged physiology in patients with severe injuries or critical illness when no other perceived options exist. Its use, however, remains controversial as it is resource consuming and represents a non-anatomic situation with the potential for severe adverse effects. Its use, therefore, should only be considered in patients who would most benefit from it. Abdominal fascia-to-fascia closure should be done as soon as the patient can physiologically tolerate it. All precautions to minimize complications should be implemented., Competing Interests: Not applicableNot applicableThe authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The open abdomen (OA) is defined as intentional decision to leave the fascial edges of the abdomen un-approximated after laparotomy (laparostomy). The abdominal contents are potentially exposed and therefore must be protected with a temporary coverage, which is referred to as temporal abdominal closure (TAC). OA use remains widely debated with many specific details deserving detailed assessment and clarification. To date, in patients with intra-abdominal emergencies, the OA has not been formally endorsed for routine utilization; although, utilization is seemingly increasing. Therefore, the World Society of Emergency Surgery (WSES), Abdominal Compartment Society (WSACS) and the Donegal Research Academy united a worldwide group of experts in an international consensus conference to review and thereafter propose the basis for evidence-directed utilization of OA management in non-trauma emergency surgery and critically ill patients. In addition to utilization recommendations, questions with insufficient evidence urgently requiring future study were identified.

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Objectives: Opioids are the preferred analgesic drugs to treat severe chronic pain conditions among dialysis patients; however, knowledge about their dialyzability features is limited. Oxycodone is increasingly used for the treatment of chronic pain conditions as oral controlled release (CR) tablets; however, evidence about this drug and its metabolites' dialyzability is lacking., Methods: We assessed, during 4-hour dialysis sessions, the effect of standard hemodialysis (HD) and online hemodiafiltration (HDF) methods on the plasma concentration of oxycodone and its metabolites in n = 20 chronic pain patients with end-stage renal disease who were stably treated with oral CR oxycodone. Chromatographic techniques were used to evaluate the studied compounds' plasma concentrations at three different time points during dialysis., Results: Mean plasma concentrations of oxycodone and noroxycodone in the sample showed an overall reduction trend over time, but it was less enhanced for noroxycodone. Mean reduction in oxycodone and noroxycodone arterial concentrations was significant and higher with HDF (54% and 27%, respectively) than with HD (22% and 17%, respectively). Analysis of the regression of these compounds' clearance on their increasing arterial concentration showed a more stable and linear clearance prediction with HDF (roughly 85 mL/min); with HD, for increasing arterial concentration, clearance of oxycodone decreased while noroxycodone clearance increased., Discussion: While no oxymorphone or noroxymorphone metabolites were detected, limited dialyzability of oxycodone and noroxycodone was documented along with insignificant postdialysis pain increment. This evidence will contribute toward considerations as to the safety of the use of oxycodone in dialysis patients in the future., (© 2016 World Institute of Pain.)

Background: The aim of this study was to ascertain the variability and to identify a trend for the outcome of cholecystectomy surgery when used to treat cholelithiasis and acute cholecystitis., Methods: This was a large retrospective cohort study following patients up to 11 years post surgery, based on administrative data collected from 2002 to 2012 in the Emilia-Romagna Region (Northern Italy) and comparing the effectiveness and efficiency of surgical activity (laparoscopic (LC) and open cholecystectomy (OC)). Analyses included patient characteristics, length of hospital stay, type of admission and mortality risk. Outcomes considered were death from all causes (during the index hospital admission or thereafter), hospital readmissions with cholecystitis or cholelithiasis as principal diagnosis and time to surgery., Results: A total of 84,628 cholecystomies were performed from 2002 to 2012 out of 123,061 admissions with primary diagnostic category of cholecystitis or cholelitiasis. Laparoscopic procedure was used in 69,842 patients. Over time there was a rising linear statistically significant trend in the use of LC. Mortality rate at 1 year of OC treated patients showed a statistically significant difference compared to LC treated patients (using a cohorts match with propensity score). Only a small number of patients with acute cholecystitis was operated according guidelines within 72 hours., Conclusions: The analysis of aggregate administrative data is a powerful tool to support regional health management, improve the quality of medical care, and assess the appropriateness of therapeutic or diagnostic approaches. It is important to stress a short hospital stay for laparoscopic cholecystectomy patients (50% less than open surgery): this shorter hospital stay leads to a significant economic advantage. Moreover, mortality is significantly higher in open surgery for acute cholecystitis. Interestingly, the same finding was confirmed after 30 days and 1 year, probably due to comorbidities that are more evident in open surgery., Key Words: Cholecystitis, Cholelithiasis, Delivery of health care, Disease management, Surgical.

Introduction: An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here., Methods: Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity., Results: Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids., Conclusions: These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients' satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients., Funding: Molteni Farmaceutici, Italy.

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria. An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.

Background/objective: Breakthrough pain (BTP) shows variable prevalence in different clinical contexts of cancer and non-cancer patients. BTP diagnostic tools with demonstrated reliability, validation and prognostic capability are lacking. We report the development, psychometric and validation properties of a diagnostic/prognostic tool, the IQ-BTP, for BTP recognition, its likelihood and clinical features among chronic-pain (CP) patients., Patients: n=120 consecutive mixed cancer/non-cancer CP in/outpatients. Development, psychometric analyses and formal validation included: Face/Content validity (by 'experts' opinion and assessing the relationship between the IQ-BTP classes and criteria derived from BTP operational-case-definition); Construct validity, by Principle Component Analysis (PCA); and the strength of Spearman correlation between IQ-BTP classes and the Brief Pain Inventory (BPI) items; Reliability, by Cronbach's alpha statistics. Associations with clinical/demographic moderators were assessed applying χ(2) analysis., Results: Potential-BTP was found in 36.7% of patients (38.4% of non-cancer and 32.4% of cancer patients). Among these the likelihood for BTP diagnosis was 'high' in 25%, 'intermediate' in 41% and, 'low' 34% of patients. Analyses showed significant differences between IQ-BTP classes and between the latter BPI pain-item scores. Correlation between IQ-BTP classes and BPI items was moderate. PCA and scree test identified 3 components accounting for 62.3% of the variance. Cronbach's alpha was 0.71., Conclusions: The IQ-BTP showed satisfactory psychometric and validation properties. With adequate feasibility it enabled the allocating of cancer/non-cancer CP patients in three prognostic classes. Results are sufficient to warrant a subsequent impact study of the IQ-BTP as prognostic model and screening tool for BTP in both CP populations., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Ultrasound guidance currently represents the gold standard for regional anesthesia. In particular for lower extremity blocks, despite the heterogeneity and the lack of large randomized controlled trials, current literature shows a modest improvement in block onset and quality compared with other localization techniques. This review aims to present the most recent findings on the application of ultrasound guidance for each single lower extremity approach.

Biased pain evaluation due to automated heuristics driven by symptom uncertainty may undermine pain treatment; medical evidence moderators are thought to play a role in such circumstances. We explored, in this cross-sectional survey, the effect of such moderators (e.g., nurse awareness of patients' pain experience and treatment) on the agreement between n = 862 inpatients' self-reported pain and n = 115 nurses' pain ratings using a numerical rating scale. We assessed the mean of absolute difference, agreement (κ-statistics), and correlation (Spearman rank) of inpatients and nurses' pain ratings and analyzed congruence categories' (CCs: underestimation, congruence, and overestimation) proportions and dependence upon pain categories for each medical evidence moderator (χ (2) analysis). Pain ratings agreement and correlation were limited; the CCs proportions were further modulated by the studied moderators. Medical evidence promoted in nurses overestimation of low and underestimation of high inpatients' self-reported pain. Knowledge of the negative influence of automated heuristics driven by symptoms uncertainty and medical-evidence moderators on pain evaluation may render pain assessment more accurate.

Introduction: Despite opioids' recognized role in the treatment of moderate/severe musculoskeletal chronic pain, their long-term benefits need investigation. We explored the lasting analgesic efficacy, tolerability, influence on life quality, and chronicity stage of the novel prolonged release (PR) opioid, tapentadol, in 30 outpatients., Methods: We evaluated patients' pain intensity and relief (Numerical Rating Scale; NRS), adverse effects, sleep quality, treatment satisfaction, health status (12-questions Health-Survey; SF-12), chronicity stage (Italian Mainz Pain-Staging System; I-MPSS) at 10, 30, 60, and 90 days after tapentadol prescription., Results: At follow-ups, the investigated outcomes showed an overall statistically significant (Wilcoxon signed-rank test) improvement and remained stable over time, as did the health status and chronicity stage. Adverse effects were limited, transitory, and tolerable., Conclusions: Twelve weeks of PR tapentadol in outpatients with moderate/severe chronic musculoskeletal pain showed satisfactory analgesic efficacy and tolerability, and had a positive influence on life quality and chronicity stage. The results are robust enough to warrant a subsequent study with a larger sample and a longer observation period.

Rationale, Aims and Objectives: Indications are lacking on which patient to refer to pain facilities. Pain-chronicity stage and outcome prognosis may be used for such aims. The Mainz pain-staging system (MPSS) classifies pain patients in three chronicity stages that respectively require more extensive management. We explored the psychometric and validation properties of its Italian version towards its application as screening/referral tool., Methods: I-MPSS was administered to n=120 mixed non-cancer-pain outpatients. Psychometric analyses and formal validation included: content validity, by assessing the hypothesis of an existing relationship between the I-MPSS classes and criteria derived from an operational case definition of chronic pain; construct validity, by principle component analysis (PCA); the autonomous construct of the I-MPSS was assessed by the strength of the Spearman correlation between its classes and the brief pain inventory (BPI) items; and reliability, by applying Cronbach's alpha statistics. Associations between psychosocial moderators and the I-MPSS were assessed applying χ(2) analyses., Results: Quantitative and qualitative analyses showed significant differences between I-MPSS classes for health care and drug utilization; BPI item scores significantly differed between the classes; Spearman correlation between I-MPSS classes and BPI items was mostly moderate or mild. PCA and scree test identified four components accounting for 63.7% of the variance. Cronbach's alpha was 0.842., Conclusions: The I-MPSS showed satisfactory psychometric and validation properties. With adequate feasibility, it enabled the screening of mixed non-cancer-pain outpatients in three chronicity/prognostic stages. Results are sufficient to warrant its use for a subsequent impact study as a prognostic model and screening tool for referring pain patients., (© 2014 John Wiley & Sons, Ltd.)

Purpose: Inguinal hernioplasty could be used as an indicator of the surgical quality offered in different health institutions and countries, thereby establishing a scientific basis from which the procedure can be critically assessed and ultimately improved. Quality assessment of hernioplasties could be conducted using two different methods: either analyzing dedicated regional/national databases (DD) or reviewing administrative databases (AD)., Methods: A retrospective study of inguinal hernioplasties was carried out in the Emilia-Romagna hospitals between 2000 and 2009. Data were obtained by analyzing Hospital Discharge records regional Databases (HDD). Descriptive and multivariate statistical analysis was performed., Results: 126,913 inguinal hernioplasty procedures were performed. The annual rate was on average 34 per 10,000 inhabitants. An increase of the case mix complexity and relevant changes in procedure technique were recorded. From multivariate analysis, the following independent factors related to a hospitalization longer than 1 day emerged: procedures in urgent setting (OR 3.6, CI 3.4-3.7), Charlson's score ≥2 (OR 3.4, CI 3.1-3.7), laparoscopy (OR 2.1, CI 1.9-2.3), no mesh use (OR 2.1, CI 2-2.3), age >65 years (OR 1.9, CI 1.8-1.9), associated interventions (OR 1.9, CI 1.8-1.9), bilateral hernia (OR 1.7, CI 1.6-1.8), recurrent hernia (OR 1.2, CI 1.1-1.2) and female gender (OR 1.2, CI 1.2-1.3). Factors related to non-prosthetic hernioplasty were: bilateral hernia (OR 2.7, CI 2.5-2.9), female gender (OR 1.8, CI 1.8-2.0), emergency setting (OR 1.6, CI 1.5-1.8), recurrences (OR 1.5, CI 1.4-1.6) and associated interventions (OR 1.5, CI 1.4-1.6)., Conclusion: Inguinal hernia should be treated as an outpatient procedure in the majority of patients. Precise guidelines are necessary. HDD demonstrated to be a good and trustworthy system to collect clinical data. When precise guidelines are lacking, legal/institutional indications play a pivotal role in shifting the hernia surgery toward a one-day surgery regimen.

Objectives: Opioid titration is the first challenging stage for rapid control of moderate/severe cancer pain. Evidence shows that sustained-release formulations may be used for opioid titration. We set a pilot assessment of the efficacy and tolerability of our in-house protocol (continuous and on demand opioids [CoDem]) of the association of sustained-release oxycodone and immediate-release morphine as rescue dose for opioid titration/rotation in opioid-naïve (NAOP, n = 13), tolerant to weak (WOP, n = 20), or strong opioids (STOP, n = 44) in-patients with moderate/severe cancer pain., Methods: Observational and retrospective analysis of cancer in-patients treated for ≥7 days with the CoDem protocol., Outcome Measures: Pain intensity (patients self-reported pain with numerical rating scale [NRS] under static [NRSs] and dynamic [NRSd] conditions), amount of drug consumption, opioid adverse effects, and patient satisfaction., Efficacy Endpoints: In more than 50 percent of the patients and in <72 hours, steady NRSs and NRSd score reduction of at least two points, NRSs ≤ 3 and NRSd ≤4; and mean daily morphine consumption < mean of one rescue dose and t1:t6 ratio of mean oxycodone daily dose < 1:2., Results: Endpoints were reached within 24 hours both within the sample and subgroups. Only NAOP patients reached NRSd ≤ 4 endpoint within 48 hours. Against moderate and transient adverse effects, most patients (84.4 percent) found pain treatment to be good or excellent., Conclusions: The CoDem protocol was shown to be effective and reasonably tolerated for titration for moderate/severe cancer pain relief in both opioid-naïve or opioid-tolerant cancer in-patients. This pilot assessment warrants prospective and comparative studies with larger samples for more generalized results.

Background: The outcomes of patients admitted to a respiratory ICU (RICU) have been evaluated in the past, but no study has considered the influence of location prior to RICU admission., Methods: We analyzed prospectively collected data from 326 consecutive patients admitted to a 7-bed RICU. The primary end points were survival and severity of morbidity-related complications, evaluated according to the patient's location prior to RICU admission. Three admission pathways were considered: step-down for patients transferred from the ICUs of our hospital; step-up for patients coming from our respiratory wards or other medical wards; and directly for patients coming from the emergency department. The secondary end point was the potential influence of several risk factors for morbidity and mortality., Results: Of the 326 subjects, 92 (28%) died. Overall, subjects admitted in a step-up process had a significantly higher mortality (P < .001) than subjects in the other groups. The mortality rate was 64% for subjects admitted from respiratory ward, 43% for those from medical wards, and 18% for subjects from both ICU and emergency department (respiratory ward vs medical ward P = .04, respiratory ward vs emergency department P < .001, respiratory ward vs ICU P < .001, medical ward vs emergency department P < .001, and medical ward vs ICU P < .001). Subjects admitted from a respiratory ward had a lower albumin level, and Simplified Acute Physiology Score II was significantly higher in subjects following a step-up admission. About 30% of the subjects admitted from a respiratory ward received noninvasive ventilation as a "ceiling treatment." The highest odds ratios related to survival were subject location prior to RICU admission and female sex. Lack of use of noninvasive ventilation, younger age, female sex, higher albumin level, lower Simplified Acute Physiology Score II, higher Barthel score, and absence of chronic heart failure were also statistically associated with a lower risk of death., Conclusions: The pathway of admission to a RICU is a determinant of outcome. Patients following a step-up pattern are more likely to die. Other major determinants of survival are age, nutritional status and female sex.

Background: The use of non-invasive ventilation (NIV) in acute hypoxemic respiratory failure (AHRF) due to H1N1 virus infection is controversial. In this multicenter study we aimed to assess the efficacy of NIV in avoiding endotracheal intubation (ETI) and to identify predictors of success or failure., Methods: In this prospective multicenter study, 98 patients with new pulmonary infiltrate(s) sustained by H1N1 virus and a PaO(2)/FiO2<300 were eligible for study; 38/98 required immediate ETI, while the others received NIV as a first line therapy; 13/60 patients failed NIV and were intubated after 5.8+5.5 hours from enrolment. The remaining 47/60 patients were successfully ventilated with NIV., Results: Hospital mortality was significantly higher in those patients who failed NIV vs. those who succeeded (53.8% vs. 2.1%; OR=0.52, P<0.001). ETI was associated with higher number of infectious complications, mainly sepsis and septic shock. The OR of having one of these events in the NIV failure group vs. NIV success was 16.7, P<0.001. According to logistic regression model, a SAPS II>29 and a PaO(2)/FIO(2)≤127 at admission and PaO2/FIO(2)≤149 after 1 hr of NIV were independently associated with the need for ETI., Conclusion: The early application of NIV, with the aim to avoid invasive ventilation, during the H1N1 pandemics was associated with an overall success rate of 47/98 (48%). Patients presenting at admission with an high SAPS II score and a low PaO(2)/FiO(2) ratio and/or unable to promptly correct gas exchange are at high risk of intubation and mortality.

Introduction: Severe abdominal sepsis and septic shock are common problems in intensive care units (ICUs), and carry high mortality. The purpose of this economic analysis was to determine the cost-effectiveness of polymyxin B immobilized fiber column (PMX-F) plus conventional therapy (CT) (PMX-F-CT) versus CT alone for patients with severe sepsis/septic shock of abdominal origin, in the perspective of the Italian hospital., Methods: This was a retrospective cost-effectiveness analysis (CEA) based on data of clinical efficacy and consumption of resources collected alongside an Italian randomized clinical trial. 64 patients were enrolled following emergency surgery for intra-abdominal infection in 10 tertiary care ICUs from December 2004 to December 2007. Direct medical costs analyzed in the study included the consumption of hospital days, ICU days, catecholamine treatment days, renal replacement therapy days, mechanical ventilation treatment days, and the use of the PMX-F device. Resources were valued using published 2010 tariffs and market values. All-cause hospital mortality was extrapolated to survival as expected life years (LY) per patient/arm: for each survivor, average age-gender-related years of life expectancy were retrieved from national life tables; for deceased patients, only the number of CRF reported survival days was retained. Baseline expected years of survival were weighed by the severity of sepsis, according to individual Acute Physiology and Chronic Health Evaluation (Apache) II scores, showing that age/disease severity were comparable in the two groups before treatment initiation. Life expectancy per patient in each treatment group was thus calculated as the combination of life expectancy from Italian National Statistics Institute life tables and intra-hospital mortality detected in the Early Use of Polymyxin B Hemoperfusion in Abdominal Septic Shock (EUPHAS) study. After all costs and 3% discounted survival years were calculated per patient per treatment arm, the incremental CEA was run to obtain the incremental cost-effectiveness ratio (ICER). Univariate sensitivity analyses and 2,000 bootstrap replications were run to test the robustness of the study results., Results: Based on the expected survival years (mean discounted PMX-F-CT 9.37 LY/patient, CT 4.92 LY/patient; difference for PMX-F-CT 4.45 LY/patient; mean undiscounted PMX-F-CT 13.92 LY/patient, CT 7.19 LY/patient; difference +6.73 LY/patient), and the expected mean cost (PMX-F-CT mean 59,922 EUR/patient, CT mean 42,712 EUR/patient; difference for PMX-F-CT 17,211 EUR/patient), the mean ICER for PMX- F-CT resulted in 3,864 EUR/life year gained (LYG; ICER 2,558/undiscounted LYG). Results of the base-case CEA were confirmed by all sensitivity analyses, with ICER values always well below commonly accepted value thresholds., Conclusion: PMX-F-CT versus CT is a cost-effective intervention for treatment of severe sepsis/septic shock of abdominal origin and could be considered for use in the Italian National Health System hospital setting., (Copyright © 2011 S. Karger AG, Basel.)

Objectives: To compare the effectiveness of oral slow-release oxycodone (group OX, n=18) with that of epidural l-bupivacaine (group LRA, n=13) for the control of moderate/severe pain of advanced-stage peripheral arterial obstructive disease (PAOD) patients., Design: Observational and retrospective analysis of advanced stage and hospitalised PAOD patients treated for pain management for at least 7 days prior to surgery or discharged from the hospital without surgery., Methods: The outcome measures were pain intensity using the visual analogue scale under static, (VASs) and dynamic (VASd) conditions; vital signs, treatment side effects and patient satisfaction., Results: In both groups, pain control was satisfactory and VAS scores median were VASs<3 and VASd<4; under dynamic conditions, pain control was better in the LRA group (p<0.01). Against few and transient side effects, most patients (n=30) found both pain treatments good or excellent. Results should be confirmed by studies with larger samples., Conclusions: In the perioperative setting, the epidural infusion of local anaesthetics, such as l-bupivacaine, is an effective technique for pain control in PAOD patients; for patients with contraindication for this technique or for non-surgical or outpatients, slow-release oxycodone is suggested as a possible alternative for the control of severe pain in these patients., (Copyright (c) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: : This study evaluated the incidence of postoperative delirium (POD) in elderly patients undergoing general surgery, the risk factors associated with POD, and its impact on hospital stay and mortality., Methods: : Patients aged over 65 years who had emergency or elective operations were eligible for this case-control study. Risk factors significantly associated with POD using univariable analysis were entered into multivariable analysis, to establish those independently associated with POD., Results: : A total of 351 patients (357 admissions) were enrolled in the study. The incidence of POD was 13.2 per cent (17.9 per cent for emergency operations). Independent variables associated with POD were: age above 75 years, co-morbidity, preoperative cognitive impairment, psychopathological symptoms and abnormal glycaemic control. Median length of hospital stay was 21 (range 1-75) days for patients with POD versus 8 (range 1-79) days for control patients (P < 0.001). The hospital mortality rate was 19 and 8.4 per cent respectively (P = 0.021)., Conclusion: : The incidence of POD is high in elderly patients for both emergency and elective surgery, leading to an increase in hospital stay and perioperative mortality. To minimize POD, associated risk factors of co-morbidity, cognitive impairment, psychopathology and abnormal glycaemic control must be identified and treated., (Copyright (c) 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

The aim of this review is to identify an evidence-based perioperative management for patients affected by Alzheimer's disease (AD) that are scheduled to undergo surgery. This will minimize the negative effects of anesthesia and postoperative sedation and correct those perioperative variables possibly responsible for a decline in cognitive status and a worsening of AD. We here gather evidence on the importance of correct preoperative assessment regarding cognitive and functional status and the presence of preoperative delirium. The potential role of anesthesia, surgery, and postoperative analgosedation as risk factors for development of delirium are herein outlined. Finally, pain assessment instruments, as well as principles of management strategies for postoperative delirium in subjects with AD, are suggested.

Objective: To enhance the awareness that biased pain estimation may undermine its treatment, we sought to determine the congruence categories (CCs) between inpatient self-reported pain (PSRP) and nurse pain-evaluation (NEP) and to look for associations between CCs and inpatient and situational moderators., Design: A point cross-sectional survey., Subjects: The inpatient population [(n=869), > or = 6 years old and hospitalised for at least 24h] and n=115 nurses of the University of Bologna's teaching hospital, Italy., Measures: Using numerical rating scale, inpatients self-reported their pain while nurses indirectly rated these patients' pain using information acquired during their professional activity prior to the study and by reviewing patients' medical charts., Outcome Measures: Congruence moderator data were: gender, age, marital status, clinical area and length of hospital stay. The study was set to assess: PSRP-NEP mean of absolute difference (MAD), agreement and correlation; and to analyse the CCs dependence upon the PSRP and the congruence moderator variables., Results: PSRP-NEP agreement and correlation were mild and moderate, respectively, while their MAD=2.0 (95% CI 1.8-2.2). Congruence was found in 50% of the cases. Under-estimation (21%) was directly proportional to the PSRP severity, while congruence and over-estimation (29%) were inversely proportional to it. The 'PSRP effect' on the CCs detected was further modulated by the moderators studied., Conclusions: PSRP-NEP congruence was limited while CCs were associated with PSRP, inpatient and situational moderators. Further prospective studies are needed to verify generalization and whether the studied moderators operate through patient stereotyping mechanisms. Awareness of the influence of such mechanisms on pain evaluation may ameliorate pain assessment.

This case report describes a case of acute necrotic-hemorrhagic pancreatitis complicated by Wernicke's encephalopathy (WE) and stresses the importance of a correct dietetic regimen. A 39-year-old Chinese male patient with negative remote pathological anamnesis was hospitalized in the Medical Department with a diagnosis of gallstones. The clinical course was complicated with the onset of acute pancreatitis. Enteral fasting was imposed with intravenous feeding without vitamin supplementation. The progressive worsening of the clinical, radiodiagnostic and laboratory profile combined with deterioration in the state of consciousness promoted, on the 36th day exploratory laparotomy revealed necrotic-hemorrhagic pancreatitis. The patient was, therefore, admitted to the Intensive Care Unit in a deep coma. The recent medical history, neurological examination, and encephalic computed tomography suggested a revealing diagnosis of WE combined with pancreatic encephalopathy.