Enhancing Enrollment in Acute Stroke Trials: Current State and Consensus Recommendations.

The Stroke Treatment Academic Industry Roundtable (STAIR) convened a session and workshop regarding enrollment in acute stroke trials during the STAIR XII meeting on March 22, 2023. This forum brought together stroke physicians and researchers, members of the National Institute of Neurological Disorders and Stroke, industry representatives, and members of the US Food and Drug Administration to discuss the current status and opportunities for improving enrollment in acute stroke trials. The workshop identified the most relevant issues impacting enrollment in acute stroke trials and addressed potential action items for each. Focus areas included emergency consent in the United States and other countries; careful consideration of eligibility criteria to maximize enrollment and representativeness; investigator, study coordinator, and pharmacist availability outside of business hours; trial enthusiasm/equipoise; site start-up including contractual issues; site champions; incorporation of study procedures into standard workflow as much as possible; centralized enrollment at remote sites by study teams using telemedicine; global trials; and coenrollment in trials when feasible. In conclusion, enrollment of participants is the lifeblood of acute stroke trials and is the rate-limiting step for testing an exciting array of new approaches to improve patient outcomes. In particular, efforts should be undertaken to broaden the medical community's understanding and implementation of emergency consent procedures and to adopt designs and processes that are easily incorporated into standard workflow and that improve trials' efficiencies and execution. Research and actions to improve enrollment in ongoing and future trials will improve stroke outcomes more broadly than any single therapy under consideration.

Human papillomavirus type 16 (HPV-16) genomes integrated in head and neck cancers and in HPV-16-immortalized human keratinocyte clones express chimeric virus-cell mRNAs similar to those found in cervical cancers.

Many human papillomavirus (HPV)-positive high-grade lesions and cancers of the uterine cervix harbor integrated HPV genomes expressing the E6 and E7 oncogenes from chimeric virus-cell mRNAs, but less is known about HPV integration in head and neck cancer (HNC). Here we compared viral DNA status and E6-E7 mRNA sequences in HPV-16-positive HNC tumors to those in independent human keratinocyte cell clones derived from primary tonsillar or foreskin epithelia immortalized with HPV-16 genomes. Three of nine HNC tumors and epithelial clones containing unintegrated HPV-16 genomes expressed mRNAs spliced from HPV-16 SD880 to SA3358 and terminating at the viral early gene p(A) signal. In contrast, most integrated HPV genomes in six HNCs and a set of 31 keratinocyte clones expressed HPV-16 major early promoter (MEP)-initiated mRNAs spliced from viral SD880 directly to diverse cellular sequences, with a minority spliced to SA3358 followed by a cellular DNA junction. Sequence analysis of chimeric virus-cell mRNAs from HNC tumors and keratinocyte clones identified viral integration sites in a variety of chromosomes, with some located in or near growth control genes, including the c-myc protooncogene and the gene encoding FAP-1 phosphatase. Taken together, these findings support the hypothesis that HPV integration in cancers is a stochastic process resulting in clonal selection of aggressively expanding cells with altered gene expression of integrated HPV genomes and potential perturbations of cellular genes at or near viral integration sites. Furthermore, our results demonstrate that this selection also takes place and can be studied in primary human keratinocytes in culture.

A test of the maintenance of the effects of imagined contact framed with supportive social norms as a teacher-led field intervention.

As the arrival of refugees and asylum seekers continues to increase, schools continue to become a vital center for children to develop positive intergroup attitudes. Teacher-led activities can become useful tools in sustainable prejudice reduction. A field intervention incorporated normative in-group influence with imagined intergroup contact to reduce children's anti-refugee bias. Ten primary school classes (N = 269, Mage = 10.69 years) were randomly assigned to one of four conditions: (a) class norm-framed imagined contact (n = 88), (b) family norm-framed imagined contact (n = 49), (c) religious in-group norm-framed imagined contact (n = 51), or (d) standard (n = 80) imagined contact. Teachers facilitated a series of four imagined contact activities over 4 weeks, with anti-refugee bias measured at baseline and 2 weeks after the final activity. Imagined contact framed in the class context was associated with significantly lower post-intervention contact intentions bias as compared to standard imagined contact. There were no significant effects of family or religion norm framed imagined contact conditions. Findings are discussed in relation to the feasibility of teacher-led school-based interventions and the importance of a supportive normative context in the classroom for anti-refugee bias.

Dominant-negative CK2alpha induces potent effects on circadian rhythmicity.

Circadian clocks organize the precise timing of cellular and behavioral events. In Drosophila, circadian clocks consist of negative feedback loops in which the clock component PERIOD (PER) represses its own transcription. PER phosphorylation is a critical step in timing the onset and termination of this feedback. The protein kinase CK2 has been linked to circadian timing, but the importance of this contribution is unclear; it is not certain where and when CK2 acts to regulate circadian rhythms. To determine its temporal and spatial functions, a dominant negative mutant of the catalytic alpha subunit, CK2alpha(Tik), was targeted to circadian neurons. Behaviorally, CK2alpha(Tik) induces severe period lengthening (approximately 33 h), greater than nearly all known circadian mutant alleles, and abolishes detectable free-running behavioral rhythmicity at high levels of expression. CK2alpha(Tik), when targeted to a subset of pacemaker neurons, generates period splitting, resulting in flies exhibiting both long and near 24-h periods. These behavioral effects are evident even when CK2alpha(Tik) expression is induced only during adulthood, implicating an acute role for CK2alpha function in circadian rhythms. CK2alpha(Tik) expression results in reduced PER phosphorylation, delayed nuclear entry, and dampened cycling with elevated trough levels of PER. Heightened trough levels of per transcript accompany increased protein levels, suggesting that CK2alpha(Tik) disturbs negative feedback of PER on its own transcription. Taken together, these in vivo data implicate a central role of CK2alpha function in timing PER negative feedback in adult circadian neurons.

Risk factors and survival by HPV-16 E6 and E7 antibody status in human papillomavirus positive head and neck cancer.

High-risk human papillomavirus types (HPV-HR) are associated with head and neck cancer (HNC) risk and better survival. Most patients with HPV-HR DNA-positive tumors develop anti-HPV E6/E7 antibodies; however, it is unclear whether those who mount an immune response have similar risk factors or clinical outcomes as those who do not. HPV-16 DNA tumor-positive HNC cases were evaluated for HPV-16 E6 and E7 antibodies using a GST capture ELISA system. Among 57 HPV-16 DNA tumor-positive HNC cases, 67% were detected with HPV-16 E6 and/or E7 antibodies. Male gender (76% vs. 42%, p = 0.02), younger age (63% vs. 16%, p = 0.001) but not tobacco or alcohol were associated with E6 and/or E7 seropositivity. Seropositivity was associated more often with late stage (76%), poor grade (65%), positive nodes (82%). and in the oropharynx (82%), Median disease-specific and recurrence-free survival were longer in E6 and/or E7 seropositive compared to E6/E7-negative cases (2.2 years vs. 1.4 years, both outcomes), although results were not statistically significant. When examined jointly with p16 expression, E6 and/or E7-positive/p16-positive cases had better disease-specific (2.1 years vs. 1.1 years, p = 0.06) and recurrence-free (2.3 years vs. 1.1 years, p = 0.03) survival compared to E6-/E7-/p16- cases. These findings suggest there are 2 distinct HNC patient groups with HPV DNA-positive tumors, distinguishable by E6 and/or E7 antibody status. Differences in antibody status are associated with distinct risk factors and clinical outcomes. This information can be available as a simple blood test at initial presentation, before the removal of tissue through biopsy or surgery.

Tobacco and alcohol use increases the risk of both HPV-associated and HPV-independent head and neck cancers.

Tobacco, alcohol, and human papillomavirus (HPV) are major risk factors for head and neck cancer (HNC), but it is unclear whether there are two distinct HNC risk groups, one associated with HPV and the other with tobacco/alcohol. Because HPV-positive HNC are clinically distinct from HPV-negative cases in treatment response and with more favorable prognoses, determining whether these differences result from infection alone or in association with other HNC risk factors is important for developing future therapeutic strategies. Incident cases of HNC (n = 201) and age-gender frequency-matched controls (n = 324) were recruited to assess anti-HPV VLP (virus like particles) antibodies 16, 18, 31, and 33. Multivariate logistic regression and stratified analyses were used to calculate adjusted odds ratios (OR). HPV-seronegative and seropositive/heavy tobacco users had similar increased adjusted risks of HNC (HPV-seronegative OR = 2.6, 1.4-5.0; HPV-seropositive OR = 2.3, 1.1-4.8), as did HPV-seronegative (OR = 4.3, 2.1-9.1) versus HPV-seropositive/heavy alcohol users (OR = 3.9, 1.6-9.4). Similar HPV/tobacco/alcohol risk profiles also were seen in oropharyngeal and oral cavity tumor sites. Our finding that tobacco/alcohol use increased the risk of HNC in both HPV-seropositive and HPV-seronegative individuals is consistent with the observation that HPV infection is not a sufficient cause of HNC but requires the accumulation of additional cellular changes.

Evidence for vertical transmission of HPV from mothers to infants.

Few large studies have evaluated concordance based on a broad spectrum of human papillomavirus (HPV) types in oral and genital specimens of mothers and their recently born infants. This information is important in determining whether HPV vaccines administered prior to pregnancy may be useful for preventing vertical transmission. HPV DNA was positive in 30% of mothers and 1.5% of newborns. Maternal/newborn concordance (HPV+/+ or HPV-/-) was 71%. Among HPV DNA+ mothers, only 3% of their infants were DNA+ and only 1 pair had the same HPV type. Among HPV- women, 0.8% of infants were HPV+. HPV DNA detected in hospitalized newborns reflects current infection transmitted to infants during pregnancy or delivery. None of the mother/baby HPV DNA+ concordance pairs detected viral types found in HPV vaccines suggesting that vaccination prior to pregnancy is unlikely to be efficacious in preventing vertical transmission.

Survey of i.v. paracetamol (acetaminophen) use in neonates and infants under 1 year of age by UK anesthetists.

BACKGROUND: The license for i.v. paracetamol has recently been extended to include term neonates and infants aged 1 year, at a uniform dose across this age range of 7.5 mg.kg(-1), total daily dose 30 mg.kg(-1).day(-1). We were interested to survey current i.v. paracetamol prescribing practices of anesthetists in the UK, in neonates and infants under 1 year of age. METHODS: We conducted an online survey of 94 linkmen of the Association of Pediatric Anesthetists of Great Britain and Ireland Linkmen representing both general and specialist hospitals and 90 members of the British Pediatric Pain Travelling Club representing the pediatric acute pain teams throughout the UK and Ireland. RESULTS: A total of 105/184 (57%) responded to the survey on behalf of 78 regions and 27 pediatric acute pain teams. Over half (54%) of the respondents indicated i.v. paracetamol use in infants under 1 year of age. A wide range of loading and maintenance doses were used. Total daily doses exceeded the license for age 1-12 months in 70% of cases; for the 36 week postconceptional age (PCA)-1 month age range the proportion was 50%. Over 80% of total daily dosing from age 36 weeks PCA to 1 year fell within dosing suggested by pharmacokinetic studies. Close to 40% of respondents who used i.v. paracetamol in infants, also indicated use in preterm age groups. The total daily dose used in preterm neonates was within the range suggested by pharmacokinetic studies, in over 90% of cases in the age range 32-36 weeks PCA, and for 60% in the under 32 weeks PCA age group. CONCLUSIONS: This survey demonstrates i.v. paracetamol dosing in infants in the UK and Ireland is frequently above the licensed dose and outside the licensed age range but is in keeping with doses suggested by pharmacokinetic studies.

Fundamental differences in cell cycle deregulation in human papillomavirus-positive and human papillomavirus-negative head/neck and cervical cancers.

Human papillomaviruses (HPV) are associated with nearly all cervical cancers, 20% to 30% of head and neck cancers (HNC), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, cervical cancers, and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV(+) HNCs and cervical cancers differed in their patterns of gene expression yet shared many changes compared with HPV(-) HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV(+) HNCs and cervical cancers were found to be up-regulated in their expression of a distinct and larger subset of cell cycle genes than that observed in HPV(-) HNC. Moreover, HPV(+) cancers overexpressed testis-specific genes that are normally expressed only in meiotic cells. Many, although not all, of the hallmark differences between HPV(+) HNC and HPV(-) HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testis-specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV(+) and HPV(-) cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV(+) cancers.

Association between p53 and human papillomavirus in head and neck cancer survival.

BACKGROUND: High-risk human papillomavirus (HPV-HR) is a significant risk factor for head and neck cancer (HNC), abrogating normal p53 function. In addition, HPV and p53 have been associated with prognosis of these tumors but the findings have been inconsistent. We examined p53 expression and HPV-HR individually and jointly for differences in predicting HNC survival. METHODS: HNC patients (n = 294) were evaluated for p53 by immunohistochemical staining. HPV was detected by PCR/dot blot hybridization and sequencing. RESULTS: HNC tumors showed 48% with p53 overexpression and 27% with HPV-HR. Multivariate analyses showed that p53 positivity was significantly associated with higher risk of disease-specific [hazard ratio (HR); 2.0; 95% confidence interval (95% CI), 1.1-3.7] and recurrence-free mortality (HR, 2.8; 95% CI, 1.4-5.3). HPV- cases had significantly worse disease-specific survival (HR, 2.8; 95% CI, 1.3-6.3) compared with HPV-HR cases. When analyzed jointly, with p53(-)/HPV-HR tumors as the reference group, p53(+)/HPV(-) patients had the worst disease-specific (HR, 5.3; 58% versus 15%, P = 0.006) and recurrence-free survival rates (HR, 9.5; 17% versus 89%, P = 0.001), in contrast to the p53(-)/HPV(-) and p53(+)/HPV-HR groups, which had less elevated and different risks for disease-specific survival (HR, 2.5 and 1.7, respectively) and recurrence-free survival (HR, 4.2 and 7.2, respectively). CONCLUSION: Joint assessment of p53/HPV status provides different HRs for each clinical outcome in the four biomarker groups that are distinct from the individual biomarkers. These findings suggest that joint assessment of p53/HPV provides a better indicator of prognosis and potentially different types of treatments.

Does pretreatment seropositivity to human papillomavirus have prognostic significance for head and neck cancers?

BACKGROUND: Human papillomavirus (HPV) is a risk factor for head and neck cancers (HNC), yet HPV-associated tumors have better prognosis than HPV-negative tumors. METHODS: We evaluated whether pretreatment presence of antibodies to HPV capsids [virus-like particles (VLP)] or to HPV-16 oncoproteins E6 and E7 was a predictor of HPV-positive HNC and clinical outcomes. Sera from 156 HNC patients were tested for antibodies to HPV-16-derived antigens using ELISA. HPV-16 in tumors was evaluated by PCR and DNA sequencing. RESULTS: HPV-16 antibodies were found in 33% with HPV-16 VLP, 21% with HPV-16 E6, and 21% with E7. HPV-16 was detected in 26% of tumors. There was a strong correlation between detection of HPV-16 tumor DNA and antibodies to HPV-16 E6 or E7 (kappa = 0.7) but not to HPV-16 VLP (kappa = 0.4). Multivariate analyses showed significantly better disease-specific survival in seropositive HPV-16 VLP [hazard ratio (HR), 0.4; 95% confidence interval (95% CI), 0.1-0.9], HPV-16 E6 (HR, 0.1; 95% CI, 0.02-0.5), and HPV-16 E7 (HR, 0.3; 95% CI, 0.1-0.9) cases. Less disease recurrence occurred among those with antibodies to both E6 and E7 compared with those negative to both (P = 0.003). There was better disease-specific survival in patients who were E6 positive at baseline and remained positive at follow-up compared with individuals who were E6 negative at both time points (P = 0.03; kappa = 0.9). CONCLUSIONS: The presence of antibodies to HPV-16 E6 and E7 is associated with HPV in tumor cells and with better clinical outcomes. These findings suggest that the presence of E6/E7 antibodies before treatment is predictive of better clinical outcomes and that they may serve as biomarkers for selecting targeted therapeutic modalities developed for HPV-associated tumors.

P16INK4a expression, human papillomavirus, and survival in head and neck cancer.

Development of head and neck cancer (HNC) is associated with human papillomavirus high-risk (HPV-HR) types. The HPV E7 oncoprotein inactivates the pRB protein increasing expression of p16(INK4a). P16 expression and HPV status have been associated with differences in clinical outcomes for HNC. This study examined whether HNC prognosis was different when these biomarkers were examined as individual or joint molecular effects. Tumor tissue from 301 HNC patients were analyzed and sequenced for HPV types. P16 was evaluated by immunohistochemical staining. p16 was expressed in 35% and HPV-HR was detected in 27% of HNC patients. After adjustment for age, tobacco, and alcohol, p16+ tumors were statistically significantly associated with HPV-HR (OR=13.3, 7.1-24.9), histology, stage, grade, tumor site, and node involvement. Compared to p16+ HNC cases, those who did not express p16 had significantly worse disease-specific (DS) survival (Hazards Ratio, adj.HR=2.0. 1.0-3.9) and recurrence (adj.HR=3.6, 1.6-8.2); and HPV- cases had worse DS survival (adj.HR=2.8, 1.1-7.1) and recurrence (adj.HR=2.0, 0.8-4.8) compared to HPV-HR patients. Each of the p16/HPV groups had different survival outcomes: p16+/HPV-HR cases (referent) had the best and p16-/HPV- cases had the worst DS survival (adj.HR=3.6; 53% versus 13%, p=0.004) whereas p16+/HPV- and p16-/HPV-HR had similar DS survival (adj.HR=2.7/2.8). p16-/HPV-HR cases had a worse recurrence rate (adj.HR=7.0; 60% versus 0%, referent, p=0.08) than p16-/HPV- (adj.HR=4.5) or p16+/HPV- (adj.HR=1.8) cases. The combined p16/HPV biomarker data are associated with different survival outcomes of HNC compared to each marker evaluated separately, indicating that the two molecular mechanisms evaluated together may provide a more accurate prediction of clinical outcomes.

A functional role for Anopheles gambiae Arrestin1 in olfactory signal transduction.

Insect sensory arrestins act to desensitize visual and olfactory signal transduction pathways, as evidenced by the phenotypic effects of mutations in the genes encoding both Arr1 and Arr2 in Drosophila melanogaster. To assess whether such arrestins play similar roles in other, more medically relevant dipterans, we examined the ability of Anopheles gambiae sensory arrestin homologs AgArr1 and AgArr2 to rescue phenotypes associated with an olfactory deficit observed in D. melanogaster arrestin mutants. Of these, only AgArr1 facilitated significant phenotypic rescue of the corresponding Drosophila arr mutant olfactory phenotype, consistent with the view that functional orthology is shared by these Arr1 homologs. These results represent the first step in the functional characterization of AgArr1, which is highly expressed in olfactory appendages of An. gambiae in which it is likely to play an essential role in olfactory signal transduction. In addition to providing insight into the common elements of the peripheral olfactory system of dipterans, this work validates the importance of AgArr1 as a potential target for novel anti-malaria strategies that focus on olfactory-based behaviors in An. gambiae.

Prevalence of human papillomavirus in the oral cavity/oropharynx in a large population of children and adolescents.

OBJECTIVE: Human papillomavirus (HPV) in the oral cavity or oropharynx is associated with an increased risk of laryngeal papillomatosis, head and neck cancer, and cervical and other genital cancers. We evaluated the prevalence of HPV DNA in the oral cavity/oropharynx in a cross section of children aged 2 weeks to 20 years. METHODS: A risk factor questionnaire and oral exfoliated cells were collected from children (N = 1235). HPV DNA was detected using PCR, dot blot hybridization, and DNA sequencing. RESULTS: The HPV prevalence was 1.9% in the oral cavity/oropharynx of children. A bimodal age distribution was observed with the highest HPV prevalence in the youngest and oldest groups: 2.5% aged <1 year, 0.8% aged 1 to 4 years, 1.2% aged 5 to 11 years, 1.5% in aged 12 to 15 years, and 3.3% in aged 16 to 20 years. The prevalence of the HPV quadrivalent vaccine types (HPV-6, 11, 16, 18) reached 0.9% in the 16- to 20-year age group. In this age group, female gender [odds ratio (OR): 6.9, P = 0.04], genital warts (OR: 19.3, P < 0.01), and current smoker (OR: 6.5, P = 0.01) were associated with a higher risk of being detected with an oral HPV infection. No risk factors in parents were identified with transmission of HPV to infants. CONCLUSIONS: The age-specific prevalence rates of HPV in this large cross section of children and adolescents demonstrate that HPV infection is acquired gradually in childhood. These data support a target age for HPV vaccination before puberty to prevent serious HPV-related genital and oral diseases.

Head and neck cancer associated with herpes simplex virus 1 and 2 and other risk factors.

We investigated whether herpes simplex viruses, HSV-1 and HSV-2, are cofactors of head and neck cancer (HNC) in association with tobacco, alcohol, or HPV-16 infection. The study included 164 HNC cases and 295 controls. Serologic tests were used to distinguish HSV-1 and HSV-2. Antibodies to anti-VLP HPV-16 and HPV-16 E6 and E7 were evaluated by ELISA. After adjusting for age, tobacco, alcohol use, and number of sexual partners, risk of cancer was not significantly increased in those with HSV-1 [adjusted odds ratio (OR)=0.7] or HSV-2 (OR=0.8) compared to HSV-negative patients. Although heavy use of tobacco, alcohol and HPV-16 infection was associated with an increased risk of HNC, the adjusted risk among those infected with HSV-1 or HSV-2 lowered the odds compared to those who were not infected. Heavy smokers (OR=1.7) and heavy drinkers infected with HSV-1 (OR=4.2) or HSV-2 (smokers: OR=1.6; drinkers: OR=3.2) had lower odds compared to seronegative HSV-1 heavy users (smokers: OR=2.5; drinkers: OR=5.5) or HSV-2 (smokers: OR=1.9; drinkers: OR=6.2). Those seropositive to HPV-16 E6 and/or E7 but not HSV-1 (OR=27.4) or HSV-2 (OR=18.0) had higher risk of HNC compared to those infected with HSV-1 (OR=16.7) or HSV-2 (not estimable). These findings suggest that seropositivity to HSV-1 and HSV-2, although not independent risk factors for HNC, may modify the risk of HNC associated with exposure to tobacco, alcohol, or HPV-HR.

Alcohol dehydrogenase 3 and risk of squamous cell carcinomas of the head and neck.

In order to examine the association between alcohol dehydrogenase 3 (ADH3) genotypes and risk of head and neck squamous cell carcinomas (HNSCC), we conducted a hospital based case-control study including 348 cases and 330 controls. DNA isolated from exfoliated cells from the oral cavity were genotyped for ADH3 polymorphisms using PCR followed by SspI digestion. Odds ratios (OR) and hazards ratios (HR) were done by unconditional logistic regression and Cox regression. Relative to ADH3(2-2) carriers, ADH3(1-1) [OR, 0.7; 95% confidence interval (CI), 0.4-1.1] and ADH3(1-2) (OR, 0.8; 95% CI, 0.5-1.2) had a nonsignificant reduced risk of HNSCC. ADH(1-2) smokers of >30 pack-years were at decreased risk of oral cavity squamous cell carcinomas compared with ADH3(2-2) (OR, 0.3, 0.1-0.9), whereas ADH3(1-1) smokers were not. After adjustment, those with ADH3(1-2) had significantly worse overall survival compared with ADH3(1-1) (HR, 0.3, 0.2-0.6) or ADH3(2-2) (HR, 0.4, 0.2-0.9) and increased recurrence (ADH3(1-1), 0.2, 0.1-0.6; ADH3(2-2), 0.6, 0.2-1.3). Our data did not show that ADH3 genotypes had a significantly independent effect on the risk of HNSCC, nor did they modify the risks increased by alcohol or tobacco consumption and high-risk human papillomavirus infection. However, participants with ADH3(1-2) genotype were associated with poorer survival compared with those who had the other two ADH3 genotypes and a higher rate of recurrence than participants with ADH3(1-1) genotype.

Gonorrhea and chlamydia infection among women visiting family planning clinics: racial variation in prevalence and predictors.

CONTEXT: Black women are disproportionately infected with gonorrhea and chlamydia. Because of the potential impact of these infections on women's reproductive health, it is important to determine whether different factors are predictive of infection in women of different races. METHODS: Data from 31,762 women aged 15-24 who were tested for gonorrhea and chlamydia at Missouri family planning clinics in 2001 were used to calculate the prevalence of each infection by selected variables. Logistic regression analysis was used to assess factors associated with the risk of infection. RESULTS: Overall, 0.7% of women had gonorrhea, and 4% had chlamydia. The gonorrhea rate was 4% for blacks and 0.4% for whites; the chlamydia rate, 9% and 4%, respectively. Independent predictors of gonorrhea in both races were symptoms, recent sexual contact with a partner who had STD symptoms, and chlamydia infection. Predictors specific to whites were visiting the clinic for STD care and having a new partner or multiple partners in the past year. Being aged 15-21 was associated with an elevated risk of gonorrhea for blacks only. In both racial groups, chlamydia infection was associated with younger age, contact with a symptomatic partner, cervicitis, cervical friability and gonorrhea positivity. Additional predictors among whites were having a new partner, having multiple partners and having pelvic inflammatory disease; no other factors were significant for blacks. CONCLUSIONS: The prevalence and predictors of gonorrhea and chlamydia infection differ significantly between blacks and whites. Until these disparities are better understood, it will be difficult to establish screening criteria for gonorrhea.

Voice disorders in the general population: prevalence, risk factors, and occupational impact.

OBJECTIVES: Epidemiologic studies of the prevalence and risk factors of voice disorders in the general adult population are rare. The purpose of this investigation was to 1) determine the prevalence of voice disorders, 2) identify variables associated with increased risk of voice disorders, and 3) establish the functional impact of voice disorders on the general population. STUDY DESIGN: Cross-sectional telephone survey. METHODS: A random sample (n = 1,326) of adults in Iowa and Utah was interviewed using a questionnaire that addressed three areas related to voice disorders: prevalence, potential risk factors, and occupational consequences/effects. RESULTS: The lifetime prevalence of a voice disorder was 29.9%, with 6.6% of participants reporting a current voice disorder. Stepwise logistic regression identified specific factors that uniquely contributed to increased odds of reporting a chronic voice disorder including sex (women), age (40-59 years), voice use patterns and demands, esophageal reflux, chemical exposures, and frequent cold/sinus infections. However, tobacco or alcohol use did not independently increase the odds of reporting of a chronic voice disorder. Voice disorders adversely impacted job performance and attendance, with 4.3% of participants indicating that their voice had limited or rendered them unable to do certain tasks in their current job. Furthermore, 7.2% of employed respondents reported that they were absent from work 1 or more days in the past year because of their voice, and 2% reported more than 4 days of voice-related absence. CONCLUSIONS: The results of this large epidemiologic study provide valuable information regarding the prevalence of voice disorders, factors that contribute to voice disorder vulnerability, and the functional impact of voice problems on the general population.

Occupational risk factors associated with voice disorders among teachers.

PURPOSE: This study was designed to determine the occupational risk factors associated with voice disorders among schoolteachers, a high-risk population for developing voice problems. METHODS: Telephone interviews were completed by 1243 teachers from Utah and Iowa. Response rates were 98% and 95%, respectively. Bivariate analyses were computed and assessed using chi-square test and Cochran-Mantel-Haenszel test, and logistic regression analyses were performed and resulting odds ratios assessed using 95% confidence intervals. RESULTS: Teachers of vocal music, drama, other performing arts and chemistry were at significantly greater risk of having a voice disorder (OR=2.2, 95% CI: 1.2-4.0; OR=2.1, 95% CI: 0.9-4.8; OR=1.6, 95% CI: 1.0-2.4; OR=2.0, 95% CI: 1.1-3.4), while teachers of special and vocational education had a significantly lower risk (OR=0.5, 95% CI: 0.3-0.7; OR=0.6, 95% CI: 0.4-0.9). When adjusted for the intensity of vocalization, only teachers of chemistry were significantly at risk (OR=2.0, 95% CI: 1.1-3.5) while teachers of special education continued to have less of a risk (OR=0.5, 95% CI: 0.4-0.8). Chronic voice disorders were more prevalent among teachers of vocal music (OR=4.1, 95% CI: 2.2-7.9) and less prevalent among teachers of vocational education (OR=0.29, 95% CI: 0.09-0.95). CONCLUSIONS: These findings suggest that teachers of specific courses are at greater risk of developing a voice disorder.

Organochlorines and risk of prostate cancer.

This pilot study examined the relationships of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) with prostate cancer. Ninety-nine controls were frequency matched by age in 5-year increments to 58 prostate cancer patients. Thirty PCBs and 18 OCPs were measured in serum by gas chromatography. Multiple logistic regression was used to assess the magnitude of association. Seven organochlorines, dieldrin, p,p'-DDE, trans-nonachlor, oxychlordane, heptachlor epoxide, and PCBs 153 and 180 were detected in at least 20% of all study participants. Adjusting for age, body mass index, and a history of prostatitis, oxychlordane and PCB 180 were associated with an increased risk of prostate cancer. This study suggests that long-term, low-dose exposure to specific OCPs and PCBs in the general population may contribute to an increased risk of prostate cancer and supports further investigation in this area.