Is intrathecal bupivacaine plus dexmedetomidine superior to bupivacaine in spinal anesthesia for a cesarean section? A systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate whether the administration of intrathecal dexmedetomidine as a bupivacaine adjuvant for caesarean section can prolong the duration of analgesia compared with bupivacaine alone. Secondary outcomes included postoperative pain, the time interval to the first analgesic request, the level of sedation, the incidence of adverse effects, and the fetal outcomes. MATERIALS AND METHODS: A systematic review and meta-analysis were conducted. The study compared the intrathecal administration of bupivacaine plus dexmedetomidine (group BD) to the intrathecal administration of bupivacaine alone (group B) for cesarean sections. RESULTS: Fourteen publications were included. Among patients who underwent spinal anesthesia for a cesarean section, 514 patients received intrathecal bupivacaine alone, and 533 patients received intrathecal bupivacaine plus dexmedetomidine. The onset of sensory and motor block was essentially the same in both groups; the time for sensory and motor block regression was significantly longer in the BD group. Postoperative Visual Analogue Scale (VAS) values were similar in group BD when compared to group B. Postoperative VAS scores remained consistently low in Group BD compared to Group B, starting from 1 hour after surgery. The level of sedation measured at the end of the cesarean section in both groups was almost similar. No difference in terms of safety, adverse events, and neonatal outcomes was found between the two groups. CONCLUSIONS: Use of intrathecal dexmedetomidine for spinal anesthesia in cesarean section significantly prolongs sensory and motor block compared to using bupivacaine alone as an adjuvant. It also improves analgesia after 1 hour with no difference in the incidence of maternal and neonatal adverse effects compared to bupivacaine alone. The optimal dose of dexmedetomidine to use remains to be ingested.

Changing the paradigm in postherpetic neuralgia treatment: lidocaine 700 mg medicated plaster.

OBJECTIVE: Chronic pain is currently considered a disease state with biopsychosocial consequences and a negative impact on patients' quality of life (QoL). Pain from postherpetic neuralgia (PHN) can persist for months or years and is a prototypical example of chronic pain. We analyzed PHN as a model of chronic pain, including its effects on QoL and clinical aspects. We explored treatment options, focusing on the topical treatment with lidocaine 700 mg medicated plaster (LMP) and how this impacts PHN management. MATERIALS AND METHODS: This article is a narrative review of published studies. Preclinical and clinical studies were retrieved from literature through a search performed in PubMed/MEDLINE. RESULTS: To choose the appropriate treatment for chronic pains, such as PHN, not only efficacy but also tolerability, manageability, practicality, and compliance are important factors, especially in the long term. It is also important to set treatment expectations with the patients as total suppression of pain may be unrealistic, and a balance needs to be found between pain control and the minimization of adverse events. In this respect, LMP may be the best currently available treatment: it is easy to use, has low systemic absorption and thus a low risk for pharmacological interactions. Therefore, treatments can be personalized, and concomitant medications can be added, if needed. Recent data from a real-world study support this view by showing that LMP has superior effectiveness in reducing pain and improving the QoL compared to other commonly used systemic treatments and confirming its good tolerability profile that is mainly characterized by localized skin reactions. CONCLUSIONS: LMP is one of the best currently available treatment options for PHN patients balancing good efficacy with an excellent tolerability profile and can therefore be considered for use as a first-line treatment for PHN.

Equianalgesia, opioid switch and opioid association in different clinical settings: a narrative review.

Emergency or postoperative pain often represents an authentic challenge in patients who were already on opioid treatment for chronic pain. Thus, their management requires not only the physician's ability to treat acute pain, but also competence in switching the opioid that lost efficacy. Different aspects should be considered, such as opioids titration, switching, association and equianalgesia. The objective of this paper is to provide a narrative review, which has been elaborated and discussed among clinicians through an iterative process involving development and review of the draft during two web-based meetings and via email. This expert opinion aims to facilitate the correct opioid use through appropriate practices with a focus on pain treatment in emergency and postoperative pain. Equianalgesia tables were reviewed and integrated by clinicians and researchers with expertise in anesthesia, postoperative medicine, intensive care, emergency medicine pharmacology and addiction medicine. Special populations (liver/kidney failure, elder, pediatric, pregnancy/lactation) are discussed in detail along with other critical scenarios, such as: (i) rapid pain worsening in chronic pain (aggravating pain due to disease progression or tolerance development to analgesic therapy); (ii) acute pain on maintenance treatment; and (iii) pain management of complicated patients in emergency care. Extended and updated equianalgesia tables and conversion rates for 17 different opioid formulations (of 9 different molecules) are presented as follows. Opioids remain the class that best suits clinical needs of emergency and post-operative medicine. However, it should be stressed that equianalgesia can be affected by drug-to-drug interactions and pharmacological imprecision, in a complex field where clinical experience may be the main guiding principle.

Lidocaine 700 mg medicated plaster for post-herpetic neuralgia: focus on Quality of Life, effectiveness and safety - a retrospective observational study.

OBJECTIVE: Postherpetic neuralgia (PHN) is a neuropathic pain syndrome following herpes zoster (HZ) infection, characterized by pain that persists for months to years after the resolution of the HZ rash. Therapeutic management remains challenging for every clinician. We report the follow-up of patients diagnosed with PHN and treated with lidocaine 700 mg medicated plaster (LMP), focusing on effectiveness, safety, and Quality of Life (QoL). MATERIALS AND METHODS: This study is a retrospective observational investigation of patients with PHN treated with LMP. Patients were regularly followed for pain intensity, co-analgesic consumption, adverse effects, QoL using the EQ-5D, and patient satisfaction for 8 weeks. RESULTS: A total of 31 patients were evaluated. At enrollment, 18 patients (58.1%) were treated with at least one PHN concomitant medication, for which the number and dosing remained constant during the study. Patients had a mean average pain intensity of 6.5±1.0 at baseline, which decreased to 3.6±1.1 at week 4 and 2.8±0.9 at week 8. Four patients reported erythema, and one complained of vesicles eruption associated with pruritus. EQ-5D at weeks 4 and 8 of treatment showed persisting improvements in all domains except for the "anxiety/depression" domain. At week 8, <80% of patients reported to be satisfied or very satisfied. CONCLUSIONS: This study adds further weight to the growing body of clinical and research evidence that LMP treatment is effective and well-tolerated in patients with PHN.

Septic shock due to Escherichia coli meningoencephalitis treated with immunoglobulin-M-enriched immunoglobulin preparation as adjuvant therapy: a case report.

BACKGROUND: Gram-negative bacteria are an uncommon etiology of spontaneous community-acquired adult meningitis and meningoencephalitis. Escherichia coli is a Gram-negative bacterium that is normally present in the intestinal microbial pool. Some Escherichia coli strains can cause diseases in humans and animals, with both intestinal and extraintestinal manifestations (extraintestinal pathogenic Escherichia coli) such as urinary tract infections, bacteremia with sepsis, and, more rarely, meningitis. Meningitis continues to be an important cause of mortality throughout the world, despite progress in antimicrobial chemotherapy and supportive therapy. The mortality rate fluctuates between 15% and 40%, and about 50% of the survivors report neurological sequelae. The majority of Escherichia coli meningitis cases develop as a result of hematogenous spread, with higher degrees of bacteremia also being related to worse prognosis. Cases presenting with impaired consciousness (that is, coma) are also reported to have poorer outcomes. CASE PRESENTATION: We describe the case of a 48-year-old caucasian woman with meningoencephalitis, with a marked alteration of consciousness on admission, and septic shock secondary to pyelonephritis caused by Escherichia coli, treated with targeted antimicrobial therapy and immunoglobulin-M-enriched immunoglobulin (Pentaglobin) preparation as adjuvant therapy. CONCLUSION: Despite the dramatic presentation of the patient on admission, the conflicting data on the use of immunoglobulins in septic shock, and the lack of evidence regarding their use in adult Escherichia coli meningoencephalitis, we obtained a remarkable improvement of her clinical condition, accompanied by partial resolution of her neurological deficits.

Physical and physiological demands and hormonal responses in basketball small-sided games with different tactical tasks and training regimes.

OBJECTIVES: To evaluate external and internal training load (TL) and hormonal responses in basketball 3-versus-3 small-sided games (SSGs). DESIGN: Randomized repeated-measures study. METHODS: Twelve male basketball players participated to four 3-versus-3 SSGs characterized by different tactical tasks (offensive; defensive) and training regimes (long-intermittent: three 4-min bouts with 2' rest in between; short-intermittent: six 2-min bouts with 1' rest in between). Variables measured were: PlayerLoad (PL); percentage of maximal heart rate (%HRmax); Edwards' TL. Before and after the SSGs, saliva samples were collected to measure cortisol (C) and testosterone (T). Two-way (task; regime) repeated-measures ANOVA was performed for PL and %HRmax; C concentrations were analysed with a three-way (task; regime; time: pre/post) repeated-measures ANOVA; non-parametric analyses were performed for Edwards' TL and T. RESULTS: PL was moderately higher in offensive task (148.0±16.8 AU) compared to defensive (137.1±15.5 AU), and short regime (147.0±18.2 AU) compared to long (137.9±14.6 AU). %HRmax was moderately higher in offensive task (91.1±4.1%) compared to defensive: (88.7±5.4%), while it did not differ between regimes (long: 90.0±5.6%) (short: 89.8±4.2%); additionally, an interaction (task*regime) effect was found (ES: strong). Edwards' TL was moderately higher in offense-long SSG (56.6+2.4 AU) compared to defense-short (52.4+4.4 AU). C increased after the SSGs (ES: strong). T decreased after offense-short (ES: moderate) and increased after defense-long (ES: moderate) SSGs. CONCLUSIONS: Tactical tasks and training regimes influence external and internal demands of basketball SSGs. Steroid hormones respond in SSGs.

Continuous intravenous low-dose diclofenac sodium to control a central fever after ischemic stroke in the intensive care unit: a case report and review of the literature.

INTRODUCTION: Elevation in body temperature within the first 24 hours of ischemic stroke is fairly common and known to be associated with worse outcomes. Only after thoroughly ruling out infection and the noninfectious etiologies and in the appropriate clinical setting should the diagnosis of central fever be made. Acetaminophen and nonsteroidal anti-inflammatory drugs are typical therapeutic options. External cooling is frequently used when pharmacologic interventions are inadequate. However, reports have suggested that neurogenic fevers are somewhat resistant to traditional pharmacologic therapies. CASE PRESENTATION: We describe a case of a Caucasian patient with central fever after ischemic stroke not responsive to acetaminophen administration and external cooling. After an initial bolus of diclofenac sodium (0.2 mg/kg in 100 ml of saline solution for 30 minutes), a continuous infusion (75 mg in 50 ml of saline solution) was started. After 5 days of treatment, the patient's body temperature was below 37.5 °C, and the diclofenac sodium infusion was stopped. CONCLUSIONS: We observed that a low-dose diclofenac sodium infusion was effective in treating fever without systemic side effects. This treatment may be suggested as an alternative to conventional antipyretic drugs, but additional clinical trials are required.

Role of p53 codon 72 arginine allele in cell survival in vitro and in the clinical outcome of patients with advanced breast cancer.

BACKGROUND: The p53 codon 72 polymorphism, which results in either an arginine or proline residue, plays a different role in vitro and in vivo in cell survival and drug resistance. We verified, in vitro, the impact of the arginine allele on cell survival under normoxia and hypoxia, and investigated in vivo the role of p53 codon 72 arginine homozygosity in the clinical outcome of advanced breast cancer patients. METHODS: Tumors at advanced stages grow in vivo in a hypoxic environment, and we mimicked such conditions in vitro using p53 null breast cancer cells transfected with either the arginine or proline allele. We also analyzed in vivo the p53 codon 72 genotype status of advanced breast cancer patients. RESULTS: In vitro transfection of the arginine allele induced higher cell death under normoxia, whereas cell death was greater in proline-transfected cells under hypoxia. The arginine allele upregulated BCRP-I, a hypoxia response gene, which increases drug resistance. Metastatic breast cancer patients homozygous for arginine had a significantly shorter time to progression and overall survival than those with heterozygous arginine/proline tumors. CONCLUSION: We provide a molecular explanation for the association of the arginine allele with tumor aggressiveness and treatment resistance in advanced breast cancer.

DNA binding of iproplatin and its divalent metabolite cis-dichloro-bis-isopropylamine platinum (II).

The quadrivalent second-generation platinum complex iproplatin and an in vivo divalent metabolite of iproplatin, cis-dichloro-bis-isopropylamine platinum (CIP) were tested for binding to DNA in vitro. DNA binding was determined according to radioactivity measured using [14C]-iproplatin and [14C]-CIP and also by platinum content. Results indicate that (a) iproplatin shows negligible binding to DNA, (b) CIP binds to DNA in a time-dependent fashion, and (c) the isopropylamine ligand is intact when CIP is bound to DNA. Glutathione (GSH) inhibits the binding of CIP to DNA, possibly by inhibiting binding to DNA of the aquated form of CIP.

Medical preparedness, incidents, and group dynamics during the analog MARS2013 mission.

Participants on spaceflights and international scientific analog Mars missions can encounter medical incidents (accidents, illnesses) and psychological issues (e.g., stress, group interaction, sleep disturbance, emotions). The aim of this study was to examine these parameters in a field crew living in a desert environment similar to Mars (Group 1) and in Mission Support Center (MSC) personnel on "Earth" (Group 2) during a 4-week mission. Of the 107 medical interventions in the field, 73 mainly minor incidents together with four near accidents and 29 medical checkup interventions were recorded. Of the 32 medical interventions, medical treatments for 23 incidents of minor severity were necessary in Group 2. Injuries (Group 1: 1.4/100 h, Group 2: 0.1/100 h) were significantly increased in the field, and illnesses (Group 1: 0.3/100 h, Group 2: 3.0/100 h) in the MSC personnel. Causes of accidents and illnesses are described. Psychological results show that emotions and stress remained stable in both groups. Sympathy, social competence, teamwork, and leadership showed high scores. These scores were lower on "Earth" but significantly increased in the last weeks. The Sahara's nighttime coldness was reflected in an increased wake-up frequency, and a longer sleeping time peaked in the third week, probably as a result of overfatigue. MARS2013 was a successful mission with highly motivated participants and minor medical incidents. For future analog missions and possibly long-distance open-space missions, some recommendations in terms of medical and psychological preparedness are made to reduce risks for field crew members and MSC personnel.

Opioids switching with transdermal systems in chronic cancer pain.

BACKGROUND: Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy OBJECTIVE: To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment. METHODS: A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks RESULTS: Pain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 +/- 20.5 (mean +/- SD) to 3.75 +/- 8.06, and 33.8 +/- 18.9 to 3.75 +/- 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment. CONCLUSION: Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.

The basal-like breast carcinoma phenotype is regulated by SLUG gene expression.

Basal-like breast carcinoma is an aggressive form of breast cancer, characterized by the absence of oestrogen receptor and HER2 expression, the presence of cytokeratin 5 and epidermal growth factor receptor expression, and by the up-regulation of stem cell regulatory genes. We show here that tumour tissues expressing high levels of SLUG mRNA show a basal-like breast carcinoma phenotype and that such tumours also express high levels of stem cell-regulatory genes, ie CD133, Bmi1. Further, we show that stem/progenitor cells, isolated from ductal breast carcinoma and from normal mammary gland as mammospheres, express SLUG, CD133, and Bmi1 mRNA and show a phenotype similar to that of basal-like breast carcinoma. We also report that SLUG expression in tumour tissues correlates with that of the hypoxia survival gene carbonic anhydrase IX. In this regard, we report that the exposure of SLUG-negative/luminal-like MCF-7 cells to a hypoxic environment promotes the onset of the basal-like breast carcinoma phenotype, together with up-regulation of the SLUG gene, which in turn blunts oestrogen receptor-alpha and boosts carbonic anhydrase IX gene expression. Finally, we show that SLUG expression promotes the invasiveness of MCF-7 cells exposed to hypoxia and sustains the in vivo aggressiveness of hypoxia-selected, MCF-7-derived cells in xenografts. These data indicate that SLUG gene expression is part of a hypoxia-induced genetic programme which sets up a basal/stem cell-like, aggressive phenotype in breast cancer cells.

The p53 codon 72 proline allele is endowed with enhanced cell-death inducing potential in cancer cells exposed to hypoxia.

The preferential retention of the arginine allele at the p53 codon 72 locus is commonly observed in tumours from arginine/proline heterozygotes. Considering that cancer cells are harboured in a hypoxic environment in vivo, we here tested the hypothesis that the p53 codon 72 proline allele confers a survival disadvantage in presence of hypoxia. Here, we show that the transient transfection of the proline allele in p53 null cancer cells exposed to low oxygen tension or to the hypoxia-mimetic drug Desferoxamine induces a higher amount of cell death than the arginine allele. Accordingly, proline allele transiently transfected cell lines express lower levels of hypoxia pro-survival genes (HIF-1alpha, carbonic anhydrase IX, vascular endothelial growth factor, heme oxygenase-I, hepatocyte growth factor receptor, vascular endothelial growth factor receptor 2), compared to those transiently transfected with the arginine allele. Further, we report that the exposure of the arginine/proline heterozygote MCF-7 breast cancer cell line to cytotoxic concentration of Desferoxamine for several weeks, gives raise to hypoxia-resistant clones, carrying the arginine, but not the proline allele. These data indicate that the p53 codon 72 proline allele is less permissive for the growth of cancer cells in a hypoxic environment, and suggest that the preferential retention of the arginine allele in the tumour tissues of arginine/proline heterozygous patients may depend upon its lowered capacity to induce cell death in a hypoxic tumour environment.

Neurobiology of pain.

The neurobiology of pain had a notable interest in research focused on the study of neuronal plasticity development, nociceptors, molecular identity, signaling mechanism, ionic channels involved in the generation, modulation and propagation of action potential in all type of excitable cells. All the findings open the possibility for developing new therapeutic treatment. Nociceptive/inflammatory pain and neuropathic pain represent two different kinds of persistent chronic pain. We have reviewed the different mechanism suggested for the maintenance of pain, like descending nociceptive mechanism and their changes after tissue damage, including suppression and facilitation of defence behavior during pain. The role of these changes in inducing NMDA and AMPA receptors gene expression, after prolonged inflammation is emphasized by several authors. Furthermore, a relation between a persistent pain and amygdale has been shown. Molecular biology is the new frontier in the study of neurobiology of pain. Since the entire genome has been studied, we will able to find new genes involved in specific condition such as pain, because an altered gene expression can regulate neuronal activity after inflammation or tissue damage.

Advance directives for elderly people: worthwhile cause or wasted effort?

This article examines whether elderly individuals who had executed an advance directive for health care were more likely to have their wishes understood by their designated surrogates than elderly individuals who had not executed an advance directive. A sample of 153 elderly people was drawn from two nursing homes and two senior citizen housing complexes; 40 of the participants had executed an advance directive. Concordance was measured using six hypothetical health care scenarios and was evaluated by assessing the percentage of agreement and directionality of discordant responses. The mere completion of an advance directive did not guarantee a surrogate decision maker's awareness of the older person's wishes. Education, communication, and supportive intervention are also needed. As educators, facilitators, and enablers, social workers are well suited for this role.

Providing tender touch massage to elderly nursing home residents: a demonstration project.

This 1-year demonstration project looked at the effects of gentle massage on two groups of elderly nursing home residents: those suffering from chronic pain and those with dementia who were exhibiting anxious or agitated behaviors. The certified nursing attendants were trained by a licensed massage therapist. The project was divided into three 12-week phases; different staff and residents were involved in each phase. Fifty-nine of 71 residents completed the 12-week program. Pain scores declined at the end of each phase, and anxiety scores declined in two of the three phases. Eighty-four percent of the nursing attendants reported that the residents enjoyed receiving tender touch, and 71% thought this type of massage improved their ability to communicate with the residents.

The awesome burden upon the child who must keep a family secret.

This paper describes a series of young patients hospitalized in a psychiatric facility because they presented symptoms indicative of a psychotic disorder when, in fact, the youngsters were dealing with the strain of keeping a family secret hidden. Case presentation oriented to how the burden prohibited proper psychological development and the manner of how these secrets came to light are offered. The commonality of patients exhibiting this phenomenon is discussed.