Opioid bowel dysfunction (OBD) is a common adverse effect associated with opioid therapy. OBD is commonly described as constipation; however, it is a constellation of adverse gastrointestinal (GI) ...effects, which also includes abdominal cramping, bloating, and gastroesophageal reflux. The mechanism for these effects is mediated primarily by stimulation of opioid receptors in the GI tract. In patients with pain, uncontrolled symptoms of OBD can add to their discomfort and may serve as a barrier to effective pain management, limiting therapy, or prompting discontinuation. Patients with cancer may have disease-related constipation, which is usually worsened by opioid therapy. However, OBD is not limited to cancer patients. A recent survey of patients taking opioid therapy for pain of noncancer origin found that approximately 40% of patients experienced constipation related to opioid therapy (<3 complete bowel movements per week) compared with 7.6% in a control group. Of subjects who required laxative therapy, only 46% of opioid-treated patients (control subjects, 84%) reported achieving the desired treatment results >50% of the time. Laxatives prescribed prophylactically and throughout opioid therapy may improve bowel movements in many patients. Nevertheless, a substantial number of patients will not obtain adequate relief of OBD because of its refractory nature. Naloxone and other tertiary opioid receptor antagonists effectively reduce the symptoms of constipation in opioid-treated patients. However, because they also act centrally, they may provoke opioid withdrawal symptoms or reverse analgesia in some patients. There are 2 peripherally selective opioid receptor antagonists, methylnaltrexone and ADL 8-2698 (Adolor Corporation, Exton, PA, USA), that are currently under investigation for their use in treating OBD. Early studies confirm that they are effective at normalizing bowel function in opioid-treated patients without entering the central nervous system and affecting analgesia. With a better understanding of the prevalence of OBD and its pathophysiology, a more aggressive approach to preventing and treating OBD is possible and will likely improve the quality of life of patients with pain.
The LHCb simulation application, Gauss, is based on the Gaudi framework and on experiment basic components such as the Event Model and Detector Description. Gauss also depends on external libraries ...for the generation of the primary events (PYTHIA 6, EvtGen, etc.) and on GEANT4 for particle transport in the experimental setup. The application supports the production of different types of events from minimum bias to B physics signals and particle guns. It is used for purely generator-level studies as well as full simulations. Gauss is used both directly by users and in massive central productions on the grid. The design and implementation of the application and its evolution due to evolving requirements will be described as in the case of the recently adopted Python-based configuration or the possibility of taking into account detectors conditions via a Simulation Conditions database. The challenge of supporting at the same time the flexibililty needed for the different tasks for which it is used, from evaluation of physics reach to background modeling, together with the stability and reliabilty of the code will also be described.
Background: Both neuropathic pain and migraine are now being treated with a variety of newer antiepileptic drugs (AEDs). The proven efficacy of gabap in postherpetic neuralgia (PHN) and painful ...diabetic neuropathy (PDN), and of divalproex sodium in the prevention of migraine has led to increased clinical investigation of the newer AEDs for these conditions. While basic and clinical research are expanding the knowledge base concerning the fundamental mechanisms of neuropathic pain and migraine, growing recognition of the similarities in the pathophysiology of epilepsy, migraine, and various chronic pain disorders has further heightened interest in exploring the newer AEDs in the treatment of these conditions.
Objective: The goals of this article were to review the empiric basis and scientific rationale for the use of AEDs in the treatment of neuropathic pain and migraine; summarize available clinical research on the use of 5 newer AEDs (gabapentin, lamotrigine, oxcarbazepine, topiramate, and zonisamide) in these conditions; and provide a summary comparison of the dosing, tolerability, and drug-interaction potential of these agents.
Methods: Relevant English-language articles were identified through searches of MEDLINE (1990-March 2003), American Academy of Neurology abstracts (1999–2003), and American Epilepsy Society abstracts (2000–2002). The search terms were
antiepileptic medication or drug, migraine headeache, neuropathic pain, pathophysiology, treatment, mechanism of action, gabapentin, lamotrigine, oxcarbazepine, topiramate, and
zonisamide.
Conclusions: The newer AEDs possess the potential advantages of better tolerability and fewer drug-drug interactions compared with standard treatments such as tricyclic antidepressants or established AEDS. However, with the excep
Tricyclic antidepressants (TCA) provide less than satisfactory pain relief for postherpetic neuralgia (PHN), and the role of opioids is controversial.
To compare the analgesic and cognitive effects ...of opioids with those of TCA and placebo in the treatment of PHN.
Seventy-six patients with PHN were randomized in a double-blind, placebo-controlled, crossover trial. Each subject was scheduled to undergo three treatment periods (opioid, TCA, and placebo), approximately 8 weeks' duration each. Doses were titrated to maximal relief or intolerable side effects. The primary outcome measures were pain intensity (0 to 10 scale), pain relief (0 to 100%), and cognitive function. Analyses included patients who provided any pain ratings after having received at least a single dose of a study medication.
Fifty patients completed two periods, and 44 patients completed all three. Mean daily maintenance doses were morphine 91 mg or methadone 15 mg and nortriptyline 89 mg or desipramine 63 mg. Opioids and TCA reduced pain (1.9 and 1.4) more than placebo (0.2; p < 0.001), with no appreciable effect on any cognitive measure. The trend favoring opioids over TCA fell short of significance (p = 0.06), and reduction in pain with opioids did not correlate with that following TCA. Treatment with opioids and TCA resulted in greater pain relief (38 and 32%) compared with placebo (11%; p < 0.001). More patients completing all three treatments preferred opioids (54%) than TCA (30%; p = 0.02).
Opioids effectively treat PHN without impairing cognition. Opioids and TCA act via independent mechanisms and with varied individual effect.
Highlights • In 2011 Italy implemented the Measles and Congenital Rubella Elimination Plan. • Measles vaccination coverage was 87% in 2013 in Italy. • Studying measles seroprevalence could support ...measles elimination programme evaluation. • People aged 18–24 showed the lowest seropositivity rates. • Universal routine vaccination changed measles epidemiological pattern among adults.
Objectives
Liver diseases have become a leading cause of death among people with AIDS (PWA). This study aimed to investigate whether PWA experienced excess mortality related to liver diseases as ...compared to the general population (non‐PWA), using a multiple cause of death (MCoD; i.e. all conditions reported on death certificates) approach.
Methods
A population‐based, nationwide, retrospective cohort study was conducted among Italian people, aged 15–74 years, who had been diagnosed with AIDS since 2006. Date of death and MCoD data were retrieved, up to December 2015, by individual record linkage with national mortality data. Sex‐ and age‐standardized mortality ratios (SMRs), with 95% confidence intervals (CIs), were estimated by dividing the observed number of deaths related to a specific condition among PWA to the expected number, based on non‐PWA mortality rates.
Results
Among 7912 PWA (34 184 person‐years), 2076 deaths occurred. The number of death certificates reporting liver diseases among MCoDs was 583 (28.1%), including 382 (18.4%) reporting viral hepatitis, 370 (17.8%) reporting nonviral liver diseases, and 41 (2.0%) reporting liver cancers. The corresponding SMRs were 40.4 (95% CI 37.2–43.8) for all liver diseases, 131.1 (95% CI 118.3–145.0) for viral hepatitis, 29.9 (95% CI 27.0–33.1) for nonviral liver diseases, and 11.2 (95% CI 8.1–15.3) for liver cancers. Particularly elevated SMRs emerged among PWA aged 15–49 years and those infected by injecting drug use.
Conclusions
The high excess liver‐related mortality observed among PWA warrants preventive actions to limit the burden of viral hepatitis coinfections, alcohol abuse, and metabolic disorders, especially among younger PWA and injecting drug users.
Contemporary standard pharmacological care for the treatment of noncancer pain includes the use of opioid medications. The responsiveness of neuropathic pain to opioids has long been an area of ...controversy. Evidence from multiple randomized controlled trials indicates that opioids can relieve pain in a variety of neuropathic pain syndromes. Opioids are typically reserved for moderate to severe pain that cannot be relieved by the nonsteroidal anti-inflammatory drugs (NSAIDs). Opioids are often used in combination with other adjuvants or other analgesic agents. The advantage of opioids is the lack of a ceiling effect of the pure mu opioid agonists. The disadvantages of these drugs are a series of mechanism-based opioids-related side effects (e.g., nausea, drowsiness, constipation) and the potential issue of their abuse and misuse. Each patient needs to undergo a comprehensive evaluation and receive education on the treatment. The physician must be well conversant with the differential diagnosis and definitions of physical dependence, tolerance, pseudotolerance, aberrant behaviors, addiction, and pseudoaddiction. No specific opioid drug is intrinsically ''better'' than the others. Opioid rotation refers to the switch from one opioid to another when the degree of analgesia obtained is limited by the persistence of adverse effects or the occurrence of clinically relevant tolerance. This approach is based on the observation that a patient's response varies from opioid to opioid. At present, after 1) appropriate selection of patients and 2) longitudinal patient care with routine assessment of degree of analgesia, functional daily activities, adverse events and aberrant behaviors is carried out, opioid therapy can be the safest and most effective treatment measure for quality of life improvement in the chronic pain patient.
Abstract Background: Approximately 30% of patients with multiple sclerosis (MS) have central pain (CP). The anticonvulsant lamotrigine has been shown to be efficacious in some types of CP, but its ...efficacy in MS-related CP has not been confirmed. Objective: The aim of this pilot trial was to provide preliminary data for a planned larger trial. Methods: A randomized, double-blind, placebo-controlled, 2-period, crossover pilot study was conducted in a sample of patients aged ≥18 years with CP due to MS. The 2 treatment periods began with an 8-week, double-blind titration period, during which the number of pills of study drug was increased until either total pain relief was achieved, 1 or more unmanageable adverse events were reported, or a maximum of 16 pills (400 mg of lamotrigine) were used daily. A 3-week maintenance period at the final prescribed amount was followed by a 2-week tapering period; there was a 2-week washout between the 2 treatment periods, after which patients were administered the alternate drug. Outcomes before, during, and after each study period were assessed using validated measures of pain and quality of life (the Brief Pain Inventory BH, the Neuropathic Pain Scale NPS, and the 54-item MS Quality of Life MSQOL-54 questionnaire). Throughout the trial, patients completed a daily diary consisting of questions from the BPI-Short Form, as well as questions about the use of other analgesic drugs, changes in health, and the occurrence of adverse events. The BPI and NPS were completed weekly during telephone calls with the research coordinator, and the MSQOL-54 was administered during clinic visits (ie, visits at screening, baseline, end of period 1, and termination). The primary outcome measure was the mean pain intensity score during the final maintenance week of each of the 2 study periods. Results: A total of 12 patients were enrolled and completed at least the first period of the study. Ten patients were women. The mean (SD) age was 49.3 (11.7) years, and the mean (SD) weight was 76.5 (19.9) kg. The analysis revealed no significant differences between the lamotrigine and placebo periods in any of the study outcomes related to pain or quality of life. Regarding adverse events, 1 patient developed a moderate rash during the study, but the physician attributed this lesion to herpes zoster; this patient completed the study. While other adverse events were mild, 2 patients were withdrawn from the study after experiencing adverse events during the first study period; 1 had been receiving lamotrigine and the other placebo. Conclusion: The results from this pilot trial did not support either the use of lamotrigine in patients with MS-related CP or the need for a larger trial.
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