Polyanalgesic Consensus Conference—2012: Consensus on Diagnosis,Detection, and Treatment of Catheter‐Tip Granulomas (Inflammatory Masses)

Introduction: Continuous intrathecal infusion of drugs to treat chronic pain and spasticity has become a standard part of the algorithm of care. The use of opioids has been associated with noninfectious inflammatory masses at the tip of the intrathecal catheter, which can result in neurologic complications. Methods: The Polyanalgesic Consensus Conference is a meeting of a group of well‐published and experienced practitioners; the purpose of the meeting is to update the standard of care for intrathecal therapies to reflect current knowledge gleaned from literature and clinical experience. An exhaustive literature search was performed, and information from this search was provided to panel members. Analysis of the published literature was coupled with the clinical experience of panel participants to form recommendations regarding intrathecal inflammatory masses or granulomas. Results: The panel has made recommendations for the prevention, diagnosis, and management of intrathecal granulomas. Conclusion: The use of chronic infusions of intrathecal opioids is associated with the formation of inflammatory masses at the intrathecal catheter tip in a small minority of treated patients. Nonetheless, the appearance of these space‐occupying lesions can lead to devastating neurologic sequelae. The prevention, early detection, and successful treatment of intraspinal granulomas are important considerations when offering intrathecal drug therapy to patients with chronic intractable pain.     

Polyanalgesic Consensus Conference—2012: Recommendations to Reduce Morbidity and Mortality in Intrathecal Drug Delivery in the Treatment of Chronic Pain

Introduction: Targeted intrathecal drug infusion to treat moderate to severe chronic pain has become a standard part of treatment algorithms when more conservative options fail. This therapy is well established in the literature, has shown efficacy, and is an important tool for the treatment of both cancer and noncancer pain; however, it has become clear in recent years that intrathecal drug delivery is associated with risks for serious morbidity and mortality. Methods: The Polyanalgesic Consensus Conference is a meeting of experienced implanting physicians who strive to improve care in those receiving implantable devices. Employing data generated through an extensive literature search combined with clinical experience, this work group formulated recommendations regarding awareness, education, and mitigation of the morbidity and mortality associated with intrathecal therapy to establish best practices for targeted intrathecal drug delivery systems. Results: Best practices for improved patient care and outcomes with targeted intrathecal infusion are recommended to minimize the risk of morbidity and mortality. Areas of focus include respiratory depression, infection, granuloma, device‐related complications, endocrinopathies, and human error. Specific guidance is given with each of these issues and the general use of the therapy. Conclusions: Targeted intrathecal drug delivery systems are associated with risks for morbidity and mortality that can be devastating. The panel has given guidance to treating physicians and healthcare providers to reduce the incidence of these problems and to improve outcomes when problems occur.     

Zip14 (Slc39a14) mediates non-transferrin-bound iron uptake into cells

Zip14 is a member of the SLC39A zinc transporter family, which is involved in zinc uptake by cells. Up-regulation of Zip14 by IL-6 appears to contribute to the hepatic zinc accumulation and hypozincemia of inflammation. At least three members of the SLC39A family transport other trace elements, such as iron and manganese, in addition to zinc. We analyzed the capability of Zip14 to mediate non-transferrin-bound iron (NTBI) uptake by overexpressing mouse Zip14 in HEK 293H cells and Sf9 insect cells. Zip14 was found to localize to the plasma membrane, and its overexpression increased the uptake of both (65)Zn and (59)Fe. Addition of bathophenanthroline sulfonate, a cell-impermeant ferrous iron chelator, inhibited Zip14-mediated iron uptake from ferric citrate, suggesting that iron is taken up by HEK cells as Fe(2+). Iron uptake by HEK and Sf9 cells expressing Zip14 was inhibited by zinc. Suppression of endogenous Zip14 expression by using Zip14 siRNA reduced the uptake of both iron and zinc by AML12 mouse hepatocytes. Zip14 siRNA treatment also decreased metallothionein mRNA levels, suggesting that compensatory mechanisms were not sufficient to restore intracellular zinc. Collectively, these results indicate that Zip14 can mediate the uptake of zinc and NTBI into cells and that it may play a role in zinc and iron metabolism in hepatocytes, where this transporter is abundantly expressed. Because NTBI is commonly found in plasma of patients with hemochromatosis and transfusional iron overload, Zip14-mediated NTBI uptake may contribute to the hepatic iron loading that characterizes these diseases.     

Pain during topical photodynamic therapy: uncomfortable and unpredictable

Background The major drawback of the widely used photodynamic therapy (PDT) is treatment‐related pain. Objective Gain insight into the intensity of and predictive factors for painful burning sensation associated with PDT. Methods A prospective cohort study was performed at the department of Dermatology in the Maastricht University Medical Centre in Maastricht, a reference centre for dermatological oncology in The Netherlands. A total of 141 lesions in 108 patients were included, treated from November 2008 until June 2009 with PDT for superficial basal cell carcinoma, Bowen’s disease (BD) or actinic keratosis (AK). Painful burning sensation was scored based on an 11‐point pain intensity numeric rating scale (PI‐NRS) (0 = no pain; 10 = worst possible pain). Results The percentage of patients with a PI‐NRS score over six was 32.6% and 37.9% during the primary and follow‐up PDT session respectively. A total of 76.6% (95/124) of the patients was consistent in pain intensity score reporting. Factors associated with higher PI‐NRS scores were treatment of AK or BD, tumour localization in the head/neck region, patient’s age over 70, Fitzpatrick skintype I/II, photosensitizer 5‐aminolevulinic acid and use of oral analgesics. After mutual adjustment of these factors, Fitzpatrick skintype remained the only independent predictor of PI‐NRS scores during PDT. Conclusion It remains difficult to decide which patients should be considered for pain relieving measures. The solution remains to support all patients treated with PDT with pain relieving techniques or to let the support of pain relieving measures depend on the reported pain score for the primary session.     

Enantioselectivity of thiopental distribution into the central neural tissue of rats: an interaction with halothane.

Thiopental is a racemate. In this study, we examined whether thiopental total body clearance and its distribution into central nervous system (CNS) tissue of rats was enantioselective. Rats, either anesthetized with halothane or conscious and restrained, were infused to stepwise steady-state targets of 5, 10, and 20 microg/mL thiopental by computer-controlled infusions. Serial arterial plasma and steady-state samples of brain and spinal cord were assayed enantiospecifically for thiopental. In both groups, concurrent total and unbound plasma concentrations of S-thiopental were approximately 10%-20% higher than those of R-thiopental, corresponding to its higher clearance. CNS tissue concentrations of S-thiopental were approximately 20% higher than those of R-thiopental. Spinal cord to plasma distribution coefficients were approximately 2 x those in the brain, with relative distribution coefficients approximately 10% greater for R-thiopental in both tissues. Plasma concentrations and distribution coefficients of both enantiomers were approximately 10%-20% lower in the halothane-anesthetized group, with a slightly greater effect on R-thiopental distribution. We conclude that the total body clearance of R-thiopental > S-thiopental, that halothane enantioselectively reduces the relative uptake of R-thiopental into brain tissue, and that composition is important in determining the CNS tissue concentrations of thiopental. The reported higher potency of S-thiopental did not seem to be due to its greater distribution into CNS tissues. IMPLICATIONS: Because thiopental is a mixture of two forms (termed R-and S-enantiomers), correct interpretation of its distribution into, and clearance from, the body requires knowledge about both enantiomers. In this study, performed in rats, we showed that the two enantiomers of thiopental differed significantly, with the R-enantiomer having the preferred profile.     

Analysis of selection effects in New York City's Medicaid managed care population prior to mandatory enrollment

It is becoming increasingly apparent that over the next several years the majority of Medicaid patients in many states will become enrolled in managed care plans, some voluntarily, but most as the result of mandatory initiatives. An important issue related to this development is the extent to which this movement to managed care is accompanied by serious selection effects, either across the board during the phase in or among individual plans or plan types with full-scale implementation. This paper examines selection effects in New York City between 1993 and 1997 during the voluntary enrollment period prior to implementation of mandatory enrollment pursuant to a Section 1115 waiver. No substantial selection bias was documented between patients entering managed care and those remaining in the fee-for-service system among the largest rate groups, although some selection effect was found among plans and plan types (with investor-owned plans enrolling patients with lower prior utilization and expenses).     

Dynamic indocyanine green angiography-guided focal thermal laser treatment of fibrotic choroidal neovascularization

Purpose  Fibrotic choroidal neovascular membranes (CNV) are the end-stage outcomes of neovascular age-related macular degeneration (AMD). No treatment is currently available for fibrotic CNV. We investigated the role of focal thermal laser ablation of the perfusing afferent arteriole as determined by dynamic indocyanine green angiography (ICGA). Methods  We conducted a retrospective study of 20 patients with fibrotic CNV associated with significant subretinal fluid or retinal edema, who also demonstrated well-defined perfusing arterioles by dynamic ICGA. Patients underwent focal thermal laser occlusion of the perfusing afferent arteriole. Six, 12 and 24 weeks post-treatment, eyes underwent repeat examination with optical coherence tomography (OCT) and visual acuity testing, and ICGA at 12 weeks. Results  Therapeutic closure of the perfusing afferent arterioles was achieved in 17 of 20 eyes immediately post-treatment. All 17 of these eyes demonstrated significant resolution of retinal edema and subretinal fluid, as evidenced by OCT, which was dramatic in some cases. Seven eyes demonstrated an improvement in visual acuity of 1 line or more. While most eyes demonstrated reperfusion within 3 months, many lesions suggested reduced vascularity and flow. Conclusion  Eyes with fibrotic CNV and associated retinal edema often demonstrate well-defined vascularity of the fibrosis with discrete perfusing arterioles when imaged by dynamic ICGA. Thermal laser occlusion of these arterioles can result in resolution of subretinal fluid, and occasionally an improvement in vision. This represents a potential therapeutic intervention for an advanced stage of AMD currently regarded as stable.