Impact of socio-economic deprivation on endometrial cancer survival in the North West of England: a prospective database analysis.

OBJECTIVE: To assess the impact of socio-economic deprivation on endometrial cancer survival. DESIGN: Single-centre prospective database study. SETTING: North West England. POPULATION: Women with endometrial cancer treated between 2010 and 2015. METHODS: Areal-level socio-economic status, using the English indices of multiple deprivation from residential postcodes, was analysed in relation to survival using Kaplan-Meier estimation and multivariable Cox regression. MAIN OUTCOME MEASURES: Overall survival, cancer-specific survival and patterns and rates of recurrence. RESULTS: A total of 539 women, with a median age of 66 years (interquartile range, IQR 56-73 years) and a body mass index (BMI) of 32 kg/m2 (IQR 26-39 kg/m2 ), were included in the analysis. Women in the most deprived social group were younger (median 64 years, IQR 55-72 years) and more obese (median 34 kg/m2 , IQR 28-42 kg/m2 ) than women in the least deprived group (median age 68 years, IQR 60-74 years; BMI 29 kg/m2 , IQR 25-36 kg/m2 ; P = 0.002 and <0.001, respectively). There were no differences in endometrial cancer type, stage or grade between social groups. There was no difference in recurrence rates, however, women in the middle and most deprived social groups were more likely to present with distant/metastatic recurrence (80.6 and 79.2%, respectively) than women in the least deprived group (43.5%, P < 0.001). Women in the middle and most deprived groups had a two-fold (adjusted hazard ratio, HR = 2.00, 95% CI 1.07-3.73, P = 0.030) and 53% (adjusted HR = 1.53, 95% CI 0.77-3.04, P = 0.221) increase in cancer-specific mortality compared with women in the least deprived group. There were no differences in overall survival. CONCLUSIONS: We found that socio-economically deprived women with endometrial cancer were more likely to develop fatal recurrence. Larger studies are needed to confirm these findings and to identify modifiable contributing factors. TWEETABLE ABSTRACT: Socio-economic deprivation is linked to an increased risk of death from endometrial cancer in the North West of England.

Risk of fracture in women treated with monthly oral ibandronate or weekly bisphosphonates: the eValuation of IBandronate Efficacy (VIBE) database fracture study.

The eValuation of IBandronate Efficacy (VIBE) head-to-head database fracture study compared fracture rates between patients treated with monthly ibandronate and weekly oral bisphosphonates (BPs). This large study included women >/=45 years old, newly prescribed monthly oral ibandronate or weekly oral alendronate or risedronate, and without malignancy or Paget's disease of bone. The primary analysis included patients who were adherent to treatment during the first 90 days after the index date. The risks of hip, nonvertebral, vertebral and any clinical fracture were compared using Cox proportional hazards models and adjusted for potential confounding factors. A secondary, "intent-to-treat" analysis included all patients who received at least one BP prescription. Sensitivity analyses based on the primary analysis compared patients receiving ibandronate with patients receiving weekly alendronate or risedronate separately, and explored the effect of excluding patients with potential confounding factors from the analysis. Further sensitivity analyses varied the requirement for adherence during the first 90 days after the index date. The primary analysis population included 7345 monthly ibandronate and 56,837 weekly BP patients. Fracture rates after the 12-month observational period were <2% and fracture risk was not significantly different between patients receiving monthly ibandronate or weekly BPs for hip, nonvertebral or any clinical fracture (adjusted relative risk: hip=1.06, p=0.84; nonvertebral=0.88, p=0.255; any clinical fracture=0.82, p=0.052). Ibandronate patients had a significantly lower risk of vertebral fracture than weekly BP patients (adjusted relative risk 0.36, 95% confidence interval 0.18-0.75, p=0.006). In the secondary, "intent-to-treat" analysis, relative risks of fracture were not significantly different between treatment groups for any fracture type. The results of the sensitivity analyses were generally consistent with the primary analysis. This retrospective cohort study found that patients treated with oral monthly ibandronate or weekly BPs (alendronate and risedronate) had similar, low risks of hip fracture, nonvertebral fracture and any clinical fracture. Ibandronate patients had a significantly lower relative risk of vertebral fracture than weekly BP patients; the clinical implications of these findings require further exploration and validation.

Impact of compliance and persistence with bisphosphonate therapy on health care costs and utilization.

UNLABELLED: The impact of persistence and compliance with bisphosphonate therapy on health care costs and utilization was examined in women newly prescribed bisphosphonates. At 3 years, women who were persistent and compliant with bisphosphonate therapy had lower total costs compared with non-persistent and non-compliant women, after controlling for relevant risk factors. INTRODUCTION: The impact of persistence and compliance with bisphosphonate therapy on health care costs and utilization was examined in bisphosphonate-naïve women. METHODS: Two claims databases were used to identify women > or = 45 years of age and who filled a new bisphosphonate prescription during 2000-2002. Persistence and compliance were evaluated over 3 years. Compliance was defined as a medication possession ratio (days of bisphosphonate supply/days of follow-up) > or = 0.80; persistence was defined as no refill gaps > or = 30 days. Multivariate models accounted for potential confounders. RESULTS: This analysis included 32,944 women (mean age, 64 years) who filled a new prescription for daily or weekly alendronate (n = 26,581) or risedronate (n = 6,363). At 3 years, 37% of women were compliant and 21% of women were persistent. Unadjusted total mean health care costs were lower for the compliant vs. non-compliant and persistent vs. non-persistent cohorts. After adjusting for potential confounders, total health care costs were reduced by 8.9% for persistent patients (p < 0.001) and 3.5% for compliant patients (p = 0.014). Persistence decreased the likelihood of inpatient admission by 47%. CONCLUSION: At 3 years, women who were persistent and compliant with bisphosphonate therapy had lower total costs compared with non-persistent and non-compliant women, after controlling for relevant risk factors.

Mechanisms of Actinobacillus actinomycetemcomitans-induced expression of interleukin-8 in gingival epithelial cells.

BACKGROUND: Gingival epithelial cells (GEC) are the first cells of the periodontium to encounter known periodontal pathogens, such as Actinobacillus actinomycetemcomitans (A.a.) and, therefore, the role of this pathogen in the initiation of the inflammatory response is critical. However, little is known about the interactions of A.a. with GEC. In the present study, the mechanisms by which extracts from A.a. induced expression of the chemotactic cytokine interleukin-8 (IL-8) in GEC, in vitro, were examined. METHODS: An established GEC line, PP, was co-cultured with sonicated extracts of A.a. under various in vitro experimental conditions, and the IL-8 secretion was determined with enzyme-linked immunosorbent assay. RESULTS: A.a. extracts induced a time- and dose-dependent expression of IL-8 from the cells. Dose-response studies indicated that the highest IL-8 secretion (7-fold, P < 0.01) was at the level of 50 micrograms/ml of A.a. extract. Time-course studies revealed a dramatic increase of IL-8 expression after 12 hours of continuous stimulation. Pretreatment with polymyxin B (lipopolysaccharide [LPS] inhibitor) did not reduce the IL-8 expression induced by A.a. extracts (P > 0.10). The introduction of p38 mitogen-activated protein kinase (MAPK) inhibitor SB 203580 markedly inhibited (> 75%, P < 0.01) A.a.-induced expression of IL-8. It is concluded that A.a. extracts upregulated the basal IL-8 expression in GEC. CONCLUSIONS: The effect was LPS-independent and involved a p38 MAPK signal transducing pathway. Understanding mechanisms of proinflammatory cytokine induction is important in periodontal pathology as it may lead to novel therapeutic approaches for periodontitis, thus controlling host inflammatory responses.

Actinobacillus actinomycetemcomitans-induced expression of IL-1alpha and IL-1beta in human gingival epithelial cells: role in IL-8 expression.

Gingival epithelial cells (GEC) are the first cells of the host that encounter the periodontal pathogens. and therefore their role in the initiation of the inflammatory response is critical. We aimed to: 1) characterize the expression of interleukin (IL)- Ialpha and IL-Ibeta in human gingiva and cultured GEC: 2) demonstrate the ability of A. actinomycetemcomitans extracts to upregulate IL-1alpha, IL-1beta and IL-8 expression in GEC in vitro: and 3) characterize the role of IL-1alpha and IL-1beta in the induction of IL-8 expression in GEC in vitro. Ten gingival biopsies (5 inflamed and 5 controls) and cultured GEC were examined for IL-1alpha and IL-Ibeta using immunohistochemical techniques. GEC were also challenged with A. actinomycetemcomitans extracts or IL-1alpha, and secretion of IL-1 and IL-8 was determined by ELISA. In vivo, IL-lalpha and IL-1beta were localized in the gingival epithelium and the infiltrating leukocytes. In vitro, A. actinomycetemcomitans extracts induced a time-dependent expression of IL-1alpha, IL-1beta and IL-8 in GEC. IL-1 inhibitors did not affect A. actinomycetemcomitans-induced IL-8. although they inhibited IL-8 induced by IL-1alpha or IL-1beta. In conclusion, GEC are a major source of IL-1alpha and IL-1beta in the periodontium, which in turn induce additional inflammatory mediators such as IL-8. Therefore GEC can be a potential target for therapeutic intervention in the future.

Oral mucosal lesions and HIV viral load in the Women's Interagency HIV Study (WIHS).

The prevalence of oral lesions was assessed in a five-center subset of the Women's Interagency HIV Study (WIHS) and correlated with other features of HIV disease. Oral examinations were performed by dental examiners on 729 women (577 HIV-positive and 152 HIV-negative) during baseline examination. Significant differences between the groups were found for the following oral lesions: pseudomembranous candidiasis, 6.1% and 2.0%, respectively; erythematous candidiasis, 6.41% and 0.7%, respectively; all oral candidiasis, pseudomembranous and/or erythematous, 13.7% and 3.3%, respectively. Hairy leukoplakia was observed in 6.1% of HIV-positive women. No significant differences were found for recurrent aphthous ulcers, herpes simplex lesions, or papillomas. Kaposi's sarcoma was seen in 0.5% of HIV-positive and 0% of HIV-negative women. Using multiple logistic regression models controlling for use of antiretrovirals and antifungals, in HIV-positive women the presence of oral candidiasis was associated with a CD4 count <200 cells/microl, cigarette smoking, and heroin/methadone use; the presence of hairy leukoplakia was not related to CD4 count but was associated with high viral load. Oral candidiasis and hairy leukoplakia are confirmed as being common features of HIV infection in women and appear to be associated with HIV viral load, immunosuppression, and various other behaviorally determined variables.

The impact of antidepressant use on social functioning: reboxetine versus fluoxetine.

Depression compromises affected individuals' functional well-being and impairs their level of social and workplace performance. Improved social functioning in depressed patients may improve their work productivity. This study evaluated the differential effects of two antidepressants on social functioning outcomes for patients with major depression comparing reboxetine, a non-tricyclic, selective noradrenaline reuptake inhibitor and fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor. A model using data from 284 depressed patients (138 reboxetine, 146 fluoxetine) in two 8-week clinical trials was developed to predict the percentage change over time in continuous outcome assessments as measured by a 21-item self-rating scale called the Social Adaptation Self-evaluation Scale (SASS). The percentage change from baseline SASS score was modelled as a function of both time-invariant and time-varying covariates. Results suggest that, by mid-study, the more severely ill subjects benefitted more from reboxetine treatment in terms of the outcome improvement rate and, by study-end, this effect also extended into the less severely ill population. In addition, a significant relationship was identified between the change in depression symptom severity as measured by the standard Hamilton Depression Rating Scale score and the change in social functioning per the SASS.

Evaluation of quick medical reference (QMR) as a teaching tool.

To determine whether the Quick Medical Reference (QMR) program can improve diagnosis or enhance learning among internal medicine residents, we compared the diagnostic accuracy of the program with that of residents at various training levels. The cases were from a prospective convenience sample of 40 patients admitted by 10 first-year residents (interns) and two chief medical residents. Four sets of differential diagnoses were created for each case--the first set by an intern, the second set by a chief resident, and the third and fourth sets by QMR, using the findings of the interns and chief residents, respectively. The diagnostic accuracy of the interns and chief residents was significantly greater than that of QMR. However, the chief residents indicated that QMR did increase their understanding of disease processes and offered educational value.

Detection of HIV in oral mucosal cells.

OBJECTIVE: To determine the prevalence of HIV DNA and RNA and the morphologic localization of HIV in the oral cavity of HIV-seropositive subjects. DESIGN: A cross-sectional analysis of saliva, buccal scrapings and buccal biopsies from HIV-seropositive injecting drug users (IDUs). SUBJECTS AND METHODS: Whole saliva, buccal mucosal scrapings and buccal biopsies were obtained from HIV-seropositive and seronegative IDUs. Presence of HIV DNA and RNA was assessed by polymerase chain reaction (PCR) and reverse transcriptase PCR (RT-PCR). RT in situ PCR was used to detect HIV tat/rev RNA in buccal mucosal scrapings. Host-cell integrated HIV-proviral DNA in buccal biopsies was detected by in situ PCR. Presence of intact HIV viral particles in buccal scrapings was assessed by electron microscopy. RESULTS: HIV DNA was detected in 40% (18/45) and HIV RNA in 69.2% (25/36) of saliva samples from HIV-seropositive IDUs. Viral particles consistent with HIV were localized in inter-epithelial spaces by electron microscopy. RT in situ PCR revealed the presence of HIV tat/rev RNA in 36% (8/22) of the seropositive samples tested. CONCLUSIONS: Our results suggest that epithelial cells can be productively infected by HIV. Epithelial cells in buccal mucosa may acquire HIV in the basal layers through contact with submucosal HIV-positive lymphocytes and/or Langerhans' cells. HIV infection may also spread by inter-epithelial cell contact. As HIV infected cells mature they travel to more superficial layers and are shed into the oral cavity.

Clinical and radiographic presentations of HIV-1 necrotizing ulcerative periodontitis.

HIV-1-associated periodontal diseases have been reported in the literature for several years. Criteria for the diagnosis of these diseases have not been universally accepted, although there are numerous papers describing the clinical entity. These case reports provide clinical and radiographic evidence of a type of periodontal disease with bone and soft tissue destruction which differentiates it from "conventional" periodontal diseases found in both HIV-1-infected patients and those not infected by the virus. It is important, from both diagnostic and therapeutic aspects, for clinicians to be able to make this distinction. The appropriate use of clinical and radiographic findings is extremely helpful in the diagnosis, particularly in the case of defining HIV-1 necrotizing ulcerative periodontitis (NUP). Whether the patterns of gingival changes and bone loss described in these case reports are specific to HIV-1-seropositive persons or rather represent severe immunosuppression requires further investigation.

Oral HIV-I recovery in the presence of periodontal disease.

OBJECTIVE: To determine whether a significant association occurs between the presence of various periodontal diseases and recoverable infectious HIV-I in the saliva of injecting drug users. DESIGN: Five hundred and fifty-one injecting drug users were recruited from various programs associated with the Beth Israel Medical Center. Examiners were 'blinded' to the subject's HIV-I serostatus. A socio-economic and risk factors' survey was conducted and a complete oral examination, including periodontal disease indices was performed. Whole saliva and blood were collected for virus culture. MAIN OUTCOME MEASUREMENTS: Recovery of infectious HIV-I in saliva related to presence of periodontal diseases. RESULTS: Those HIV-I seropositive subjects with periodontal diseases did not differ from those HIV-I seropositive subjects without periodontal disease in mean age and immune status. Less than 1% of the HIV-I seropositive subjects had cultivable HIV-I in their saliva while it was present in 78% of PBMCs and 35% of the sera. There was no significant association between infectious HIV-I in saliva, serum, or PBMCs and any of the various periodontal diseases. CONCLUSIONS: The presence of periodontal disease in HIV-I seropositive injecting drug users does not appear to be a potential risk factor for infectious HIV-I in saliva, probably due to the various anti-viral components of saliva.

Periodontal problems related to HIV-1 infection.

The prevalence of periodontal diseases in HIV-infected infected persons is unresolved. While numerous reports have been published, the data are conflicting in part due to different populations studied, lack of consensus criteria for disease, study location, and biased samples. This presentation will be a collation of information available for the diagnosis and treatment of HIV/AIDS-associated periodontal diseases. The use of "HIV" is no longer accepted as a diagnostic designation. Instead, the diagnostic categories of atypical gingivitis (erythematous gingival banding), necrotizing gingivitis, necrotizing periodontitis, and necrotizing stomatitis and distinguishing characteristics will be presented. It is essential that a distinction be made between those periodontal lesions that may occur in seropositive and seronegative individuals and those which appear to have more specific signs and symptoms associated with HIV infection and with immunosuppression in general. A simplified algorithm has been developed to help differentiate between periodontal diseases specific to the HIV-positive individual and those in the general population. Additionally, the grid may also be used to distinguish the different periodontal diseases known to be associated with HIV infection.

Infection of oral mucosal cells by human immunodeficiency virus type 1 in seropositive persons.

Molecular studies have revealed significant amounts of human immunodeficiency virus type 1 (HIV-1) provirus DNA in saliva of HIV-infected persons. However, cellular localization has not been determined. In situ polymerase chain reaction (IS-PCR) was done on saliva-associated cells for localization of HIV-1 provirus DNA. Results indicate its presence in the nuclei of saliva-associated epithelial cells in 29 (83%) of 35 HIV-1-seropositive subjects. In 24 (83%) of the 29 IS-PCR-positive samples, 0.1%-4.0% of the mucosal epithelial cells exhibited nuclear localization of HIV-1 DNA. In addition, HIV-1 provirus DNA was detected in monocytes or lymphocytes of all salivary samples from the 35 subjects. The localization of HIV-1 provirus DNA indicates that epithelial cells are another cell type infected by HIV-1 in vivo. These findings suggest epithelial cells in other body sites might also be infected with HIV-1.

Practical considerations in the treatment of the HIV-infected patient.

The HIV-infected patient presents a special challenge to the dentist because of the concerns relative to the diagnosis and management of their oral problems. Concerns about the patient's medical history, medications, and compromising health status, however, make the HIV-positive patient no more special than any other patient with these concerns. These principles of concern apply to all patients; infection control in the dental office no longer relates to any particular group of patients but to all who seek care and all who provide it. Through continuing education, dentists should become more comfortable in accepting HIV-positive patients in their offices, and through actually providing necessary dental treatment to all individuals, they should no longer consider the HIV-positive patient as special. Dentists need to maintain close contact with the infected patient's physician, however, to ensure maximum appropriate care and minimize any risk to the patient's general health as a result of dental treatment.

HIV-associated oral lesions; immunologic, virologic and salivary parameters.

There are numerous reports of oral lesions in HIV-infected individuals. However, few correlate the oral lesions with laboratory parameters. This study examined oral candidiasis and hairy leukoplakia, the two most common HIV-associated oral lesions, in relation to T-cell counts, p24 core antigen levels and salivary flow rates. Oral mucosal examinations, immunologic and virologic studies and stimulated whole and parotid saliva flow rates were conducted on 135 (HIV+ = 102, HIV- = 33) homosexual or bisexual men. Results indicate that, among HIV-infected subjects, the odds of having oral candidiasis is 6 times (95% CI = 0.6-56.6) greater for subjects with T4 counts between 200-399 per mm3, and 23 times (95% CI = 2.8-193.0) greater for subjects with T4 counts less than 200/mm3 compared to subjects with T4 counts of 400/mm3 or greater. Subjects had an equal likelihood of having hairy leukoplakia at different levels of immunocompetence. The prevalence of oral candidiasis and hairy leukoplakia was higher among subjects with infectious virus in their serum, but was only statistically significant for hairy leukoplakia (p = 0.01).

Longitudinal study of parotid saliva in HIV-1 infection.

Parotid flow rate and chemistry of 78 HIV + gay/bisexual men and 27 HIV-gay/bisexual controls were compared on a longitudinal basis at 4-month intervals over a 1 yr period for changes indicative of inflammatory or autoimmune diseases of the salivary glands, or reduced protective capacity toward oral opportunistic infection. Parotid saliva was examined for concentrations of sodium, chloride, phosphate, total protein, lysozyme, lactoferrin, secretory IgA, salivary peroxidase, histatin and albumin. Chloride, lysozyme and peroxidase were significantly higher in HIV + at all 3 examinations and increased in concentration over time. Although mean values for stimulated flow rate were not significantly different in the two groups over the year, there was a significant increase in the number of HIV + with reduced flow over time. In 6% of HIV + there was a marked reduction in flow rate and Sjögren's syndrome-like elevations in parotid chemistry but no enlargement. At all examinations low flow rate was significantly related to oral candidiasis; T4 levels were inversely related to oral candidiasis, but not to concentration of salivary components or flow rate; nor was AZT use. As a group the HIV + patients maintained normal flow rate and secreted normal or elevated concentrations of protective proteins. A subgroup, however, exhibited diminished flow over time and an increasing tendency to oral candidiasis and a diminution in output of histatins.

Oral manifestations of HIV infection. Definitions, diagnostic criteria, and principles of therapy. The U.S.A. Oral AIDS Collaborative Group.

A set of definitions and diagnostic criteria for the more common oral features of human immunodeficiency virus infection were prepared as the result of a consensus reached by a group of dental and medical clinicians, epidemiologists, and other experts. These are intended for use in epidemiologic surveys, where the presumptive diagnoses are recommended, and in clinical care, pathogenesis and therapy studies, where the definitive diagnoses are appropriate.

Recovery of infectious HIV-1 from whole saliva.

Whole saliva and serum samples were collected from 75 HIV-infected homosexual or bisexual men. Thirty-eight percent of cultured sera were positive for cell-free, infectious virus while only 1 percent of the 218 cultured whole salivas contained cell-free, infectious virus. These data support previous studies suggesting unlikely potential transmissibility of HIV infection by saliva.