Cost-effectiveness of gallbladder histopathology after cholecystectomy for benign disease.

BACKGROUND: The prevalence of incidental gallbladder cancer is low when performing cholecystectomy for benign disease. The performance of routine or selective histological examination of the gallbladder is still a subject for discussion. The aim of this study was to assess the cost-effectiveness of these different approaches. METHODS: Four management strategies were evaluated using decision-analytical modelling: no histology, current selective histology as practised in Sweden, macroscopic selective histology, and routine histology. Healthcare costs and life-years were estimated for a lifetime perspective and combined into incremental cost-effectiveness ratios (ICERs) to assess the additional cost of achieving an additional life-year for each management strategy. RESULTS: In the analysis of the four strategies, current selective histology was ruled out due to a higher ICER compared with macroscopic selective histology, which showed better health outcomes (extended dominance). Comparison of routine histology with macroscopic selective histology resulted in a gain of 12 life-years and an incremental healthcare cost of approximately €1 000 000 in a cohort of 10 000 patients, yielding an estimated ICER of €76 508. When comparing a macroscopic selective strategy with no histological assessment, 50 life-years would be saved and the ICER was estimated to be €20 708 in a cohort of 10 000 patients undergoing cholecystectomy. CONCLUSION: A macroscopic selective strategy appears to be the most cost-effective approach.

Management of incidental gallbladder cancer in a national cohort.

BACKGROUND: Incidental gallbladder cancer is a rare event, and its prognosis is largely affected by the tumour stage and treatment. The aim of this study was to analyse the management, treatment and survival of patients with incidental gallbladder cancer in a national cohort over a decade. METHODS: Patients were identified through the Swedish Registry of Gallstone Surgery (GallRiks). Data were cross-linked to the national registry for liver surgery (SweLiv) and the Cancer Registry. Medical records were collected if registry data were missing. Survival was measured as disease-specific survival. The study was divided into two intervals (2007-2011 and 2012-2016) to evaluate changes over time. RESULTS: In total, 249 patients were identified with incidental gallbladder cancer, of whom 92 (36·9 per cent) underwent re-resection with curative intent. For patients with pT2 and pT3 disease, median disease-specific survival improved after re-resection (12·4 versus 44·1 months for pT2, and 9·7 versus 23·0 months for pT3). Residual disease was present in 53 per cent of patients with pT2 tumours who underwent re-resection; these patients had a median disease-specific survival of 32·2 months, whereas the median was not reached in patients without residual disease. Median survival increased by 11 months for all patients between the early and late periods (P = 0·030). CONCLUSION: Re-resection of pT2 and pT3 incidental gallbladder cancer was associated with improved survival, but survival was impaired when residual disease was present. A higher re-resection rate and more R0 resections in the later time period may have been associated with improved survival.

A Personal Computer Freeware as a Tool for Surgeons to Plan Liver Resections.

BACKGROUND AND AIMS: The increase in liver surgery and the proportion of resections done on the margin to postoperative liver failure make preoperative calculations regarding liver volume important. Earlier studies have shown good correlation between calculations done with ImageJ and specimen weight as well as volume calculations done with more robust systems. The correlation to actual volumes of resected liver tissue has not been investigated, and this was the aim of this study. MATERIAL AND METHODS: A total of 30 patients undergoing well-defined liver resections were included in this study. Volumes calculated with ImageJ were compared to volume measurements done after the retrieval of resected liver tissue. RESULTS AND CONCLUSIONS: A strong correlation between calculated and measured liver volume was found with sample concordance correlation coefficient (ρc) = 0.9950. The knowledge on the nature of liver resections sets liver surgeons in a unique position to be able to accurately predict the volumes to be resected and, therefore, also the volume that will remain after surgery. This becomes increasingly important with the evolvement of methods to extend the boundaries of liver surgery. ImageJ is a reliable tool to preoperatively assess liver volume.

Anterior cruciate ligament injury after more than 20 years: I. Physical activity level and knee function.

Little is known about physical activity level and knee function including jump capacity and fear of movement/reinjury more than 20 years after injury of the anterior cruciate ligament (ACL). Seventy persons with unilateral ACL injury participated (23 ± 2 years post-injury): 33 treated with physiotherapy in combination with surgical reconstruction (ACLR ), and 37 treated with physiotherapy alone (ACLPT ). These were compared with 33 age- and gender-matched controls. Assessment included knee-specific and general physical activity level [Tegner activity scale, International Physical Activity Questionnaire (IPAQ)], knee function [Lysholm score, Knee injury and Osteoarthritis Outcome Score (KOOS)], jump capacity (one-leg hop, vertical jump, side hops), and fear of movement/reinjury [Tampa Scale for Kinesiophobia (TSK)]. Outcomes were related to degree of osteoarthritis (OA). ACL-injured had lower Lysholm, KOOS, and Tegner scores than controls (P < 0.001), while IPAQ score was similar. ACL-injured demonstrated inferior jump capacity in injured compared with noninjured leg (6-25%, P < 0.001-P = 0.010 in the different jumps), while noninjured leg had equal jump capacity as controls. ACL groups scored 33 ± 7 and 32 ± 7 of 68 on TSK. Lower scores on Lysholm and KOOS symptom were seen for persons with moderate-to-high OA than for no-or-low OA, while there were no differences for physical activity and jump capacity. Regardless of treatment, there are still negative knee-related effects of ACL injury more than 20 years later.

The clinical significance of BRAF and NRAS mutations in a clinic-based metastatic melanoma cohort.

BACKGROUND: BRAF and NRAS mutations are frequently found in melanoma tumours, and recently developed BRAF-targeted therapies demonstrate significant clinical benefit. OBJECTIVES: We sought to investigate the clinical significance of BRAF and NRAS mutations in a clinic-based metastatic melanoma cohort. METHODS: In total, 237 tumours, mostly metastatic lesions, from 203 patients were screened for mutations in exon 15 of BRAF and exon 2 of NRAS using Sanger sequencing. BRAF and NRAS mutation status was analysed in relation to clinical and histopathological characteristics, and outcome. RESULTS: Mutation in BRAF and NRAS was present in 43% (88% V600E, 10% V600K) and 30% (48% Q61K, 40% Q61R) of metastatic melanomas, respectively. We found consistent BRAF and NRAS mutation status in all but one of 27 patients with multiple metastases. BRAF mutation was associated with younger age at primary diagnosis (P = 0.02). Among patients with distant metastatic melanoma, patients with BRAF-mutant tumours without BRAF inhibitor treatment had inferior survival compared with patients with BRAF inhibitor treatment [hazard ratio (HR) 2.35, 95% confidence interval (CI) 1.10-5.01, P = 0.03]. We also observed a trend towards better prognosis for patients with wild-type and NRAS-mutant tumours compared with BRAF V600E-mutant tumours (HR 0.64, 95% CI 0.39-1.04, P = 0.07; and HR 0.76, 95% CI 0.48-1.21, P = 0.25, respectively). CONCLUSIONS: We were able to confirm the effect of BRAF inhibitor treatment in a single clinical institution. The results suggest further that BRAF mutation is a weak prognostic factor but a strong predictive factor and that BRAF-mutant melanoma might constitute one or more distinct subtypes of the disease with certain aetiology and clinical outcome.

Barriers to implementing evidence-based practices in addiction treatment programs: comparing staff reports on Motivational Interviewing, Adolescent Community Reinforcement Approach, Assertive Community Treatment, and Cognitive-behavioral Therapy.

PURPOSE: This qualitative study explored barriers to implementing evidence-based practices (EBPs) in community-based addiction treatment organizations (CBOs) by comparing staff descriptions of barriers for four EBPs: Motivational Interviewing (MI), Adolescent Community Reinforcement Approach (A-CRA), Assertive Community Treatment (ACT), and Cognitive-behavioral Therapy (CBT). METHODS: The CBOs received CSAT/SAMHSA funding from 2003 to 2008 to deliver services using EBPs. Phone interview responses from 172 CBO staff directly involved in EBP implementation were analyzed using content analysis, a method for making inferences and developing themes from the systematic review of participant narratives (Berelson, 1952). RESULTS: Staff described different types of barriers to implementing each EBP. For MI, the majority of barriers involved staff resistance or organizational setting. For A-CRA, the majority of barriers involved specific characteristics of the EBP or client resistance. For CBT, the majority of barriers were associated with client resistance, and for ACT, the majority of barriers were associated with resources. DISCUSSION: EBP designers, policy makers who support EBP dissemination and funders should include explicit strategies to address such barriers. Addiction programs proposing to use specific EBPs must consider whether their programs have the organizational capacity and community capacity to meet the demands of the EBP selected.

Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study.

BACKGROUND: This phase II study evaluated the safety and activity of ipilimumab, a fully human mAb that blocks cytotoxic T-lymphocyte antigen-4, in patients with advanced melanoma. PATIENTS AND METHODS: Patients with previously treated, unresectable stage III/stage IV melanoma received 10 mg/kg ipilimumab every 3 weeks for four cycles (induction) followed by maintenance therapy every 3 months. The primary end point was best overall response rate (BORR) using modified World Health Organization (WHO) criteria. We also carried out an exploratory analysis of proposed immune-related response criteria (irRC). RESULTS: BORR was 5.8% with a disease control rate (DCR) of 27% (N = 155). One- and 2-year survival rates (95% confidence interval) were 47.2% (39.5% to 55.1%) and 32.8% (25.4% to 40.5%), respectively, with a median overall survival of 10.2 months (7.6-16.3). Of 43 patients with disease progression by modified WHO criteria, 12 had disease control by irRC (8% of all treated patients), resulting in a total DCR of 35%. Adverse events (AEs) were largely immune related, occurring mainly in the skin and gastrointestinal tract, with 19% grade 3 and 3.2% grade 4. Immune-related AEs were manageable and generally reversible with corticosteroids. CONCLUSION: Ipilimumab demonstrated clinical activity with encouraging long-term survival in a previously treated advanced melanoma population.

Quantitative determination of airborne respirable non-fibrous alpha-silicon carbide by x-ray powder diffractometry.

OBJECTIVES: The purpose of the present investigation was to establish a method for the determination of airborne respirable non-fibrous silicon carbide (SiC). The main application is within the industrial production of SiC. METHODS: Due to the complex airborne aerosol mixture of crystalline compounds in the SiC industry, X-ray powder diffractometry was selected as the most appropriate method. Without any international standard material for the respirable fraction of non-fibrous SiC, pure and suitable products from three SiC plants in Norway were selected. These products have a median particle diameter in the range 4.4-5.1 mum. The method is based on thin sample technique, with the dust deposited on a polycarbonate filter. Absorption correction is done by standard procedures with the use of a silver filter, situated below the polycarbonate filter. RESULTS: The diffraction line used for quantitative determination was selected carefully. This was done to avoid interferences from quartz, cristobalite, and graphite, which all are airborne components present in the atmosphere during the industrial process. The instrumental limit of detection for the method is 12 microg. CONCLUSIONS: This method has been used to determine airborne non-fibrous SiC in a comprehensive ongoing project in the Norwegian SiC industry for further epidemiological studies. The method is fully applicable for compliance work.

Factors associated with HIV/AIDS high-risk behaviours among female injection drug users.

This study examined factors associated with reporting engaging in HIV/AIDS high-risk behaviours at two different time points spaced one year apart for a sample of 185 women who were active injection drug users (IDUs). The high-risk behaviours included injecting drugs in the past six months, having shared needles in the past six months and having engaged in unprotected sexual activity in the past thirty days. Through logistic regression modelling it was identified that living with a spouse at year one was significantly and positively associated with high-risk behaviours at both time points. Being prescribed medications for psychological or emotional problems as well as testing positive for the HIV/AIDS virus were significantly and negatively associated with reporting high-risk behaviours at both time points. These results suggest that spousal relationships may play an important role in HIV/AIDS high-risk behaviours of women drug users. An implication of this study is the need to focus on how spousal relationships and issues such as gender and empowerment should be incorporated into the design and implementation of HIV/AIDS prevention and treatment programs. The benefits of comprehensive mental health diagnosis and treatment services as well as HIV testing in reducing harm to female IDUs and their partners are also discussed.

Accumulation of eosinophils and T-lymphocytes in the lungs after exposure to pinewood dust.

Exposure to wood dust within the woodworking industry has been shown to cause a variety of respiratory disorders. The aim of this study was to investigate the cellular effects in bronchoalveolar lavage (BAL) fluid and peripheral blood from healthy individuals exposed to pinewood dust. Eleven healthy volunteers were exposed to pinewood dust for 1 h in a whole-body exposure chamber. BAL fluid and blood cells were differentially counted and the expression of activation, adhesion and subset markers on alveolar macrophages and T-lymphocytes was determined 2-6 weeks before and 20 h after the exposure. Following pinewood dust exposure, the total BAL fluid cell concentration increased from 81.4 (64.1-97.5) x 10(6) cells x L(-1) (median (interquartile range)) to 195.3 (154.6-341.2) x 10(6) cells x L(-1). The BAL fluid T-lymphocyte concentration increased from 3.8% (3.5-6.5%) to 7.6% (4.9-11.2%), and BAL fluid eosinophil concentration from 0.0% (0.0-0.2%) to 1.8% (0.6-3.5%). Inhalation of pinewood dust leads to the recruitment of inflammatory cells to the airways of healthy individuals. The increase in numbers of eosinophils, T-lymphocytes and mast cells, i.e. cells of crucial importance to airway inflammation, in the lungs may be related to the increased risk of developing respiratory disorders among woodworkers.

Lung accumulations of eosinophil granulocytes after exposure to cornstarch glove powder.

Starch is a main component of wheat flour, which, besides being an occupational allergen can also induce irritative symptoms in the airways. A purified starch product (cornstarch glove powder) was used to investigate whether starch alone could induce airway inflammation. The aim of the study was to investigate a role for starch in wheat flour-induced airway inflammation. Ten healthy individuals were exposed to cornstarch glove powder in a whole-body exposure chamber. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 2-3 weeks before and 1 day after exposure, and the BAL cells were counted differentially. In addition, the expression of activation, adhesion and subset markers on alveolar macrophages and BAL T-cells were investigated using flow cytometry. A three-fold increase in BAL cell concentrations was found, with a selective accumulation and activation of eosinophilic granulocytes, as well as an influx of nonactivated monocytes and polyclonal CD4+ T-cells into the airways. The results show that inhalation of cornstarch glove powder leads to the development of a subclinical inflammation in the airways, with an accumulation of eosinophilic granulocytes. The authors suggest that such exposure may be an interesting model for studying factors contributing to lung accumulations of eosinophil granulocytes in humans.

Racial and ethnic differences in drug treatment entry of injection drug users in Massachusetts.

This article examines patterns of drug treatment entry among 28,000 adult injection drug users (IDUs), with special attention to racial and ethnic differences. The data analyzed originates from a statewide drug-treatment database covering four years. Through the use of logistic regression analysis, the study identified significant population differences between those who used detoxification only, those who used residential treatment and those who used methadone maintenance. Latino IDUs were approximately a third less likely than Caucasian IDUs to enter residential treatment and African American IDUs were half as likely as Caucasian IDUs to enter methadone maintenance treatment. This article discusses specific programmatic and research implications including the need to determine whether differential entry rates are due to access, client awareness, cultural, referral or other factors.

An oligomer from flaxseed composed of secoisolariciresinoldiglucoside and 3-hydroxy-3-methyl glutaric acid residues.

A straight-chain oligomeric structure composed of five secoisolariciresinoldiglucoside (SDG) residues interconnected by four 3-hydroxy-3-methyl glutaric acid (HMGA) residues (molecular weight ca. 4000 Da) was assigned to the main lignan of flaxseed on the basis of nuclear magnetic resonance spectroscopy (NMR).

Pyrone and pyridone compounds in the liquid culture of Physisporinus sanguinolentus.

Chromatographic separation of the liquid culture filtrate of the basidiomycete fungus Physisporinus sanguinolentus has yielded three new compounds viz., 2-methyl-4-pyrone, 2-methyl-5,6-dihydro-4-pyrone and the pyridone form of 4-hydroxy-2-methylpyridine, together with the known triacetic acid lactone, the sesquiterpene dialdehyde merulidial and a derivative of merulidial. Their structures were elucidated by spectroscopic analysis and by comparison to literature data and a synthetic sample. One of the compounds, merulidial, was shown to inhibit the germination of spores and the hyphal growth of the wood-rotting basidiomycete Heterobasidion annosum and the saprophytic mould Cladosporium cucumerinum.

Identification of a sucrose diester of a substituted beta-truxinic acid in oats.

A novel compound, 4,4'-dihydroxy-3,3'-dimethoxy-beta-truxinic acid esterified to sucrose through the fructosyl 3-and 6-carbons (1), was isolated from oat grains (Avena sativa L.). Its structure was determined by a combination of mass spectrometry and 1-D and 2-D NMR. The amounts of 1 in groats of six different oat cultivars ranged from 101 to 150 microg g(-1) (dry wt). None was detected in the hulls. The free diacid, 4,4'-dihydroxy-3,3'-dimethoxy-beta-truxinic acid (2), could not be detected in groats nor in hulls.

HPLC method for analysis of secoisolariciresinol diglucoside in flaxseeds.

A method was developed for the analysis of secoisolariciresinol diglucoside (SDG) in flaxseeds. The analytical method involves extraction of defatted flaxseed flour with dioxane/ethanol, aqueous base-hydrolysis, solid-phase purification of an SDG-containing fraction, and quantitative analysis by high-performance liquid chromatography (HPLC). Pure SDG was isolated from flaxseed using different column chromatographic methods and used, as external standard, for the calibration of the method and for quantification. The method was then applied to study the variation in SDG content in flaxseeds from 14 cultivars grown in Sweden and 15 cultivars grown in Denmark. The SDG content varied between 11.7 and 24.1 mg/g in defatted flaxseed flour and between 6.1 and 13.3 mg/g in whole flaxseeds.

Streptomyces halstedii K122 produces the antifungal compounds bafilomycin B1 and C1.

Streptomyces halstedii K122 was previously found to produce antifungal compounds on solid substrates that inhibit radial growth of fungi among Ascomycetes, Basidiomycetes, Deuteromycetes, Oomycetes, and Zygomycetes, and strongly affected hyphal branching and morphology. During growth of S. halstedii K122 in submerged culture, no antifungal activity could be detected. However, cultivation of S. halstedii in thin (1 mm) liquid substrate layers in large surface-area tissue culture flasks caused intense growth and sporulation of S. halstedii K122, and the biologically active compounds could be extracted from the mycelium with methanol. Antifungal compounds were purified using C18 solid phase extraction and silica gel column chromatography, and identified as bafilomycins B1 and C1, using 2D NMR and FAB MS. Production of bafilomycins, which are specific inhibitors of vacuolar ATPases, has not been reported from S. halstedii previously. Minimum inhibitory concentrations (MIC) of bafilomycins B1 and C1, amphotericin B, and nikkomycin Z were determined at pH 5.5 and 7.0 for the target fungi Aspergillus fumigatus, Mucor hiemalis, Penicillium roqueforti, and Paecilomyces variotii. Penicillium roqueforti was the most sensitive species to all the compounds investigated. The MIC values for amphotericin B were 0.5-4 micrograms.mL-1 for the fungi tested, and pH did not affect the toxicity. The MIC values for nikkomycin Z ranged from < 0.5 microgram.mL-1 for Mucor hiemalis to > 500 micrograms.mL-1 for Aspergillus fumigatus, and pH had no influence on toxicity. Bafilomycins B1 and C1 were equally active against the fungal species tested, with MIC values in the range of < 0.5-64 micrograms.mL-1. All fungi were more sensitive to both bafilomycin B1 and C1 at pH 7.0 than at pH 5.5.

African-American injection drug users: association between pre-treatment services and entry into and completion of detoxification.

Research suggests that African-American injection drug users, when compared with other ethnic and racial groups of injection drug users, are more likely to have no history of substance abuse treatment. The project evaluated was designed to attract African-American injection drug users to treatment by providing comprehensive pre-treatment services including street outreach, drop-in center services, case management, and motivational counseling. The overall program goal was to facilitate clients' acceptance of referral to treatment and readiness to utilize treatment. The evaluation described here examines whether, for this African-American population of hard-core drug users, utilization of pre-treatment services improved the intermediary treatment outcomes of entry into and completion of detoxification. Findings showed that high utilization of drop-in center services increased the frequency of entrance into detoxification programs. Entrance into detoxification has been shown to be significantly correlated with (a) entrance into further treatment, (b) reduced HIV/AIDS risk, and (c) successful linkage with health care and social services. Contrary to expectations, high utilization of pre-treatment services was not significantly correlated to increased completion of detoxification.

A new whole-body exposure chamber for human skin and lung challenge experiments--the generation of wheat flour aerosols.

A new whole-body exposure chamber for human skin and lung challenge offers possibilities for experimental exposure challenges carried out in clinical practice, for exposure of patients, in research and for investigations of the effects of exposure on the skin and in the respiratory tract. The chamber system can be used for both aerosols and gases. Dynamically controlled, the chamber is relatively easy to operate and to clean. Air exchange rates can be varied between 6-12/h. Initial studies with wheat flour have been carried out. The homogeneity and stability of the wheat flour aerosol concentration (the spatial and the temporal variation) inside the chamber can be kept at acceptable levels.