The effects of glycemic index on prostate cancer progression in a xenograft mouse model.

BACKGROUND: Previously, we found low-carbohydrate diets slowed prostate cancer (PC) growth and increased survival vs. a Western diet in mice, by inhibiting the insulin/IGF-1 axis. Thus, we tested whether modifying carbohydrate quality to lower glycemic index (GI) without changing quantity results in similar benefits as with reduced quantity. METHODS: Male SCID mice injected with LAPC-4 cells were single-housed and randomized when their tumors reached 200 mm3 on average to a LoGI (48% carbohydrate kcal, from Hylon-VII) or HiGI Western diet (48% carbohydrate kcal, from sucrose). Body weight and tumor volume were measured weekly. Body composition was assessed 35 days after randomization. Blood glucose and serum insulin, IGF-1 and IGFBP3 were measured at study end when tumor volumes reached 800 mm3. We analyzed gene expression of mice tumors by RNA-sequencing and human tumors using the Prostate Cancer Transcriptome Atlas. RESULTS: There were no significant differences in tumor volume (P > 0.05), tumor proliferation (P = 0.29), and overall survival (P = 0.15) between groups. At 35 days after randomization, the LoGI group had 30% lower body fat (P = 0.007) despite similar body weight (P = 0.58). At sacrifice, LoGI mice had smaller livers (P < 0.001) and lower glucose (P = 0.15), insulin (P = 0.11), IGF-1 (P = 0.07) and IGF-1:IGFBP3 ratio (P = 0.05), and higher IGFBP3 (P = 0.09) vs. HiGI, although none of these metabolic differences reached statistical significance. We observed differential gene expression and pathway enrichment in mice tumors by diet. The most upregulated and downregulated gene in the LoGI group showed expression patterns more closely resembling expression in human benign prostate tissue vs. PC. CONCLUSIONS: In this single mouse xenograft model, consuming a low GI diet did not delay PC growth or survival vs. a high GI diet despite suggestions of decreased activation of the insulin/IGF-1 pathway. These data suggest that improving carbohydrate quality alone while consuming a high carbohydrate diet may not effectively slow PC growth.

Validation of the prostate cancer comorbidity index in predicting cause-specific mortality in men undergoing radical prostatectomy.

PURPOSE: Accurate prediction of competing risks of mortality remains a key component of prostate cancer treatment decision-making. We sought to validate the Prostate Cancer Comorbidity Index (PCCI) score for predicting other-cause mortality (OCM) and cancer outcomes in men undergoing radical prostatectomy (RP). MATERIALS AND METHODS: We sampled 4857 men with prostate cancer treated with RP in the VA from 2000-2018. Risks of OCM, 90-day all-cause mortality (ACM), prostate cancer-specific mortality, metastasis, and biochemical recurrence by PCCI score were assessed using Cox proportional hazards and logistic regression. We compared prediction of 90-day ACM between PCCI and the American Society of Anesthesiology (ASA) score, a validated predictor of short-term mortality. RESULTS: Over median follow-up of 6.7 years (IQR 3.7-10.3), there was a stepwise increase in risk of OCM with higher PCCI score, with hazards (95%CI) of 1.53 (1.14-2.04), 2.11 (1.55-2.88), 2.36 (1.68-3.31), 3.61 (2.61-4.98), and 4.99 (3.58-6.96) for PCCI 1-2, 3-4, 5-6, 7-9, and 10 + (vs. 0), respectively. Projected 10-year cumulative incidence of OCM was 8%, 12%, 16%, 19%, 26%, and 32% for scores of 0, 1-2, 3-4, 5-6, 7-9, and 10+ , respectively. Men with PCCI 7+ had greater odds of 90-day ACM (OR 3.48, 95%CI 1.26-9.63) while men with higher ASA did not. Higher PCCI score was associated with worse cancer outcomes, with the highest categories driving the associations. CONCLUSIONS: The PCCI is a robust measure of short- and long-term OCM after RP, validated for use in clinical care and health services research focusing on surgical patient populations.

Associations between Awareness of Sexually Transmitted Infections (STIs) and Prevalence of STIs among Sub-Saharan African Men and Women.

Treatments for HIV and other STIs are not readily available in sub-Saharan Africa and other resource-limited areas, where the prevalence of HIV and other STIs is high. In the absence of treatment and laboratory infrastructure to monitor treatment efficacy, increasing awareness of STIs and STI screening are crucial components of STI prevention programs. In the current study, we sought to estimate the awareness of STIs in resource-limited countries and evaluate the strength of the association between the awareness of STIs and STIs infection. We did a secondary analysis of data obtained from 2019 women and 794 men enrolled in a community-based study that was conducted from November 2002 to March 2003 in the Moshi Urban District of Northern Tanzania. We found gonorrhea, syphilis, and HIV/AIDS were well-known among the study participants. However, their awareness of other STIs, including herpes, was very low. We also found that the awareness of STIs was not associated with STIs in men, but women who had prior knowledge of gonorrhea, syphilis, and HIV had a twofold higher risk of testing positive for an STI. Education programs aimed at increasing awareness of STIs are needed in the region. The majority of the existing STI education programs in the region focus exclusively on HIV/AIDS. The expansion of the existing AIDS/HIV education programs needs to be strengthened to include information about other STIs.

Association of the COVID-19 Pandemic With Rates of Prostate Cancer Biopsies and Diagnoses in Black vs White US Veterans.

Importance: Several studies have assessed the negative effect of the COVID-19 pandemic on cancer screening and diagnosis rates. However, this has not been evaluated for prostate biopsy and prostate cancer (PC) diagnosis in an equal-access health care system. Objective: To determine the association of the pandemic with prostate biopsy and PC diagnosis rates among Black vs White patients in the Veterans Affairs Health Care System (VAHCS). Design, Setting, and Participants: This cohort study included a retrospective analysis of all prostate biopsies performed on patients in the VAHCS without a preexisting PC diagnosis between January 2018 and March 2021. The base population included all living male patients who had at least 1 visit to the VAHCS during the 3 years prior to each month of the study. Exposure: The COVID-19 pandemic. Main Outcomes and Measures: The main outcomes were the number of prostate biopsies and PC diagnoses by month. The influence of the pandemic on prostate biopsy volume and the incidence of PC diagnoses was modeled using an interrupted time-series analysis. Poisson generalized linear models were fitted to project the expected number of prostate biopsies and PC diagnoses had there been no pandemic interruption. Additional models were used to test for differences by race. Results: Prior to the pandemic (January 2018 through February 2020), monthly biopsy numbers among 51 606 included men ranged between 1230 and 1695, of which 56% to 60% of results were positive for PC. The estimated number of missed PC diagnoses from March 2020 through March 2021 ranged from 97 cases (October 2020: 752 cases expected, 655 cases observed) to 573 cases (April 2020: 794 cases expected, 221 cases observed). Prior to the pandemic, biopsy rates were statistically significantly higher among Black vs White men (incidence rate ratio, 2.25; 95% CI, 2.06-2.46; P < .001). There was no change in biopsy rates associated with race at the onset of the pandemic nor during the recovery period from March 2020 to March 2021. Similar trends were observed for PC diagnosis rates. Conclusions and Relevance: Results of this cohort study demonstrate that during the COVID-19 pandemic, prostate biopsy and PC diagnosis rates decreased, particularly during the peak of the pandemic. However, there were no statistically significant changes in rates by race.

Radium-223 Utilization Patterns and Outcomes in Clinical Practice.

INTRODUCTION: Radium-223 was approved for metastatic castration-resistant prostate cancer based on the ALSYMPCA trial. We characterize radium-223 treatment patterns and overall survival (OS) in a large equal access health system. METHODS: We identified all men within the Veterans Affairs (VA) Healthcare System who received radium-223 between January 2013 and September 2017. Patients were followed until death or last followup. We abstracted all treatments received prior to radium; no treatments after radium were abstracted. Our primary aim was understanding practice patterns, and secondary outcome was the association between treatment pattern and OS measured using Cox models. RESULTS: We identified 318 bone metastatic castration-resistant prostate cancer patients who received radium-223 within the VA Healthcare System. Of these patients 277 (87%) died during followup. The 5 predominant treatment patterns that encompassed 88% of patients (279/318) were 1) androgen receptor-targeted agent (ARTA)-radium, 2) docetaxel-ARTA-radium, 3) ARTA-docetaxel-radium, 4) docetaxel-ARTA-cabazitaxel-radium and 5) radium alone. Median OS was 11 months (95% CI 9.7-12.5). Men who received ARTA-docetaxel-radium had the worst survival. All other treatments had similar outcomes. Only 42% of patients completed the full 6 injections; 25% received only 1 or 2 injections. CONCLUSIONS: We identified the most common radium-223 treatment patterns and their association with OS within the VA population. The better survival in ALSYMPCA (14.9 months) vs our study (11 months) along with 58% of patients not receiving the full radium-223 course suggests radium is being used later in the disease course in the real world in a more heterogeneous population.

Association between Delay to Radical Prostatectomy and Clinically Meaningful Outcomes among Patients with Intermediate and High-Risk Localized Prostate Cancer.

PURPOSE: There are limited data regarding the effect of treatment delays on important long-term outcomes among men with intermediate/high-risk prostate cancer (PC). MATERIALS AND METHODS: We identified 3,962 men with intermediate/high-risk disease from the SEARCH cohort treated with radical prostatectomy (RP) from 1988 to 2018. Cox proportional hazard models assessed the association between time from biopsy to RP (up to 1 year) and time to castration-resistant PC (CRPC), metastasis and all-cause mortality. Interaction terms were used to test for effect modification by risk group. RESULTS: Of the 3,962 men, 167 developed CRPC, 248 developed metastases and 884 died after a median followup of 85 months. Longer delays between biopsy and RP were associated with a decreased risk of CRPC (adjusted HR=0.88, 95% CI: 0.80-0.98, p=0.02), independent of D'Amico risk group (interaction p >0.05). In men with intermediate and high-risk disease, we found no statistically significant association between length of time to RP and risk of developing metastases (p=0.5 and 0.9, respectively) or all-cause mortality (p=0.1 and 0.1, respectively). CONCLUSIONS: Among men with intermediate and high-risk PC, we found no statistically significant increased risk of adverse long-term outcomes, including CRPC, metastasis and death, for men who had treatment delays up to 1 year following PC diagnosis.

Non-Disposable Assignments for Remote Neuroscience Laboratory Teaching Using Analysis of Human Data.

To accomplish discovery learning in a remote educational context, while also addressing disparities in laboratory facility/equipment access, instructors can assign Non-Disposable Assignments (NDA) whereby students design research projects, extract data from public sources, analyze data in a cloud-based environment, and share potentially original findings. Unlike typical course assignments (e.g., lab-reports, tests) that remain in the student-teacher dyad, NDAs (e.g., disseminated presentations, visualizations, manuscripts) are associated with enhanced learning and facilitate the integration of diverse student perspectives in the creation, analysis and dissemination of neuroscience. Illustrating the design of a project-based approach to teaching neuroscience laboratory courses, we provide two example NDAs using neural imaging and physiological information available from public databases. We provide a data set in a directly usable form for teaching with R, and present an overview of two user-friendly tools, RStudio and R-Markdown, for remote teaching and learning through data analysis.

A Novel Test of the Duchenne Marker: Smiles After Botulinum Toxin Treatment for Crow's Feet Wrinkles.

Smiles that vary in muscular configuration also vary in how they are perceived. Previous research suggests that "Duchenne smiles," indicated by the combined actions of the orbicularis oculi (cheek raiser) and the zygomaticus major muscles (lip corner puller), signal enjoyment. This research has compared perceptions of Duchenne smiles with non-Duchenne smiles among individuals voluntarily innervating or inhibiting the orbicularis oculi muscle. Here we used a novel set of highly controlled stimuli: photographs of patients taken before and after receiving botulinum toxin treatment for crow's feet lines that selectively paralyzed the lateral orbicularis oculi muscle and removed visible lateral eye wrinkles, to test perception of smiles. Smiles in which the orbicularis muscle was active (prior to treatment) were rated as more felt, spontaneous, intense, and happier. Post treatment patients looked younger, although not more attractive. We discuss the potential implications of these findings within the context of emotion science and clinical research on botulinum toxin.

Factors contributing to disparities in mortality among patients with non-small-cell lung cancer.

Historically, non-small-cell lung cancer (NSCLC) patients who are non-white, have low incomes, low educational attainment, and non-private insurance have worse survival. We assessed whether differences in survival were attributable to sociodemographic factors, clinical characteristics at diagnosis, or treatments received. We surveyed a multiregional cohort of patients diagnosed with NSCLC from 2003 to 2005 and followed through 2012. We used Cox proportional hazard analyses to estimate the risk of death associated with race/ethnicity, annual income, educational attainment, and insurance status, unadjusted and sequentially adjusting for sociodemographic factors, clinical characteristics, and receipt of surgery, chemotherapy, and radiotherapy. Of 3250 patients, 64% were white, 16% black, 7% Hispanic, and 7% Asian; 36% of patients had incomes <$20 000/y; 23% had not completed high school; and 74% had non-private insurance. In unadjusted analyses, black race, Hispanic ethnicity, income <$60 000/y, not attending college, and not having private insurance were all associated with an increased risk of mortality. Black-white differences were not statistically significant after adjustment for sociodemographic factors, although patients with patients without a high school diploma and patients with incomes <$40 000/y continued to have an increased risk of mortality. Differences by educational attainment were not statistically significant after adjustment for clinical characteristics. Differences by income were not statistically significant after adjustment for clinical characteristics and treatments. Clinical characteristics and treatments received primarily contributed to mortality disparities by race/ethnicity and socioeconomic status in patients with NSCLC. Additional efforts are needed to assure timely diagnosis and use of effective treatment to lessen these disparities.

Reemergence of Intravenous Drug Use as Risk Factor for Candidemia, Massachusetts, USA.

The epidemic of illicit intravenous drug use (IVDU) in the United States has been accompanied by a surge in drug overdose deaths and infectious sequelae. Candida albicans infections were associated with injection of contaminated impure brown heroin in the 1970s-1990s; however, candidiasis accompanying IVDU became considerably rarer as the purity of the heroin supply increased. We reviewed cases of candidemia occurring over a recent 7-year period in persons >14 years of age at a tertiary care hospital in central Massachusetts. Of the 198 patients with candidemia, 24 cases occurred in patients with a history of IVDU. Compared with non-IVDU patients, those with a history of IVDU were more likely to have non-albicans Candida, be co-infected with hepatitis C, and have end-organ involvement, including endocarditis and osteomyelitis. Thus, IVDU appears to be reemerging as a risk factor for invasive candidiasis.

Topical Clonazepam Solution for the Management of Burning Mouth Syndrome: A Retrospective Study.

AIMS: To evaluate and compare the effectiveness of two concentrations of topical clonazepam solution in improving symptoms of burning mouth syndrome (BMS). METHODS: A retrospective chart review was conducted of patients diagnosed with BMS and managed with topical clonazepam solution between 2008 and 2015. A 0.5-mg/mL solution was prescribed until 2012, when this was changed to a 0.1 mg/mL solution. Patients were instructed to swish with 5 mL for 5 minutes and spit two to four times daily. The efficacies of the two concentrations were compared using patient-reported outcome measures at the first follow-up, including the reported percentage of improvement in burning symptoms and the change in burning severity from baseline ranked on an 11-point numeric rating scale (NRS). Response to treatment was compared between the two concentrations using Wilcoxon rank sum test. RESULTS: A total of 57 subjects were included, 32 in the 0.1-mg/mL cohort and 25 in the 0.5-mg/mL cohort, and evaluated at a median follow-up of 7 weeks. The median overall percentage improvement was 32.5% in the 0.1-mg/mL cohort and 75% in the 0.5-mg/mL cohort. The median reduction in NRS score was 0.5 points in the 0.1-mg/mL cohort and 6 points in the 0.5-mg/mL cohort. The use of either outcome measure revealed that the response to treatment with the 0.5-mg/mL solution was superior to that of the 0.1 mg/mL solution (P < .01). CONCLUSION: These findings suggest that a 0.5-mg/mL topical clonazepam solution is effective in the management of BMS. Future randomized clinical trials are warranted.

Safety and tolerability of topical clonazepam solution for management of oral dysesthesia.

OBJECTIVES: The aim of the study was to determine the absolute and relative safety of treatment with 2 concentrations of topical clonazepam solution (0.1 mg/mL, 0.5 mg/mL) for management of oral dysesthesia. STUDY DESIGN: The study was a retrospective chart review of patients diagnosed with oral dysesthesia and managed with topical clonazepam solution (swish and spit) between 2008 and 2015. The relative safety of the 2 concentrations was evaluated in terms of occurrence of adverse drug reactions (ADRs) and occurrence of change to treatment plan secondary to ADRs. RESULTS: For the study, 162 patients were included-84 patients in the 0.1 mg/mL cohort and 78 in the 0.5 mg/mL cohort, who were evaluated for a median follow-up period of 6 weeks. Thirty-eight (23%) patients developed ADRs. The most frequently reported ADR was sedation (62% of ADRs), followed by altered mental status and dizziness (7% each). Dose adjustments were required in 9 patients (6%) and treatment discontinuation in 13 (8%). ADRs were more frequently reported in the 0.5 mg/mL cohort, but no significant difference was found in terms of occurrence of ADRs, change to treatment plan secondary to ADRs, or types of ADRs (P > .05). CONCLUSIONS: Treatment with topical clonazepam solution in either 0.5 mg/mL or 0.1 mg/mL concentration appears to be safe and well-tolerated. Future prospective studies are needed to confirm this finding.

Utilization of Compounded Medications in an Oral Medicine Practice.

For many oral medicine conditions, the use of compounded topical therapies that are locally absorbed and act directly at the affected site can provide greater efficacy compared with systemically delivered medications while minimizing systemic side effects. The objective of this study was to characterize the utilization and costs associated with the use of compounded medications in an academic, hospital-based oral medicine practice. This was a retrospective analysis of outpatients treated at the Center for Oral Disease at Brigham and Women's Hospital (Boston, Massachusetts) during the five-year period from November 2006 through November 2011. Patient prescription and payment information were obtained from the pharmacy's patient database. Variables included prescription compound, number of prescriptions refilled, prescription cost, and payment contributions from insurance and patients. An electronic medical record review was conducted to obtain patient demographics and diagnoses. There were 510 unique perscriptions corresponding to 423 patients filled during the study period. Four distinct medications comprised the majority (479/510; 94%) of prescriptions filled. The vast majority (94%) of prescriptions filled were at least partially paid for by insurance, with median patient co-pays ranging from $21 (clonazepam solution) to $34 (ketoprofen cream). Compound medications provide an affordable, flexible therapeutic option for patients being treated for a variety of oral medicine conditions.

Survival among Never-Smokers with Lung Cancer in the Cancer Care Outcomes Research and Surveillance Study.

RATIONALE: Differences in patient characteristics and outcomes have been observed among current, former, and never-smokers with lung cancer, but most prior studies included few never-smokers and were not prospective. OBJECTIVES: We used data from a large, prospective study of lung cancer care and outcomes in the United States to compare characteristics of never-smokers and smokers with lung cancer and to examine survival among the never-smokers. METHODS: Smoking status at diagnosis was determined by self-report and survival was determined from medical records and cancer registries, with follow-up through June 2010 or later. Cox regression was used to examine the association between smoking and survival, and to identify predictors of survival among never-smokers. MEASUREMENTS AND MAIN RESULTS: Among 3,410 patients with lung cancer diagnosed between September 1, 2003 and October 14, 2005 who completed a baseline patient survey, there were 274 never-smokers (8%), 1,612 former smokers (47%), 1,496 current smokers or smokers who quit recently (44%), and 28 with missing information about smoking status (<1%). Never-smokers appeared more likely than former and current/recent smokers to be female and of Asian or Hispanic race/ethnicity, and to have adenocarcinoma histology, fewer comorbidities, private insurance, and higher income and education. Compared with never-smokers, the adjusted hazard of death from any cause was 29% higher among former smokers (hazard ratio, 1.29; 95% confidence interval, 1.08-1.55), and 39% higher among current/recent smokers (hazard ratio, 1.39; 95% confidence interval, 1.16-1.67). Factors predicting worse overall survival among never-smokers included Hispanic ethnicity, severe comorbidity, undifferentiated histology, and regional or distant stage. Never-smoking Hispanics appeared more likely to have regional or advanced disease at diagnosis and less likely to undergo surgical resection, although these differences were not statistically significant. CONCLUSIONS: Never-smokers with lung cancer are more likely than ever-smokers to be female, Asian or Hispanic, and more advantaged socioeconomically, suggesting possible etiologic differences in lung cancer by smoking status. Among never-smokers, Hispanics with lung cancer had worse survival than non-Hispanic whites.

Pain severity and mobility one year after spinal cord injury: a multicenter, cross-sectional study.

BACKGROUND: Following a spinal cord injury, patients are often burdened by chronic pain. Preliminary research points to activation of the motor cortex through increased mobility as a potential means of alleviating postinjury chronic pain. AIM: The aim of this study was to assess the relationship between pain severity and mobility among patients who have sustained a traumatic spinal cord injury while controlling for clinically-relevant covariates. DESIGN: A multi-center, cross-sectional study. SETTING: The SCIMS is composed of 14 centers, all located in the United States and funded by the National Institute on Disability and Rehabilitation Research (NIDRR). POPULATION: The study cohort included 1980 patients who completed the one-year SCIMS follow-up assessment between October 2000- December 2013. METHODS: A multi-center, cross-sectional study was performed to assess the impact of mobility on self-reported pain using information from 1980 subjects who sustained a traumatic spinal cord injury and completed a year-one follow-up interview between October 2000 and December 2013. Patient information was acquired using the Spinal Cord Injury National Database, compiled by the affiliated Spinal Cord Injury Model Systems. Analyses included a multivariable linear regression of patients' self-reported pain scores on mobility, quantified using the CHART-SF mobility total score, and other clinically relevant covariates. RESULTS: After controlling for potential confounders, a significant quadratic relationship between mobility and patients' self-reported pain was observed (P=0.016). Furthermore, female gender, "unemployed" occupational status, paraplegia, and the presence of depressive symptoms were associated with significantly higher pain scores (P<0.02 for all variables). Statistically significant quadratic associations between pain scores and age at injury, life satisfaction total score, and the CHART-SF occupational total subscale were also observed (P≤0.03 for all variables). CONCLUSIONS: Among patients with moderate to high levels of mobility, pain scores decreased with increasing mobility. CLINICAL REHABILITATION IMPACT: Enhancing a patient's physical activity by increasing his or her mobility may reduce neuropathic pain if begun shortly after a spinal cord injury.

Racial Disparities in Health-Related Quality of Life After Lung Cancer Surgery: Findings From the Cancer Care Outcomes Research and Surveillance Consortium.

INTRODUCTION: This study investigated racial disparities in postsurgical health-related quality of life (HRQOL) among patients with non-small-cell lung cancer (NSCLC). METHODS: Data were collected by the Cancer Care Outcomes Research and Surveillance Consortium. Inclusion criteria were greater than or equal to 21 years of age, NSCLC, and receipt of surgery. HRQOL data were available from patients' surveys, and complete medical record abstraction was performed to obtain clinical data. HRQOL was assessed by the physical/mental component summary scores (PCS/MCS) of the 12-item Short-Form Health Survey at two time points. Mean time between surgery and the initial assessment (time 1) after surgery was 4.1 (SD 2.2) months and between surgery and second assessment (time 2) was 12.7 (SD 3.8) months. Multivariable linear regression models were used to examine associations between race and HRQOL. RESULTS: Of 650 patients, 80.5% were White, 8.8% Black, and 10.7% other races. At second assessment, Blacks reported lower MCS than Whites (47.4 versus 52.6, p = 0.002). In multivariable analysis, Blacks had lower MCS compared with Whites. No difference was found between Whites and Blacks on PCS. Those with less than high school education reported lower MCSs. Older age and receipt of adjuvant chemotherapy after surgery were associated with gain in MCS. Male, less than college education, and comorbidities were associated with impaired PCS. Older age was associated with improved PCS. CONCLUSION: Racial disparities exist in postoperative mental HRQOL. Results highlight the need for interventions after lung cancer surgery to improve mental health in Black and younger patients.

Oral Medicine referrals at a hospital-based practice in the United States.

OBJECTIVE: The objective of this study was to characterize the outpatient oral medicine (OM) clinic at Brigham and Women's Hospital (BWH), with particular emphasis on patient demographic characteristics and referral patterns. MATERIALS AND METHODS: A retrospective case record review of all initial consultations with OM experts at BWH from 2008 to 2010 was conducted. Data included demographic information, type of medical insurance, reason for referral, referring doctor's specialty, and distance between the patient's home and the referring doctor as well as BWH, number of prior doctors seen for the presenting problem (per patient report), tests ordered at the consultation visit, and clinical diagnoses. RESULTS: There were 1043 new outpatient consultation visits. Patients lived a median distance of 9.5 miles from the referring doctor and 18.9 miles from BWH and saw a median of one doctor (range 0-9) before consultation. Two thirds of patients were referred by physicians. The most common diagnoses included immune-mediated mucosal conditions (27.2%), orofacial pain disorders (25.1%), benign tumors or neoplasms (10.3%), and dysplasia and cancerous conditions (7.6%). Biopsy was the most frequent test performed at consultation. CONCLUSIONS: Patients with oral conditions often see more than one doctor, before being referred to an OM expert and typically travel twice the distance to the expert compared with that between their home and the referring doctor. Equal efforts should be made to increase awareness of the importance of the specialty of OM among dentists, physicians, and the public.

A randomized placebo-controlled pilot study of pravastatin as an adjunctive therapy in schizophrenia patients: effect on inflammation, psychopathology, cognition and lipid metabolism.

OBJECTIVE: The aim of this study was to investigate the role of pravastatin, as an adjunctive therapy, on inflammatory markers, lipid and glucose metabolism, psychopathology, and cognition in subjects with schizophrenia and schizoaffective disorder. METHODS: Schizophrenia or schizoaffective subjects (N=60) were randomized to receive either a 12-week supply of pravastatin 40 mg/day or placebo treatment. Anthropometric measures, lipids and glucose metabolism, inflammatory markers, psychopathology and cognitive performance were assessed at baseline, 6 weeks and 12 weeks. RESULTS: Pravastatin use was associated with a significant decrease in total cholesterol, low density lipoprotein (LDL) cholesterol and LDL particle number levels, but was not associated with any significant changes in cognition or psychopathology in the participants, except a significant decrease in the Positive and Negative Syndrome Scale (PANSS) positive symptom score from baseline to week 6. However, this decrease failed to remain significant at 12 weeks. Interestingly, triglycerides, LDL-cholesterol, total cholesterol, LDL particle number, small LDL particle number, large very low density lipoprotein (VLDL) particle number and C-reactive protein (CRP) followed a similar pattern at 6 and 12 weeks as psychopathology. CONCLUSIONS: These results suggest that a randomized trial with a larger sample size and a higher dosage of pravastatin would be helpful in further evaluating the anti-inflammatory properties of pravastatin, its association with improvements in cognitive symptoms, and its potential to reduce positive and negative symptoms associated with schizophrenia or schizoaffective disorders.

Multimodality vaccination against clade C SHIV: partial protection against mucosal challenges with a heterologous tier 2 virus.

We sought to test whether vaccine-induced immune responses could protect rhesus macaques (RMs) against upfront heterologous challenges with an R5 simian-human immunodeficiency virus, SHIV-2873Nip. This SHIV strain exhibits many properties of transmitted HIV-1, such as tier 2 phenotype (relatively difficult to neutralize), exclusive CCR5 tropism, and gradual disease progression in infected RMs. Since no human AIDS vaccine recipient is likely to encounter an HIV-1 strain that exactly matches the immunogens, we immunized the RMs with recombinant Env proteins heterologous to the challenge virus. For induction of immune responses against Gag, Tat, and Nef, we explored a strategy of immunization with overlapping synthetic peptides (OSP). The immune responses against Gag and Tat were finally boosted with recombinant proteins. The vaccinees and a group of ten control animals were given five low-dose intrarectal (i.r.) challenges with SHIV-2873Nip. All controls and seven out of eight vaccinees became systemically infected; there was no significant difference in viremia levels of vaccinees vs. controls. Prevention of viremia was observed in one vaccinee which showed strong boosting of virus-specific cellular immunity during virus exposures. The protected animal showed no challenge virus-specific neutralizing antibodies in the TZM-bl or A3R5 cell-based assays and had low-level ADCC activity after the virus exposures. Microarray data strongly supported a role for cellular immunity in the protected animal. Our study represents a case of protection against heterologous tier 2 SHIV-C by vaccine-induced, virus-specific cellular immune responses.