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Objectives To develop key messages for methadone and buprenorphine safety education material based on an analysis of calls to the NYC Poison Control Center (NYC PCC) and designed for distribution to caregivers of young children. Methods Retrospective review of all calls for children 5 years of age and younger involving methadone or buprenorphine from January 1, 2000, to June 15, 2014. A data abstraction form was completed for each case to capture patient demographics, exposure and caller sites, caller relation to patient, qualitative information regarding the exposure scenario, the product information, if naloxone was given, and the medical outcome of the case. Results A total of 123 cases were identified. The ages of the children ranged from 4 days to 5 years; 55% were boys. All exposures occurred in a home environment. The majority of the calls were made to the NYC PCC by the doctor (74%) or nurse (2%) at a health care facility. Approximately one-fourth of the calls came from the home and were made by the parent (22%) or grandparent (2%). More than one-half of the exposures involved methadone (64%). Naloxone was administered in 28% of cases. Approximately one-fourth of the children did not experience any effect after the reported exposure, one-half (51%) experienced some effect (minor, moderate, or major), and there was 1 death (1%). More than one-half of the children were admitted to the hospital, with 40% admitted to critical care and 13% to noncritical care. Approximately 23% were treated and released from the hospital, and 20% were lost to follow-up or never arrived to the hospital. The remaining 4% were managed on site without a visit to the hospital. Conclusion Exposures to methadone and buprenorphine are dangerous with some leading to serious health effects. Safe storage and disposal instructions are needed for homes where children may be present.

Background: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. Methods: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799 500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). Results: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22–5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82–1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. Conclusions: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.

Background: Excessive alcohol consumption is a well-established risk factor for liver disease and hepatocellular carcinoma (HCC). Previous studies have found that increased alcohol consumption can lead to lower absorption of folate. Conversely, higher folate intake has been inversely associated with liver damage and HCC. In the current study, we investigate the effect of alcohol consumption and folate intake on HCC incidence and liver disease mortality in the NIH–American Association of Retired Persons Diet and Health Study. Methods: The study population included 494,743 participants who reported at baseline their dietary intake for the previous year. Alcohol and folate were analyzed with hazards ratios (HR) and 95% confidence intervals (CI) using multivariate Cox proportional hazards regression models adjusted for age, sex, race, education, smoking, body mass index, and diabetes. HCC incidence (n = 435) was determined through 2006 via linkage with cancer registries, and liver disease mortality (n = 789) was determined through 2008 via linkage to the U.S. Social Security Administration Death Master File and the National Death Index Plus by the National Center for Health Statistics. Results: Consumption of more than three drinks per day was positively associated with both HCC incidence (HR: 1.92; 95%CI: 1.42–2.60) and liver disease mortality (HR: 5.84; 95%CI: 4.81–7.10), whereas folate intake was associated with neither outcome. Folate, however, modified the relationship between alcohol and HCC incidence (Pinteraction = 0.03), but had no effect on the relationship between alcohol and liver disease mortality (Pinteraction = 0.54). Conclusions: These results suggest that higher folate intake may ameliorate the effect of alcohol consumption on the development of HCC. Impact: Folate intake may be beneficial in the prevention of alcohol-associated HCC. Cancer Epidemiol Biomarkers Prev; 22(3); 415–21. ©2013 AACR.

Purpose: Cytology-based screening has limited sensitivity to detect prevalent cervical precancers. Human papilloma virus (HPV) DNA testing is highly sensitive and provides a high, long-term reassurance of low risk of cervical cancer. However, the specificity of HPV DNA testing is limited, requiring additional, more disease-specific markers for efficient screening approaches. Experimental Design: Liquid-based cytology samples were collected from 625 women referred to colposcopy. A slide was stained using the CINtec plus cytology assay. Pap cytology and HPV genotyping were conducted from the same vial. Clinical performance characteristics were calculated for all women, stratified by age, and for women referred with a low-grade squamous intraepithelial lesion (LSIL) Pap. Results: p16/Ki-67 positivity increased with histologic severity, from 26.8% in normal histology, 46.5% in CIN1, 82.8% in CIN2 to 92.8% in CIN3. Among women with CIN3, p16/Ki-67 positivity increased from 77.8% for women younger than 30 years without HPV16 to 100% for women 30 years and older with HPV16. The sensitivity and specificity to detect CIN3+ were 93.2% and 46.1%, respectively, and increased to 97.2% and 60.0% among women 30 years and older. In women with high-risk (HR)-HPV–positive atypical squamous cells of undetermined significance (ASC-US) and LSIL, sensitivity and specificity for detection of CIN3 were 90.6% and 48.6%, respectively. Conclusions: p16/Ki-67 testing could reduce referral to colposcopy by almost half while detecting the most severe cases of CIN3. The high sensitivity of p16/Ki-67 with significantly improved specificity compared with HPV testing makes p16/Ki-67 a viable option for LSIL triage. Further studies are required to evaluate p16/Ki-67 as triage marker in HPV-based screening strategies. Clin Cancer Res; 18(15); 4154–62. ©2012 AACR.

BACKGROUND: The majority of anal cancers are caused by persistent infections with carcinogenic human papillomaviruses (HPV). Similar to cervical carcinogenesis, the progression from HPV infection to anal cancer occurs through precancerous lesions that can be treated to prevent invasion. In analogy to cervical cytology, anal cytology has been proposed as a screening tool for anal cancer precursors in high-risk populations. METHODS: The authors analyzed the interobserver reproducibility of anal cytology in a population of 363 human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Liquid-based cytology (LBC) specimens were collected in the anal dysplasia clinic before the performance of high-resolution anoscopy on all patients. Papanicolaou-stained LBC slides were evaluated by 2 cytopathologists, each of whom was blinded to the clinical outcome and the other pathologist's results, using the revised Bethesda terminology. RESULTS: Overall agreement between the 2 observers was 66% (kappa, 0.54; linear-weighted kappa, 0.69). Using dichotomizing cytology results (atypical squamous cells of undetermined significance [ASC-US] or worse vs less than ASC-US), the agreement increased to 86% (kappa, 0.69). An increasing likelihood of testing positive for markers associated with HPV-related transformation, p16/Ki-67, and HPV oncogene messenger RNA was observed, with increasing severity of cytology results noted both for individual cytologists and for consensus cytology interpretation (P value for trend [ptrend] < .0001 for all). CONCLUSIONS: Moderate to good agreement was observed between 2 cytopathologists evaluating anal cytology samples collected from HIV-positive MSM. A higher severity of anal cytology was associated with biomarkers of anal precancerous lesions. Anal cytology may be used for anal cancer screening in high-risk populations, and biomarkers of HPV-related transformation can serve as quality control for anal cytology. Cancer (Cancer Cytopathol) 2013. Published 2012 by the American Cancer Society.

Preface The leadership of Women in Neurosurgery (WINS) has been asked by the Board of Directors of the American Association of Neurological Surgeons (AANS) to compose a white paper on the recruitment and retention of female neurosurgical residents and practitioners. Introduction Neurosurgery must attract the best and the brightest. Women now constitute a larger percentage of medical school classes than men, representing approximately 60% of each graduating medical school class. Neurosurgery is facing a potential crisis in the US workforce pipeline, with the number of neurosurgeons in the US (per capita) decreasing. Women in the Neurosurgery Workforce The number of women entering neurosurgery training programs and the number of board-certified female neurosurgeons is not increasing. Personal anecdotes demonstrating gender inequity abound among female neurosurgeons at every level of training and career development. Gender inequity exists in neurosurgery training programs, in the neurosurgery workplace, and within organized neurosurgery. Obstacles The consistently low numbers of women in neurosurgery training programs and in the workplace results in a dearth of female role models for the mentoring of residents and junior faculty/practitioners. This lack of guidance contributes to perpetuation of barriers to women considering careers in neurosurgery, and to the lack of professional advancement experienced by women already in the field. There is ample evidence that mentors and role models play a critical role in the training and retention of women faculty within academic medicine. The absence of a critical mass of female neurosurgeons in academic medicine may serve as a deterrent to female medical students deciding whether or not to pursue careers in neurosurgery. There is limited exposure to neurosurgery during medical school. Medical students have concerns regarding gender inequities (acceptance into residency, salaries, promotion, and achieving leadership positions). Gender inequity in academic medicine is not unique to neurosurgery; nonetheless, promotion to full professor, to neurosurgery department chair, or to a national leadership position is exceedingly rare within neurosurgery. Bright, competent, committed female neurosurgeons exist in the workforce, yet they are not being promoted in numbers comparable to their male counterparts. No female neurosurgeon has ever been president of the AANS, Congress of Neurological Surgeons, or Society of Neurological Surgeons (SNS), or chair of the American Board of Neurological Surgery (ABNS). No female neurosurgeon has even been on the ABNS or the Neurological Surgery Residency Review Committee and, until this year, no more than 2 women have simultaneously been members of the SNS. Gender inequity serves as a barrier to the advancement of women within both academic and community-based neurosurgery. Strategic Approach to Address Issues Identified. To overcome the issues identified above, the authors recommend that the AANS join WINS in implementing a strategic plan, as follows: 1) Characterize the barriers. 2) Identify and eliminate discriminatory practices in the recruitment of medical students, in the training of residents, and in the hiring and advancement of neurosurgeons. 3) Promote women into leadership positions within organized neurosurgery. 4) Foster the development of female neurosurgeon role models by the training and promotion of competent, enthusiastic, female trainees and surgeons.

An essential component of quality care for limited English proficient (LEP) patients is language access. Linguistically accessible medication instructions are particularly important, given the serious consequences of error and patient responsibility for managing often complex medication regimens on their own. Approximately 21 million people in the U.S. were LEP at the time of the 2000 census, representing a 50% increase since 1990. Little information is available on their access to comprehensible medication instructions. In an effort to address this knowledge gap, we conducted a telephone survey of 200 randomly selected NYC pharmacies. The primary focus of the survey was translation need, capacity, and practice. The majority of pharmacists reported that they had LEP patients daily (88.0%) and had the capacity to translate prescription labels (79.5%). Among pharmacies serving LEP patients on a daily basis, just 38.6% translated labels daily; 22.7% never translated. In multivariate analysis, pharmacy type (OR = 4.08, 95%CI = 1.55-10.74, independent versus chain pharmacies) and proportion of Spanish-speaking LEP persons in the pharmacy's census tract (OR = 1.09, 95%CI = 1.05-1.13 for each 1% increase in Spanish LEP population) were associated with increased label translation. Although 88.5% of the pharmacies had bilingual staff, less than half were pharmacists or pharmacy interns and thus qualified to provide medication counseling. More than 80% of the pharmacies surveyed lacked systematic methods for identifying linguistic needs and for informing patients of translation capabilities. Consistent with efforts to improve language access in other health care settings, the critical gap in language appropriate pharmacy services must be addressed to meet the needs of the nation's large and ever-growing immigrant communities. Pharmacists may require supplemental training on the need and resources for meeting the verbal and written language requirements of their LEP patients. Dispensing software with accurate translation capability and telephonic interpretation services should be utilized in pharmacies serving LEP patients. Pharmacists should post signs and make other efforts to inform patients about the language resources available to them.

Objective. To examine the association between pain-coping strategies and adjustment to cerebral palsy (CP)-related pain. Design. Longitudinal study of 48 adults with CP-related chronic pain. Study participants were interviewed on two occasions, separated by 6 months, to assess pain-coping strategies used and two domains of adjustment to chronic pain: depression and pain interference. Results. Changes in coping strategy use were associated with changes in functioning. Specifically, decreased use of catastrophizing and rest, and increased use of task persistence were associated with decreases in depression over a 6-month period. Increased use of task persistence was also associated with decreases in pain interference. Conclusion. Changes in pain-coping strategies over time are associated with changes in functioning in persons with CP-related pain, consistent with biopsychosocial models of chronic pain. Some coping strategies (e.g., catastrophizing, task persistence), however, appear to be more closely linked to functioning than others. These results provide preliminary empiric guidance for the coping strategies that may be most fruitfully targeted in the treatment of CP-related pain.

Operant behavioral models of chronic pain posit that the pain behaviors and disability of patients with chronic pain can be influenced by social contingencies, such as significant others’ responses to pain and well behaviors. The aim of the present study was to develop and evaluate a comprehensive measure of spouse responses to patient pain and well behaviors, the Spouse Response Inventory (SRI). One hundred four patients with chronic pain and their spouses completed a battery of questionnaires, including the SRI. The final analysis yielded a 39-item inventory divided into 4 scales that assess spouse solicitous and negative responses to patient pain behaviors and spouse encouraging and negative responses to patient well behaviors. Analyses yielded results that were consistent with previous research demonstrating an association between spouse solicitous and negative responses to patient pain behaviors and measures of patient functioning, providing preliminary support for the validity of the SRI scales. The results are discussed in terms of implications for further research and the clinical applicability of the SRI. Perspective This article presents the psychometric properties of a new measure of spouse responses to patient chronic pain and well behavior. This measure could potentially be helpful to clinicians seeking to assess the extent to which spouse responses may contribute to patient pain and disability and also to researchers who wish to test hypotheses derived from operant theory as applied to chronic pain.

Objectives To determine if cerebral palsy-related pain and frequency of use of pain treatments change over time and to examine the association between use of pain treatments and changes in pain intensity. Design Longitudinal study of 50 adults with cerebral palsy-related chronic pain, interviewed five times during the course of 2 yrs (6 mos between each interview). Subjects ranged in age from 18 to 76 yrs old and included 25 women and 25 men. Results Pain intensity did not change significantly during the time period of the study (2 yrs), although there was a substantial increase in the frequency of use of several pain treatments from the initial to the second interview. Participants reported that many pain treatments were at least moderately helpful, but only three of the treatments (whirlpool, ultrasound, and transcutaneous electrical nerve stimulation) seemed to be associated with a decrease in pain among those who started using these treatments during the study. Conclusion Pain does not seem to become systematically better or worse during the course of a 2-yr time period in adults with cerebral palsy-related pain. Although several pain treatments are reported to provide pain relief, many of these were rarely used by (or provided to) the study participants. There is a need for more research to determine which pain treatments are most helpful for cerebral palsy-related pain and to increase patient accessibility to effective pain treatments.

Slit ventricle syndrome is a rare condition whereby brain compliance is reduced and can be associated with intermittent intracranial hypertension. A 19-year-old male with a ventriculoperitoneal shunt for congenital hydrocephalus presented with a 1-day history of headache and drowsiness-symptoms from which he suffered in many recurrent episodes over the past 5 years. The improvement of headaches without surgical intervention led to the diagnosis of migraine. During this hospitalization, episodes of intermittent intracranial hypertension were documented along with the remission and relapse of the symptoms. While the patient’s intracranial pressure was within normal range in over 90% of his monitoring period, which postponed shunting, replacement of his ventriculoperitoneal shut eventually resolved his symptoms. Slit ventricle syndrome with reduced ventricular compliances should be considered in patients with clinical evidence of intermittent intracranial hypertension and small ventricular size. The authors advocate shunt replacement as an appropriate treatment for this condition.

PURPOSE: There is now substantial data that poly (ADP-ribose) polymerase-1 (PARP) inhibitors have activity in tumors with defects in homologous recombination, in particular BRCA-related cancers. One of the challenges, however, is identifying patients that may best respond to these class of drugs. 18F-FTT (fluorthanotrace) is a novel PET imaging tracer that can quantify PARP enzyme activity in vivo. We report results on an initial pilot study of 18F-FTT imaging in patients with ovarian carcinoma. METHODS: Eight patients with newly diagnosed or recurrent ovarian, primary peritoneal, or fallopian tube carcinoma and measurable disease underwent both 18F-FDG PET/CT and 18F-FTT PET/CT imaging within 30 days of each other. Patients who were undergoing surgery or had disease amenable to biopsy underwent dynamic imaging of the abdomen/pelvis and static skull base to mid-thigh imaging following injection of approximately 10mCi of 18F-FTT. Patients with no biopsy accessible disease underwent a series of whole body PET/CT scans over 4 hours following injection of 18F-FTT to evaluate the biodistribution and dosimetry of 18F-FTT. Standardized uptake value (SUV) was calculated for primary and/or metastatic implants on all patients with quantifiable tumor on both PET/CT scans. Quantitative assessment of the 18F-FTT PET/CT was performed first using the 18F-FDG PET/CT to identify and match lesions. Regions of interest were then drawn over the tumor implant using multiple planar view. Up to three lesions were quantified on each dataset (primary and metastases if present). Ex vivo autoradiography with [ 125I]-KX (a novel radio-iodinated PARP radiotracer that can quantitatively assess PARP-1 enzyme expression in vitro), immunohistochemical staining with γh2ax, CD45, and keratin was performed on tumor samples. RESULTS: Active regions of disease was noted for 7/8 patients on 18F-FDG PET/CT imaging and 18F-FTT PET/CT imaging. Maximum SUV of primary or metastases on 18F-FDG PET/CT ranged from 1.97-14.54 and on 18F-FTT PET/CT ranged from 3.04-12.13. We acquired tumor tissue on four patients for analysis. SUV on 18F-FTT PET/CT correlated with average counts/area on [ 125I]-KX autoradiography (R=0.70) and gammh2ax immunohistochemistry staining on tumor specimens. Low SUV FTT:FDG ratio was noted in 4/4 patients with platinum resistant disease and/or low PARP-1 expression on [ 125I]-KX autoradiography and high FTT:FDG ratio was noted in 2/3 patients with platinum sensitivity and/or high binding on [ 125I] KX auto-radiography. CONCLUSION: Our initial preliminary studies demonstrate that 18F-FTT localizes to known areas of tumor and may distinguish between tumors with low level expression of PARP and platinum resistance vs high levels of PARP and platinum sensitivity and may be a promising biomarker for PARP inhibitor and platinum sensitivity. Citation Format: Lilie Lin MD, Mehran Makvandi PharmD, Austin Pantel MD, Robert Doot PhD, Lauren Schwartz MD, Fiona Simpkins MD, David Mankoff MD PHD, Robert Mach PhD. A PILOT STUDY OF A POLY (ADP–RIBOSE) POLYMERASE–1 (PARP) TARGETED NOVEL PET TRACER (18F–FLUOURTHANOTRACE) IN PATIENTS WITH OVARIAN CARCINOMA [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr AP20.

Pain is a serious secondary problem for many persons with cerebral palsy (CP). Cognitive-behavioral models of pain hypothesize that how patients cope with painful episodes plays an important role in their adjustment to chronic pain. The utility of this model, however, has never been tested in persons with CP-related pain. Fifty adults with CP and chronic pain were interviewed to assess pain experience, the interference of pain on activities (BPI), depressive symptoms (CES-D), and coping strategies used for the pain (CSQ and CPCI). The results indicated that pain-contingent rest and catastrophizing were both significantly associated with pain interference and depressive symptoms even when controlling for pain severity. These findings support a cognitive-behavioral model of chronic pain as it might be applied to persons with CP. The results also support the need for research to determine if, and to what extent, cognitive-behavioral interventions that provide training in specific coping responses reduce depressive symptoms and pain interference in persons with CP.

Research in the area of family issues and multiple sclerosis has mainly focused on the impact of multiple sclerosis on the spouse. The aim of the current study was to examine the relationship between patients' ratings of their spouses' responses to multiple sclerosis patient disability behaviors and the impact on patient psychological and physical functioning. Multiple sclerosis patients were interviewed over the telephone using standardized questionnaires to assess patient physical and psychological functioning, spouse responses to patient disability and well behaviors (i.e., how does the spouse respond when you're having difficulties related to multiple sclerosis ?), and family environment factors. The study was set in a large university-based Multiple Sclerosis Clinical Center. Forty-four of 64 patients approached with definite multiple sclerosis participated in the study. Physical functioning was assessed by the Kurtzke-EDSS, SIP, SF-36, and psychological functioning was assessed by the CES-D and SF-36. Scores on the SF-36 were generally lower compared with a normative sample of individuals with major medical problems; however, mean Kurtzke scores of 5.60 reflected moderate to severe impairment. Exploring spouse responses to disability, correlation analyses revealed that solicitous spouse responses to patient disability behaviors were significantly associated with greater multiple sclerosis-related physical disability. This relationship was stronger for patients who were more depressed. Spouse negative responses to patient disability behaviors were associated with poorer mental health, whereas spouses' encouragement of patient well behaviors was associated with lower emotional distress. Poorer psychological functioning was found in patients with families who were reported to have higher conflict and/or who were more controlling. Higher levels of independence in families were associated with better psychological and physical functioning in the patients. These preliminary findings suggest that patients' perceptions of their families' responses to disability and family environment factors may be important areas for further research. The findings may also provide potential targets for clinical intervention in the future.

Objective: To examine the nature and scope of pain in persons with cerebral palsy (CP). Design: Standardized interviews to assess demographics, pain experiences, and the impact of pain on activities. Subjects: Ninety-three adults with CP recruited from medical clinics at the University of Washington and local residential and community housing for persons with developmental disabilities. Main Outcome Measures: Weekly and 3-month pain intensities, chronic pain grade, interference in daily activities caused by pain, and pain-exacerbating and pain-relieving factors. Results: Sixty-two subjects (67%) reported one or more areas of pain of ≥3 months' duration. Lower extremity pain and back pain were the most common complaints. Fifty-six percent of the subjects reporting pain indicated it occurred daily. Mean average pain intensity, graded on a scale of 0 (no pain) to 10 (pain as bad as could be), was 3.16 (SD = 2.45) in the preceding week and 4.45 (SD = 2.34) in the previous 3 months. Approximately 53% of subjects reporting pain indicated their average pain was of moderate to severe intensity (average pain rated as ≥5). Using Von Korff's Chronic Pain Grade classification system, the majority of subjects who reported pain fell into either grade II(low disability, low pain intensity; 51%) or grade II (low disability, high pain intensity; 39%). Subjects reported many factors that exacerbate pain (eg, stress or weather) or decrease it (eg, exercise or rest). Conclusions: The data suggest that pain is common in adults with CP. In many subjects, pain levels were moderate to intense

Complex regional pain syndrome (CRPS) remains a poorly understood chronic pain disorder. Little data has been published assessing the epidemiology of CRPS (and reflex sympathetic dystrophy, RSD). This study assessed epidemiological variables in 134 CRPS patients evaluated at a tertiary chronic pain clinic in the US, including demographic, health care utilization and legal/workman's compensation measures. In addition, the frequency of physician-imposed immobilization of the CRPS limb was assessed, as was physical examination evidence of myofascial dysfunction. This study found that these patients had seen on average 4.8 different physicians before referral to the pain center and had received an average of five different kinds of treatments both prior to and during pain clinic treatment. The mean duration of CRPS symptoms prior to pain center evaluation was 30 months. Seventeen percent had a lawsuit and 54% had a worker compensation claim related to the CRPS. Fifty-one patients received a bone scan, but only 53% of which were interpreted as consistent with the diagnosis of RSD/CRPS. Forty-seven percent had a history of physician-imposed immobilization, and 56% had a myofascial component present at evaluation. The duration of CRPS symptoms and the involvement of the upper extremity was significantly associated with the presence of myofascial dysfunction. Thus, this study found that most CRPS patients are referred to a pain specialty clinic after several years of symptoms and many failed therapies. The data also suggest the lack of utility of a diagnostic bone scan and highlight the prominence of myofascial dysfunction in a majority of CRPS patients.

Anal cancer is relatively uncommon in the United States, with an expected 6000 new cases in 2012 and an overall annual incidence rate of 2/100 000 [1, 2]. Most anal cancers are caused by human papillomavirus (HPV) infection [3]. Certain populations, such as human immunodeficiency virus (HIV)–infected and other immunosuppressed individuals, appear to have an increased risk of both HPV infection and anal cancer. A recent worldwide metaanalysis showed that HIV-infected men who have sex with men (MSM) have an estimated 46/100 000 incident anal cancer cases per year compared with HIV-negative MSM who have 5/100 000 incident cases per year [4]. Since the advent of highly active antiretroviral therapy (HAART), the life expectancy for HIV-infected individuals has significantly increased. This may have allowed time for progression of carcinogenic HPV infections to anal cancer and possibly explains an increase in anal cancer incidence in the United States [5–8]. Anal cancer natural history presumably follows the same steps as cervical cancer natural history: HPV acquisition, HPV persistence, progression of persistent HPV infections to high-grade anal intraepithelial neoplasia (AIN), and invasion to anal cancer [5]. Studies have identified risk factors for each stage in the progression from cervical HPV infection to cervical cancer [9–11], and we are beginning to find similar risk factors in anal cancer natural history. Risk factors for anal HPV infection are related to sexual behavior, such as lifetime number of sexual partners, as well as low CD4 count in HIV-infected populations [12–15]. Smoking history has been shown to be associated with anal HPV persistence [16, 17] and anal cancer [18, 19], but it is unclear at what stage smoking influences the natural history. To add to our understanding of risk factors that influence the natural history of HPV and anal cancer, we conducted a study of lifestyle characteristics and clinical parameters for HIV-infected MSM undergoing routine anal cancer screening at Kaiser Permanente Northern California (KPNC) Health Maintenance Organization.

Background Excess alcohol consumption adversely affects one-carbon metabolism and increases the risk of liver disease and liver cancer. Conversely, higher folate levels have been inversely associated with liver damage. The current study investigated the effects of alcohol and one-carbon metabolite intake on liver cancer incidence and liver disease mortality within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Methods Cox proportional hazards modeling was used to calculate hazard ratios and 95% confidence intervals (CIs) in a population of 27,086 Finnish males with 194 incident liver cancers and 213 liver disease deaths. In a nested case-control subset (95 liver cancers, 103 controls), logistic regression was used to calculate odds ratios and 95% CIs for serum one-carbon metabolites in relation to liver cancer risk. Results Daily alcohol consumption of more than 20.44 g was associated with an increased risk of both liver cancer incidence (Hazard Ratio (HR) 1.52, 95%CI 1.06–2.18) and liver disease mortality (HR 6.68, 95%CI 4.16–10.71). These risks were unaffected by one-carbon metabolite intake. Similarly, in the case-control study, none of the serum one-carbon metabolites were associated with liver cancer. Conclusions The current study provided no convincing evidence for a protective association of one-carbon metabolite intake or serum level on the risk of liver cancer or liver disease mortality.

Background. The prevention of human papillomavirus (HPV)–induced anal cancer in high-risk populations such as human immunodeficiency virus (HIV)-infected men who have sex with men (MSM) remains an urgent priority, given rising incidence rates despite widespread antiretroviral therapy use. Methods. HPV genotypes and anal disease prevalence, by cytology and histopathologic findings, were evaluated among 363 HIV-infected MSM. We modeled fractions of high-grade anal intraepithelial neoplasia (HGAIN) attributable to individual carcinogenic HPV genotypes and estimated the range of the proportion of HGAIN cases potentially preventable by prophylactic HPV vaccines. Results. HPV16 was the most common genotype overall (26.4% of cases) and among HGAIN cases (55%). Prevalence of multiple (≥2) carcinogenic HPV genotypes increased from 30.9% in cases of AIN grade

Result s Aspirin users had statistically significant reduced risks of incidence of HCC (RR = 0.59; 95% CI = 0.45 to 0.77) and mortality due to CLD (RR = 0.55; 95% CI = 0.45 to 0.67) compared to those who did not use aspirin. In contrast, users of nonaspirin NSAIDs had a reduced risk of mortality due to CLD (RR = 0.74; 95% CI= 0.61 to 0.90) but did not have lower risk of incidence of HCC (RR = 1.08; 95% CI = 0.84 to 1.39) compared to those who did not use nonaspirin NSAIDs. The risk estimates did not vary in statistical significance by frequency (monthly, weekly, daily) of aspirin use, but the reduced risk of mortality due to CLD was statistically significant only among monthly users of nonaspirin NSAIDs compared to non-users. Conclusions Aspirin use was associated with reduced risk of developing HCC and of death due to CLD whereas nonaspirin NSAID use was only associated with reduced risk of death due to CLD. J Natl Cancer Inst 2012:104;1808–1814

Author(s): Wentzensen, Nicolas; Follansbee, Stephen; Borgonovo, Sylvia; Tokugawa, Diane; Schwartz, Lauren; Lorey, Thomas S; Sahasrabuddhe, Vikrant V; Lamere, Brandon; Gage, Julia C; Fetterman, Barbara; Darragh, Teresa M; Castle, Philip E | Abstract: ObjectiveAnal cancer incidence is high in HIV-infected MSM. Screening for anal intraepithelial lesions and cancers is performed at specialized clinics and relies on high-resolution anoscopy (HRA) and anal cytology. Both approaches have limited reproducibility and sensitivity for detecting anal cancer precursors. We evaluated biomarkers for human papillomavirus (HPV)-related disease in a population of HIV-infected MSM.MethodsA cross-sectional screening study with passive follow-up included 363 MSM followed at a HIV/AIDS clinic. All men had anal cytology samples taken and were evaluated using HRA and anal biopsies. Using a composite endpoint of biopsy results and cytology, we compared the performance of HPV16/18 genotyping, HPVE6/E7 mRNA expression, and p16/Ki-67 cytology to detect high-grade anal intraepithelial neoplasias (AINs).ResultsFor all biomarkers analyzed, there was a significant trend of increasing percentage of men testing positive with increasing severity of disease (P l 0.001). HPV DNA testing had the highest sensitivity for anal intraepithelial neoplasia grade 2 and anal intraepithelial neoplasia grade 3 (AIN3), followed by p16/Ki-67, HPVE6/E7 mRNA testing, and HPV16/18 genotyping. The highest Youden's index was observed for HPVE6/E7 mRNA testing, followed by HPV16/18 genotyping, p16/Ki-67 cytology, and HPV DNA testing. Increasing the threshold for positivity of p16/Ki-67 to five or more positive cells led to significantly higher specificity, but unchanged sensitivity for detecting AIN3.ConclusionMolecular features of anal disease categories are similar to those of corresponding cervical lesions. Biomarkers evaluated for cervical cancer screening may be used for primary anal cancer screening or to decide who should require immediate treatment vs. expectant management.

Previous studies have reported that lung cancer risk may be decreased, increased, or unaffected by prior use of menopausal hormone therapy (MHT).To assess this issue further, we examined relationships among 118,008 women, ages 50-71 years who were recruited during 1995-1996 for the NIH-AARP Diet and Health Study and in whom 2,097 incident lung carcinomas were identified during follow-up through 2006. Multivariable Cox proportional hazards models estimated relative risks (RR) and 95% confidence intervals (CIs) associated with various measures of self-reported MHT use.We found no evidence that either estrogen therapy (ET)-only or estrogen plus progestin therapy (EPT) use was substantially related to subsequent lung cancer risk (respective RRs and 95% CIs for ever use = 0.97, 0.86-1.09 and 1.03, 0.90-1.17). There were no significant variations according to currency or duration of use of either formulation, nor was there evidence that risks varied within subgroups defined by cigarette smoking or body size. The absence of effect was seen for nearly all lung cancer subtypes, with the exception of an increased risk of undifferentiated/large cell cancers associated with long-term ET-only use (p (trend) = 0.02), a relationship not observed among EPT users.Our results failed to support any substantial alterations in lung cancer risk associated with use of either unopposed estrogen or estrogen plus progestin MHT, even when detailed exposure measures and other risk predictors were considered.

Fifty-nine adults with cerebral palsy (CP) were administered, via in-person interviews, measures of pain intensity, pain-related disability, and psychological functioning, in addition to a measure of pain coping (Waldron/Varni Pediatric Pain Coping Inventory; PPCI). Regression analyses indicated that the PPCI scales made a nonsignificant contribution to the prediction of pain intensity, but did make a significant contribution to the prediction of psychological functioning when controlling for pain intensity. Only the PPCI Catastrophizing subscale made a significant independent contribution to the prediction of psychological functioning, and only the PPCI Seek Social Support subscale made a significant independent contribution to the prediction of pain-related disability. These findings support a link between coping and functioning among adults with CP, and suggest that catastrophizing responses and some aspects of support seeking may be maladaptive for coping with CP-related pain. Limitations of the study include a correlational design, a reliance on self-report data, and a small subject population. Experimental research is needed to determine if changes in coping lead to changes in psychological and physical functioning.

Chronic pain is a common secondary problem associated with cerebral palsy (CP). This pain may be due to the musculoskeletal problems that often accompany CP, including spasticity, scoliosis, and bony deformity. The purpose of this study was to determine the effects of biofeedback-assisted relaxation training on self-reported pain and muscle tension in 3 adults with CP using a multiple baseline design across subjects. Two of 3 participants reported decreases in their pain experiences posttreatment. Their subjective reports, however, did not correspond with physiological changes. Complications in the use of progressive relaxation exercises and EMG biofeedback equipment are described and suggestions for future research provided.

Tyler EJ, Jensen MP, Engel JM, Schwartz L. The reliability and validity of pain interference measures in persons with cerebral palsy. Arch Phys Med Rehabil 2002;83:236-9. Objective: To evaluate the reliability and validity of 2 measures of pain interference in persons with cerebral palsy (CP). Design: Standardized interviews to assess pain and impact of pain on activities. Setting: University medical center. Participants: Fifty adults with CP. Interventions: Patients asked to rate pain's intensity, interference with general activities, and depression levels. Main Outcome Measures: Pain interference scales: Chronic Pain Grade (CPG) and Brief Pain Inventory (BPI); rating of disability: Craig Handicap Assessment and Reporting Technique (CHART); rating of depression: Center for Epidemiologic Studies Depression (CES-D) Scale. Results: Mean interference of pain on 3 CPG items (pain interference with daily activities, social activities, work) were 1.74 ± 2.45, 1.06 ± 2.05, and.89 ± 1.84 (out of 10), respectively. Mean interference on 10 modified BPI interference items ranged from 2.28 ± 3.01 to 3.67 ± 3.15 (out of 10). The composite CPG interference score did not correlate significantly with pain intensity. However, the composite BPI interference score did correlate significantly with pain intensity ( r =.66, P r = −.21, NS). Pain showed a significant association with CES-D score ( r =.45, P Conclusions: The pain interference items of the BPI serve as a reliable and valid measure of pain's impact on persons with CP-related pain. © 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Objective To evaluate the relationships between patient and physician pretreatment expectations of pain relief and subsequent pain relief reported by chronic pain patients immediately after treatment. Design Prospective study of consecutive patients undergoing a procedure in a pain clinic for treatment of chronic pain. Patients rated their current pain level and their expectation of pain relief immediately prior to undergoing a procedure (e.g., intravenous drug infusion, nerve block) for the treatment of chronic pain. Simultaneously and independently, the treating physician completed a similar questionnaire. At completion of the procedure, patients rated their current pain level and degree of pain relief. Setting University of Washington Multidisciplinary Pain Center procedure suite. Patients Forty-six consecutive chronic pain patients. Intervention Intravenous drug infusions and nerve blocks. Outcome measures Current pain and pain relief ratings. Results Patients' pain relief expectation ratings were not correlated significantly with their postprocedure pain relief ratings or pre-post procedure changes in pain ratings. However, a statistically significant correlation was found between physician expectations of pain relief and patient pain relief ratings and patient pre-post procedure changes in pain. Conclusions The results of this study suggest that physicians are better predictors than are patients of patients responses to these procedures and/or that physicians may somehow subtly communicate their expectations to patients during the procedure, and these expectations then influence patient response. Patient pretreatment expectations may not always play a significant role in nonspecific treatment effects.

Although several studies have shown that spouses of chronic pain patients may experience clinically significant depressive symptoms few studies have comprehensively examined the role of both patient and spouse-related factors in the development and maintenance of this emotional distress. Twenty-nine married male chronic benign low back pain patients and their spouses were recruited in order to examine the role of patient, spouse, and marital factors in spouse depressive symptomatology. The results indicated that 28% percent of the spouses in the sample reported significantly depressed mood. A 2-stage regression analysis was employed that revealed 3 significant predictors of spouse's depressed mood, namely patient's average pain, patient's reported levels of anger and hostility, and the spouse's level of marital satisfaction. These findings are discussed in terms of their implications for clinical interventions for pain patients and their families.

What the scalpel is to the surgeon, words are to the clinician... the conversation between doctor and patient is the heart of the practice of medicine. 1 The physician-patient relationship is built through communication and the effective use of language. Along with clinical reasoning, observations, and nonverbal cues, skillful use of language endows the history with its clinical power and establishes the medical interview as the clinician's most powerful tool. 2-5 Language is the means by which a physician accesses a patient's beliefs about health and illness, 6 creating an opportunity to address and reconcile different belief systems. Furthermore, it is through language that physicians and patients achieve an empathic connection that may be therapeutic in itself. 7 Because of language barriers, millions of US residents cannot have this connection with their physician. According to the 1990 US Census, 8 almost 14 million people living in the United States do

Dengue has become the most rapidly expanding mosquito-borne infectious disease on the planet, surpassing malaria and infecting at least 390 million people per year. There is no effective treatment for dengue illness other than supportive care, especially for severe cases. Symptoms can be mild or life-threatening as in dengue hemorrhagic fever and dengue shock syndrome. Vector control has been only partially successful in decreasing dengue transmission. The potential use of safe and effective tetravalent dengue vaccines is an attractive addition to prevent disease or minimize the possibility of epidemics. There are currently no licensed dengue vaccines. This review summarizes the current status of all dengue vaccine candidates in clinical evaluation. Currently five candidate vaccines are in human clinical trials. One has completed two Phase III trials, two are in Phase II trials, and three are in Phase I testing.

Development and Phase 3 testing of the most advanced malaria vaccine, RTS,S/AS01, indicates that malaria vaccine R&D is moving into a new phase. Field trials of several research malaria vaccines have also confirmed that it is possible to impact the host-parasite relationship through vaccine-induced immune responses to multiple antigenic targets using different platforms. Other approaches have been appropriately tested but turned out to be disappointing after clinical evaluation. As the malaria community considers the potential role of a first-generation malaria vaccine in malaria control efforts, it is an apposite time to carefully document terminated and ongoing malaria vaccine research projects so that lessons learned can be applied to increase the chances of success for second-generation malaria vaccines over the next 10 years. The most comprehensive resource of malaria vaccine projects is a spreadsheet compiled by WHO thanks to the input from funding agencies, sponsors and investigators worldwide. This spreadsheet, available from WHO's website, is known as "the rainbow table". By summarizing the published and some unpublished information available for each project on the rainbow table, the most comprehensive review of malaria vaccine projects to be published in the last several years is provided below.