A phase IIb, open-label, randomized controlled dose ranging multi-centre trial to evaluate the safety, tolerability, pharmacokinetics and exposure-response relationship of different doses of delpazolid in combination with bedaquiline delamanid moxifloxacin in adult subjects with newly diagnosed, uncomplicated, smear-positive, drug-sensitive pulmonary tuberculosis.

BACKGROUND: Linezolid is an effective, but toxic anti-tuberculosis drug that is currently recommended for the treatment of drug-resistant tuberculosis. Improved oxazolidinones should have a better safety profile, while preserving efficacy. Delpazolid is a novel oxazolidinone developed by LegoChem Biosciences Inc. that has been evaluated up to phase 2a clinical trials. Since oxazolidinone toxicity can occur late in treatment, LegoChem Biosciences Inc. and the PanACEA Consortium designed DECODE to be an innovative dose-ranging study with long-term follow-up for determining the exposure-response and exposure-toxicity relationship of delpazolid to support dose selection for later studies. Delpazolid is administered in combination with bedaquiline, delamanid and moxifloxacin. METHODS: Seventy-five participants with drug-sensitive, pulmonary tuberculosis will receive bedaquiline, delamanid and moxifloxacin, and will be randomized to delpazolid dosages of 0 mg, 400 mg, 800 mg, 1200 mg once daily, or 800 mg twice daily, for 16 weeks. The primary efficacy endpoint will be the rate of decline of bacterial load on treatment, measured by MGIT liquid culture time to detection from weekly sputum cultures. The primary safety endpoint will be the proportion of oxazolidinone class toxicities; neuropathy, myelosuppression, or tyramine pressor response. Participants who convert to negative liquid media culture by week 8 will stop treatment after the end of their 16-week course and will be observed for relapse until week 52. Participants who do not convert to negative culture will receive continuation phase treatment with rifampicin and isoniazid to complete a six-month treatment course. DISCUSSION: DECODE is an innovative dose-finding trial, designed to support exposure-response modelling for safe and effective dose selection. The trial design allows assessment of occurrence of late toxicities as observed with linezolid, which is necessary in clinical evaluation of novel oxazolidinones. The primary efficacy endpoint is the change in bacterial load, an endpoint conventionally used in shorter dose-finding trials. Long-term follow-up after shortened treatment is possible through a safety rule excluding slow-and non-responders from potentially poorly performing dosages. TRIAL REGISTRATION: DECODE was registered in ClinicalTrials.gov before recruitment start on 22 October 2021 (NCT04550832).

Endocrine and physiological responses of hatchling American kestrels (Falco sparverius) following embryonic exposure to technical short-chain chlorinated paraffins (C10-13).

Short chain chlorinated paraffins (SCCPs) are complex mixtures of polychlorinated n-alkanes, shown to bioaccumulate but with unknown effects in wild birds. The present study examined development-related effects of SCCPs on captive American kestrels (Falco sparverius) treated in ovo on embryonic day (ED) 5 by injection with technical Chloroparaffin® (C10-13, 55.5% Cl) at environmentally relevant nominal (measured) concentrations of 10 (10), 50 (29) or 100 (97) ng ΣSCCP/g egg ww, and artificially incubated until hatching (ED27-ED29). The SCCP concentrations measured in the yolk sacs of the hatchling kestrels bracketed concentrations reported in the eggs of wild birds. Uptake and deposition of these SCCPs differed between male and female hatchlings, with only males showing differences in SCCP concentrations, being highest in the high-dose males than each of the other male groups. Embryonic exposure to SCCPs suppressed glandular total thyroxine (TT4) (20-33%) and reduced circulating triiodothyronine (TT3) (37-40%) in male hatchlings only when compared to control males, but had no effect on glandular TT3 or circulating TT4 in male or female kestrels. Histological assessments of thyroid glands showed that both sexes experienced significant structural changes indicative of gland activation. These thyroid glandular changes and the variations in SCCP concentrations were related to circulating TT3 in female hatchlings. Hepatic deiodinase enzyme (D1, D2) activities were stable and no SCCP-related changes were observed in hatching success, hatchling size, or immune organ size. However, several of the thyroid function indicators were correlated with hatchling size and smaller bursas and spleens, possibly indirectly through SCCP-induced changes in thyroid function. Because changes in thyroid function were evident at concentrations measured in wild bird eggs, similar changes may occur in wild nestlings. The potential impact of these changes on thyroid-mediated growth and survival in wild birds requires further investigation.

Pulseless electrical activity following traumatic cardiac arrest: Sign of life or death?

BACKGROUND: Generally considered a sign of life, PEA is the most common arrhythmia encountered following pre-hospital traumatic cardiac arrest. Some recommend cardiac ultrasound (CUS) to determine cardiac wall motion (CWM) prior to terminating resuscitation efforts. This purpose of this study was to evaluate the outcomes of patients with traumatic cardiac arrest presenting with PEA, with and without CWM. METHODS: Trauma patients who underwent pre-hospital CPR were identified from the registries of two level-1 trauma centers. Pre-hospital management by emergency medical transport services was guided by advanced life support protocols. The on-duty trauma surgeon directed the resuscitations and performed or supervised CUS and determined CWM. RESULTS: Among 277 patients who underwent pre-hospital CPR, 110 patients had PEA on arrival to ED. 69 (62.7%) were injured by blunt mechanisms. Median CPR duration was 20.0 and 8.0 min for pre-hospital and ED, respectively. Sixty-three patients (22.7%) underwent resuscitative thoracotomy. One hundred seventy-two patients (62.1%) received CUS and of these 32 (18.6%) had CWM. CWM was significantly associated with survival to hospital admission (21.9% vs. 1.4%; P < 0.001); however, no patient with CUS survived to hospital discharge. Overall, only one patient with PEA on arrival survived to discharge. CONCLUSION: Following pre-hospital traumatic cardiac arrest, PEA on arrival portends death. Although CWM is associated with survival to admission, it is not associated with meaningful survival. Heroic resuscitative measures may be unwarranted for PEA following pre-hospital traumatic arrest, regardless of CWM.

Inactivation of the bacterial pathogens Staphylococcus pseudintermedius and Acinetobacter baumannii by butanoic acid.

AIMS: This study was performed to evaluate the efficacy of butanoic acid against bacterial pathogens including Acinetobacter baumannii and Staphylococcus pseudintermedius. METHODS AND RESULTS: Vegetative bacteria were exposed to butanoic acid in vitro and log reduction was quantified using viable count assays. The maximum (8 and 9) log inactivation was determined by qualitatively assaying for growth/no-growth after a 48-h incubation (37°C). Membrane integrity after exposure to butanoic acid was determined by propidium iodide staining, scanning electron microscopy, membrane depolarization and inductively coupled plasma analysis. Cytosolic pH was measured by 5-(6-)carboxyfluorescein succinimidyl ester. CONCLUSIONS: Inhibitory concentrations of butanoic acid ranged between 11 and 21 mmol l-1 for Gram-positive and Gram-negative species tested. The maximum log reduction of A. baumannii was achieved with a 10-s exposure of 0·50 mol l-1 of butanoic acid. Staphylococcus pseudintermedius required 0·40 mol l-1 of butanoic acid to achieve the same level of reduction in the same time period. Inactivation was associated with membrane permeability and acidification of the cytosol. SIGNIFICANCE AND IMPACT OF THE STUDY: Antibiotic resistance among bacterial pathogens necessitates the utilization of novel therapeutics for disinfection and biological control. These results may facilitate the development of butanoic acid as an effective agent against a broad-spectrum of antibiotic-resistant bacterial pathogens.

Effects on the Underlying Water Column by Extensive Floating Treatment Wetlands.

Floating treatment wetlands (FTWs) are an emerging engineering option with promise for simultaneous water quality improvement and habitat creation. Relatively little research has been published regarding their construction or effects on the underlying water column. In this field-scale experiment, four different extensive FTW designs were constructed using minimal materials, including drainpipe, burlap, mulch, utility netting, and reused polyethylene bottles. The FTWs were then planted with spp. (cattail) and L. (common rush). Over 28 mo, the water column beneath FTWs in two test ponds was compared to that in an open water control pond. The ponds (190 ± 10 m) were fed with well water enriched with nitrate to emulate agricultural ponds. Although observed differences were relatively small, statistically significant differences were noted. With respect to the control, waters underneath FTWs had lower dissolved oxygen, sulfate, nitrate, and pH, dampened diurnal temperature fluctuations, and greater alkalinity. The FTWs created habitat and were colonized by species of insects, birds, amphibians, snails, and spiders. Results indicated that spp. is suitable for FTW creation. However, a more supportive planting matrix is suggested to encourage faster plant growth and protect against wind and wave action damage. Although plant growth was limited, results suggest that FTWs may be applied to encourage less aerobic and more organic rich and thermally insulated conditions for water quality improvement in agricultural ponds and other aquatic systems while also creating valuable habitat.

Performance in a GO/NOGO perceptual task reflects a balance between impulsive and instrumental components of behaviour.

In recent years, simple GO/NOGO behavioural tasks have become popular due to the relative ease with which they can be combined with technologies such as in vivo multiphoton imaging. To date, it has been assumed that behavioural performance can be captured by the average performance across a session, however this neglects the effect of motivation on behaviour within individual sessions. We investigated the effect of motivation on mice performing a GO/NOGO visual discrimination task. Performance within a session tended to follow a stereotypical trajectory on a Receiver Operating Characteristic (ROC) chart, beginning with an over-motivated state with many false positives, and transitioning through a more or less optimal regime to end with a low hit rate after satiation. Our observations are reproduced by a new model, the Motivated Actor-Critic, introduced here. Our results suggest that standard measures of discriminability, obtained by averaging across a session, may significantly underestimate behavioural performance.

Prognostic Relevance of Circulating Tumor Cells in Molecular Subtypes of Breast Cancer.

Circulating tumor cells (CTCs) can be detected in the peripheral blood of breast cancer patients with early and metastatic disease. Recent data suggest that immune pathologic characteristics between the primary tumor, metastatic colonies and CTCs are discordant and that CTCs possess an independent phenotype that is associated with prognosis and treatment efficacy. Large scale gene expression analysis has provided the possibility to stratify breast cancer according to the gene expression fingerprint of primary tumor tissue into five intrinsic molecular subtypes which can be associated with different clinical outcome. As a consequence of the different prognostic power of primary tumors' characteristics and CTCs several groups have started to investigate if CTCs might be disseminated differentially within these breast cancer subtypes. They determined the CTC number in immunohistochemical subtypes to validate if CTCs may provide differential and more specific prognostic information within each subtype. This review provides an overview of the outcome of some recently published data gathered from early and metastatic breast cancer.

How strict is galactose restriction in adults with galactosaemia? International practice.

Dietary management of 418 adult patients with galactosaemia (from 39 centres/12 countries) was compared. All centres advised lactose restriction, 6 restricted galactose from galactosides ± fruits and vegetables and 12 offal. 38% (n=15) relaxed diet by: 1) allowing traces of lactose in manufactured foods (n=13) or 2) giving fruits, vegetables and galactosides (n=2). Only 15% (n=6) calculated dietary galactose. 32% of patients were lost to dietetic follow-up. In adult galactosaemia, there is limited diet relaxation.

Responsiveness of stem-like human glioma cells to all-trans retinoic acid and requirement of retinoic acid receptor isotypes α, ß and γ.

Retinoic acid (RA) is required for development and homeostasis of the normal mammalian brain and may play a role in the initiation and progression of malignant brain tumors, such as the glioblastoma multiforme (GBM) and the gliosarcoma (Gsarc). The subpopulation of stem-like glioma cells (SLGCs) was shown to resist standard glioma radio-/chemotherapy and to propagate tumor regrowth. We used phenotypically distinct, self-renewing SLGC lines from six human GBMs, two Gsarcs, and two subcloned SLGC derivatives in order to investigate their responsiveness to all-trans retinoic acid (atRA) and to identify the RA-receptor (RAR) isotypes involved. In general, atRA exerted a pro-proliferative and pro-survival effect on SLGCs, though the efficacy was distinct. By means of RAR isotype-selective retinoids we disclosed that these effects were mediated by RARα and RARγ, except for one SLGC line, in which the pro-proliferative signal was induced by the RARß-selective retinoid. Only one GBM-derived cell line (T1338) and a subpopulation of another (T1389) displayed neural differentiation in response to atRA. Differentiation of T1338 was induced by RARα and RARγ isotype-selective retinoids, associated with down-regulation of Sox2, and the failure to induce orthotopic tumors in the brains of SCID mice. The differential responsiveness of the SLGC lines appeared unrelated to the expression of RARß, as (i) atRA augmented RAR isotype mRNA expression and particularly rarß mRNA in all SLGC lines, (ii) rarß promoter hypomethylation in the SLGC lines was not related to differentiation and (iii) the induction of T1338 differentiation was by RARα- and RARγ-selective ligands.

PKU patients on a relaxed diet may be at risk for micronutrient deficiencies.

OBJECTIVE: To investigate micronutrient supply in phenylketonuria (PKU) patients on a relaxed diet. SUBJECTS/METHODS: Sixty-seven patients (6-45 years) with a phenylalanine tolerance ≥ 600 mg/day were included in the study. From a 3-day diet record, protein supply as well as consumption of essential amino acids and several micronutrients were assessed and compared with the current recommendations and data for the healthy population. RESULTS: Protein supply and consumption of all essential amino acids were sufficient in all patients. Supply of micronutrients depended on dietary regime. Patients with a total protein supply of 120% or more of the recommended amount and at least 0.5 g protein per kg body weight from amino-acid mixture (AAM) were sufficiently supplied with all investigated micronutrients. All patients without AAM supplement showed severe micronutrient deficiencies in their diet records. CONCLUSION: PKU patients under a relaxed diet are at risk of an insufficient nutrient supply, if they have first no substitution with AAM, second a protein supply less than 0.5 g per kg body weight from AAM or third a total protein supply less than 120% of the recommendations. Therefore, close monitoring, specific dietary counseling and potential supplementation is mandatory to prevent micronutrient deficiencies in PKU patients.

Somatic deleterious mutation rate in a woody plant: estimation from phenotypic data.

We conducted controlled crosses in populations of the long-lived clonal shrub, Vaccinium angustifolium (lowbush blueberry) to estimate inbreeding depression and mutation parameters associated with somatic deleterious mutation. Inbreeding depression level was high, with many plants failing to set fruit after self-pollination. We also compared fruit set from autogamous pollinations (pollen collected from within the same inflorescence) with fruit set from geitonogamous pollinations (pollen collected from the same plant but from inflorescences separated by several meters of branch growth). The difference between geitonogamous versus autogamous fitness within single plants is referred to as 'autogamy depression' (AD). AD can be caused by somatic deleterious mutation. AD was significantly different from zero for fruit set. We developed a maximum-likelihood procedure to estimate somatic mutation parameters from AD, and applied it to geitonogamous and autogamous fruit set data from this experiment. We infer that, on average, approximately three sublethal, partially dominant somatic mutations exist within the crowns of the plants studied. We conclude that somatic mutation in this woody plant results in an overall genomic deleterious mutation rate that exceeds the rate measured to date for annual plants. Some implications of this result for evolutionary biology and agriculture are discussed.

Identifying cases of congestive heart failure from administrative data: a validation study using primary care patient records.

INTRODUCTION: To determine if using a combination of hospital administrative data and ambulatory care physician billings can accurately identify patients with congestive heart failure (CHF), we tested 9 algorithms for identifying individuals with CHF from administrative data. METHODS: The validation cohort against which the 9 algorithms were tested combined data from a random sample of adult patients from EMRALD, an electronic medical record database of primary care physicians in Ontario, Canada, and data collected in 2004/05 from a random sample of primary care patients for a study of hypertension. Algorithms were evaluated on sensitivity, specificity, positive predictive value, area under the curve on the ROC graph and the combination of likelihood ratio positive and negative. RESULTS: We found that that one hospital record or one physician billing followed by a second record from either source within one year had the best result, with a sensitivity of 84.8% and a specificity of 97.0%. CONCLUSION: Population prevalence of CHF can be accurately measured using combined administrative data from hospitalization and ambulatory care.

TITLE: Repérage des cas d'insuffisance cardiaque congestive à partir de données administratives : étude de validation utilisant des dossiers de patients en soins primaires. INTRODUCTION: En vue de déterminer si l'utilisation conjuguée des données administratives hospitalières et des factures présentées par les médecins au titre des soins ambulatoires pouvait permettre de repérer avec exactitude les patients souffrant d'insuffisance cardiaque congestive (ICC), nous avons mis à l'essai neuf algorithmes pour repérer à partir de données administratives les personnes souffrant d'ICC. MÉTHODOLOGIE: La cohorte de validation par rapport à laquelle les essais ont été effectués combinait des données provenant d'un échantillon aléatoire de patients adultes inscrits dans la base de données EMRALD de dossiers médicaux électroniques des médecins de premier recours en Ontario, au Canada, et des données recueillies en 2004-2005 à partir d'un échantillon aléatoire de patients en soins primaires pour une étude sur l'hypertension. On a évalué la sensibilité, la spécificité, la valeur prédictive positive, l'aire sous la courbe ROC et la combinaison des rapports de vraisemblance positif et négatif des algorithmes. RÉSULTATS: Nous avons constaté qu'un dossier d'hospitalisation ou de facturation de médecin suivi d'un second dossier provenant de l'une ou l'autre de ces sources dans la même année produisait les meilleurs résultats, avec une sensibilité de 84,8 % et une spécificité de 97,0 %. CONCLUSION: Nous concluons que la prévalence de l'ICC dans la population peut être mesurée avec exactitude à partir de données administratives issues de l'hospitalisation et des soins ambulatoires.

Slab coupled optical fiber sensor calibration.

This paper presents a method for calibrating slab coupled optical fiber sensors (SCOS). An automated system is presented for selecting the optimal laser wavelength for use in SCOS interrogation. The wavelength calibration technique uses a computer sound card for both the creation of the applied electric field and the signal detection. The method used to determine the ratio between the measured SCOS signal and the applied electric field is also described along with a demonstration of the calibrated SCOS involving measuring the dielectric breakdown of air.

Progestogens and membrane-initiated effects on the proliferation of human breast cancer cells.

OBJECTIVES: Evidence is accumulating that progestogens may play a crucial role in the development of breast cancer under contraception and hormone therapy in reproductive and menopausal women. Progesterone receptor membrane component 1 (PGRMC1) expressed in breast cancer may be important in tumorigenesis and thus may increase breast cancer risk. The aim of this project was to investigate the influence of progesterone and nine synthetic progestins on MCF-7 breast cancer cells overexpressing PGRMC1. METHODS: MCF-7 cells were stably transfected with PGRMC1 expression plasmid (WT-12). To test the effects of progestogerone (P) and the synthetic progestins chlormadinone acetate (CMA), desogestrel (DSG), drospirenone (DRSP), dydrogesterone (DYD), levonorgestrel (LNG), medroxyprogesterone acetate (MPA), nomegestrol (NOM) and norethisterone (NET) on cell proliferation, MCF-7 and WT-12 cells were stimulated with different concentrations (0.01-1 µmol/l). RESULTS: In MCF-7 cells, DRSP, DSG, DYD, LNG and NET increased the proliferation at 1 µmol/l, the effect being highest for NET with about 20%. In WT-12 cells, the same progestins, but additionally MPA, showed a significant increase, which was much higher (30-245%) than in MCF-7 cells. Here again, NET showed the highest proliferative effect. No effect was found for CMA, NOM and P. CONCLUSION: Some synthetic progestins trigger a proliferative response of PGRMC1-overexpressed MCF-7 cancer cells. The effect of progestogens on breast cancer tumorigenesis may clearly depend on the specific pharmacology of the various synthetic progestins.

Electrical responses to chemosensory stimulation recorded from the vomeronasal duct and the respiratory epithelium in humans.

The physiological significance of the human vomeronasal duct (VND) is still unclear. The aim of the present study was to investigate the question whether mucosal responses obtained from the VND are different from those obtained from the respiratory epithelium. There were 15 healthy subjects (8 male, 7 female; age range 19-45 years; 14 normosmic subjects, 1 anosmic subject). All subjects participated in two sessions whereby the first session was used to acquaint them with the experimental conditions. For chemical stimulation, an olfactometer was used which delivered chemical stimulants without altering mechanical or thermal conditions at the stimulated nasal mucosa. For stimulation we used substances previously reported to produce vomeronasal activation ("estra"=estra-1,3,5(10),16-tetraen-3ol and "andro"=androsta-4,16-dien-3-on); in addition, gaseous CO(2) was used as a non-odorous, relatively specific stimulant of the trigeminal nerve. Placement of electrodes either in the VND or on the respiratory epithelium was performed under endoscopical guidance. Subjects rated the overall intensity of the stimuli, the strength of trigeminally mediated sensations, and the hedonic tone of the stimulants. Responses could not be recorded from all subjects. For the remaining 7 subjects, intensity was strongest for CO(2) stimuli (p<0.001), whereas no significant difference was observed between "andro" and "estra" (p=0.33). All three stimulants produced responses at the respiratory epithelium with largest responses obtained after stimulation with CO(2). Similar findings were made for recordings inside the VND. Due to the small sample size sexual dimorphisms could not be addressed. In summary, these results seem to indicate that the presently used stimulants produce similar responses at the respiratory epithelium and in the VND which argues against a specific responsiveness of the VND epithelium to chemosensory stimuli although it has to be kept in mind that the effective sample size was small.

Afrontamiento primario con elásticos vasculares en el manejo del cierre progresivo de fasciotomías / Vessel loops for primary closure of fasciotomies

Background: Compartment syndrome of the extremity may occur after severe trauma with vascular lesions secondary to fractures, crushes or gunshots. To prevent it a fasciotomy must be done. Aim To report the use vessel loop shoelace technique for the progressive closure of the fasciotomy. Material and methods: Descnptive study of 24 patients aged 26 +/- 9 years (21 males) that required fasciotomy to prevent compartment syndromes. The fasciotomy wound was closed progressively using vessel loops anchored to the skin with staples or sutures, which were tightened progressively, according to the evolution. Results: The studied patients required a total of 56 fasciotomies. In all patients a complete or near complete closure of the wound was achieved. The mean closure time was 9.5 +/- 3.3 days. Mean hospital stay was 12.3 +/- 4.3 days. Conclusions: Vessel loop shoelace technique is effective for fasciotomy wound closure.

Frente al cada vez más frecuente manejo del trauma vascular en extremidades, debido a lesiones de distinta etiología, ya sea por accidentes de tránsito de alta velocidad, caídas de altura, o las crecientes tasas de lesiones en la vida civil por arma blanca y por arma de fuego, es que nos vemos enfrentados a múltiples tipos de lesiones vasculares que comprometen arterias y venas, asociados a extenso compromiso de partes blandas o a reintervenciones en períodos posteriores a las 6 hrs post trauma. De este modo es que el manejo asociado de la fasciotomía como método de prevención o tratamiento del síndrome compartamental es fundamental. Se presentan un total de 24 casos en los que se efectuaron 56 fasciotomías primarias o secundarias como profilaxis o tratamiento del síndrome compartamental, en las que se utilizaron elásticos vasculares para el cierre progresivo del defecto cutáneo de las fasciotomías, para disminuir el tiempo de evolución y así evitar el uso de injertos de piel en el cierre de los defectos.

Patterns of care for the initial management of cervical cancer in Ontario.

OBJECTIVE: To facilitate the planning of resources for cancer services in Ontario, Cancer Care Ontario commissioned an evaluation of operative services delivered for cervical cancer. METHODS: Women with an incident diagnosis of cervical cancer were identified from 1 April, 2003 to 31 March, 2004 using the Ontario Cancer Registry. Record linkages were created to other provincial health databases such as the Ontario Health Insurance Plan. RESULTS: There were 513 incident cases. Disease-specific rates of cancer were higher in rural areas and those from lower income quintiles. Forty-three percent of women had no surgery. Use of surgery did not appear to vary by SEC, urban/rural residence or LHIN. Women of younger age were more like to receive surgery for cervical cancer. Gynecologists conducted 63% of the operations. Gynecologics were most likely to complete a lymphadenectomy (70.3%). All women were assessed by CXR. Only 22% of women had a CT scan of the abdomen and pelvis. Radiation consults were performed in half of the women with cervix cancer but treatment was only delivered to half of those seen. Medical oncologists saw about 10% of women with cervical cancers. CONCLUSIONS: There appear to be variations in incidence rates of cervical cancer, with cancers being more frequent in rural areas. In two-thirds of the population, surgery is performed in the region where the patient lives. Subspecialty care from gynecologic oncologists was provided to one-third of women. These preliminary data would be enhanced with further information such as comorbidity, treatment intent (palliative/curative), histology, grade and stage.

Patterns of care in the initial management of women with vulvar cancers in Ontario.

BACKGROUND: To facilitate the planning of future resources for cancer services in Ontario, Cancer Care Ontario commissioned an evaluation of operative services delivered for vulvar cancer. METHODS: Women with an incident diagnosis of vulvar malignancy were identified from 1, April 2003 to 31 March, 2004 using the Ontario Cancer Registry. Record linkages were created to other provincial health databases such as the Ontario Health Insurance Plan. RESULTS: Vulvar cancers affected 148 women. Disease specific rates of cancer were higher in rural areas and in women in the lower income quintiles. No surgery occurred in 17.6% of women. Use of surgery did not appear to vary by urban/rural residence or LHIN. Ontario's 17 gynecologic oncologists performed 75% of the surgeries. Groin lymphadenectomy rate was 52.8%. Surgery was performed in the LHIN of residence for 41% of women. All women were assessed by CXR. CT scan of the abdomen and pelvis occurred in 77%. MRIs were done infrequently. Radiation consults were preformed in half of the women with vulvar cancer but treatment was only delivered in half of those seen. Medical oncologists saw about 10% of women with gynecologic cancers. CONCLUSIONS: There appear to be variations in incidence rates of vulvar cancer with disease being more frequent in rural areas. Subspecialty care from gynecologic oncologists was provided to 75% of women. Rates of lymphadenectomy as part of a surgical attempt occurred in 52.8% of women. These data would be enhanced with further information such as comorbidity, treatment intent (palliative/curative), histology, grade and stage.