The efficacy of heart rate variability biofeedback training on sleep disorders and impact of fibromyalgia: Results of a phase II randomized controlled trial.

OBJECTIVE: Fibromyalgia syndrome (FMs) is a chronic, musculoskeletal pain disorder characterized by sleep disturbances, fatigue, and cognitive dysfunction. Heart rate variability biofeedback (HRV-BF) aiming to improve self-regulation and strengthen the parasympathetic nervous system has been shown to be effective in several pain syndromes, but its efficacy in FMs has not been adequately investigated. This Phase II trial aimed to assess the feasibility and preliminary measurement of the improvement induced by HRV-BF in FMs. METHODS: Sixty-four patients with FMs were recruited. Patients were randomly assigned to either the experimental group (EG) or the control group (CG). The EG received 10 HRV-BF training sessions in addition to pharmacological standard therapy. The CG received standard therapies for 10 weeks. The FMs impact on daily life, sleep regularity, sense of coherence, depression symptoms and pain has been assessed as primary outcomes, quality of life as secondary. RESULT: 23 (71.9%) of EG patients completed the intervention and 20 (62.5%) of the CG were re-evaluated at time T1. No side effects were reported. It was not found any statistical differences between groups over time in primary and secondary outcomes. CONCLUSIONS: The HRV-BF intervention did not demonstrate efficacy in both primary and secondary outcomes. However, it is quite feasible in terms of drop-out rate and side effects. Further studies with larger sample sizes are needed to determine its actual efficacy. CLINICALTRIALS: gov with code: NCT04121832.

Exploring Outcome Priorities and Real-Life Management of Chemotherapy-Induced Peripheral Neurotoxicity: A Survey of the Italian Association for the Study of Pain members.

Introduction: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects nearly 70% of cancer patients after chemotherapy, causing sensory, motor, autonomic dysfunction, and neuropathic pain. The Desirability of Outcome Ranking (DOOR) framework is proposed as a better way to assess preventive or therapeutic interventions for CIPN. Methods: A survey was conducted among Italian healthcare professionals and researchers affiliated to the Italian Chapter of the International Association for the Study of Pain (AISD) to identify the most important outcomes in clinical management and research. Results: Among the 73 respondents, 61 qualified for the survey, with an overall response rate of 1.2%. The vast majority were physicians (77%), most of whom were anesthesiologists (47.5%). The results showed that pain, survival, sensory impairment, motor impairment, and quality of life were consistently ranked as the most important outcomes, but there was significant disagreement in the outcomes relative ranking, making it difficult to develop a DOOR algorithm. The study also revealed that clinicians commonly use structured interviews to evaluate patients with CIPN, and the most prescribed drugs or supplements were palmitoylethanolamide, pregabalin, gabapentin and alpha lipoic acid as preventive agents and pregabalin, palmitoylethanolamide, duloxetine, gabapentin, and amitriptyline as therapeutic agents. However, many of these drugs have not been clinically proven to be effective for CIPN. Discussion: This study suggests that the implementation of a DOOR framework for CIPN using healthcare professionals is more difficult than expected, given the significant disagreement in our respondents' ranking of outcomes. Our work provides interesting topics for future research in CIPN, but its limitations include a small sample size, a low response rate, and a possible selection bias.

Pulmonary Vasodilator and Inodilator Drugs in Cardiac Surgery: A Systematic Review With Bayesian Network Meta-Analysis.

OBJECTIVE: The authors performed a systematic review to evaluate the effect of pharmacologic therapy on pulmonary hypertension in the perioperative setting of elective cardiac surgery (PROSPERO CRD42023321041). DESIGN: Systematic review of randomized controlled trials with a Bayesian network meta-analysis. SETTING: The authors searched biomedical databases for randomized controlled trials on the perioperative use of inodilators and pulmonary vasodilators in adult cardiac surgery, with in-hospital mortality as the primary outcome and duration of ventilation, length of stay in the intensive care unit, stage 3 acute kidney injury, cardiogenic shock requiring mechanical support, and change in mean pulmonary artery pressure as secondary outcomes. PARTICIPANTS: Twenty-eight studies randomizing 1,879 patients were included. INTERVENTIONS: Catecholamines and noncatecholamine inodilators, arterial pulmonary vasodilators, vasodilators, or their combination were considered eligible interventions compared with placebo or standard care. MEASUREMENTS AND MAIN RESULTS: Ten studies reported in-hospital mortality and assigned 855 patients to 12 interventions. Only inhaled prostacyclin use was supported by a statistically discernible improvement in mortality, with a number-needed-to-treat estimate of at least 3.3, but a wide credible interval (relative risk 1.26 × 10-17 - 0.7). Inhaled prostacyclin and nitric oxide were associated with a reduction in intensive care unit stay, and none of the included interventions reached a statistically evident difference compared to usual care or placebo in the other secondary clinical outcomes. CONCLUSIONS: Inhaled prostacyclin was the only pharmacologic intervention whose use is supported by a statistically discernible improvement in mortality in the perioperative cardiac surgery setting as treatment of pulmonary hypertension. However, available evidence has significant limitations, mainly the low number of events and imprecision.

Persistent Idiopathic Facial Pain (PIFP) in Patients Referred to a Multidisciplinary Centre in Italy: A Retrospective Observational Study.

BACKGROUND: Persistent Idiopathic Facial Pain (PIFP), previously named Atypical Facial Pain (AFP) is a poorly understood condition, often diagnosed after several inconclusive investigations. The aim of this retrospective study was to evaluate the demographic and clinical characteristics of patients with PIFP referred to a Facial Pain Center. METHODS: Between May 2011 and September 2014, data on 41 PIFP patients were analyzed regarding temporal, topographical and descriptive pain features, including onset, localization, pain descriptors and intensity. Pharmacological pain treatments were also registered. Finally, the presence and type of previous minor oro-surgery procedures in the painful area were investigated. RESULTS: Demographic and clinical characterization were similar to PIFP patients reported in literature. The presence of previous minor oro-surgery procedures in the painful area was reported in most of these patients, in particular endodontic treatments and tooth extractions. CONCLUSIONS: This retrospective analysis showed a high prevalence of minor oro-surgery procedures in our population, while its role in PIFP pathophysiology remains unknown. A new classification of PIFP built around the main discriminant factor of presence of these procedures in the painful area could be considered while available data were still insufficient to define specific diagnostic criteria.

Bone fractures in patients using tapentadol or oxycodone: an exploratory US claims database study.

Aim: To explore fracture outcomes with tapentadol or oxycodone, two opioids with differing mechanisms of action. Materials & methods: Retrospective cohort pilot study, using MarketScan® Commercial and Medicare Supplemental claims databases, on patients with postoperative pain, back pain, or osteoarthritis and ≥1 claim for tapentadol (n = 16,457), oxycodone (n = 1,356,920), or both (n = 15,893) between June 2009 and December 2015. Results: During 266,826 and 9,007,889 days of tapentadol and oxycodone treatment, patients evidenced 1080 and 72,275 fractures, respectively. Fracture rates per treatment-year were 1.512 for tapentadol and 3.013 for oxycodone. Conclusion: Examination of administrative claims has inherent limitations, but this exploratory analysis indicates a lower fracture rate with tapentadol than oxycodone in the analyzed dataset, which needs confirmation by further clinical trials.

Metabolomics and psychological features in fibromyalgia and electromagnetic sensitivity.

Fibromyalgia (FM) as Fibromyalgia and Electromagnetic Sensitivity (IEI-EMF) are a chronic and systemic syndrome. The main symptom is represented by strong and widespread pain in the musculoskeletal system. The exact causes that lead to the development of FM and IEI-EMF are still unknown. Interestingly, the proximity to electrical and electromagnetic devices seems to trigger and/or amplify the symptoms. We investigated the blood plasma metabolome in IEI-EMF and healthy subjects using 1H NMR spectroscopy coupled with multivariate statistical analysis. All the individuals were subjected to tests for the evaluation of psychological and physical features. No significant differences between IEI-EMF and controls relative to personality aspects, Locus of Control, and anxiety were found. Multivariate statistical analysis on the metabolites identified by NMR analysis allowed the identification of a distinct metabolic profile between IEI-EMF and healthy subjects. IEI-EMF were characterized by higher levels of glycine and pyroglutamate, and lower levels of 2-hydroxyisocaproate, choline, glutamine, and isoleucine compared to healthy subjects. These metabolites are involved in several metabolic pathways mainly related to oxidative stress defense, pain mechanisms, and muscle metabolism. The results here obtained highlight possible physiopathological mechanisms in IEI-EMF patients to be better defined.

BEEP-Bodily and Emotional Perception of Pain. A Questionnaire to Measure Reaction to Pain in Chronic Pain Disorders.

Background: The assessment of pain and its impact on quality of life is central to the evaluation of chronic pain syndromes. However, most available tools focus on the nociceptive experience of pain, and at best only consider the occurrence of anxious, depressive, or cognitive problems. Here is a new questionnaire aimed at measuring the multifaceted impact of pain in chronic pain syndromes, the Bodily and Emotional pErception of Pain (BEEP). Methods: All consecutive patients who accessed a center for the treatment of pain were invited to take part in the study. The sample included 222 participants (51 with fibromyalgia, 84 with low back pain; 87 with other chronic pain syndromes). Women were 77% of the sample, the mean age was 61 ± 15. Participants completed the BEEP, the Patient Health Questionnaire-9 (PHQ-9), and the Mood Disorder Questionnaire (MDQ). Results: Reliability was good for all questionnaires. The expected three dimensions of the BEEP were confirmed by confirmatory factor analysis, and a bifactor model with three orthogonal factors showed a good fit as well. Participants diagnosed with fibromyalgia showed higher scores on the BEEP than the participants who had been diagnosed with low back pain or other chronic pain syndromes. The prevalence of probable cases of major depression and bipolar disorder in the sample was higher than expected for non-clinical samples. Levels of depression, as measured by the PHQ-9, were associated with the three dimensions of the BEEP and with the intensity of pain. Conclusions: The BEEP is a promising measure of the impact of pain in daily life and differentiates fibromyalgia from other chronic pain syndromes. The BEEP may be helpful to evaluate the patient's response to the treatment over time and may favor the identification of unmet needs in patients' personal, social, and daily functioning.

Postural counseling represents a novel option in pain management of fibromyalgia patients.

BACKGROUND: Chronic pain is a key symptom in fibromyalgia (FM), and its management is still challenging for rheumatologists in daily practice. FM patients show psychological and psychiatric manifestations, going from mood and emotional disorders to depression and alexithymia that negatively impact their quality of life, limiting their daily activities. Since pharmacological strategies have a limited efficacy in FM pain, alternative or complementary non-pharmacological approaches have been introduced in the clinical management of FM. PATIENTS AND METHODS: This is a retrospective study on FM patients (n=52) treated with a novel integrated postural counseling (PC) rehabilitation program carried out by a counselor physiotherapist. The clinical impact of PC was evaluated by 1) a semi-structured interview using an ad hoc modified questionnaire McGill Illness Narrative Interview (MINI) 1 to obtain data on pain management by highlighting everyday experience of living with pain and 2) an FM impact questionnaire (FIQ) total score. RESULTS: Two main structures of narrative emplotment of FM illness were recognized: 1) the cumulative life narrative structure (46.15%) and 2) the broken life (53.85%) narrative structure. Baseline FIQ score was 77.38±7.77, and it was significantly reduced after PC to 39.12±13.27 (P<0.0001). Although well-being still requires further definition as outcome in pain management, it is important for FM patients, dealing with pain-related sensations, thoughts and feelings and limiting their daily activities. In our study, 87.5% of interviewed FM patients reported an improvement in their well-being after PC. CONCLUSION: Our data suggest that an integrated PC program positively impacts chronic pain and fatigue based on self-management strategies. PC allows FM patients to resume their own life and regenerate their own image. Finally, we propose the introduction of the evaluation of the ability to resume daily activities as the target of rehabilitation programs in FM.

Nitric Oxide in Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To investigate the efficacy and safety of perioperative administration of nitric oxide in cardiac surgery. DESIGN: Meta-analysis of randomized controlled trials (RCTs). PARTICIPANTS: Cardiac surgery patients. INTERVENTIONS: A search of Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE for RCTs that compared nitric oxide with placebo or other comparators. MEASUREMENTS AND MAIN RESULTS: The primary outcome was intensive care unit (ICU) stay, and secondary outcomes were mortality, duration of mechanical ventilation, and reduction of mean pulmonary artery pressure. The study included 18 RCTs comprising 958 patients. The authors calculated the pooled odds ratio (OR) and the mean difference (MD) with random-effects model. Quantitative synthesis of data demonstrated a clinically negligible reduction in the length of ICU stay (MD -0.38 days, confidence interval CI [-0.65 to -0.11]; p = 0.005) and mechanical ventilation duration (MD -4.81 hours, CI [-7.79 to -1.83]; p = 0.002) compared with all control interventions with no benefit on mortality. CONCLUSIONS: Perioperative delivery of inhaled nitric oxide resulted to be of no or minimal benefit in patients with pulmonary hypertension undergoing cardiac surgery. Large, randomized trials are needed to further assess its effect on major clinical outcomes and its cost-effectiveness.

Comparison of the Tolerability Profile of Controlled-Release Oral Morphine and Oxycodone for Cancer Pain Treatment. An Open-Label Randomized Controlled Trial.

CONTEXT: Oxycodone and morphine are recommended as first-choice opioids for moderate/severe cancer pain, but evidence about their relative tolerability has significant methodological limitations. OBJECTIVES: This study was mainly aimed at comparing the risk of developing adverse events (AEs) with controlled-release oral morphine vs. oxycodone; secondary aims were comparing their analgesic efficacy and testing heterogeneity in tolerability across different age and renal function subgroups. METHODS: An open-label multicenter RCT (EudraCT number: 2006-003151-21) was carried out in patients with moderate/severe cancer pain. At baseline, 7 and 14 days, patients scored on 0-10 rating scales (0-10 numerical rating scale) the intensity of pain and of a list of common opioid side effects. The primary end point was the percentage of patients reporting an AE (a worsening ≥ 2 points on any of the listed side effects); tolerability by subgroups and average follow-up pain intensity were compared through regression models. RESULTS: One hundred eighty-seven patients were enrolled (47% of originally planned). Intention to treat (ITT) analysis (N = 185, morphine 94, oxycodone 91) did not show any difference in the risk of developing AEs (risk difference -0.6%, 95% CI -11.0% to 9.9%) nor in analgesia (0-10 numerical rating scale pain intensity difference -0.28, 95% CI -0.83 to 0.27). No evidence of heterogeneity of tolerability across age and renal function patient subgroups emerged. CONCLUSION: This trial failed to show any difference in tolerability and analgesic efficacy of morphine and oxycodone as first-line treatment for moderate/severe cancer pain but results interpretation is difficult due to lack of power, potential bias from open-label design, and concerns about assay sensitivity. These data, however, can significantly contribute to future meta-analyses comparing WHO Step-III opioids and are relevant in designing future randomized studies.

Outcome of cardiac surgery in patients with low preoperative ejection fraction.

BACKGROUND: In patients undergoing cardiac surgery, a reduced preoperative left ventricular ejection fraction (LVEF) is common and is associated with a worse outcome. Available outcome data for these patients address specific surgical procedures, mainly coronary artery bypass graft (CABG). Aim of our study was to investigate perioperative outcome of surgery on patients with low pre-operative LVEF undergoing a broad range of cardiac surgical procedures. METHODS: Data from patients with pre-operative LVEF ≤40 % undergoing cardiac surgery at a university hospital were reviewed and analyzed. A subgroup analysis on patients with pre-operative LVEF ≤30 % was also performed. RESULTS: A total of 7313 patients underwent cardiac surgery during the study period. Out of these, 781 patients (11 %) had a pre-operative LVEF ≤40 % and were included in the analysis. Mean pre-operative LVEF was 33.9 ± 6.1 % and in 290 patients (37 %) LVEF was ≤30 %. The most frequently performed operation was CABG (31 % of procedures), followed by mitral valve surgery (22 %) and aortic valve surgery (19 %). Overall perioperative mortality was 5.6 %. Mitral valve surgery was more frequent among patients who did not survive, while survivors underwent more frequently CABG. Post-operative myocardial infarction occurred in 19 (2.4 %) of patients, low cardiac output syndrome in 271 (35 %). Acute kidney injury occurred in 195 (25 %) of patients. Duration of mechanical ventilation was 18 (12-48) hours. Incidence of complications was higher in patients with LVEF ≤30 %. Stepwise multivariate analysis identified chronic obstructive pulmonary disease, pre-operative insertion of intra-aortic balloon pump, and pre-operative need for inotropes as independent predictors of mortality among patients with LVEF ≤40 %. CONCLUSIONS: We confirmed that patients with low pre-operative LVEF undergoing cardiac surgery are at higher risk of post-operative complications. Cardiac surgery can be performed with acceptable mortality rates; however, mitral valve surgery, was found to be associated with higher mortality rates in this population. Accurate selection of patients, risk/benefit evaluation, and planning of surgical and anesthesiological management are mandatory to improve outcome.

Non-Adrenergic Vasopressors in Patients with or at Risk for Vasodilatory Shock. A Systematic Review and Meta-Analysis of Randomized Trials.

INTRODUCTION: Hypotensive state is frequently observed in several critical conditions. If an adequate mean arterial pressure is not promptly restored, insufficient tissue perfusion and organ dysfunction may develop. Fluids and catecholamines are the cornerstone of critical hypotensive states management. Catecholamines side effects such as increased myocardial oxygen consumption and development of arrhythmias are well known. Thus, in recent years, interest in catecholamine-sparing agents such as vasopressin, terlipressin and methylene blue has increased; however, few randomized trials, mostly with small sample sizes, have been performed. We therefore conducted a meta-analysis of randomized trials to investigate the effect of non-catecholaminergic vasopressors on mortality. METHODS: PubMed, BioMed Central and Embase were searched (update December 31st, 2014) by two independent investigators. Inclusion criteria were: random allocation to treatment, at least one group receiving a non-catecholaminergic vasopressor, patients with or at risk for vasodilatory shock. Exclusion criteria were: crossover studies, pediatric population, non-human studies, studies published as abstract only, lack of data on mortality. Studied drugs were vasopressin, terlipressin and methylene blue. Primary endpoint was mortality at the longest follow-up available. RESULTS: A total of 1,608 patients from 20 studies were included in our analysis. The studied settings were sepsis (10/20 studies [50%]), cardiac surgery (7/20 [35%]), vasodilatory shock due to any cause (2/20 [19%]), and acute traumatic injury (1/20 [5%]). Overall, pooled estimates showed that treatment with non-catecholaminergic agents improves survival (278/810 [34.3%] versus 309/798 [38.7%], risk ratio = 0.88, 95% confidence interval = 0.79 to 0.98, p = 0.02). None of the drugs was associated with significant reduction in mortality when analyzed independently. Results were not confirmed when analyzing studies with a low risk of bias. CONCLUSIONS: Catecholamine-sparing agents in patients with or at risk for vasodilatory shock may improve survival. Further researches on this topic are needed to confirm the finding.

Acquired factor VIII inhibitor and subsequent development of non-Hodgkin's lymphoma: a case report and review of the literature.

Acquired hemophilia A (AHA) is a rare disorder caused by the development of factor VIII autoantibodies. It can induce acute and major hemorrhages in patients with negative personal and family history of bleeding. AHA is frequently associated with hematologic malignancies. This study describes the first case of AHA in a patient who developed a mantle cell lymphoma after a year and half of complete remission. It also provides an example of an initial wrong approach in terms of diagnosis and treatment, as well as of a very long course of the disease. Further, a review of AHA-associated lymphomas from 1974 to 2014 is also presented.Clinical and laboratory staff should be alert to the possibility of such an event when the medical history of patients is enriched with new symptoms or signs. A follow-up of at least 2 years might therefore be required.

Additive Effect on Survival of Anaesthetic Cardiac Protection and Remote Ischemic Preconditioning in Cardiac Surgery: A Bayesian Network Meta-Analysis of Randomized Trials.

INTRODUCTION: Cardioprotective properties of volatile agents and of remote ischemic preconditioning have survival effects in patients undergoing cardiac surgery. We performed a Bayesian network meta-analysis to confirm the beneficial effects of these strategies on survival in cardiac surgery, to evaluate which is the best strategy and if these strategies have additive or competitive effects. METHODS: Pertinent studies were independently searched in BioMedCentral, MEDLINE/PubMed, Embase, and the Cochrane Central Register (updated November 2013). A Bayesian network meta-analysis was performed. Four groups of patients were compared: total intravenous anesthesia (with or without remote ischemic preconditioning) and an anesthesia plan including volatile agents (with or without remote ischemic preconditioning). Mortality was the main investigated outcome. RESULTS: We identified 55 randomized trials published between 1991 and 2013 and including 6,921 patients undergoing cardiac surgery. The use of volatile agents (posterior mean of odds ratio = 0.50, 95% CrI 0.28-0.91) and the combination of volatile agents with remote preconditioning (posterior mean of odds ratio = 0.15, 95% CrI 0.04-0.55) were associated with a reduction in mortality when compared to total intravenous anesthesia. Posterior distribution of the probability of each treatment to be the best one, showed that the association of volatile anesthetic and remote ischemic preconditioning is the best treatment to improve short- and long-term survival after cardiac surgery, suggesting an additive effect of these two strategies. CONCLUSIONS: In patients undergoing cardiac surgery, the use of volatile anesthetics and the combination of volatile agents with remote preconditioning reduce mortality when compared to TIVA and have additive effects. It is necessary to confirm these results with large, multicenter, randomized, double-blinded trials comparing these different strategies in cardiac and non-cardiac surgery, to establish which volatile agent is more protective than the others and how to best apply remote ischemic preconditioning.

Cardiac surgery in 260 octogenarians: a case series.

BACKGROUND: The elderly undergo cardiac surgery more and more frequently, often present multiple comorbidities, assume chronic therapies, and present a unique physiology. Aim of our study was to analyze the experience of a referral cardiac surgery center with all types of cardiac surgery interventions performed in patients ≥80 years old over a six years' period. METHODS: A retrospective observational study performed in a university hospital. 260 patients were included in the study (3.5% of the patients undergoing cardiac surgery in the study period). RESULTS: Mean age was 82 ± 1.8 years. Eighty-five percent of patients underwent elective surgery, 15% unplanned surgery and 4.2% redo surgery. Intervention for aortic valve pathology and coronary artery bypass grafting were performed in 51% and 46% of the patients, respectively. Interventions involving the mitral valve were the 26% of the total, those on the tricuspid valve were 13% and those on the ascending aortic arch the 9.6%. Postoperative low output syndrome was identified in 44 patients (17%). Mortality was 3.9% and most of the patients (91%) were discharged from hospital in good clinical conditions. Hospital mortality was lower in planned vs unplanned surgery: 3.8% vs 14% respectively. Chronic obstructive pulmonary disease (OR 9.106, CI 2.275 - 36.450) was the unique independent predictor of mortality. CONCLUSIONS: Clinicians should be aware that cardiac surgery can be safely performed at all ages, that risk stratification is mandatory and that hemodynamic treatment to avoid complications is expected.

Preoperative intra-aortic balloon pump to reduce mortality in coronary artery bypass graft: a meta-analysis of randomized controlled trials.

INTRODUCTION: The intra-aortic balloon pump is routinely used in cardiac surgery; however, its impact on outcome is still a matter of debate and several randomized trials have been published recently. We perform an updated meta-analysis of randomized controlled trials that investigated the use of preoperative intra-aortic balloon pump in adult patients undergoing coronary artery bypass grafting. METHODS: Potentially eligible trials were identified by searching the Medline, Embase, Scopus, ISI Web of Knowledge and The Cochrane Library. Searches were not restricted by language or publication status and were updated in August 2014. Randomized controlled trials on preoperative intra-aortic balloon pump in patients undergoing coronary artery bypass grafting either with or without cardiopulmonary bypass were identified. The primary end point was mortality at the longest follow-up available and the secondary end point was 30-day mortality. RESULTS: The eight included randomized clinical trials enrolled 625 patients (312 to the intra-aortic balloon pump group and 313 to control). The use of intra-aortic balloon pump was associated with a significant reduction in the risk of mortality (11 of 312 (3.5%) versus 33 of 313 (11%), risk ratio = 0.38 (0.20 to 0.73), P for effect = 0.004, P for heterogeneity = 0.7, I-square = 0%, with eight studies included). The benefit on mortality reduction was confirmed restricting the analysis to trials with low risk of bias, to those reporting 30-day follow-up and to patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. CONCLUSIONS: Preoperative intra-aortic balloon pump reduces perioperative and 30-day mortality in high-risk patients undergoing elective coronary artery bypass grafting.

Reducing mortality in acute kidney injury patients: systematic review and international web-based survey.

OBJECTIVE: To identify all interventions that increase or reduce mortality in patients with acute kidney injury (AKI) and to establish the agreement between stated beliefs and actual practice in this setting. DESIGN AND SETTING: Systematic literature review and international web-based survey. PARTICIPANTS: More than 300 physicians from 62 countries. INTERVENTIONS: Several databases, including MEDLINE/PubMed, were searched with no time limits (updated February 14, 2012) to identify all the drugs/techniques/strategies that fulfilled all the following criteria: (a) published in a peer-reviewed journal, (b) dealing with critically ill adult patients with or at risk for acute kidney injury, and (c) reporting a statistically significant reduction or increase in mortality. MEASUREMENTS AND MAIN RESULTS: Of the 18 identified interventions, 15 reduced mortality and 3 increased mortality. Perioperative hemodynamic optimization, albumin in cirrhotic patients, terlipressin for hepatorenal syndrome type 1, human immunoglobulin, peri-angiography hemofiltration, fenoldopam, plasma exchange in multiple-myeloma-associated AKI, increased intensity of renal replacement therapy (RRT), CVVH in severely burned patients, vasopressin in septic shock, furosemide by continuous infusion, citrate in continuous RRT, N-acetylcysteine, continuous and early RRT might reduce mortality in critically ill patients with or at risk for AKI; positive fluid balance, hydroxyethyl starch and loop diuretics might increase mortality in critically ill patients with or at risk for AKI. Web-based opinion differed from consensus opinion for 30% of interventions and self-reported practice for 3 interventions. CONCLUSION: The authors identified all interventions with at least 1 study suggesting a significant effect on mortality in patients with or at risk of AKI and found that there is discordance between participant stated beliefs and actual practice regarding these topics.

Randomized evidence for reduction of perioperative mortality.

OBJECTIVE: With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence. DESIGN AND SETTING: A web-based international consensus conference. PARTICIPANTS: More than 1,000 physicians from 77 countries participated in this web-based consensus conference. INTERVENTIONS: Systematic literature searches (MEDLINE/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials. MEASUREMENTS AND MAIN RESULTS: Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality. CONCLUSIONS: Future research and health care funding should be directed toward studying and evaluating these interventions.

Fungal infections in pediatric intensive care units.

Pediatric fungal infections are associated with significant morbidity and mortality. Few adequately powered antifungal trials have been performed in neonates and children. Neonatologists and pediatricians are reliant on adult trials when managing candidemia. Recent guidelines from the Infectious Diseases Society of America recommend fluconazole or an echinocandin for empiric therapy in suitable candidates, with a preference for an echinocandin in patients with moderate-to severe disease, recent azole exposure, or high risk of C. glabrata or C. krusei infection.

Use of hydromorphone, with particular reference to the OROS formulation, in the elderly.

The prevalence of pain increases with age. However, pain is often inadequately managed in elderly people, which undermines quality of life. Pain has been associated with depression, sleep disturbances, impaired ambulation, and increased healthcare use and costs. Effective treatment of pain improves the overall quality of life. However, pain management is complicated by the presence of multiple co-morbidities in elderly people, which increases the likelihood of polypharmacy, and therefore increases the chance of potential drug-drug interactions. Polypharmacy is also associated with poor adherence to therapy. Age-related pharmacokinetic and pharmacodynamic changes reduce the therapeutic index of drugs. Therefore, elderly people are more likely to suffer from adverse events and increased sensitivity to the analgesic properties of opioids. OROS hydromorphone (Jurnista) is a once-daily, extended-release formulation that uses the OROS push-pull technology to provide controlled release of the semi-synthetic opioid hydromorphone. Compared with conventional immediate-release hydromorphone, OROS hydromorphone provides more consistent delivery of hydromorphone with lower peak concentrations and less variability in plasma concentrations over time. The bioavailability of hydromorphone from OROS hydromorphone is minimally affected by food or alcohol (ethanol). Hydromorphone is mainly metabolized in the liver and is excreted in the urine. Unlike morphine, hydromorphone does not have an active 6-glucuronide metabolite. This metabolite of morphine can accumulate in the presence of renal failure; therefore, the lack of an active 6-glucuronide metabolite makes hydromorphone a useful alternative to morphine in elderly patients with renal failure. However, hydromorphone is similar to morphine in that it is metabolized to hydromorphone-3-glucuronide, which may be neuroexcitatory. Because of its low plasma protein binding and low probability of interfering with the metabolism of other drugs, hydromorphone may be especially suitable for patients taking multiple medications. OROS hydromorphone is an effective analgesic that is well tolerated and provides more stable plasma concentrations than immediate-release forms of hydromorphone. Its once-daily administration offers an advantage over immediate-release forms and longer-acting formulations that require twice-daily administration. This means OROS hydromorphone will be more convenient for elderly patients and may improve adherence, resulting in improved pain relief and quality of life.