The long and winding road of non steroidal antinflammatory drugs and paracetamol in cancer pain management: A critical review

The aim of this review was to assess the value of NSAIDs and paracetamol in patients with cancer pain to update a previous review performed ten years ago on this topic. The approach was analytic and based on clinical considerations, rather than on raw evidence, which often does not provide useful information in clinical practice. Both published reports from an extensive search of electronic data bases were collected from January 2001 to December 2011. A free-text search method was used including the following words and their combination: “Anti-inflammatory drugs OR paracetamol OR acetaminophen” AND/OR “cancer pain”. Any randomized-controlled trial was considered. Thirteen reports fulfitted inclusion criteria in this systematic review. Randomized trials have been performed by using different modalities of intervention. Single drugs added on opioid therapy or during opioid substitution with opioids as rescue drugs through a patient controlled analgesia, were compared with placebo or between them. Five studies regarded paracetamol. Other four studies assessed the efficacy dipyrone, ketorolac, dexketoprofen, and subcutaneous ketoprofen in cancer pain management, mainly on top of an opioid regimen. The role of paracetamol and NSAIDs in the management of cancer pain still remains controversial. The papers published in this last decade were unable to answer the main questions. There is no proof that they should be used to start the treatment and how long they should be administered when opioid treatment is added on top. While paracetamol seems to be devoid of any benefit, particularly if given at usual clinical doses which should be less than 4 g/day, ketorolac seems to provide an additive analgesic effect even in patients receiving different doses of opioids. The main indication from the analysis of these data is that NSAIDs could be given in patients receiving opioids, evaluating their benefit and weight on opioid therapy in individual patients who have a favorable response to justify a prolonged use

The anesthesiologist and end-of-life care

Purpose of review Anesthesiologists may face problematic situations when patients are close to death, in which clinical problems, decision-making processes, and ethical issues are often interconnected and dependent on each of them. The aim of this review is to assess the recent literature regarding the anesthesiological role for advanced cancer patients. Recent findings Palliative sedation in the dying patients, end-of-life problems in the ICU, and pain control in advanced cancer patients have been the subject of recent research. All these issues have shown that anesthesiologist would be expert in the field of pain and symptom control at the end of life. End-of-life care problems are common in ICU, and a decision-making process requires knowledge and management of patients’ wishes, past and projected future quality of life, severity and prognosis of illness, patients’ age, regarding withholding and withdrawing of futile treatments in anticipation of death, or relieving symptoms close to death. Summary Anesthesiologists should be competent in all aspects of terminal care, including the practical and ethical aspects of withdrawing different modalities of life-sustaining treatment and the use of sedatives, analgesics, and nonpharmacologic approaches to easing the suffering of the dying process. More research is needed to provide models which should be spread in the scientific community to afford this difficult task

US Food and Drug Administration's Risk Evaluation and Mitigation Strategy for Extended-Release and Long-Acting Opioids Pros and Cons, and a European Perspective

Prescriptions for opioid analgesics to manage moderate-to-severe chronic non-cancer pain have increased markedly over the last decade. An unintentional consequence of greater prescription opioid utilization has been the parallel increase in misuse, abuse and overdose, which are serious risks associated with all opioid analgesics. In response to disturbing rises in prescription opioid abuse, the US Food and Drug Administration (FDA) has proposed the implementation of aggressive Risk Evaluation and Mitigation Strategies (REMS). While REMS could dramatically change the development, release, marketing and prescription of extended-release opioids, questions remain on how these programmes may influence prescribing practices, patient safety and ultimately patient access to these agents. The extent of the availability and misuse of prescription opioids in Europe is difficult to assess from the data currently available, due in large part to the considerable differences in prescribing patterns and regulations between countries. Balancing the availability of prescription opioids for those patients who have pain, while discouraging illicit use, is a complex challenge and requires effective efforts on many levels, particularly in Europe where policies are quite different between countries

Outcome of after-hours surgery: Setting, skill and timing may explain the outcome:

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TLR4 Up-regulation and Reduced Foxp3 Expression in Mechanically Ventilated Smokers with Obstructive Chronic Bronchitis

Background: Chronic bronchitis (CB) is a risk factor in chronic obstructive pulmonary disease (COPD) for accelerated lung function decline and increased mortality. The lung and systemic inflammatory and immunological profile of COPD patients with CB which acutely experience respiratory failure upon a disease exacerbation is unknown. Methods: In this study, we explored the expression of Foxp3 by western blot analysis, TLR4 by immunocytochemistry and the concentrations of IP-10 and IL-8 by ELISA in the mini-bronchoalveolar lavages (mini-BAL) and in the peripheral blood of patients with respiratory failure requiring intubation and mechanical ventilation. The recruited subjects were separated into three different groups: smokers with CB and COPD (COPD, n = 18), smokers with CB but without COPD (S, n = 8) and patients without CB and without COPD (C, n = 10). Results: In mini-BAL of COPD group, Foxp3 and IP-10 were significantly reduced while TLR4 was significantly increased in comparison to C. TLR4 was also increased in mini-BAL of S. In COPD peripheral blood, Foxp3 was reduced in comparison to C but no significant differences were observed for TLR4 and for IP-10. No significant differences were observed for IL-8 concentrations in the mini-BAL and in the blood of the recruited patients. The mini-BAL TLR4 expression correlated with the Clinical Infective Pulmonary Score. Conclusions: In exacerbated COPD patients with respiratory failure, lung and systemic reduced immune regulatory events (low Foxp3 expression) and lung increased innate immunity responses (high TLR4 expression) occur. These events may contribute to the increased inflammatory events leading to respiratory failure

Opioid use and effectiveness of its prescription at discharge in an acute pain relief and palliative care unit

The aim of this study was to present how opioids are used in an acute pain relief and palliative care unit (APRPCU), where many patients with difficult pain conditions are admitted from GPs, home palliative care programs, oncology departments, other hospitals or emergency units, and other regional places. From a consecutive sample of cancer patients admitted to an APRPCU for a period of 6 months, patients who had been administered opioids were included in this survey. Basic information was collected as well as opioid therapy prescribed at admission and, subsequently, during admission and at time of discharge. Patients were discharged once stabilization of pain and symptoms were obtained and the treatment was considered to be optimized. One week after being discharged, patients or relatives were contacted by phone to gather information about the availability of opioids at dosages prescribed at time of discharge. One hundred eighty six of 231 patients were specifically admitted for uncontrolled pain, with a mean pain intensity of 6.8 (SD 2.5). The mean dose of oral morphine equivalents in patients receiving opioids before admission was 45 mg/day (range 10–500 mg). One hundred seventy five patients (75.7 %) were prescribed around the clock opioids at admission. About one third of patients changed treatment (opioid or route). Forty two of 175 (24 %), 27/58 (46.5 %), 10/22 (45.4 %), and 2/4 (50 %) patients were receiving more than 200 mg of oral morphine equivalents, as maximum dose of the first, second, third, and fourth opioid prescriptions, respectively. The pattern of opioids changed, with the highest doses administered with subsequent line options. The mean final dose of opioids, expressed as oral morphine equivalents, for all patients was 318 mg/day (SD 798), that is more than six times the doses of pre-admission opioid doses. One hundred eighty six patients (80.5 %) were prescribed a breakthrough cancer pain (BTcP) medication at admission. Sixty five patients changed their BTcP prescription, and further 27 patients changed again. Finally, eight patients were prescribed a fourth BTcP medication. Of 46 patients available for interview, the majority of them (n=39, 84 %) did not have problems with their GPs, who facilitated prescription and availability of opioids at the dosages prescribed at discharge. For patients with severe distress, APRPCUs may guarantee a high-level support to optimize pain and symptom intensities providing intensive approach and resolving highly distressing situations in a short time by optimizing the use of opioids

Rapid detection of carbapenem resistance: targeting a zero level of inadequate empiric antibiotic exposure?

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