Long-Term Safety Experience with Telotristat Ethyl Across Five Clinical Studies in Patients with Carcinoid Syndrome.

BACKGROUND: Patients with neuroendocrine tumors (NETs) and carcinoid syndrome experience considerable morbidity and mortality; carcinoid syndrome may be associated with shorter survival. Carcinoid syndrome is linked to tumoral secretion of serotonin and other bioactive substances. The subsequent debilitating diarrhea and urgency to defecate pose significant health risks. In previous studies, telotristat ethyl, a tryptophan hydroxylase inhibitor, was effective and well tolerated in treating carcinoid syndrome diarrhea. We present pooled safety data from five clinical trials with telotristat ethyl in patients with carcinoid syndrome. SUBJECTS, MATERIALS, AND METHODS: Adverse events reported during telotristat ethyl treatment were pooled from two phase II and three phase III clinical trials in 239 patients with carcinoid syndrome. Long-term safety of telotristat ethyl and causes of hospitalization and death were reviewed; overall survival was estimated. RESULTS: Mean (median; range) duration of exposure and follow-up was 1.3 years (1.1 years; 1 week to 5.7 years), with 309 total patient-years of exposure. Leading causes of hospitalization were gastrointestinal disorders or were related to the underlying tumor and related treatment. Survival estimates at 1, 2, and 3 years were 93%, 88%, and 77%. Nearly all deaths were due to progression or complication of the underlying disease; none were attributable to telotristat ethyl. There was one death in year 4. CONCLUSION: Based on long-term safety data, telotristat ethyl is well tolerated and has a favorable long-term safety profile in patients with carcinoid syndrome. IMPLICATIONS FOR PRACTICE: Carcinoid syndrome can cause persistent diarrhea, even in patients treated with somatostatin analogs. Across five clinical trials in patients with carcinoid syndrome, telotristat ethyl has been well tolerated and efficacious, providing clinicians with a new approach to help control carcinoid syndrome diarrhea, in addition to somatostatin analog therapy. By reducing the stool frequency in patients with carcinoid syndrome whose diarrhea is refractory to anticholinergics, such as loperamide and atropine/diphenoxylate, and somatostatin analog dose escalation, improvement in quality of life becomes an achievable goal.

Suburban white-tailed deer seropositive for Toxoplasma gondii from Chicago, Illinois.

The presence and abundance of vertebrates influences the circulation of zoonotic diseases. White-tailed deer (Odocoileus virginianus) are widely distributed in North America and deer densities are frequently high in unhunted areas, including most major metropolitan regions. This study investigated the seroprevalence for Toxoplasma gondii from live-captured and culled deer sampled in two suburban forest preserves around Chicago, Illinois, from 1995 to 1999. Seroprevalence for T. gondii was 55.9% (n = 443) and was significantly higher at the northern study site, Des Plaines. Seroprevalence for T. gondii varied by year and month. Multivariate logistic regression (LR) screened main effect variables (age, sex, site, year, and month) by backward stepwise elimination. The final LR model for T. gondii contained all main effect variables. This study provides baseline data for future T. gondii suburban deer studies and information to public health and wildlife officials regarding the prevalence a parasitic pathogen present in two public forest preserves in Chicago, Illinois.

Assessing the Impact of Removing Select Materials from Coal Mine Overburden, Central Appalachia Region, USA.

The exposure of readily soluble components of overburden materials from surface coal mining to air and water results in mineral oxidation and carbonate mineral dissolution, thus increasing coal mine water conductivity. A conductivity benchmark of 300 µS/cm for mine water discharges in the Appalachian region has been suggested to protect aquatic life and the environment. A USGS screening-level leach test was applied to individual strata from three cores collected from a surface mine site in the Central Appalachian region to generate preliminary conductivity rankings, which were used to classify strata for two disposal scenarios: (i) Unmodified Scenario, which included all extracted strata and (ii) Modified Scenario, which excluded 15% (by mass) of the overburden materials with the highest conductivities. We evaluated overburden leaching conductivity using EPA Method 1627 in 18 dry-wet cycles, generating conductivities of 1,020-1,150 µS/cm for the Unmodified Scenario and 624-979 µS/cm for the Modified Scenario. Hence, overburden segregation was successful in reducing the leachate conductivity, but did not reach the proposed benchmark. The leachate was dominated by sulfate in the first four cycles and by bicarbonates in cycles 5-18 in columns with higher sulfur content, while bicarbonates were dominant throughout experiments with lower sulfur content in overburden. The use of conductivity rankings, isolation of potentially problematic overburden strata, and appropriate materials management could reduce conductivity in Central Appalachian streams and other surface mining areas.

Prognostic significance of lymph node metastases in small intestinal neuroendocrine tumors.

BACKGROUND/AIMS: Current staging guidelines for small intestinal neuroendocrine tumors (SI-NETs) differentiate between the presence (N1) and absence (N0) of lymph node (LN) metastases. However, the prognostic significance of the extent of LN involvement remains unknown. In this study, we used data from a population-based cancer registry to examine whether involvement of a higher number of LNs is associated with worse survival. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with histologically confirmed, surgically resected SI-NETS diagnosed between 1988 and 2010. Patients were classified into three groups by the LN ratio (number of positive LNs/number of total LNs examined, LNR): ≤0.2, >0.2-0.5, and >0.5. We used the Kaplan-Meier method and Cox models to assess NET cancer-specific survival differences (up to 10 years from diagnosis) according to LNR status. RESULTS: We identified 2,984 surgically resected patients with stage IIIb (N1, M0) SI-NETs with detailed LN data. More than half of the NETs were located in the ileum. A higher LNR was significantly associated with worse NET cancer-specific survival (p < 0.0001). Ten-year NET-specific survival was 85, 77, and 74% for patients in the ≤0.2, >0.2-0.5, and >0.5 LNR groups, respectively. In stratified analyses, higher LNR groups had worse survival only in early tumor (T1, T2) disease (p < 0.0001). CONCLUSIONS: The extent of LN involvement provides independent prognostic information on patients with LN-positive SI-NETs. This information may be used to identify patients at high risk of recurrence and inform decisions about the use of adjuvant therapy.

Management and disease outcome of type I gastric neuroendocrine tumors: the Mount Sinai experience.

BACKGROUND AND AIM: The incidence of gastric neuroendocrine tumors (NETs) has increased tenfold since the 1970s. Our aim was to describe the clinicopathologic profile, management, and outcomes of type I gastric NETs at The Mount Sinai Hospital. METHODS: From existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation, we identified 56 patients with type I gastric NETs seen at The Mount Sinai Hospital from 1993 to 2012. We generated a comprehensive dataset encompassing demographic, clinical, endoscopic, and pathologic factors. Survival information was determined from medical records and the Social Security Death Index. Tumor-node-metastasis staging was conducted, and tumors were graded based on mitotic counts and Ki67 index. RESULTS: Median NET size was 3.0 mm; 55.8 % displayed multifocal disease. Stages I, II, III, and IV disease were observed in 83.8, 10.8, 5.4, and 0 %, respectively. Tumors were either low (69.7 %) or intermediate (30.3 %) grade. Furthermore, 3.6 % of patients developed gastric dysplasia, and 5.5 % had gastric adenocarcinoma. Patients underwent endoscopy every 15 months, while 28.6 % underwent polypectomy, 32.7 % somatostatin therapy, and 46.4 % surgical resection. 5- and 10-year disease-specific survival was 100 %. CONCLUSIONS: Most patients received annual endoscopic surveillance, with a minority undergoing surgical resection, though outcomes remained excellent independent of therapeutic approach. We identified a very low but real rate of loco-regional spread, despite the generally indolent behavior of type I gastric NETs. Several patients demonstrated concurrent dysplasia or adenocarcinoma, underscoring the efficacy of regular endoscopic management not only for gastric NETs, but also for dysplasia and adenocarcinoma.

Carcinoid Heart Disease without Liver Involvement Caused by a Primary Ovarian Carcinoid Tumour.

Carcinoid heart disease, caused by primary ovarian carcinoid tumour, is a rare form of valvular heart disease. This form of heart disease usually presents with symptoms of right-sided valvular dysfunction, ultimately leading to right-sided heart failure. This entity is unique as it develops in the absence of liver metastasis. We report a case of 75 year-old woman with primary ovarian carcinoid tumour who presented with symptoms of severe right-sided heart failure and successfully underwent pulmonic and tricuspid valve replacement along with a right ventricular (RV) outflow patch enlargement. This patient later underwent uneventful resection of the primary ovarian carcinoid tumour, with complete resolution of her symptoms.

Invited commentary on . . . Ethnic variations in pathways into early intervention services for psychosis.

Advocates of early intervention in psychosis choose to treat the association between long duration of untreated psychosis (DUP) and poor outcome as evidence that reducing DUP will improve outcomes. I question this view and argue that DUP does not predict outcome but rather that mode of onset of psychosis predicts DUP and outcome.

Clinical and prognostic features of rectal neuroendocrine tumors.

BACKGROUND: Rectal neuroendocrine tumors (NETs) are among the most common NETs. The aim was to validate European Neuroendocrine Tumor Society (ENETS)/North American Neuroendocrine Tumor Society (NANETS) staging and grading systems with regard to clinical outcomes. METHODS: A comprehensive database was constructed from existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation. Analysis was performed on 141 patients identified with rectal NETs seen at Mount Sinai Hospital between 1972 and 2011. RESULTS: The median age was 52.7 years; 43% were males. Average tumor size was 0.88 cm. NETs <1 cm accounted for 75.6% of the tumors. Stage I, II, III and IV accounted for 79.4, 2.8, 5.0 and 12.8% of the tumors, respectively. G1 tumors accounted for 88.1%, G2 8.3% and G3 3.6%. Of G1 tumors, 94.6% were stage I and 5.4% were stage IV. The median survival time for all 141 patients was 6.8 years (range, 0.8-34.7 years). The overall 5-year survival rate was 84.4%. The 5-year survival rates for patients in stages I-IV were 92.7, 75.0, 42.9 and 33.2%, respectively. The 5-year survival rates for patients with G1-G3 tumors were 87.7, 47.6 and 33.3%, respectively. Univariate analysis of increased survival showed significance for lower stage, lower grade, smaller size, absence of symptoms and endoscopically treated tumors. Multivariate analysis showed that stage alone was statistically significant as the strongest predictor of survival. CONCLUSION: The results of our study validated ENETS/NANETS guidelines for staging and grading of rectal NETs in the US setting of a tertiary referral center. Staging according to ENETS/NANETS guidelines should be used in the treatment algorithm rather than size alone.

Serum pancreastatin: the next predictive neuroendocrine tumor marker.

BACKGROUND AND OBJECTIVES: Pancreastatin is a derived peptide of chromogranin A (CgA). Pancreastatin has the potential to be a diagnostic and predictive tumor marker in detecting NETs. METHODS: Radioimmunoassay tests of pancreastatin and CgA were performed on 103 patient specimens collected at Mount Sinai Medical Center between 1/2010 and 7/2012. Patient demographics, diagnostic tests, surgical procedures, pathologic findings, adjuvant treatments, and survival were retrospectively reviewed. Statistical analysis utilized SPSS v20 software. RESULTS: Mean pancreastatin levels were significantly higher in the 92 NETs patients than in the 11 non-NETs patients (227.261 vs. 59.727, P < 0.05). Twenty-seven of the 92 patients with elevated pancreastatin levels (mean = 240.67), had normal CgA levels (mean = 4.65). Pancreastatin had sensitivity and specificity of 64% (59/92), and 100% (11/11). CgA had lower sensitivity and specificity of 43% (40/92), and 64% (7/11). In all 27 instances the pancreastatin concentration was found to be sole indicator of NET disease. When controlling for the level of CgA for the entire sample, a statistically significant difference was not found in the mean pancreastatin levels between both patient groups (P = 0.139, R = 0.484). CONCLUSION: Pancreastatin has greater sensitivity and specificity in diagnosing NETs than CgA. Further investigation of pancreastatin's diagnostic and predictive value is warranted.

Ixodes scapularis (Acari: Ixodidae) distribution surveys in the Chicago metropolitan region.

Considering recent studies confirming an increased risk of contracting Lyme disease near metropolitan Chicago, we surveyed a more comprehensive area to assess whether the geographical distribution and establishment of Ixodes scapularis (Say) populations across northeast Illinois are widespread or limited in occurrence. From May through October 2008 and from April through October 2009, 602 I. scapularis ticks of all three life stages (larva, nymph, adult) were collected from sites in Cook, DuPage, Lake, and McHenry counties in northeast Illinois. The surveys were conducted by drag sampling vegetation in public-access forested areas. I. scapularis comprised 56.4% of ticks collected (n = 1,067) at 17 of 32 survey sites. In addition, four other tick species were incidentally collected: Dermacentor variabilis (Say), Haemaphysalis leporispalustris (Packard), Ixodes dentatus (Marx), and Amblyomma americanum (L.). This study updates the I. scapularis distribution in northeast Illinois. Our random sampling of suitable tick habitats across a large geographic area of the Chicago metropolitan area suggests a widespread human exposure to I. scapularis, and, potentially, to their associated pathogens throughout the region. These results prompt continued monitoring and investigation of the distribution, emergence, and expansion of I. scapularis populations and Borrelia burgdorferi transmission within this heavily populated region of Illinois.

Water quality characteristics of discharge from reforested loose-dumped mine spoil in eastern Kentucky.

Surface mining is a common method for extracting coal in the coal fields of eastern Kentucky. Using the Forestry Reclamation Approach (FRA), which emphasizes the use of minimally compacted or loose-dumped spoil as a growth medium for trees, reclamation practitioners are successfully reestablishing forests. Yet, questions remain regarding the effects FRA has on the quality of waters discharged to receiving streams. To examine the effect of FRA on water quality, this study compared waters that were discharged from three types of spoils: predominantly brown, weathered sandstone (BROWN); predominantly gray, unweathered sandstone (GRAY); and an equal mixture of both aforementioned sandstones and shale (MIXED). The water quality parameters pH, EC, Ca, K, Mg, Na, NO-N, NH-N, SO, Cl, TC, suspended sediment concentration (SSC), settleable solids (SS), and turbidity were monitored over a 2-yr period on six 0.4-ha plots (two replications per spoil type). Generally, levels of Cl, SO, Ca, NO-N, NH-N, SS, SSC, and turbidity decreased over time. The pH for all spoils increased from about 7.5 to 8.5. The EC remained relatively level in the BROWN spoil, whereas the GRAY and MIXED spoils had downward trajectories that were approaching 500 µS cm. The value of 500 µS cm has been reported as the apparent threshold at which certain taxa such as Ephemeroptera (e.g., Mayfly) recolonize disturbed headwater streams of eastern Kentucky and adjacent coal-producing Appalachian states.

Female sticklebacks transfer information via eggs: effects of maternal experience with predators on offspring.

There is growing evidence that maternal experience influences offspring via non-genetic mechanisms. When female three-spined sticklebacks (Gasterosteus aculeatus) were exposed to the threat of predation, they produced larger eggs with higher cortisol content, which consumed more oxygen shortly after fertilization compared with a control group. As juveniles, the offspring of predator-exposed mothers exhibited tighter shoaling behaviour, an antipredator defence. We did not detect an effect of maternal exposure to predation risk on the somatic growth of fry. Altogether, we found that exposure to an ecologically relevant stressor during egg formation had several long-lasting consequences for offspring, some of which might be mediated by exposure to maternally derived cortisol. These results support the hypothesis that female sticklebacks might influence the development, growth and behaviour of their offspring via eggs to match their future environment.

Review of the pathogenesis, diagnosis, and management of type I gastric carcinoid tumor.

Gastric carcinoid tumors comprise 7% of all gastrointestinal carcinoids and have significantly increased in incidence over the past few decades. Seventy to 80% of gastric carcinoids are type I, which usually are clinically asymptomatic and found incidentally at endoscopic evaluation for abdominal pain or anemia. In this review, advances in understanding the pathophysiology of type I gastric carcinoid are highlighted. In addition, various current diagnostic and treatment options are discussed. Although type I carcinoids generally hold a benign course, rigorous investigation is needed to ensure accurate diagnosis and optimal treatment. This includes appropriate diagnostic procedures and imaging and accurate staging of tumor. Tumor size, depth of invasion, presence of metastasis, and the tumor's gastrin dependency dictate treatment options. Appropriate treatments can consist of endoscopic resection, antrectomy, medical management, or frequent follow-up. This article provides a systematic method of evaluating and treating type I gastric carcinoid.

Schizophrenia outcomes in the 21st century: A systematic review.

OBJECTIVE: We report a review of outcomes in schizophrenia in the twenty-first century, replicating and extending work undertaken by the late Richard Warner in his seminal book, "Recovery from Schizophrenia: Psychiatry and Political Economy" (1985;2004). METHOD: Warner's methods were followed as closely as possible. Only observational/naturalistic studies were included. Six scientific databases were searched from 2000 to 2020. 6,640 records were retrieved. 47 met inclusion criteria. RESULTS: Overall, complete recovery is higher in this study than in Warner's (37.75% cf 20.4%), especially for first episode psychosis (FEP) (57.1% cf 20.7%). Clinical recovery, annualized remission rate (ARR), and employment outcomes were significantly superior for first episode psychosis compared with multiple episode psychosis (MEP). ARR shows a trend toward reduction over time, from 2.2 before the financial crash of 2008 to 1.6 after (t = 1.85 df 40 p = .07). The decline is statistically significant for the MEP group (t = 2.32 df18 p = .03). There were no differences in outcome by region, sample characteristics, outcome measures used, or quality of studies. Heterogeneity of clinical outcome measures across the literature makes evidence synthesis difficult. Weak and inconsistent reporting of functional and employment outcomes mean that findings lack meaning with respect to lived experience. CONCLUSION: Future research strategies should aim to reduce heterogeneity in clinical outcome measures and to increase the emphasis on capture and reporting of more sophisticated measures of social and functional outcome. Outcome domains should be disaggregated rather than conflated into unitary recovery constructs.

Time to Sustained Improvement in Bowel Movement Frequency with Telotristat Ethyl: Analyses of Phase III Studies in Carcinoid Syndrome.

BACKGROUND: Telotristat ethyl is approved to treat carcinoid syndrome diarrhea in combination with somatostatin analogs. In TELESTAR and TELECAST phase III studies, patients with carcinoid syndrome received telotristat ethyl 250 or 500 mg 3 times per day (tid) or placebo tid in addition to somatostatin analogs. The aim of this prespecified analysis was to examine the time to reductions in bowel movements (BMs) in the TELESTAR and TELECAST studies using survival analysis methods. METHODS: First occurrence of sustained response was defined as the time to the first day of 2 consecutive weeks with a mean BM frequency improvement of ≥ 30% from baseline during the 12-week double-blind treatment periods. Time to first ≥ 30% worsening in BM frequency was also measured. Treatments were compared with the log-rank test; Cox regression models provided point and confidence interval estimates of the hazard ratios for each trial. RESULTS: In TELESTAR and TELECAST, majority of patients (69%) on telotristat ethyl experienced a sustained ≥ 30% improvement in BM frequency. The median time to sustained reduction of at least 30% in BM frequency was significantly faster (fewer days to onset) for telotristat ethyl compared with placebo in both TELESTAR (250 mg, HR = 2.3 [95% CI, 1.3-4.1, P = 0.004]; 500 mg, HR = 2.2 [95% CI, 1.2-3.9, P = 0.009]) and TELECAST (250 mg, HR = 3.9 [95% CI, 1.6-11.1, P = 0.003]; 500 mg, HR = 4.2 [95% CI, 1.7-11.7, P = 0.002]). In TELECAST, 42% of patients on placebo experienced sustained worsening in BM frequency compared with 20% on telotristat ethyl; no significant difference was observed in TELESTAR. CONCLUSION: The time of onset of sustained BM frequency improvement mean and range are important when considering use of telotristat ethyl in patients with carcinoid syndrome diarrhea. Telotristat ethyl may also reduce sustained worsening in BM frequency. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01677910, NCT02063659.

Laparoscopic antrectomy for the treatment of type I gastric carcinoid tumors.

BACKGROUND: While the optimal treatment for type I gastric carcinoid tumors remains controversial, there is evidence to suggest that in multifocal disease, antrectomy may not only control local disease but also may lead to enterochromaffin-like cell (ECL) hyperplasia regression compared to medical and endoscopic treatments. MATERIALS AND METHODS: A single institution retrospective review of eight consecutive patients with multifocal type I gastric carcinoid tumor patients with no evidence of metastatic disease was performed from 2005 to 2006. All of these patients underwent laparoscopic antrectomy with Billroth II reconstruction. Patients' preoperative gastrin, chromogranin A levels, and biopsy and surgical specimen slides were compared with postoperative laboratory and biopsy slides. Pathology slides were reanalyzed by a blinded pathologist from our institution for evidence of tumor and ECL hyperplasia regression. RESULTS: All patients tolerated the procedure well with no reoperations or mortalities. Six of eight patient complained of mild reflux which was treated medically. One of eight had a mild wound infection which resolved with a course of cephalexin. Gastrin levels significantly decreased (98.9%) in all patients (P = 0.001). Furthermore, chromogranin A levels also significantly decreased (81.4%). Eight of eight patients showed no evidence of carcinoid tumor after surgery at mean biopsy follow-up of 17 mo (range 2-35 mo), however there was ECL hyperplasia after resection. Four of eight patients (50%) showed regression of ECL hyperplasia on postop biopsy, while the remaining four of eight showed no evidence of regression. CONCLUSIONS: This is the largest case series to investigate the surgical, clinical, and histologic outcomes of laparoscopic antrectomy in type I gastric carcinoid. Our data suggest that laparoscopic antrectomy is a safe and minimally invasive approach to treat nonmetastatic type I gastric carcinoid. All patients had no evidence of gross or microscopic disease at follow-up biopsy and almost half had regression of ECL hyperplasia at follow-up suggesting that antrectomy may be sufficient to prevent tumor recurrence. However, continued regular endoscopic surveillance and medical follow-up of patients with ECL hyperplasia are recommended.

The clinical utility of Ki-67 in assessing tumor biology and aggressiveness in patients with appendiceal carcinoids.

BACKGROUND/OBJECTIVE: To elucidate the correlation of Ki-67 with tumor biology and survival in appendiceal carcinoid tumors. METHOD: A retrospective chart review conducted on 51 patients with appendiceal carcinoid tumors who underwent surgical intervention from 1991 to 2008. MIB-1, an antibody of Ki-67, was used to determine cell proliferation and correlated with clinical and histological parameters. MIB-1 index was categorized according to the World Health Organization (WHO) classification. RESULT: Of the 51 patients, 32 had tumors <2 cm; 3 >2 cm; and 16 with unspecified tumor size. Increased MIB proliferative index did not significantly correlate with increasing tumor size (P = 0.426). Twelve patients had metastatic disease on presentation: 9 had MIB-1 index <2%, 1 had index 2-15% and 2 with index >15%. No significant correlation between MIB index and metastasis was demonstrated (P = 0.68). Median follow-up was 40 months (range 10-183 months) with a 51% follow-up rate. Seven mortalities and three recurrences presented in 26 patients. Assessment of survival demonstrated significantly decreased survival by increasing MIB index. Survival rate by MIB index was as follows: <2% was 97%, 2-15% was 85% and >15% was 67% (P = 0.02). CONCLUSION: Increased MIB index significantly correlated with decreased survival. No correlation was demonstrated by MIB index and tumor size or presentation with metastatic disease.

Gastroduodenal ulceration associated with radioembolization for the treatment of hepatic tumors: an institutional experience and review of the literature.

BACKGROUND: Microsphere radioembolization is a method of delivering radiation therapy directly to tumors, thereby minimizing toxicity to adjacent structures. Despite the relatively high precision of this modality, numerous adverse effects have been recognized. One particularly untoward complication is the development of severe gastroduodenal ulceration. METHODS: In order to further characterize gastroduodenal ulceration associated with radioembolization, our institutional experience as well as the reported literature were reviewed. RESULTS: The current evidence suggests that radioembolization-associated gastroduodenal ulceration results from inadvertent delivery of microspheres to the microvasculature of the gastrointestinal tract, leading to direct radiation toxicity. The reported incidence of this entity ranges between 2.9% and 4.8%. Most patients with this complication present with abdominal pain, often associated with nausea, vomiting, and anorexia. Symptoms can arise from hours to months after radioembolization treatment; diagnosis is made by endoscopic biopsy and histopathologic evaluation of the ulcer specimen. Radiation-induced ulcers have proven to be extremely difficult to treat. Current therapy based on acid suppression has had limited success, and the evidence for the addition of antioxidants and anti-inflammatory agents is still sparse. CONCLUSIONS: The increasing utilization of radioembolization will lead to adverse events including gastroduodenal ulceration. This entity must be considered in any patient treated with radioactive microspheres presenting with symptoms of dyspepsia. Accurate diagnosis and aggressive treatment are necessary to improve patient outcomes.

The roots of hospital alternative care.

British hospital alternatives inherit some of their most valuable features, such as the use of small, domestic environments and the avoidance of coercion and confinement, from the early 19th-century moral management movement. The North American experience illustrates that these advantages can be lost if clinical benefits are overridden by cost and other practical concerns.

The consultant nurse - expert practitioner and much more.

The consultant nurse (CN) role is usually described in terms of four domains devised by the Department of Health - clinical practice, education and training, leadership, and research and service development. This study set out to explicate the diversity and complexity of CN roles in an NHS trust; to describe aspects of extraordinary practice and to identify perceived differences between this role and other advanced practice roles. Accounts were written by six CNs and subjected to concept mapping to facilitate identification of extraordinary practice. Four themes emerged: entrepreneurial activity and innovation; clinical autonomy and role dynamism; influential national and international research conduct; consultancy and education across discipline boundaries. These included descriptions of higher order skills that surpass usual requirements of 'expert' or 'advanced' practice. Comparisons with other advanced practice roles are drawn from the literature and data collected in this study. Differences between the roles have implications for sustainability.