Localizing Molecules in Plant Cell Walls Using Fluorescence Microscopy.

Autofluorescence of plant tissues can be used as a label-free method to detect a range of phenolic-based cell wall components including lignin, suberin, and ferulate using widefield or confocal fluorescence microscopy. Likewise, fluorescently labeled antibodies can be used to localize specific carbohydrate molecules including arabinoxylan, ß-1,4 galactan, glucomannan, glucuronoxylan, pectins, and xyloglucan. When combined, these two methods allow detailed study of topochemistry in different plant tissues for phenotyping of mutant varieties and plant biology studies. This article describes the protocols for fluorescent detection and imaging of molecules in plant cell walls using autofluorescence and immunofluorescence.

Evaluation of repeat cytoreductive surgery and heated intraperitoneal chemotherapy for patients with recurrent peritoneal carcinomatosis from appendiceal and colorectal cancers: a multicentre Canadian study

Background: Peritoneal recurrences after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for appendiceal and colorectal cancers are frequent. This study aimed to evaluate the safety, technical feasibility and perioperative and long-term outcomes of repeat CRS/HIPEC in patients with recurrent peritoneal carcinomatosis of colorectal and appendiceal origin. Methods: Data were collected from patients treated from 2000 to 2016 for recurrent peritoneal carcinomatosis from appendiceal or colorectal cancer with CRS/HIPEC at 2 specialist centres. Data on demographics, procedure details, morbidity and survival were recorded. Analyses compared the iterations of CRS/HIPEC to assess the safety and effectiveness of repeat surgery. Results: Of all patients who underwent CRS/HIPEC in the 2 centres, 37 patients underwent a repeat procedure. Operative time was similar for the first and second surgeries (412.1 v. 412.5 min, p = 0.74) but patients had a significantly lower peritoneal carcinoma index score with the second surgery (21.8 in the first iteration v. 9.53 in the second iteration, p < 0.001) and significantly less blood loss (1762 mL in the first iteration v. 790 mL in the second iteration, p = 0.001). There was a nonsignificant decrease in grade III­IV complications and there was no 30-day mortality associated with repeat procedures. For patients with colorectal cancer, median disease-free survival was 9.6 months and median overall survival was 40 months. For patients with appendiceal cancer, median disease-free survival was 15 months and overall survival was 64.4 months. Conclusion: Repeat CRS/HIPEC procedures for recurrent appendiceal and colorectal peritoneal carcinomatosis are safe in well-selected patients, without increased morbidity or mortality, and they are associated with significant long-term survival, particularly for patients with appendiceal cancers. These results support the use of repeat CRS/HIPEC in these patients.

Contexte: Les récurrences péritonéales après une chirurgie cytoréductrice (CCR) et une chimiothérapie hyperthermique intrapéritonéale (CHIP) pour les cancers de l'appendice et colorectaux sont fréquentes. Cette étude visait à évaluer l'innocuité, la faisabilité technique et les résultats périopératoires et à long terme d'une reprise de CCR/CHIP chez les patients qui présentent une récurrence de carcinomatose péritonéale ayant son origine au niveau colorectal ou de l'appendice. Méthodes: Des données ont été recueillies sur des patients traités entre 2000 et 2016 pour une récurrence de carcinomatose péritonéale ayant son origine au niveau colorectal ou de l'appendice par CCR/CHIP dans 2 centres spécialisés. On a tenu compte des données démographiques, des détails des interventions, ainsi que de la morbidité et de la survie. Des analyses ont permis de comparer les premières et deuxièmes CCR/CHIP pour évaluer l'innocuité et l'efficacité des chirurgies répétées. Résultats: De tous les patients soumis à des CCR/CHIP dans les 2 centres, 37 ont subi l'intervention de nouveau. Le temps opératoire a été similaire pour les premières et les deuxièmes chirurgies (412,1 c. 412,5 min, p = 0,74), mais les patients présentaient un score de carcinomatose péritonéale beaucoup plus bas lors de la deuxième chirurgie (21,8 pour la première intervention c. 9,53 pour la seconde, p < 0,001) et des pertes sanguines significativement moindres (1762 mL pour la première intervention c. 790 mL pour la seconde, p = 0,001). On a noté une diminution non significative des complications de grades III­IV et on n'a déploré aucune mortalité à 30 jours en lien avec la reprise de l'intervention. Pour les patients atteints d'un cancer colorectal, la survie médiane sans maladie a été de 9,6 mois et la survie médiane globale a été de 40 mois. Pour les patients atteints d'un cancer de l'appendice, la survie médiane sans maladie a été de 15 mois et la survie médiane globale a été de 64,4 mois. Conclusion: La reprise des CCR/CHIP pour les récurrences de carcinomatose péritonéale ayant leur origine au niveau colorectal ou de l'appendice est sécuritaire chez les patients soigneusement sélectionnés, sans accroissement de la morbidité ou de la mortalité, et elles sont associées à une survie à long terme significative, particulièrement chez les patients ayant un cancer de l'appendice. Ces résultats appuient la reprise des CCR/CHIP chez ces patients.

Epidural analgesia? A prospective analysis of perioperative coagulation in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is beneficial in peritoneal carcinomatosis. Epidurals provide excellent pain relief for laparotomies. Coagulopathy (platelet count <100 × 109/L, INR>1.5 or PTT >45) occurs with CRS and HIPEC, increasing risk for bleeding complications with epidurals. This prospective study characterizes clot kinetics with thromboelastography (TEG) to determine suitability for epidural analgesia. METHODS: After Research Ethics approval, thirty consented patients had blood collected. Primary data collected included TEG and conventional coagulation measures (platelets, PTT and INR). Secondary data collected included demographics, disease, surgical, intraoperative factors and complications from epidural placement. RESULTS: Of 30 patients analyzed, two had incomplete data. Four developed abnormal coagulation between the second and fifth post-operative day. For all patients, TEG values remained normal. Postoperative INR was elevated until day 3 (all INR < 1.5). 17 patients received epidural analgesia, 3 demonstrated abnormal conventional coagulopathic criteria despite normal TEG. CONCLUSIONS: In this study CRS and HIPEC do not contribute to the conventional definition of clinical coagulopathy. Clot kinetics indicate that epidural catheters may be recommended for post-operative analgesia.

Dental Homes for Children With Autism: A Longitudinal Analysis of Iowa Medicaid's I-Smile Program.

INTRODUCTION: Medicaid-enrolled children with autism spectrum disorder (ASD) encounter significant barriers to dental care. Iowa's I-Smile Program was implemented in 2006 to improve dental use for all children in Medicaid. This study compared dental home and preventive dental utilization rates for Medicaid-enrolled children by ASD status and within three time periods (pre-implementation, initial implementation, maturation) and determined I-Smile's longitudinal influence on ASD-related dental use disparities. METHODS: Data from 2002-2011 were analyzed for newly Medicaid-enrolled children aged 3-17 years (N=30,059); identified each child's ASD status; and assessed whether the child had a dental home or utilized preventive dental care. Log-linear regression models were used to generate rate ratios. Analyses were conducted in 2015. RESULTS: In 2003-2011, 9.8% of children with ASD had dental homes compared with 8% of children without ASD; 36.3% of children with ASD utilized preventive care compared to 45.7% of children without ASD. There were no significant differences in dental home rates by ASD status during pre-implementation, initial implementation, or maturation. There were no significant differences in preventive dental utilization by ASD status during pre-implementation or initial implementation, but children with ASD were significantly less likely to utilize preventive care during maturation (rate ratio=0.79, p<0.001). Longitudinal trends in dental home and preventive dental utilization rates were not significant (p=0.54 and p=0.71, respectively). CONCLUSIONS: Among newly Medicaid-enrolled children in Iowa's I-Smile Program, those with ASDs were not less likely than those without ASD to have dental homes but were significantly less likely to utilize preventive dental care.

Hyperthermic intraperitoneal chemotherapy + early postoperative intraperitoneal chemotherapy versus hyperthermic intraperitoneal chemotherapy alone: assessment of survival outcomes for colorectal and high-grade appendiceal peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival for colorectal and high-grade appendiceal carcinomatosis. We compared the overall and recurrence-free survival (OS and RFS) of patients treated with HIPEC with mitomycin c and early postoperative intraperitoneal chemotherapy (EPIC) with fluorouracil versus HIPEC alone using oxaliplatin and simultaneous IV infusion of fluorouracil. METHODS: Ninety-three patients with colorectal or high-grade appendiceal carcinomatosis were treated with CRS and HIPEC + EPIC or HIPEC alone. OS and RFS were analyzed using Kaplan-Meier curves and log-rank testing. RESULTS: Survival did not differ between HIPEC regimens. The 3-year OS and RFS rates were 50% and 21% for HIPEC + EPIC and 46% and 6% for HIPEC alone (P = .72 and P = .89, respectively). HIPEC + EPIC patients experienced more grade III/IV complications (43.2% vs 19.6%, P = .01). CONCLUSIONS: There was no difference in OS and RFS between colorectal and high-grade appendiceal adenocarcinoma patients treated with CRS and HIPEC + EPIC versus HIPEC alone. However, HIPEC + EPIC patients suffered greater morbidity, making HIPEC alone the preferable regimen.

Cytoreduction and heated intraperitoneal chemotherapy for colorectal cancer: are we excluding patients who may benefit?

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are increasingly used to treat peritoneal carcinomatosis from colorectal cancer. It is still relatively unknown which poor prognostic factors to avoid in order to optimize patient selection for CRS + HIPEC. METHODS: Between February 2003 and October 2011, 68 consecutive colorectal cancer patients who underwent CRS + HIPEC with a complete cytoreduction were identified from a prospective database. Survival analysis was performed using the Kaplan-Meier method, with log rank testing of differences between groups. Multivariate analysis was conducted using Cox proportional hazard regression. RESULTS: Median follow-up was 30.3 (range, 2-88) months amongst survivors. Patients with a peritoneal cancer index (PCI) of 10 or less showed improved survival over those with a PCI of 11 or higher (P = 0.03). No difference in survival was seen for the other potentially poor prognostic variables including lymph node status, synchronous peritoneal disease, peri-operative systemic chemotherapy, and rectal cancer primary. CONCLUSIONS: A low PCI was associated with improved survival. Complete CRS + HIPEC appears to result in similar survival outcomes regardless of delivery of peri-operative systemic chemotherapy. Rectal origin, lymph node status, and synchronous peritoneal disease should not be used as an absolute exclusion criteria for CRS + HIPEC based on current data.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: an emerging treatment option for advanced goblet cell tumors of the appendix.

BACKGROUND: The debate remains whether appendiceal goblet cell cancers behave as classical carcinoid or adenocarcinoma. Treatment options are unclear and reports of outcomes are scarce. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) is considered optimal treatment for peritoneal involvement of other epithelial appendiceal tumors. METHODS: Prospective cohorts of patients treated for advanced appendiceal tumors from three peritoneal malignancy centres were collected (1994-2011). All patients underwent complete CRS+HIPEC, when possible, or tumor debulking. Demographic and outcome data for patients with goblet cell cancers were compared to patients with low- or high-grade epithelial appendiceal tumors treated during the same time period. RESULTS: Details on 45 goblet cell cancer patients were compared to 708 patients with epithelial appendix lesions. In the goblet cell group, 57.8 % were female, median age was 53 years, median peritoneal cancer index (PCI) was 24, and CRS+HIPEC was achieved in 71.1 %. These details were similar in patients with low- or high-grade epithelial tumors. Lymph nodes were involved in 52 % of goblet cell patients, similar to rates in high-grade cancers, but significantly higher than in low-grade lesions (6.4 %; p < 0.001). At 3 years, overall survival (OS) was 63.4 % for goblet cell patients, intermediate between that for high-grade (40.4-52.2 %) and low-grade (80.6 %) tumors. On multivariate analysis, tumor histology, PCI, and achievement of CRS+HIPEC were independently associated with OS. CONCLUSIONS: This data supports the concept that appendiceal goblet cell cancers behave more as high-grade adenocarcinomas than as low-grade lesions. These patients have reasonable long-term survival when treated using CRS+HIPEC, and this strategy should be considered.

The inverse association of cancer and Alzheimer's: a bioenergetic mechanism.

The sporadic forms of cancer and Alzheimer's disease (AD) are both age-related metabolic disorders. However, the molecular mechanisms underlying the two diseases are distinct: cancer is described by essentially limitless replicative potential, whereas neuronal death is a key feature of AD. Studies of the origin of both diseases indicate that their sporadic forms are the result of metabolic dysregulation, and a compensatory increase in energy transduction that is inversely related. In cancer, the compensatory metabolic effect is the upregulation of glycolysis-the Warburg effect; in AD, a bioenergetic model based on the interaction between astrocytes and neurons indicates that the compensatory metabolic alteration is the upregulation of oxidative phosphorylation-an inverse Warburg effect. These two modes of metabolic alteration could contribute to an inverse relation between the incidence of the two diseases. We invoke this bioenergetic mechanism to furnish a molecular basis for an epidemiological observation, namely the incidence of sporadic forms of cancer and AD is inversely related. We furthermore exploit the molecular mechanisms underlying the diseases to propose common therapeutic strategies for cancer and AD based on metabolic intervention.

Impact of the treatment-free interval on health-related quality of life in patients with multiple myeloma: a UK cross-sectional survey.

BACKGROUND: While the impact of various treatments on myeloma patients' health-related quality of life (HRQL) has been reported, the impact of a treatment-free interval (TFI) is currently unclear. The aims of this study were to assess if (1) a TFI is associated with a better HRQL vs. other treatment phases and (2) the length of the TFI influences HRQL. METHODS: A cross-sectional postal survey was conducted in the UK. The survey was sent to 605 multiple myeloma patients via the charity Myeloma UK and asked patients to rate their HRQL using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), EORTC QLQ-MY20 and the EQ-5D. The results were analysed using ordinary least squares regression. RESULTS: Surveys of 402 (67 %) were returned; 370 (61 %) were considered eligible for analysis. Results demonstrated that being in a first TFI relative to other treatment phases and experiencing a longer TFI were significantly associated with better HRQL as assessed by various domains of the QLQ-C30, MY20 and EQ-5D. CONCLUSION: Patients enjoy better HRQL when in their first TFI, and the length of the TFI also positively impacts on HRQL This information may be important for patients and their physicians making treatment decisions and has implications for treatment protocols incorporating extended therapy.

HIPEC + EPIC versus HIPEC-alone: differences in major complications following cytoreduction surgery for peritoneal malignancy.

INTRODUCTION: Peritoneal metastases (PM) can be treated with cytoreduction surgery (CRS) with intraoperative heated intraperitoneal chemotherapy (HIPEC) plus or minus early postoperative intraperitoneal chemotherapy (EPIC). HIPEC + EPIC may be associated with more complications than HIPEC alone. METHODS: A prospective database of consecutive patients undergoing CRS + HIPEC ± EPIC at the University of Calgary between February 2000 and May 2011 was reviewed. Patient, tumor, and perioperative variables included peritoneal cancer index (PCI), completeness of cytoreduction (CCR) score, HIPEC ± EPIC type, and grade III/IV complications. RESULTS: 198 patients had a CCR score of 0/1 and received: (1) HIPEC mitomycin C + EPIC 5-fluorouracil for 5 days (n = 85; February 2000-January 2008); or (2) HIPEC oxaliplatin with IV 5-fluorouracil + no EPIC (n = 113; February 2008-May 2011). Clinicodemographics were similar except PCI was higher in the HIPEC-alone group (mean PCI 22 vs. 17; P = 0.02). The rate of grade III/IV complications was higher in the HIPEC + EPIC group (44.7% vs. 31.0%; P = 0.05). On multivariate logistic regression only HIPEC + EPIC and PCI > 26 were associated with an increased rate of complications. CONCLUSION: In patients with PM, the use of EPIC, in combination with CRS and HIPEC, is associated with an increased rate of complications. Surgeons should consider using HIPEC only (without EPIC).

Prevalence of sexually acquired antiretroviral drug resistance in a community sample of HIV-positive men who have sex with men in New York City.

To examine antiretroviral (ARV) drug resistance, we recruited a community sample (n=347) of sexually active HIV-positive men who have sex with men (MSM) in New York City, each of whom completed a structured interview and donated a blood sample for HIV genotyping. Participants reported high levels of sexual activity, with 94.6% reporting at least one sexual contact in the past month, and an average of 3.13 partners during this time. Anal intercourse was common, with 70.7% reporting at least one act of insertive anal intercourse (21% of whom reported ejaculating inside their partner without a condom) and 62.1% reporting at least one act of receptive anal intercourse during this time (22.6% of whom received ejaculate without a condom). Seventeen percent reported having sex with a woman in the past year. Although 17.4% of participants reported having ever injected drugs, no association was found between injection and antiretroviral resistance. Average HIV diagnosis was 12.1 years prior to the interview, and 92.1% had taken ARV medication. Sexually transmitted infections (STIs) were widely reported, with 78% having been diagnosed with an STI since being diagnosed with HIV. A genotype was obtained for 188 (54.7%) of the samples and 44.7% revealed mutations conferring resistance to at least one ARV. Resistance to at least one ARV within a given class of medication was most common for nucleoside reverse transcriptase inhibitors (30.3%) and non-nucleoside reverse transcriptase inhibitors (27.7%) and least common for protease inhibitors (18.1%). The combination of high prevalence of antiretroviral resistance and risky sexual practices makes transmission between sex partners a likely mode of acquisition.

Colorectal cancer screening among first-degree relatives of colorectal cancer patients: benefits and barriers.

BACKGROUND: Individuals with a first-degree family history of colorectal cancer (CRC) are at increased risk of CRC. Study objectives were: (1) to estimate the proportion of first-degree relatives (FDR) of CRC patients being screened for CRC and (2) to identify predictors of screened behavior. METHODS: A questionnaire was mailed to 640 stage I-III CRC patients from a population-based registry to identify FDR. A survey was sent to 747 FDR, aged 40 or older, to assess CRC screening, knowledge, demographics, access, benefits, and barriers of CRC screening. Factor analysis was used to detect underlying constructs. Predictors of screening were explored by multivariate analysis (MVA). RESULTS: There was a 54% and 51% response for patients and FDR, respectively. Among FDR, 86% were born in Canada, 94% spoke English, 93.5% had a high school education, 73% were married, and 55% were employed. The age distribution was: 40-44 years (19.7%), 45-49 (19.1%), 50-54 (16%), 55-59 (15.2%), 60-64 (9.8%), and >65 (18%). Seventy percent had undergone CRC screening with 60% adherent to current guidelines. Of those screened, 33.7% had fecal occult blood testing, 19.4% had barium enema, 10.7% had sigmoidoscopy, and 58.7% had colonoscopy. Five constructs influencing CRC screening include: salience and coherence, perceived susceptibility, response efficacy, social influence, and cancer worries. MVA determined age >50 years as the most important predictor of screening. CONCLUSION: In this survey, 70% of FDR of CRC patients had undergone screening; age was the most important predictor. Understanding underlying constructs influencing screening behavior may improve uptake of CRC screening in this population.

Phase II study of regional treatment for peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy is becoming an accepted treatment of carcinomatosis. METHODS: Between February 2000 and January 2008, there were 101 consecutive patients with carcinomatosis who were treated with cytoreductive surgery + hyperthermic intraperitoneal chemotherapy and early postoperative intraperitoneal chemotherapy. Patient and tumor characteristics, surgical details, complications, disease-free survival (DFS), and overall survival (OS) were recorded prospectively. RESULTS: The majority (82%) of patients, median age 49 years (range, 18-77 y), had complete macroscopic cytoreduction (completeness of cytoreduction score, 0) despite a generally extensive tumor burden. Perioperative mortality and grade III/IV morbidity rates were 4% and 39%, respectively. Preliminary median DFS and OS have not been defined for appendix tumors at a median follow-up period of 16 months (range, 1-86 mo). Median DFS and OS for colonic tumors are 8 months and 26 months, respectively, with a median follow-up period of 12 months (range, 1-48 mo). CONCLUSIONS: Combined regional treatment is feasible and holds significant promise for the treatment of peritoneal carcinomatosis.

A prospective evaluation of venous thromboembolism in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: We sought to investigate the incidence of perioperative venous thromboembolism (VTE)--pulmonary embolism, superior mesenteris vein thrombosis and deep vein thrombosis--in patients with peritoneal carcinomatosis after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. METHODS: We performed cytoreductive surgery and hyperthermic intraperitoneal chemotherapy on 60 consecutive patients with a mean age of 52 (range 24-76) years. We reviewed a prospective database recording complications and patient, tumour and surgical characteristics to determine the incidence of VTE. We reviewed hospital charts of patients with VTE to obtain clinical information including vital signs, risk factors, presence of comorbid conditions, VTE prophylaxis and subjective clinical symptoms. RESULTS: A total of 6 of 60 patients (10%) who had cytoreductive surgery and hyperthermic intraperitoneal chemotherapy experienced VTE. All patients with VTE had extensive peritoneal disease and long durations of surgery: the median duration was 431 (range 330-683) minutes. Tachycardia (mean 104 beats/min) was the only consistent abnormal vital sign recorded, with only 33% of patients experiencing clinical symptoms. CONCLUSION: This prospective study demonstrates a high rate of VTE in this patient population. Unfortunately, clinical signs and symptoms are a poor predictor of VTE. Therefore, routine screening of this specific population at high risk for VTE is warranted.

Determination of phytoestrogens in dietary supplements by LC-MS/MS.

Labelling data quantifying the exact content of individual phytoestrogen analytes in dietary supplements are generally poor. As these products are commonly used in the management of menopause symptoms, any clinical benefits would be dependent on the exact dosage of isoflavones received. Well-established extraction procedures and updated isotope dilution mass spectrometry liquid chromatography coupled with tandem mass spectrometry detection (LC-MS/MS) have been used to accurately quantify the concentrations of ten common isoflavones in 35 dietary supplement samples on sale in the UK, Canada and Italy. Concentration-specific ionization suppression is described for biochanin A and formononetin. All supplements contained phytoestrogens. The soya isoflavones (genistein, daidzein, glycitein) were present in all products and the majority also contained the red clover isoflavones (biochanin A, formononetin) and some the Kudzu isoflavones (daidzein, puerarin). The content of total isoflavones per dose ranged from <1 to 53 mg. Trace amounts of coumestrol were found in six products. Other less common analytes, the prenylnaringenins (6-prenylnaringenin, 8-prenylnaringenin, 6,8-diprenylnaringenin) were not found in any of the products. Only 14 of 35 supplements were found to deliver more than or equal to 40 mg day(-1) of aglycone isoflavones, a consensus dose value recognized as delivering therapeutic benefit. Eleven did not match label claims. Six delivered less than 10 mg day (-1) of isoflavones. There has been little improvement in the overall quality of industry labelling in the five years since this was last investigated. Consequently, the public, retailers and healthcare professionals should consider using standardized isoflavone supplements, which are supported by analytical measurements.

A cost-minimisation analysis comparing moxifloxacin with levofloxacin plus ceftriaxone for the treatment of patients with community-acquired pneumonia in Germany: results from the MOTIV trial.

OBJECTIVE: This study presents a cost-minimisation analysis of moxifloxacin compared to combination treatment with levofloxacin and ceftriaxone in patients hospitalised with community-acquired pneumonia (CAP) in Germany. RESEARCH DESIGN AND METHODS: In the MOTIV study, 738 adult patients with CAP requiring hospitalisation and initial parenteral antibiotic therapy were randomised to sequential IV/oral therapy with either moxifloxacin (n = 368), or levofloxacin and ceftriaxone (n = 365). The primary effectiveness endpoint was the proportion of patients demonstrating clinical improvement 5-7 days after the completion of study treatment. Subgroup analysis considered patients with severe CAP according to pneumonia severity index (PSI) risk class IV and V, microbiologically proven infection, a history of chronic obstructive pulmonary disease, and a history of cardiovascular disease. The analysis included the cost of study medication, hospital stay, readmission and inpatient procedures and diagnostics. Event frequency in the study was multiplied by German unit costs to estimate per-patient expenditure. The analysis was conducted from a hospital perspective. Sensitivity analysis investigated the effect of costing from an insurer perspective. RESULTS: No significant difference was found in the percentage of successfully treated patients. Average per patient cost was euro 2190 for the moxifloxacin group, and euro 2619 for the levofloxacin + ceftriaxone group (difference -euro 430, 95% CI: -euro 138, -euro 740; p < 0.05). Variability in total costs was wide, with some patients accruing up to euro 18,000. Medication cost was significantly lower with moxifloxacin than levofloxacin + ceftriaxone (-euro 470, 95% CI: -euro 522, -euro 421), and accounted for between 15 and 30% of total costs. CONCLUSIONS: In this analysis of patients hospitalised with CAP in Germany, treatment with moxifloxacin was significantly less costly than treatment with levofloxacin and ceftriaxone.

Comparison of biochemical effects of statins and fish oil in brain: the battle of the titans.

Neural membranes are composed of glycerophospholipids, sphingolipids, cholesterol and proteins. The distribution of these lipids within the neural membrane is not random but organized. Neural membranes contain lipid rafts or microdomains that are enriched in sphingolipids and cholesterol. These rafts act as platforms for the generation of glycerophospholipid-, sphingolipid-, and cholesterol-derived second messengers, lipid mediators that are necessary for normal cellular function. Glycerophospholipid-derived lipid mediators include eicosanoids, docosanoids, lipoxins, and platelet-activating factor. Sphingolipid-derived lipid mediators include ceramides, ceramide 1-phosphates, and sphingosine 1-phosphate. Cholesterol-derived lipid mediators include 24-hydroxycholesterol, 25-hydroxycholesterol, and 7-ketocholesterol. Abnormal signal transduction processes and enhanced production of lipid mediators cause oxidative stress and inflammation. These processes are closely associated with the pathogenesis of acute neural trauma (stroke, spinal cord injury, and head injury) and neurodegenerative diseases such as Alzheimer disease. Statins, the HMG-CoA reductase inhibitors, are effective lipid lowering agents that significantly reduce risk for cardiovascular and cerebrovascular diseases. Beneficial effects of statins in neurological diseases are due to their anti-excitotoxic, antioxidant, and anti-inflammatory properties. Fish oil omega-3 fatty acids, eicosapentaenoic acid and docosahexaenoic acid, have similar anti-excitotoxic, antioxidant and anti-inflammatory effects in brain tissue. Thus the lipid mediators, resolvins, protectins, and neuroprotectins, derived from eicosapentaenoic acid and docosahexaenoic acid retard neuroinflammation, oxidative stress, and apoptotic cell death in brain tissue. Like statins, ingredients of fish oil inhibit generation of beta-amyloid and provide protection from oxidative stress and inflammatory processes. Collective evidence suggests that antioxidant, anti-inflammatory, and anti-apoptotic properties of statins and fish oil contribute to the clinical efficacy of treating neurological disorders with statins and fish oil. We speculate that there is an overlap between neurochemical events associated with neural cell injury in stroke and neurodegenerative diseases. This commentary compares the neurochemical effects of statins with those of fish oil.

An evidence-based approach to the treatment of thyroid lymphoma.

BACKGROUND: Primary thyroid lymphoma is a rare tumor that makes up 1-5% of thyroid malignancies and less than 2% of extranodal lymphomas. The treatment and prognosis of thyroid lymphomas can be divided into two distinct clinicopathologic entities: pure mucosa-associated lymphoid tissue (MALT) lymphomas and diffuse large B-cell or mixed subtypes. METHODS: An evidence-based review was performed to determine the role of fine-needle aspiration (FNA) biopsy and adjuncts as the first diagnostic test for thyroid lymphoma, the role of open surgical biopsy, the role of palliative surgery as well as the best treatment (combined chemoradiation versus single modality surgery or radiation) for thyroid lymphoma. The ideal treatment of thyroid lymphoma was further assessed for both diffuse B-cell and MALT histologic subtypes. RESULTS: Although an evidence-based review was challenging primarily due to a lack of high-level evidence, several recommendations are possible and presented regarding the optimal diagnostic methods and treatment of thyroid lymphoma. FNA and adjuncts are recommended as the first test to diagnose thyroid lymphoma, but open surgical biopsy may still be required in many cases. Combined chemoradiation therapy is recommended for all diffuse B-cell or mixed lymphomas. Single modality therapy with surgery or radiation alone may be considered for early-stage (IE) intrathyroidal MALT lymphomas. No recommendations could be made regarding the role of palliative surgery. CONCLUSION: Evidence-based recommendations can be applied to the individual patient with thyroid lymphoma with the involvement of an experienced multidisciplinary team consisting of an endocrine/oncology surgeon, radiation oncologist, and medical oncologist.

Daily pain coping among patients with chronic temporomandibular disorder pain: an electronic diary study.

AIMS: To describe patients' daily coping with the pain of chronic temporomandibular disorders (TMD), the conservative treatment received, and the self-care strategies used, and to examine the relationships between these strategies and daily pain intensity, activity interference, and jaw use limitations. METHODS: TMD clinic patients (n = 137, 88% women) completed electronic diary measures of pain, interference, jaw use limitations, and use of 20 strategies 3 times daily for 2 weeks. RESULTS: Reliability and validity were demonstrated for 4 scales of related coping items: cognitive coping, relaxation, activity reduction, and emotional support. Average scores were higher on the relaxation and activity reduction scales than on the cognitive coping and emotional support scales. Among the coping items not included in the scales, "did something to try to reduce pain" (direct action) was endorsed most frequently (reported in a median of 74% of interviews). Heat, cold, and seeking spiritual support were used least (< or = 5%). At times of increased pain, patients were more likely to use almost all types of strategies. Pain intensity was associated strongly with concurrent activity interference and jaw use limitations. When the design controlled for pain intensity, activity reduction and seeking emotional support were associated positively within-subjects with interference and jaw use limitations. CONCLUSION: TMD clinic patients use a variety of treatment, self-care, and coping strategies to contend with daily pain. Inquiring about a broad range of strategies might help clinicians better understand how individual patients approach pain management. Research is needed to examine whether decreasing activity reduction and emotional support coping results in improved outcomes.