Use and perceived effectiveness of non-analgesic medical therapies for chronic pancreatitis in the United States

Aliment Pharmacol Ther 2011; 33: 149–159Effectiveness of medical therapies in chronic pancreatitis has been described in small studies of selected patients.To describe frequency and perceived effectiveness of non-analgesic medical therapies in chronic pancreatitis patients evaluated at US referral centres.Using data on 516 chronic pancreatitis patients enrolled prospectively in the NAPS2 Study, we evaluated how often medical therapies [pancreatic enzyme replacement therapy (PERT), vitamins/antioxidants (AO), octreotide, coeliac plexus block (CPB)] were utilized and considered useful by physicians.Oral PERT was commonly used (70%), more frequently in the presence of exocrine insufficiency (EI) (88% vs. 61%, P  < 0.001) and pain (74% vs. 59%, P  < 0.002). On multivariable analyses, predictors of PERT usage were EI (OR 5.14, 95% CI 2.87–9.18), constant (OR 3.42, 95% CI 1.93–6.04) or intermittent pain (OR 1.98, 95% CI 1.14–3.45). Efficacy of PERT was predicted only by EI (OR 2.16, 95% CI 1.36–3.42). AO were tried less often (14%) and were more effective in idiopathic and obstructive vs. alcoholic chronic pancreatitis (25% vs. 4%, P  = 0.03). Other therapies were infrequently used (CPB – 5%, octreotide – 7%) with efficacy generally <50%.Pancreatic enzyme replacement therapy is commonly utilized, but is considered useful in only subsets of chronic pancreatitis patients. Other medical therapies are used infrequently and have limited efficacy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79114/1/j.1365-2036.2010.04491.x.pd

An analysis of the utilisation of chemoprophylaxis against Pneumocystis jirovecii pneumonia in patients with malignancy receiving corticosteroid therapy at a cancer hospital

Pneumocystis jirovecii pneumonia (PCP) is associated with high mortality in immunocompromised patients without human immunodeficiency virus infection. However, chemoprophylaxis is highly effective. In patients with solid tumours or haematologic malignancy, several risk factors for developing PCP have been identified, predominantly corticosteroid therapy. The aims of this study were to identify the potentially preventable cases of PCP in patients receiving corticosteroid therapy at a tertiary care cancer centre and to estimate the frequency of utilisation of chemoprophylaxis in these patients. Two retrospective reviews were performed. Over a 10-year period, 14 cases of PCP were identified: no cases were attributable to failed chemoprophylaxis, drug allergy or intolerance. During a 6-month period, 73 patients received high-dose corticosteroid therapy (⩾25 mg prednisolone or ⩾4 mg dexamethasone daily) for ⩾4 weeks. Of these, 22 (30%) had haematologic malignancy, and 51 (70%) had solid tumours. Fewer patients with solid tumours received prophylaxis compared to patients with haematologic malignancy (3.9 vs 63.6%, P<0.0001). Guidelines for PCP chemoprophylaxis in patients with haematologic malignancy or solid tumours who receive corticosteroid therapy are proposed. Successful primary prevention of PCP in this population will require a multifaceted approach targeting the suboptimal prescribing patterns for chemoprophylaxis

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Regulation of intracellular free arachidonic acid in Aplysia nervous system

We have studied the regulation of arachidonic acid (AA) uptake, metabolism, and release in Aplysia nervous system. Following uptake of [ 3 H]AA, the distribution of radioactivity in intracellular and extracellular lipid pools was measured as a function of time in the presence or absence of exogenous AA. The greatest amount of AA was esterified into phosphatidylinositol (relative to pool size). We found that the intracellular free AA pool underwent rapid turnover, and that radioactive free AA and eicosanoids were released at a rapid rate into the extracellular medium, both in the presence and absence of exogenous AA. Most of the released radioactivity originated from phosphatidylinositol.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48020/1/232_2005_Article_BF01868464.pd

Strong Fluctuations Of Energetic Electrons At Low Altitudes

Strong fluctuations (SF) of energetic electrons within the local loss cone (LC) from high resolution data on Active, a low altitude, high inclination satellite, are reviewed. The pitch angle diffusion rate of electrons at L > 4 is rapidly changing by one order up to the isotropic pitch angle distribution, corresponding to strong diffusion. The duration of the spikes to nearly strong diffusion limit is increasing with latitude. The statistical study shows the maximum occurrence of fluctuations within LC is in the noon sector and at latitudes 65-70°. Strong geomagnetic activity increases the probability of SF occurrence. One of the possible mechanisms consistent with the observations is the nonlinear precipitation oscillator (Davidson 1986; Davidson and Chiu, 1991). © 1997 COSPAR. Published by Elsevier Science Ltd.203499503Davidson, G.T., Pitch angle diffusion in Morningside Aurorae 1. The role of the loss cone in the formation of impulsive bursts of precipitation (1986) J. Geophys. Res., 91, p. 4413Davidson, G.T., Pitch-angle diffusion and the origin of temporal and spatial structures in Morningside Aurorae (1990) Space Sci. Rev., 53, p. 45Davidson, G.T., Chiu, Y.T., An unusual nonlinear system in the magnetosphere: A possible driver for auroral pulsations (1991) J. Geophys. Res., 96, p. 19353Imhof, W.L., Characteristics of short-duration electron precipitation bursts and their relationship with VLF wave activity (1989) J. Geophys. Res., 94, p. 10079Imhof, W.L., Relativistic electron microbursts (1992) J. Geophys. Res., 97, p. 13829Imhof, W.L., Relativistic electron flux comparison at low and high altitudes with fast time resolution and broad spatial coverage (1994) J. Geophys. Res., 99 (9), p. 17241Kudela, K., Inner zone electron peaks observed by the active satellite (1992) J. Gephys. Res., 97, p. 8681Rycroft, R.J., Interactions between whistler-mode waves and energetic electrons in the coupled system formed by the magnetosphere, ionosphere and atmosphere (1991) J. Atmos. Terr. Physics, 53, p. 849Sandahl, I., (1984) Pitch Angle Scattering and Particle Precipitation in a Pulsating Aurora - An Experimental Study, , Rep. 185, Kiruna SRI, SwedenTrakhtengerts, V.Yu., Mechanism of formation of pulsating auroras (1992) Proceedings of the ICS-1 Conference on Subbstorms, pp. 463-468. , Kiruna, Sweden, ESA SP-335Vampola, A.L., Gorney, D.J., Electron energy deposition in the middle atmosphere (1983) J. Geophys. Res., 88, p. 6267Vampola, A.L., (1994) RADMODLS, Ver. 4.20, , Augus

Response

We would like to thank Dr Balderramo for his interest in our study, and we thank the editors for an opportunity to preview and respond to his letter. Dr Balderramo brings up several important points and questions, which we can respond to. The first question raised relates to the isolated accuracy of probe-based confocal laser endomicroscopy (pCLE) compared with the accuracy of tissue sampling. Previous studies have examined the \u201cisolated\u201d performance of pCLE to diagnose cholangiocarcinoma by consensus and individual review of edited images in a blinded fashion.1 and 2 In this study, we recognized that the treating physician is never unbiased when performing pCLE, having met and examined the patient and reviewed all previous studies. We therefore chose to study the clinical impression of the physician at the time of pCLE and after tissue sampling returned because these are the metrics that drive decision making. Thus, the performance of pCLE alone cannot be determined in this study design because it cannot be isolated from the clinical impression of the treating physician at the time of pCLE, as we have done in prior studies. We apologize for any confusion generated by Table 3 in our article, where the last column shows the performance of ERCP plus tissue sampling of the blinded reviewer (second investigator), who had access only to single images of ERCP, CT, and a brief clinical vignette along with the tissue sampling results. Dr Balderramo asks for the clinical ERCP impression of the second investigator, which we had chosen not to present. This blinded investigator\u2019s impression of ERCP underperformed compared with the primary investigator, with accuracy, sensitivity, and specificity of 69%, 78%, and 53%, respectively. This is not surprising, given the limited data that were transmitted by electronic packages. We did this analysis to estimate routine clinical care without pCLE. Dr Balderramo also asked whether prior stenting of the common bile duct has an impact on the performance of pCLE. This was previously addressed in a separate study that showed slightly better performance in unstented patients.3 For the purposes of this response, we calculated the performance of ERCP plus pCLE in patients with prior stents (accuracy 80%, sensitivity 89%, specificity 71%) and in patients without prior stents (accuracy 85%, sensitivity 88%, specificity 79%) and found a nonsignificant trend toward better accuracy of pCLE in patients who had not been previously stented. Finally, we agree with Dr Balderramo that the accuracy of ERCP with pCLE should be compared with the accuracy of ERCP and tissue sampling. In our study, this could be done only by comparing data obtained from the treating physician who performed pCLE with data from the blinded second investigator, as shown in Table 3 of our article. This difference in accuracy between these 2 groups was not significant (82% for ERCP plus pCLE vs 79% for ERCP plus tissue sampling). We stand by our conclusion that the addition of pCLE to clinical impression and tissue sampling may allow for more accurate assessment of patients with indeterminate biliary strictures

Reply: To PMID 25616752

Reply: To PMID 2561675

Validation of the diagnostic accuracy of probe-based confocal laser endomicroscopy for the characterization of indeterminate biliary strictures: results of a prospective multicenter international study

Characterization of indeterminate biliary strictures remains problematic. Tissue sampling is the criterion standard for confirming malignancy but has low sensitivity. Probe-based confocal laser endomicroscopy (pCLE) showed excellent sensitivity in a registry; however, it has not been validated in a prospective study