Response Letter to: “Next Steps for Measures of Physical Activity in Pregnancy”

Maternal and Child Health Journal -     

Adjuvant use of intravenous lidocaine for procedural burn pain relief: a randomized double-blind, placebo-controlled, cross-over trial

Background

Pain is a major issue for patients with severe burn. High dose intravenous opioids form the mainstay of procedural burns pain management; however it was suggested that intravenous lidocaine assists with minimising the pain experience. This study aimed to evaluate whether intravenous lidocaine improved analgesic efficacy and decreased opioid consumption during a burn wound care procedure.

Methods

A prospective double-blind randomized crossover study compared intravenous lidocaine versus placebo alongside patient controlled analgesia (PCA) in 45 patients with severe burn undergoing wound care procedures (i.e. dressing change ± debridement) on two consecutive days. Subjects were randomised to either the intervention or control condition on the first dressing day, and received the alternate condition on the second dressing day. During the intervention condition, subjects received lidocaine of 1.5 mg/kg/body weight followed by two boluses of 0.5 mg/kg at 5-min intervals followed by a continuous infusion. During the control condition, 0.9% sodium chloride was administered at an equivalent volume, dose and rate to that of lidocaine. Primary end points included pain intensity as measured by verbal rating scale (VRS), time to rescue analgesia, opioid requests and consumption and overall anxiety and level of satisfaction.

Results

Changes in the VRS score was significantly lower for lidocaine [difference (95% CI) = 0.36 (0.17 − 0.55)] as compared to placebo. However, there were no significant clinical or statistical differences regarding the effects of lidocaine and placebo on opioid requests and consumption, anxiety or level of satisfaction during the first and second dressing procedures.

Conclusions

In this study, the clinical benefit of intravenous lidocaine for pain relief during burn wound dressing changes in terms of overall pain scores and opioid consumption was unremarkable. Further investigations using different lidocaine regimes for the management of procedural burn pain are warranted.     

Thyroid function in childhood obesity and metabolic comorbidity

Childhood obesity is a worldwide health problem and its prevalence is increasing steadily and dramatically all over the world. Obese subjects have a much greater likelihood than normal-weight children of acquiring dyslipidemia, elevated blood pressure, and impaired glucose metabolism, which significantly increase their risk of cardiovascular and metabolic diseases. Elevated TSH concentrations in association with normal or slightly elevated free T4 and/or free T3 levels have been consistently found in obese subjects, but the mechanisms underlying these thyroid hormonal changes are still unclear. Whether higher TSH in childhood obesity is adaptive, increasing metabolic rate in an attempt to reduce further weight gain, or indicates subclinical hypothyroidism or resistance and thereby contributes to lipid and/or glucose dysmetabolism, remains controversial. This review highlights current evidence on thyroid involvement in obese children and discusses the current controversy regarding the relationship between thyroid hormonal derangements and obesity-related metabolic changes (hypertension, dyslipidemia, hyperglycemia and insulin resistance, nonalcoholic fatty liver disease) in such population. Moreover, the possible mechanisms linking thyroid dysfunction and pediatric obesity are reviewed. Finally, the potential role of lifestyle intervention as well as of therapy with thyroid hormone in the treatment of thyroid abnormalities in childhood obesity is discussed.     

Case–control association analysis of polymorphisms in the delta-opioid receptor,OPRD1, with cocaine and opioid addicted populations

BackgroundAddiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The μ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR).MethodsThe present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n = 336, CA n = 503) and European American (OA n = 1007, CA n = 336) populations.ResultsThe primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p = 0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p = 4.53 × 10^?5; n = 993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p = 8.5 × 10^?7) (p-values non-FDR corrected).ConclusionThe present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence.     

Antidiuretic effect of desmopressin chimera agglomerates by nasal administration in rats

In the present study, a nasal powder of the antidiuretic peptide desmopressin (DDAVP) formulated as chimera agglomerates was studied to improve drug bioavailability and provide a flexible drug product. Firstly, DDAVP was spray-dried along with mannitol and lecithin to produce primary microparticles capable of instantaneous dissolution in water. The chimera agglomerates were spontaneously formed by mechanically vibrating the microparticles on two stacked sieves. Agglomerate formation and strength were favored by the presence of lecithin. Drug content and dissolution rate remained unmodified after agglomeration. However, owing to the agglomerate larger size, powder flowability was greatly improved in comparison with the original microparticles, allowing accurate powder dosing into the nasal delivery device. DDAVP in vitro permeation across excised rabbit nasal mucosa from the agglomerates was significantly higher than that obtained from a commercial liquid nasal spray.     

Habituation to pain in "medication overuse headache": a CO2 laser-evoked potential study

(Headache 2012;52:792‐807) Objective.— Our aim was to investigate CO₂ laser‐evoked potential (LEP) habituation to experimental pain in a group of patients affected by medication‐overuse headache, with a history of episodic migraine becoming chronic, before and after treatment, consisting in acute medication withdrawal and a preventive treatment cycle. Background.— One of the main features of LEPs in migraineurs is a lower habituation to repetitive noxious stimuli during the interictal phase. Methods.— LEPs were recorded to stimulation of both the right hand and the right perioral region in 14 patients and in 14 healthy subjects. The habituation of both the N1 and the vertex N2/P2 components was assessed by measuring the LEP amplitude changes across 3 consecutive repetitions of 30 trials each. Results.— In the 8 patients who had clinically improved after treatment, the N2/P2 amplitude habituation was significantly higher after treatment than before treatment following both hand (F = 43.2, P < .0001) and face stimulation (F = 6.9, P = .01). In these patients, the N2/P2 amplitude habituation after treatment was not different from that obtained in healthy controls (P = .18 and P = .73 for hand and face stimulation, respectively). On the contrary, in the patients who did not improve, the N2/P2 amplitude still showed reduced habituation after both hand (F = 3.1, P = .08) and face (F = 0.7, P = .4) stimulation. Conclusion.— The deficient habituation of the vertex N2/P2 complex was partly restored after successful treatment of medication‐overuse headache, reflecting a modification in pain‐processing pathways.     

The prognostic value of plasma fibrinogen concentrations of patients with ST-elevation myocardial infarction and treated by primary percutaneous coronary intervention: A cautionary message

Abstract Background. Fibrinogen elevation is associated with a worse prognosis in patients with acute coronary syndrome (ACS). The aim of the present study was to assess the prognostic value of increased fibrinogen concentrations in ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). Methods. A total of 428 STEMI patients treated with primary PCI were retrospectively selected (median age: 62 years; 82.5% males) from a continuous case series of 832 ACS patients. Plasma fibrinogen concentrations were measured before PCI and after 24, 48, and 72 hours. In the 4-year follow-up, one major adverse cardiovascular event (MACE) occurred in 111 patients (40%): 17 re-STEMI (7%), 64 re-PCI (22%), 22 cardiac deaths (7%), and eight non ST-elevated acute coronary syndromes (NSTEACS, 4%). Results. According to the reference change value, fibrinogen concentrations increased in 25% of patients at 24 h, 64% at 48 h and 19% at 72 h. Only fibrinogen concentrations at 48 h showed a mild association with overall MACEs (p =?0.036): the risk increased, starting from a concentration of 4 g/L. However a further multivariate model did not confirm any prognostic value. No association with specific MACEs emerged. Conclusions. In contrast to NSTEACS patients, fibrinogen concentrations increased slightly in STEMI patients after primary PCI, however, they were not as prognostic as for MACEs.     

Opiate agonist-induced re-distribution of Wntless, a mu-opioid receptor interacting protein, in rat striatal neurons

Wntless (WLS), a mu-opioid receptor (MOR) interacting protein, mediates Wnt protein secretion that is critical for neuronal development. We investigated whether MOR agonists induce re-distribution of WLS within rat striatal neurons. Adult male rats received either saline, morphine or [d-Ala2, N-Me-Phe4, Gly-ol5]-enkephalin (DAMGO) directly into the lateral ventricles. Following thirty minutes, brains were extracted and tissue sections were processed for immunogold silver detection of WLS. In saline-treated rats, WLS was distributed along the plasma membrane and within the cytoplasmic compartment of striatal dendrites as previously described. The ratio of cytoplasmic to total dendritic WLS labeling was 0.70±0.03 in saline-treated striatal tissue. Morphine treatment decreased this ratio to 0.48±0.03 indicating a shift of WLS from the intracellular compartment to the plasma membrane. However, following DAMGO treatment, the ratio was 0.85±0.05 indicating a greater distribution of WLS intracellularly. The difference in the re-distribution of the WLS following different agonist exposure may be related to DAMGO's well known ability to induce internalization of MOR in contrast to morphine, which is less effective in producing receptor internalization. Furthermore, these data are consistent with our hypothesis that MOR agonists promote dimerization of WLS and MOR, thereby preventing WLS from mediating Wnt secretion. In summary, our findings indicate differential agonist-induced trafficking of WLS in striatal neurons following distinct agonist exposure. Adaptations in WLS trafficking may represent a novel pharmacological target in the treatment of opiate addiction and/or pain.