Quantifying bias due to missing data in quality of life surveys of advanced-stage cancer patients.

PURPOSE: Many studies on cancer patients investigate the impact of treatment on health-related quality of life (QoL). Typically, QoL is measured longitudinally, at baseline and at predefined timepoints thereafter. The question is whether, at a given timepoint, patients who return their questionnaire (available cases, AC) have a different QoL than those who do not return their questionnaire (non-AC). METHODS: We employed augmented inverse probability weighting (AIPW) to estimate the average QoL of non-AC in two studies on advanced-stage cancer patients. The AIPW estimator assumed data to be missing at random (MAR) and used machine learning (ML)-based methods to estimate answering probabilities of individuals at given timepoints as well as their reported QoL, as a function of auxiliary variables. These auxiliary variables were selected by medical oncologists based on domain expertise. We aggregated results both by timepoint and by time until death and compared AIPW estimates to the AC averages. Additionally, we used a pattern mixture model (PMM) to check sensitivity of our AIPW estimates against violation of the MAR assumption. RESULTS: Our study included 1927 patients with advanced pancreatic and 797 patients with advanced breast cancer. The AIPW estimate for average QoL of non-AC was below the average QoL of AC when aggregated by timepoint. The difference vanished when aggregated by time until death. PMM estimates were below AIPW estimates. CONCLUSIONS: Our results indicate that non-AC have a lower average QoL than AC. However, estimates for QoL of non-AC are subject to unverifiable assumptions about the missingness mechanism.

Effectiveness, safety and quality of life of trifluridine/tipiracil in pretreated patients with metastatic colorectal cancer: Real-world data from the noninterventional TACTIC study in Germany.

The prospective, multicenter, noninterventional TACTIC study assessed effectiveness and safety of trifluridine/tipiracil (FTD/TPI) in patients with metastatic colorectal cancer (mCRC) in a real-world setting in Germany, thus evaluating the external validity of the findings from the pivotal RECOURSE trial. Primary endpoint was overall survival (OS). Secondary objectives included progression-free survival (PFS), safety, and quality of life (QoL). Subgroups comprised patients with good (<3 metastatic sites at inclusion, ≥18 months from diagnosis of first metastasis to inclusion) or poor (remaining patients) prognostic characteristics (GPC/PPC). GPC without liver metastases was considered best prognostic characteristics (BPC). In total, 307 eligible patients (pretreated or not suitable for other available therapies) were treated with FTD/TPI. Overall, median [95%-CI] OS was 7.4 months [6.4-8.6], median PFS was 2.9 months [2.8-3.3]. In BPC (n = 65) and GPC (n = 176) compared to PPC (n = 124) subgroup, median OS (13.3 [9.1-17.6] vs 8.9 [7.6-9.8] vs 5.1 [4.4-7.0] months) and median PFS (4.0 [3.3-5.3] vs 3.4 [3.0-3.7] vs 2.6 [2.4-2.8] months) were longer. Patient-reported QoL, assessed by validated questionnaires (EQ-5D-5L, PRO-CTCAE), was stable throughout FTD/TPI treatment. Predominant FTD/TPI-related adverse events of grades 3 or 4 were neutropenia (13.0%), leukopenia (7.5%), and anemia (5.2%). Altogether, palliative FTD/TPI therapy in patients with pretreated mCRC was associated with prolonged survival, delayed progression, maintained health-related QoL, and manageable toxicity. Low metastatic burden and indolent disease were favorable prognostic factors for survival. TACTIC confirms the effectiveness and safety of FTD/TPI, highlighting its value in routine clinical practice.

PERFORM: a non-interventional study assessing the patients' treatment starting with 1L palbociclib in HR+/HER2- ABC.

The prospective, non-interventional PERFORM study describes and analyzes the effectiveness of palbociclib in combination with endocrine therapy (aromatase inhibitor or fulvestrant) as first-line treatment for patients with locally advanced or metastatic HR+/HER2- breast cancer in the real-world setting in Germany and Austria. PERFORM will reflect current patient characteristics and routine treatment patterns including treatment sequences and time to subsequent (chemo)therapy. Besides, second-line treatment effectiveness and patient-relevant end points such as longitudinal patient-reported outcome measurements beyond disease progression will be analyzed. Accounting for the heterogenous real-world patient population, data on clinicopathologic subgroups underrepresented in clinical trials such as elderly or male will be analyzed. Taken together, PERFORM will close knowledge gaps from clinical trials in real world.

Palbociclib in combination with endocrine therapy is the standard first-line treatment for patients with advanced HR+/HER2- breast cancer. Data from clinical trials have shown high response rates and good tolerability. To support these data and close potential knowledge gaps, we conduct the multicenter, observational PERFORM study to evaluate the effectiveness and patient-reported outcomes in patients with advanced HR+/HER2- breast cancer treated with endocrine-based palbociclib therapy in routine clinical practice in Germany. Clinical Trial Registration: NCT04767594 (ClinicalTrials.gov) Sponsor: Pfizer Pharma GmbH, Linkstraße 10, D-10785 Berlin, Germany.

Routine treatment and outcome of breast cancer in younger versus elderly patients: results from the SENORA project of the prospective German TMK cohort study.

PURPOSE: There is an ongoing discussion about 'undertreatment' of breast cancer in elderly patients. Due to low accrual into clinical trials, level 1 evidence is scarce. We report prospective data of elderly patients with breast cancer treated by medical oncologists in Germany. METHODS: The SENORA project within the prospective cohort study TMK (Tumour Registry Breast Cancer) was conducted in 82 centres from 2007-2015. Among 2316 patients, half were enrolled with curative and half with palliative treatment intention. Overall, 478 patients (21%) were aged ≥ 70. RESULTS: In the adjuvant setting, elderly patients aged ≥ 70 had more advanced tumour stages at diagnosis and a higher prevalence of comorbidities than younger patients. Elderly patients received adjuvant chemotherapy less frequently, yet the 3-year disease-free survival was similar (86% vs. 88%). In the palliative setting, elderly patients more frequently received endocrine therapy and less frequently chemotherapy. Their median overall survival [24.9 months, 95% CI (confidence interval) 20.0-30.2] was significantly shorter than that of younger patients (39.7 months, 95% CI 34.9-44.2). A Cox proportional hazards model showed a significantly increased risk of mortality for: age ≥ 70 at start of therapy, negative HR- or HER2-status, higher number of metastatic sites, more comorbidities and high tumour grading at diagnosis. CONCLUSIONS: Our results shed light on the routine treatment of elderly patients with breast cancer. A regression model demonstrated that age is but one of various prognostic factors determining the shorter overall survival of elderly patients.

Shunt age-related complications in adult patients with suspected shunt dysfunction. A recommended diagnostic workup.

BACKGROUND: Patients admitted for suspicion of shunt dysfunction (SD) often show unspecific symptoms and require time-consuming, expensive and even invasive diagnostics involving significant radiation exposure. The purpose of this retrospective study was to analyse the current diagnostic procedures and to propose a process optimisation. METHOD: As all patients admitted for suspicion of SD receive imaging studies, we searched for adult patients receiving neuroimaging in the period from January 2010 to July 2013, analysing referring diagnosis, clinical signs, products, diagnostic process and final diagnosis. Recursive partitioning was used to define time intervals for differentiating types of SD. RESULTS: A total of 148 patients, aged 18-89 (mean, 54) years, were studied. Forty-two percent were referred by a hospital or rehabilitation centre, 30% by general practitioners and 24% were self-referrals. The admission diagnosis was in the majority "shunt dysfunction" only. Further differentiations were rarely made. An SD was confirmed in 46% of the patients. In 17%, the symptoms were based on another cause and in 37% they could not be clearly attributed to any specific disorder. Abdominal dislocations (2%) and shunt infections (5%) were found within the first 6 months. Over- (3%) and under-drainage (14%) were the most frequent complications during the first 4 years. Disconnections (13%) occurred generally 4 years or more after implantation. Only shunt obstruction (9%) showed no temporal pattern. CONCLUSIONS: Symptoms of SD remain mostly unspecific. This study showed that the type of SD depends on the time interval from implantation. We propose a workup strategy for patients with SD based on the temporal profile.

Decreased monocyte activation with daily acyclovir use in HIV-1/HSV-2 coinfected women.

OBJECTIVES: Several clinical trials have demonstrated that daily treatment of HIV-infected individuals with the antiherpes drug acyclovir slightly decreases HIV-1 viral load and slows disease progression. This study examines if this slowing in clinical progression is a direct cause of the decrease in viral load or an indirect effect of lower immune activation due to lower levels of herpetic reactivation. METHODS: Women who participated in a randomised clinical trial of daily acyclovir use (n=301) were monitored every 6 months for changes in immune activation. Soluble CD14 (sCD14), a marker for monocyte activation, and C-reactive protein (CRP), a marker for general immune activation, were measured by ELISA. RESULTS: Initial levels of sCD14 and CRP were not predictive of HIV disease progression when controlling for initial CD4+ cell count and HIV viral load. sCD14 levels, but not CRP, decreased in the acyclovir treatment arm at a significantly faster rate than the placebo group, which was independent of changes in HIV viral load and CD4+ cell count in a multivariant mixed-effects model (p=0.039). However, the magnitude of this decrease was relatively small with a total estimated decrease of sCD14 of 15% of initial levels. CONCLUSIONS: These data suggest that decreased monocyte activation may play a minor role in the ability of daily acyclovir use to slow HIV disease progression. CLINICAL TRIAL REGISTRATION NUMBER: NCT00405821.

Real-world patient-reported outcomes of breast cancer or prostate cancer patients receiving antiresorptive therapy for bone metastases: Final results of the PROBone registry study.

Background: In breast cancer and prostate cancer patients, bone metastases (BM) present the main cause of morbidity and often cause debilitating pain, impaired functioning and subsequent deterioration of quality of life (QoL). The management of BM is still challenging. Maintenance or improvement in QoL is the main goal of treatment. Antiresorptive treatment, such as denosumab and bisphosphonates, can help to reduce the frequency of skeletal complications, to control bone pain and potentially to improve QoL. The optimal time point for initiation of antiresorptive therapy is still discussed controversially. In patients with BM, bone pain can be used as a surrogate measure of QoL. However, limited data exist on health-related QoL in patients with BM under antiresorptive treatment. The PROBone registry study evaluated complaints and limitations caused by BM of breast and prostate cancer patients using patient-reported outcomes (PROs) in real-world in Germany. Methods: Between 2014 and 2019, 500 patients with histological confirmation of advanced breast or prostate cancer, diagnosed with BM at start of their first antiresorptive therapy were prospectively enrolled in 65 outpatient-centers specialized in medical oncology across Germany. Changes of QoL were assessed monthly from baseline until a maximum of 12 months using the validated pain score Functional Assessment of Cancer Therapy Quality of Life Measurement in patients with bone pain (FACT-BP) supplemented by questions on general pain and on the impact of time spent for treatment of illness on patients' daily activities. Statistical analysis was performed descriptively by relative and absolute frequencies. Results: In total, 486 patients were eligible for final analysis, of these 310 were diagnosed with breast cancer and 176 with prostate cancer. Median age was 67 years for breast cancer and 76 years for prostate cancer patients. 79.7% of breast cancer and 59.7% of prostate patients started antiresorptive treatment within 3 months after diagnosis of BM. More than 75% of patients suffered from bone pain at study inclusion. In total 52% of breast cancer patients and 47.9% of prostate cancer patients reported to take pain medication during the observation period. In breast and prostate cancer patients an initial pain reduction after start of BTA was observed: General pain and bone pain levels as well as the median FACT-BP score showed a constant improvement over the first months and maintained stable at a constant level afterwards. Subgroup analysis showed that patients without pain at baseline reported distinctly better FACT-BP scores throughout the whole observation period than patients with pain at baseline. Looking at time-stress (M)-scores, younger breast cancer patients (<65 years) showed highest burden especially during the first months of treatment. Conclusions: Our results indicate overall good adherence to current guideline recommendation, with most breast and prostate cancer patients starting antiresorptive therapy within the first 3 months after diagnosis of BM. This point gains even more importance as our data support current recommendations by ESMO guidelines as well as by German evidence-based S3-guidelines for diagnosis and treatment of breast and prostate cancer to initiate bone-targeted agents (BTA) as soon as BM are diagnosed, to keep pain levels at the lowest level possible, to minimize the debilitating effects of metastatic bone pain and maintain a good QoL. Bone pain management by an early use of BTA following BM diagnosis might improve patient care.

Long-term Follow-up Reveals High Posttreatment Mortality Rate Among Patients With Extensively Drug-Resistant Tuberculosis in the Country of Georgia.

BACKGROUND: Given very limited data, we assessed the long-term outcomes among patients with extensively drug-resistant (XDR) tuberculosis (TB). METHODS: A retrospective population-based cohort study was performed in patients with XDR-TB diagnosed during 2011-2013 in the country of Georgia. Data were abstracted from the National TB Program, medical charts, interviews, and the national Georgian death registry. RESULTS: Among 111 patients starting treatment for XDR-TB, 59 (53.2%) had newly diagnosed tuberculosis, and 3 (2.9%) had human immunodeficiency virus (HIV) coinfection. The median length of follow-up from diagnosis of XDR-TB to death or the end of study was 53.9 months (interquartile range, 27.2-66.3 months). End-of-treatment outcomes were available for 106 patients; 35 (33.0%) had a favorable outcome, and 71 (67.0%) had an unfavorable outcome, including death in 16 (15.1%). An additional 20 patients died after cessation of initial treatment, increasing the overall mortality rate to 34.0%. In multivariable analysis, an unfavorable initial end-of-treatment outcome was associated with posttreatment death (adjusted odds ratio, 14.41; 95% confidence interval, 1.78-117.13). CONCLUSIONS: The overall mortality rate and specifically the posttreatment mortality rate were high among patients with XDR-TB. Patients with an unfavorable end-of-treatment outcome had an increased risk of death during follow-up. Our findings highlight the need for improved adherence, better-tolerated and shorter therapies, and enhanced posttreatment surveillance among patients treated for XDR-TB.

Use of vitamin and mineral supplements among adolescents living in Germany-Results from EsKiMo II.

Dietary supplements may contribute to nutrient intake; however, actual data on dietary supplement use among adolescents living in Germany are rare. The aim of this analysis was to describe the current use of dietary supplements, its determinants, and reasons of use. Changes in supplement use over time were evaluated by comparing the results with those from EsKiMo I (2006). Data from the Eating Study as a KiGGS Module EsKiMo II (2015-2017) were used to analyze supplement intake according to sociodemographic, health characteristics, and physical exercise behavior of 12-17-year-olds (n = 1356). Supplement use during the past four weeks was assessed by a standardized computer assisted personal interview. Multivariable logistic regression was used to identify the association between supplement use and its determinants. Between 2015-2017, 16.4% (95%-CI: 13.0-19.7%) of the adolescents used dietary supplements, and its use decreased with lower levels of physical exercise and overweight. Most supplement users used only one supplement, often containing both vitamins and minerals. The most frequently supplemented nutrients were vitamin C and magnesium. The main reported reason to use supplements was 'to improve health'. Prevalence of supplement use was slightly lower in 2015-2017 than in 2006 (18.5%; 95%-CI: 15.8-21.2%). The results underline the importance of including nutrient intake through dietary supplements in nutrition surveys.

SWITCH II: Phase III randomized, sequential, open-label study to evaluate the efficacy and safety of sorafenib-pazopanib versus pazopanib-sorafenib in the treatment of advanced or metastatic renal cell carcinoma (AUO AN 33/11).

PURPOSE: This trial compared the sequential therapy with the multikinase inhibitor sorafenib (So) followed by pazopanib (Pa) or vice versa in advanced/metastatic renal cell carcinoma (mRCC) patients. METHODS: This multicenter, randomized phase 3 study assessed the sequential use of So-Pa versus Pa-So in patients with mRCC without prior systemic therapy. Pts were randomized to So 2 × 400 mg/day followed by Pa 1 × 800 mg/day in case of progression or intolerable toxicity or vice versa. Primary endpoint was total PFS (tPFS), defined as time from randomization to progression, or death during second-line therapy. Key secondary endpoints included overall survival (OS), first-line PFS, disease control rate (DCR) and safety. RESULTS: A total of 377 pts were randomized (So-Pa, n = 189; Pa-So, n = 188). Recruitment of a total 544 pts was calculated, but actual accrual rate turned out to be lower than expected. The primary endpoint median tPFS was 8.6 mo (95% CI 7.7-10.2) for So-Pa and 12.9 mo (95% CI 10.8-15.2) for Pa-So with a hazard ratio (HR) of 1.36 (upper limit of one-sided 95% CI 1.68), which exceeded a predefined HR <1.225 as a one-sided 95% confidence interval. Non-inferiority of So-Pa regarding tPFS was not met. Secondary endpoints displayed marked statistical differences in favor of Pa-So in first-line PFS and DCR but not for OS and 2nd-line PFS. Side effect profiles were consistent with known toxicities of the respective multikinase-inhibitor including diarrhea, fatigue, hand-foot skin reaction and hypertension. CONCLUSIONS: Non-inferiority of the primary endpoint tPFS could not be demonstrated for So-Pa. The results for first-line PFS and DCR favored the Pa-So sequence. TRIAL REGISTRATION: NCT01613846, www.clinicaltrials.gov.

Adjuvant chemotherapeutic treatment of 1650 patients with early breast cancer in routine care in Germany: data from the prospective TMK cohort study.

BACKGROUND: Several regimens for which efficacy was established in randomized controlled trials are recommended in current treatment guidelines for early breast cancer. However, knowledge on use and effectiveness of commonly administered chemotherapeutic agents in real-life care and across all breast cancer subtypes is limited. METHODS: The prospective, multicentre German TMK cohort study (Tumour Registry Breast Cancer) recruited patients in 148 oncology outpatient-centres. Data from 1650 patients who completed adjuvant chemotherapy were analysed regarding treatment regimens and taxane use from 2007 to 2014. The association of patient characteristics with application of taxane-free regimens was examined with a multivariate regression model. RESULTS: The preferred adjuvant treatment shifted from fluorouracil, anthracycline and cyclophosphamide containing regimens to anthracycline/taxane combinations. Taxane use increased for all subtypes, and the greatest rise was among node-negative patients. Older age, node-negativity, lower grading, HR-positive/HER2-negative subtype and earlier start year of therapy were significantly associated with taxane-free therapy. CONCLUSIONS: Treatment with anthracycline/taxane-based chemotherapy in Germany has been rising for every subtype. The increased taxane use reflects updated guideline recommendations over the past decade. Cohort studies like the TMK provide insight into real-life treatment of patients outside of clinical trials.

Factors Associated with High-Grade Anal Intraepithelial Lesion in HIV-Positive Men in a Southern U.S. City.

The incidence of anal cancer is increased in HIV-infected patients compared with the general population. Risk factors associated with the anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), have not been extensively studied in an urban black population with late-stage HIV disease. We performed a retrospective chart review of HIV-infected men at the Grady Ponce de Leon Center HIV Clinic (Atlanta, GA) referred for high-resolution anoscopy (HRA), a procedure where anal tissue is examined under magnification and abnormal areas are biopsied. Between December 2013 and September 2015, 147 men underwent HRA: 72% were black, and 94% were men who have sex with men. CD4 count closest to time of HRA was a median 325 cells/mm3 (interquartile range 203-473), and 69% had an undetectable HIV viral load. Ninety-four percent had abnormal anal cytology [80% atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (LSIL) and 20% atypical squamous cells, cannot exclude HSIL/HSIL], and 97% had abnormal histology (35% LSIL, 65% HSIL). Statistically significant variables associated with HSIL included number of biopsies [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.13-2.14] and having ≥1 high-grade anal cytology in the last 12 months (OR 3.76, 95% CI 1.38-10.23). No significant association was found between HSIL and CD4, HIV viral load, or recent sexually transmitted infection. In this population, the burden of anal HSIL was extremely high, regardless of most recent anal cytology result. In newly diagnosed HIV-infected men with no history of anal cancer screening, performing HRA as primary anal cancer screening instead of cytology appears to be a viable option.

EsKiMo II - the Eating study as a KiGGS Module in KiGGS Wave 2.

Nutrition plays an important role for health, in particular of children and adolescents. In addition to the baseline German Health Interview and Examination Survey for Children and Adolescents (KiGGS, 2003-2006), the nutrition survey EsKiMo (Eating study as a KiGGS Module) assessed the dietary habits of children and adolescents aged 6 to 17 in detail. In KiGGS Wave 2 (2014-2017) the corresponding module is EsKiMo II. Between June 2015 and September 2017, specially trained nutritionists will visit EsKiMo II participants at their homes. The parents of 6-to 11-year-olds are instructed on how to complete food records on four randomly chosen days - three consecutive days, followed later by an additional day. Participants aged 12 to 17 are interviewed personally on their food intake during the past four weeks with the dietary interview programme DISHES. Further information, for example, regarding dietary supplements is also recorded. EsKiMo II will provide an up-to-date and representative overview of the current nutrition status of 6-to 17-year-olds living in Germany, and it allows analysing changes in dietary behaviour over time. EsKiMo II can identify shortcomings in the nutrition of children and adolescents and thus may contribute with important information to nutrition and health policy.

Antianemic Treatment of Cancer Patients in German Routine Practice: Data from a Prospective Cohort Study-The Tumor Anemia Registry.

The aim of this prospective cohort study was to assess current antianemic treatment of cancer patients in German routine practice, including diagnostics, treatments, and quality of life (QoL). 88 study sites recruited 1018 patients at the start of antianemic treatment with hemoglobin (Hb) levels <11 g/dL (females) or <12 g/dL (males). Patients were followed up for 12 weeks. 63% of the patients had inoperable solid tumors, 22% operable solid tumors, and 15% hematological malignancies. Over 85% received chemotherapy. Median age was 67 years; 48% were male. Red blood cell transfusions (RBCTx) were given to 59% of all patients and to 55% of the patients with Hb ≥8 g/dL on day 1 of the observation period (day 1 treatment). Erythropoiesis-stimulating agents (ESAs) were the second most frequently applied day 1 treatment (20%), followed by intravenous (IV) iron (15%) and ESA + IV iron (6%). Only about a third of patients were tested for blood serum iron parameters at the start of treatment. Overall, more than half of the patients had long-term responses to antianemic therapy. Our data suggest that in routine practice diagnostics for treatable causes of anemia are underused. A high proportion of cancer patients receive RBCTx. It should be discussed whether thorough diagnostics and earlier intervention could decrease the need for RBCTx. This trial is registered with NCT01795690.

Oxaliplatin-based first-line chemotherapy is associated with improved overall survival compared to first-line treatment with irinotecan-based chemotherapy in patients with metastatic colorectal cancer - Results from a prospective cohort study.

PURPOSE: Several randomized trials investigating the preferable first-line combination chemotherapy regimen for metastatic colorectal cancer have shown inconsistent findings. Because a substantial number of patients are still being treated with "chemo-only" first-line therapies without targeted agents, we compared overall survival (OS) of patients treated in routine practice with oxaliplatin-fluoropyrimidine and irinotecan-fluoropyrimidine. PATIENTS AND METHODS: Using the database of the Tumor Registry Colorectal Cancer, we identified 605 patients with metastatic colorectal cancer who received first-line fluoropyrimidine combination chemotherapy with either oxaliplatin (n=430) or irinotecan (n=175). The Tumor Registry Colorectal Cancer is a cohort study that prospectively documents treatment of colorectal cancer by office-based medical oncologists in Germany and has recruited over 5,000 patients. OS was estimated using the Kaplan-Meier method, and a multivariate Cox proportional hazard model was used to adjust for potentially confounding variables. RESULTS: Median OS was 26.8 (95% confidence interval [CI] 22.4-31.9) months with an oxaliplatin-fluoropyrimidine combination and 18.3 (95% CI 15.1-23.2) months with irinotecan-fluoropyrimidine first-line "chemo-only" therapy. Median progression-free survival was 9.0 (8.1-10.2) and 7.9 (7.2-10.2) months, respectively. The difference in OS was confirmed if analysis was restricted to patients with synchronous metastases (no prior treatment). Among other variables, proportion of patients receiving any second-line therapy did not differ between groups. Oxaliplatin-based first-line therapy was associated with improved OS in multivariate analysis adjusted for potentially confounding variables (hazard ratio 0.678, 95% CI 0.510-0.901, P=0.007). CONCLUSION: In clinical routine practice, first-line treatment with oxaliplatin-fluoropyrimidine combination chemotherapy compared to irinotecan-fluoropyrimidine combination is associated with improved survival in patients with metastatic colorectal cancer, independent of all examined potentially confounding factors.

Prevalence and factors associated with herpes simplex virus type 2 infection in patients attending a Baltimore City emergency department.

OBJECTIVES: Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted disease, but there is limited data on its epidemiology among urban populations. The urban Emergency Department (ED) is a potential venue for surveillance as it predominantly serves an inner city minority population. We evaluate the seroprevalence and factors associated with HSV-2 infection among patients attending the Johns Hopkins Hospital Adult Emergency Department (JHH ED). METHODS: An identity unlinked-serosurvey was conducted between 6/2007 and 9/2007 in the JHH ED; sera were tested by the Focus HerpeSelect ELISA. Prevalence risk ratios (PRR) were used to determine factors associated with HSV-2 infection. RESULTS: Of 3,408 serum samples, 1,853 (54.4%) were seropositive for HSV-2. Females (adjPRR  = 1.47, 95% CI 1.38-1.56), non-Hispanic blacks (adjPRR  = 2.03, 95% CI 1.82-2.27), single (adjPRR  = 1.15, 95% CI 1.07-1.25), divorced (adjPRR  = 1.28, 95% CI 1.15-1.41), and unemployed patients (adjPRR  = 1.13, 95% CI 1.05-1.21) had significantly higher rates of HSV-2 infection. Though certain zip codes had significantly higher seroprevalence of HSV-2, this effect was completely attenuated when controlling for age and gender. CONCLUSIONS: Seroprevalence of HSV-2 in the JHH ED was higher than U.S. national estimates; however, factors associated with HSV-2 infection were similar. The high seroprevalence of HSV-2 in this urban ED highlights the need for targeted testing and treatment. Cross-sectional serosurveys in the urban ED may help to examine the epidemiology of HSV-2.

Inhibitor of differentiation proteins do not influence prognosis of biliary tract cancer.

AIM: To investigate the expression and clinical relevance of inhibitor of differentiation (ID) proteins in biliary tract cancer. METHODS: ID protein expression was analyzed in 129 samples from patients with advanced biliary tract cancer (BTC) (45 extrahepatic, 50 intrahepatic, and 34 gallbladder cancers), compared to normal controls and correlated with clinical an pathological parameters. RESULTS: ID1-3 proteins are frequently overexpressed in all BTC subtypes analyzed. No correlation between increased ID protein expression and tumor grading, tumor subtype or treatment response was detected. Survival was influenced primary tumor localization (extrahepatic vs intrahepatic and gall bladder cancer, OS 1.5 years vs 0.9 years vs 0.7 years, P = 0.002), by stage at diagnosis (OS 2.7 years in stage I vs 0.6 years in stage IV, P < 0.001), resection status and response to systemic chemotherapy. In a multivariate model, ID protein expression did not correlate with clinical prognosis. Nevertheless, there was a trend of shorter OS in patients with loss of cytoplasmic ID4 protein expression (P = 0.076). CONCLUSION: ID protein expression is frequently deregulated in BTC but does not influence clinical prognosis. Their usefulness as prognostic biomarkers in BTC is very limited.