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PURPOSE: Sexual and gender minority (SGM) populations experience cancer treatment and survival disparities; however, inconsistent sexual orientation and gender identity (SOGI) data collection within clinical settings and the cancer surveillance system precludes population-based research toward health equity for this population. This qualitative study examined how hospital and central registry abstractors receive and interact with SOGI information and the challenges that they face in doing so. METHODS: We conducted semi-structured interviews with 18 abstractors at five Surveillance, Epidemiology, and End Results (SEER) registries, as well as seven abstractors from commission on cancer (CoC)-accredited hospital programs in Iowa. Interviews were transcribed, cleaned, and coded using a combination of a priori and emergent codes. These codes were then used to conduct a descriptive analysis and to identify domains across the interviews. RESULTS: Interviews revealed that abstractors had difficulty locating SOGI information in the medical record: this information was largely never recorded, and when included, was inconsistently/not uniformly located in the medical record. On occasion, abstractors reported situational recording of SOGI information when relevant to the patient's cancer diagnosis. Abstractors further noticed that, where reported, the source of SOGI information (i.e., patient, physician) is largely unknown. CONCLUSION: Efforts are needed to ensure standardized implementation of the collection of SOGI variables within the clinical setting, such that this information can be collected by the central cancer registry system to support population-based equity research addressing LGBTQ + disparities.

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BACKGROUND: Centralization of rectal cancer surgery has been associated with high-quality oncologic care. However, several patient, disease and system-related factors can impact where patients receive care. We hypothesized that patients with low rectal tumors would undergo treatment at high-volume centers and would be more likely to receive guideline-based multidisciplinary treatment. METHODS: Adults who underwent proctectomy for stage II/III rectal cancer were included from the Iowa Cancer Registry and supplemented with tumor location data. Multinomial logistic regression was employed to analyze factors associated with receiving care in high-volume hospital, while logistic regression for those associated with ≥ 12 lymph node yield, pre-operative chemoradiation and sphincter-preserving surgery. RESULTS: Of 414 patients, 38%, 39%, and 22% had low, mid, and high rectal cancers, respectively. Thirty-two percent were > 65 years, 38% female, and 68% had stage III tumors. Older age and rural residence, but not tumor location, were associated with surgical treatment in low-volume hospitals. Higher tumor location, high-volume, and NCI-designated hospitals had higher nodal yield (≥ 12). Hospital-volume was not associated with neoadjuvant chemoradiation rates or circumferential resection margin status. Sphincter-sparing surgery was independently associated with high tumor location, female sex, and stage III cancer, but not hospital volume. CONCLUSIONS: Low tumor location was not associated with care in high-volume hospitals. High-volume and NCI-designated hospitals had higher nodal yields, but not significantly higher neoadjuvant chemoradiation, negative circumferential margin, or sphincter preservation rates. Therefore, providing educational/quality improvement support in lower volume centers may be more pragmatic than attempting to centralize rectal cancer care among high-volume centers.

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AIM: Conversion rates from laparoscopic to open colectomy and associated factors are traditionally reported in clinical trials or reviews of outcomes from experienced institutions. Indications and selection criteria for laparoscopic colectomy may be more narrowly defined in these circumstances. With the increased adoption of laparoscopy, conversion rates using national data need to be closely examined. The purpose of this study was to use data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) to identify factors associated with conversion of laparoscopic to open colectomy at a national scale in the United States. METHOD: The ACS-NSQIP Participant Use Data Files for 2006-2011 were used to identify patients who had undergone laparoscopic colectomy. Converted cases were identified using open colectomy as the primary procedure and laparoscopic colectomy as 'other procedure'. Preoperative variables were identified and statistics were calculated using sas version 9.3. Logistic regression was used to model the multivariate relationship between patient variables and conversion status. RESULTS: Laparoscopy was successfully performed in 41 585 patients, of whom 2508 (5.8%) required conversion to an open procedure. On univariate analysis the following factors were significant: age, body mass index (BMI), American Society of Anesthesiologists (ASA) class, presence of diabetes, smoking, chronic obstructive pulmonary disease, ascites, stroke, weight loss and chemotherapy (P < 0.05). The following factors remained significant on multivariate analysis: age, BMI, ASA class, smoking, ascites and weight loss. CONCLUSION: Multiple significant factors for conversion from laparoscopic to open colectomy were identified. A novel finding was the increased risk of conversion for underweight patients. As laparoscopic colectomy is become increasingly utilized, factors predictive of conversion to open procedures should be sought via large national cohorts.

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Despite the clinical significance of complications due to intravascular catheters, the inappropriate use of intravascular catheters in hospitalised patients has not been adequately characterised. The objective of this prospective observational study was to develop definitions for appropriate intravascular device use, to estimate the frequency of inappropriate use of intravascular devices, and to examine risk factors and outcomes associated with inappropriate use in hospitalised patients. Among 436 patients admitted between October and December 2007, a total of 2909 hospitalisation days and use of 876 intravascular devices was observed. Of the 3806 total catheter-days recorded, 1179 (31%) were found to be inappropriate based on the study criteria. Logistic regression analysis indicated that age, total number of catheters used and total duration of catheterisation were risk factors for inappropriate device use (P<0.05). Inappropriate usage was strongly associated with increased intensive care unit admission (P<0.05) and length of hospital stay (4.9±4.3 days for appropriate vs 8.5±12.6 days for inappropriate; P<0.05). Use of central venous catheters was not a predictor for inappropriate device use. Inappropriate intravascular device use is a very common phenomenon in hospitalised patients and is strongly linked to adverse device-related outcomes. These results may be used to develop strategies to systematically reduce excessive intravascular device use which would be expected to reduce adverse events associated with morbidity, mortality, and excess healthcare costs.

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The objective of this study was to determine whether inequality in stillbirth risk between social strata has changed over time. Subjects were all 288,869 births in Cumbria, northwest England, 1950-1993 and all 8,039,269 births in England and Wales, 1981-1992. Social class of Cumbrian babies was ascertained from birth registrations. Community deprivation scores were calculated from census data for (i) enumeration districts in Cumbria and (ii) county districts in England and Wales. The relative index of inequality was used to measure inequality of stillbirth risk between social strata. Results indicate inequality in stillbirth risk in Cumbria has fallen significantly since 1966 (P< or =0.02) and was not evident in more recent time periods. In England and Wales, there was significant inequality in stillbirth risk in all time periods and no evidence that this has changed over time. Inequality in stillbirth risk has not increased and in some areas has attenuated in recent years.

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The nuclear installation at Sellafield, in west Cumbria in the north of England, has discharged radioactive waste into the Irish Sea since 1952. The objective of this paper was to investigate whether women living near to the coast in Cumbria had an increased risk of having stillborn children. A retrospective cohort analysis was carried out using all 259,050 births (4017 stillbirths) to women normally resident in Cumbria during 1950-89, allowing for year of birth, social class and birth order using (i) comparison of observed and expected numbers of stillbirths in distance bands relative to the coast, (ii) comparison of cumulative observed and expected numbers of stillbirths by distance from the coast, and (iii) logistic regression analysis of stillbirth risk in relation to distance from the coast. Comparison of observed and expected numbers of stillbirths in distance bands within 10 km of the coast did not provide evidence of an excess risk of stillbirth closer to the coast. The comparison of the cumulative observed and expected numbers of stillbirths within 10 km of the coast supported this result. Logistic regression analysis of all births in Cumbria showed that distance from the coast did not significantly influence stillbirth risk (P > 0.05). There was no evidence to suggest an increased risk of stillbirth in mothers resident nearer to the coast.

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BACKGROUND: The aim of the study was to investigate whether proximity to the nuclear installation at Sellafield, in Cumbria, North West of England, increases the risk of stillbirth in the resident population. The cohort consisted of all 256066 live and 4034 stillbirths to mothers usually domiciled in Cumbria, 1950-1989. METHODS: The study was a retrospective cohort analysis allowing for year of birth, social class and birth order using: (i) Poisson probability mapping, (ii) comparison of cumulative observed and expected numbers of stillbirths by distance from Sellafield, (iii) logistic regression of stillbirth risk in relation to distance and direction from Sellafield. RESULTS: Poisson probability mapping of stillbirths within 25 km of Sellafield provided no evidence to suggest that proximity to Sellafield increased the risk of stillbirth, either overall or in any specific direction. Comparison of the cumulative observed and expected numbers of stillbirths also showed no increased risk with proximity to Sellafield. Logistic regression analysis of all Cumbrian births supported these results, showing, in particular, that distance from Sellafield did not significantly influence stillbirth risk (P = 0.30). Although there was significant variation in stillbirth risk with direction (P = 0.0004), this was due to stillbirths in areas much further than 25 km from Sellafield. There was no significant effect with distance from Sellafield within any of six directional sectors (P > 0.05). CONCLUSIONS: There was no evidence to suggest that proximity to Sellafield increases the risk of stillbirth in the resident population.

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Using a degenerate PCR based approach, a fragment of the novel G protein-coupled receptor, VTR 15-20, was identified from the rat ventral tegmentum. Hybridization screening and RACE PCR were employed to isolate the full length clone. The cDNA encodes a protein of 305 amino acids which shares homology to several orphan as well as known G protein-coupled receptors. Amino acid analysis demonstrates the VTR 15-20 contains specific regions conserved among the G protein-coupled receptor superfamily. Messenger RNA encoding VTR 15-20 is expressed throughout the mammalian nervous system. Using primary rat culture systems we have demonstrated the expression of VTR 15-20 mRNA in both microglia and astrocytes. The highest levels of VTR 15-20 mRNA expression are detected in peripheral tissues including the spleen. Moreover, we have found that the expression of VTR 15-20 mRNA in brain and spleen is regulated by immunologic challenge. Based on the cellular distribution and regulation by immune challenge and neuronal insult, we hypothesize that VTR 15-20 plays a role in neuroimmune function.

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Ethanol dependence and tolerance involve perturbation of GABAergic neurotransmission. Previous studies have demonstrated that ethanol treatment regulates the function and expression of GABAA receptors throughout the CNS. Conceivably, changes in receptor function may be associated with alterations of subunit composition. In the present study, a comprehensive (1-12 weeks) ethanol treatment paradigm was used to evaluate changes in GABAA receptor subunit expression in several brain regions including the cerebellum, cerebral cortex, ventral tegmental area (VTA) (a region implicated in drug reward/dependence), and the hippocampus (a region involved in memory/cognition). Expression of alpha 1 and alpha 5 subunits was regulated by ethanol in a region-specific and time-dependent manner. Following 2-4 weeks of administration, cortical and cerebellar alpha 1 and alpha 5 subunits immunoreactivity was reduced. In the VTA, levels of alpha 1 subunit immunoreactivity were significantly decreased after 12 weeks but not 1-4 weeks of treatment. Hippocampal alpha 1 subunit immunoreactivity and mRNA content were also significantly reduced after 12 but not after 4 weeks of treatment. In contrast, alpha 5 mRNA content was increased in this brain region. These data indicate that chronic ethanol administration alters GABAA receptor subunit expression in the VTA and hippocampus, effects that may play a role in the abuse potential and detrimental cognitive effects of alcohol.

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STUDY OBJECTIVE: To test the hypothesis that children born to mothers living near the sea are at increased risk of limb reduction defects. DESIGN: Descriptive data analysis. SETTING: The northern health region of England. PATIENTS: All children born between 1 January 1985 and 31 December 1992 in the northern region of England with isolated limb reduction defects. MAIN RESULTS: The birth prevalence of isolated limb reduction defects was not affected by the distance the mother lived from the sea. There was some evidence of space-time clustering, but there was no evidence of statistically significant variation in the occurrence of the condition with sex, time of birth (monthly or yearly), or county of birth. CONCLUSIONS: There is no evidence that children born to mothers living near the sea are at increased risk of limb reduction defects.

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It was previously demonstrated that daily administration of N-methyl-D-aspartate (NMDA) to primary cultures of cerebellar granule neurons for 5 days in vitro mediates an increase in the relative content of mRNAs encoding selected subunits of the gamma-aminobutyric acid (GABA)A receptor. This analysis was extended using a competitive polymerase chain reaction assay with internal standards to quantitate changes that occur in the absolute amounts of selected GABAA receptor subunit mRNAs in cerebellar granule neurons in vitro after the single administration of nontoxic doses of either NMDA or glutamate. For these studies, we focused on the alpha 1, alpha 5, and alpha 6 receptor subunit mRNAs and examined their absolute contents in cultures maintained in low KCl (12.5 mM), maintained in low KCl and treated with NMDA (10 microM) for 24 hr, or maintained in high KCl (25 mM). The absolute amounts of each mRNA varied in these paradigms; whereas the alpha 1 and alpha 5 receptor subunit mRNAs increased in response to NMDA-selective glutamate receptor stimulation, the alpha 6 receptor subunit mRNA did not. The time course of the alpha 1 and alpha 5 mRNA increases, dose dependence, and effects of glutamate in the presence or absence of MK-801 were also analyzed. Treatment of cultures maintained in 12.5 mM KCl with 5 microM glutamate resulted in comparable changes in the alpha 1 and alpha 5 receptor subunit mRNA contents, and a somewhat smaller increase in the alpha 6 mRNA content was observed. Using corresponding GABAA receptor subunit-specific antibodies, it was shown that the observed mRNA changes are accompanied by increased expression of alpha 1- and alpha 5-like receptor subunit immunoreactivity. Collectively, these data demonstrate that signal transduction mechanisms triggered by NMDA-selective glutamate receptor stimulation differentially modulate the levels of selected GABAA receptor subunit mRNAs and the corresponding proteins they encode.

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The binding of HIV-1 envelope glycoprotein, gp120, to the CD4 receptor is an important step in productive infection. The development of agents which interrupt this binding phenomenon should be of therapeutic interest. The present study characterizes a whole cell gp120/CD4 radioligand binding assay (radioligand binding assay) modified for use in a high volume screening format. Modifications include the use of human CD4 receptor stably expressed in a Chinese hamster ovary cell line and the gentle fixation (paraformaldehyde) of the CD4 receptor just prior to assay. Binding of [125I]gp120 to fixed CD4 was of high affinity (KD = 6 nM), saturable, reversible, and specific. The kinetics of binding were identical to those of viable (non-fixed) CD4 receptor. [125I]gp120 binding was inhibited by unlabeled recombinant gp120, soluble CD4, and the anti-CD4 monoclonals OKT4A and LEU3A. A number of compounds reported to inhibit gp120 binding and/or gp120 induced syncytium formation were also active in this assay. This modified radioligand binding assay was developed to initiate a rational and extensive screening program to assist in the identification of potential chemotherapeutic agents based on their ability to inhibit gp120 binding to host cells.

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