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1.
J Morphol ; 284(7): e21606, 2023 07.
Article in English | MEDLINE | ID: mdl-37313768

ABSTRACT

The main cannabinoid receptor CB1R first shows expression during early neurula stage in chicken (Gallus gallus) embryos, and at early tailbud stage in the frog (Xenopus laevis) embryos. This raises the question of whether CB1R regulates similar or distinct processes during the embryonic development of these two species. Here, we examined whether CB1R influences the migration and morphogenesis of neural crest cells and derivatives in both chicken and frog embryos. Early neurula stage chicken embryos were exposed to arachidonyl-2'-chloroethylamide (ACEA; a CB1R agonist), N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251; a CB1R inverse agonist) or Blebbistatin (nonmuscle Myosin II inhibitor) in ovo and examined during migration of neural crest cells and at condensing cranial ganglia stage. Early tailbud stage frog embryos were bathed in ACEA, AM251 or Blebbistatin, and analyzed at late tailbud stage for changes in craniofacial and eye morphogenesis, and in patterning and morphology of melanophores (neural crest-derived pigment cells). In chicken embryos exposed to ACEA and Myosin II inhibitor, cranial neural crest cells migrated erratically from the neural tube, and the right, but not the left, ophthalmic nerve of the trigeminal ganglia was affected in ACEA- and AM251-treated embryos. In frog embryos with inactivation or activation of CB1R, or inhibition of Myosin II, the craniofacial and eye regions were smaller and/or less developed, and the melanophores overlying the posterior midbrain were more dense, and stellate in morphology, than the same tissues and cells in control embryos. This data suggests that despite differences in the time of onset of expression, normal activity of CB1R is required for sequential steps in migration and morphogenesis of neural crest cells and derivatives in both chicken and frog embryos. In addition, CB1R may signal through Myosin II to regulate migration and morphogenesis of neural crest cells and derivatives in chicken and frog embryos.


Subject(s)
Chickens , Neural Crest , Chick Embryo , Animals , Female , Drug Inverse Agonism , Morphogenesis , Embryonic Development , Anura
2.
Cancers (Basel) ; 14(24)2022 Dec 13.
Article in English | MEDLINE | ID: mdl-36551632

ABSTRACT

This study reports characteristics and outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) receiving nivolumab in second-line or later (2L+) in France and Germany between 2015 and 2020. Patients with aNSCLC (stage IIIB-C/IV) receiving nivolumab in 2L+ were included from the retrospective Epidemiological Strategy and Medical Economics of Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015-2019) and Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients (CRISP, Germany; 2016-2020). Overall, 2262 ESME-AMLC and 522 CRISP patients were included. Median treatment duration (95% confidence intervals) was 2.8 months (2.5-3.2) in squamous and 2.5 months (2.3-2.8) in non-squamous/others patients in ESME-AMLC, and 2.3 months (1.4-3.1) and 2.3 months (2.0-2.8), respectively in CRISP. One-year and two-year overall survival (OS) were 47.2% and 26.7% in squamous and 50.8% and 32.8% in non-squamous/others patients in ESME-AMLC, and 43.1% and 20.9%, and 37.7% and 18.9%, respectively in CRISP. Poorer performance score and shorter time from start of previous line of therapy initiation were significantly associated with shorter treatment duration and OS. This study confirms, in real-world clinical databases, the efficacy of nivolumab previously observed in clinical trials.

3.
Lung Cancer ; 172: 65-74, 2022 10.
Article in English | MEDLINE | ID: mdl-36007281

ABSTRACT

OBJECTIVES: To describe the impact of immune checkpoint inhibitors (ICIs) on treatment patterns and survival outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) in France and Germany. MATERIALS AND METHODS: Patients with aNSCLC without known ALK or EGFR mutations receiving first-line (1L) therapy were included from (i) the retrospective Epidemiological-Strategy and Medical Economics Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015-2018) and (ii) the prospective Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients platform (CRISP, Germany; 2016-2018). Analyses were stratified according to histology. Survival outcomes were estimated using Kaplan-Meier methodology and stratified by year of 1L therapy. Data sources were analysed separately. RESULTS: In ESME-AMLC and CRISP, 8,046 and 2,359 patients were included in the study, respectively. In both countries, approximately 20 % of all patients received pembrolizumab monotherapy as 1L treatment in 2018. In ESME-AMLC, the proportion receiving an ICI over the course of treatment (any line) increased from 42.2 % (2015) to 56.1 % (2018) in patients with squamous histology, and 28.9 % to 51.9 % with non-squamous/other; in CRISP, it increased from 50.6 % (2016) to 65.2 % (2018) with squamous histology, and 40.8 % to 62.7 % with non-squamous/other. Two-year overall survival from 1L initiation was 36.8 % and 25.6 % in the squamous cohorts and 36.5 % and 30.8 % in the non-squamous/other cohorts in ESME-AMLC and CRISP, respectively. No significant change in overall survival was observed over time; however, the follow-up time available was limited in the later years of the analysis. CONCLUSION: The results of this joint research from two large clinical databases in France and Germany demonstrate the growing use of ICIs in the management of aNSCLC. Future analyses will allow for the evaluation of the impact of ICIs on long-term survival of patients with aNSCLC.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/epidemiology , ErbB Receptors , Humans , Immune Checkpoint Inhibitors , Lung Neoplasms/drug therapy , Lung Neoplasms/epidemiology , Lung Neoplasms/metabolism , Prospective Studies , Receptor Protein-Tyrosine Kinases/therapeutic use , Retrospective Studies
4.
Viruses ; 13(2)2021 01 27.
Article in English | MEDLINE | ID: mdl-33513748

ABSTRACT

High-throughput HPV typing assays with increased automation, faster turnaround and type-specific digital readout would facilitate studies monitoring the impact of HPV vaccination. We evaluated the NanoString nCounter® platform for detection and digital readout of 48 HPV types in a single reaction. NanoString (NS) used proprietary software to design CodeSets: type-specific probe pairs targeting 48 HPV types and the globin gene. We tested residual DNA extracts from epidemiologic specimens and defined samples (HPV plasmids at 10 to 104 copies/reaction) directly (No-PCR) as well as after L1 consensus PCR of 45 (PCR-45) or 15 cycles (PCR-15). Assay and interpretation followed NS recommendations. We evaluated analytic performance by comparing NanoString results for types included in prior assays: Roche Linear Array (LA) or HPV TypeSeq assay. No-PCR results on 40 samples showed good type-specific agreement with LA (k = 0.621) but sensitivity was 65% with lower limit of detection (LOD) at 104 plasmid copies. PCR-45 results showed almost perfect type-specific agreement with LA (k = 0.862), 82% sensitivity and LOD at 10 copies. PCR-15 results on 75 samples showed substantial type-specific agreement with LA (k = 0.796, 92% sensitivity) and TypeSeq (k = 0.777, 87% sensitivity), and LOD at 10 copies of plasmids. This proof-of-principle study demonstrates the efficacy of the NS platform with HPV CodeSet for type-specific detection using a low number of PCR cycles (PCR-15). Studies are in progress to evaluate assay reproducibility and analytic validation with a larger number of samples.


Subject(s)
Alphapapillomavirus/classification , Alphapapillomavirus/genetics , Human Papillomavirus DNA Tests , Cell Line, Tumor , DNA Probes, HPV , DNA, Viral/classification , DNA, Viral/genetics , Genotype , Humans , Nucleic Acid Hybridization , Polymerase Chain Reaction , Software
6.
Surg Endosc ; 32(3): 1389-1396, 2018 03.
Article in English | MEDLINE | ID: mdl-28840332

ABSTRACT

OBJECTIVE: To study the effects of fatigue on general surgery residents' performance on the da Vinci Skills Simulator (dVSS). METHODS: 15 General Surgery residents from various postgraduate training years (PGY2, PGY3, PGY4, and PGY5) performed 5 simulation tasks on the dVSS as recommended by the Robotic Training Network (RTN). The General Surgery residents had no prior experience with the dVSS. Participants were assigned to either the Pre-call group or Post-call group based on call schedule. As a measure of subjective fatigue, residents were given the Epworth Sleepiness Scale (ESS) prior to their dVSS testing. The dVSS MScore™ software recorded various metrics (Objective Structured Assessment of Technical Skills, OSATS) that were used to evaluate the performance of each resident to compare the robotic simulation proficiency between the Pre-call and Post-call groups. RESULTS: Six general surgery residents were stratified into the Pre-call group and nine into the Post-call group. These residents were also stratified into Fatigued (10) or Nonfatigued (5) groups, as determined by their reported ESS scores. A statistically significant difference was found between the Pre-call and Post-call reported sleep hours (p = 0.036). There was no statistically significant difference between the Pre-call and Post-call groups or between the Fatigued and Nonfatigued groups in time to complete exercise, number of attempts, and high MScore™ score. CONCLUSION: Despite variation in fatigue levels, there was no effect on the acquisition of robotic simulator skills.


Subject(s)
Fatigue/complications , General Surgery/education , Internship and Residency , Learning Curve , Robotic Surgical Procedures/education , Clinical Competence , Georgia , Humans
7.
Bull Hosp Jt Dis (2013) ; 72(3): 197-203, 2014.
Article in English | MEDLINE | ID: mdl-25429387

ABSTRACT

BACKGROUND: Standardized pediatric hospitalist and orthopaedic co-management of spinal fusion patients may improve quality processes and outcomes. This approach has not been studied in a general academic center. OBJECTIVE: Estimate relative effects and feasibility of the interventions on quality outcomes, length of stay (LOS), catheter-acquired urinary tract infections (CAUTI), medication errors, and pain scores. DESIGN AND SETTING: Retrospective cohort using interrupted time series, analyzing data from 83 patients aged 5 to 18 years admitted for posterior spinal fusion (PSF) in 2009 (N = 27), 2010 (N = 28), and 2011 (N = 28) on a children's service at a general academic tertiary care center. INTERVENTIONS: Multimodal approach to standardizing pediatric PSF postoperative care with interdepartmental development of order sets, clinical care guidelines, and routine pediatric hospitalist co-management of all pediatric PSF patients. MEASUREMENTS: Chi-square analysis of order set use, guideline use measured by proxy medication and documentation data. ANOVA for comparison of CAUTI and medication error rate and multivariate linear regression of LOS and pain scores. RESULTS: Pediatric hospitalist co-management documentation increased from 64% to 80%. Guideline use increased from 40% to 79%, and order set use was < 15%. CAUTI and medication error ratios remained low. Adjusted mean LOS decreased by 0.8 days (p = 0.039, 95% CI 0.7, 1.1). Pain scores did not differ. CONCLUSION: Interdisciplinary, clinical guideline development and postoperative co-management significantly decreased hospital LOS in pediatric PSF patients. In a general academic medical center, this change may be attributed to a pediatric hospitalist academic team, a universal co-management process with well-communicated roles, and a pediatric hospital-based physician development of and adherence to standardized practice.


Subject(s)
Length of Stay , Patient Care Team/organization & administration , Postoperative Care , Postoperative Complications , Spinal Fusion , Adolescent , Child , Female , Guideline Adherence , Hospitals, Pediatric/statistics & numerical data , Humans , Interrupted Time Series Analysis , Male , New York , Postoperative Care/methods , Postoperative Care/standards , Postoperative Complications/classification , Postoperative Complications/etiology , Postoperative Complications/therapy , Quality Improvement , Retrospective Studies , Spinal Fusion/adverse effects , Spinal Fusion/methods , Spinal Fusion/statistics & numerical data , Treatment Outcome
8.
Am J Obstet Gynecol ; 211(4): 354.e1-6, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24813971

ABSTRACT

OBJECTIVE: The primary cervical cancer screening strategy for women over age 30 is high-risk human papillomavirus (HPV) testing combined with Papanicolaou (Pap) testing (cotesting) every 5 years. This combination strategy is a preventive service that is required by the Affordable Care Act to be covered with no cost-sharing by most health insurance plans. The cotesting recommendation was made based entirely on prospective data from an insured population that may have a lower proportion of women with HPV positive and Pap negative results (ie, discordant results). The discordant group represents a very difficult group to manage. If the frequency of discordant results among underserved women is higher, health care providers may perceive the cotesting strategy to be a less favorable screening strategy than traditional Pap testing every 3 years. STUDY DESIGN: The Centers for Disease Control and Prevention's Cervical Cancer Study was conducted at 15 clinics in 6 federally qualified health centers across Illinois. Providers at these clinics were given the option of cotesting for routine cervical cancer screening. Type-specific HPV detection was performed on residual extracts using linear array. RESULTS: Pap test results were abnormal in 6.0% and HPV was positive in 7.2% of the underserved women screened in this study (mean age, 45.1 years). HPV prevalence decreased with age, from 10.3% among 30- to 39-year-olds to 4.5% among 50- to 60-year-olds. About 5% of the women had a combination of a positive HPV test and normal Pap test results; HPV 16/18 was identified in 14% of discordant women. CONCLUSION: The rate of discordant results among underserved women was similar to those reported throughout the US in a variety of populations. Typing for HPV 16/18 appears to assist in the management in a small proportion of women with discordant results.


Subject(s)
Papanicolaou Test , Papillomavirus Infections/diagnosis , Poverty , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Vaginal Smears , Vulnerable Populations , Adult , Cross-Sectional Studies , Early Detection of Cancer , Female , Humans , Illinois , Middle Aged , Papillomavirus Infections/complications , Prospective Studies , Uterine Cervical Neoplasms/virology , Uterine Cervical Dysplasia/virology
9.
Int J Cancer ; 133(5): 1101-6, 2013 Sep 01.
Article in English | MEDLINE | ID: mdl-23420411

ABSTRACT

As immunization programs for human papillomavirus (HPV) are implemented more widely around the world, interest is increasing in measuring their impact. One early measurable impact of HPV vaccine is on the prevalence of specific HPV types in a population. In low-resource settings, a potentially attractive strategy would be to monitor HPV prevalence using clinical cervical cancer screening test results to triage specimens for HPV typing. We assessed this approach in a nationally representative population of U.S. females aged 14-59 years. Using self-collected cervico-vaginal swab specimens from 4,150 women participating in the National Health and Nutrition Examination Survey during 2003-2006, we evaluated type-specific HPV prevalence detected by the Roche linear array (LA) research test on all specimens, compared with type-specific HPV prevalence detected by LA conducted only on specimens positive by the digene hybrid capture 2 (HC-2) clinical test. We calculated weighted prevalence estimates and their 95% confidence intervals (CIs), and examined relative type-specific HPV prevalence according to the two testing approaches. The population prevalence of oncogenic HPV vaccine types 16/18 was 6.2% (CI:5.4-7.1) by LA if all specimens were tested, and 2.4% (CI:1.9-3.0) if restricted to positive HC-2. Relative prevalence of individual HPV types was similar for both approaches. Compared with typing all specimens, a triage approach would require testing fewer specimens, but a greater reduction in HPV prevalence or a larger group of specimens would be needed to detect vaccine impact. Further investigation is warranted to inform type-specific HPV monitoring approaches around the world.


Subject(s)
Papillomavirus Infections/epidemiology , Papillomavirus Vaccines/immunology , Adolescent , Adult , Female , Humans , Middle Aged , Papillomaviridae/isolation & purification , Prevalence
10.
J Clin Oncol ; 31(7): 952-60, 2013 Mar 01.
Article in English | MEDLINE | ID: mdl-23341529

ABSTRACT

PURPOSE: Many cancer centers offer acupuncture services. To date, a comprehensive systematic review of acupuncture in cancer care has not been conducted. The purpose of this review was to evaluate the efficacy of acupuncture for symptom management in patients with cancer. METHODS: Medline, Embase, CINAHL, Cochrane (all databases), Scopus, and PubMed were searched from inception through December 2011 for prospective randomized clinical trials (RCT) evaluating acupuncture for symptom management in cancer care. Only studies involving needle insertion into acupuncture points were included. No language limitations were applied. Studies were assessed for risk of bias (ROB) according to Cochrane criteria. Outcomes by symptom were designated as positive, negative, or unclear. RESULTS: A total of 2,151 publications were screened. Of those, 41 RCTs involving eight symptoms (pain, nausea, hot flashes, fatigue, radiation-induced xerostomia, prolonged postoperative ileus, anxiety/mood disorders, and sleep disturbance) met all inclusion criteria. One positive trial of acupuncture for chemotherapy-induced nausea and vomiting had low ROB. Of the remaining studies, eight had unclear ROB (four positive, three negative, and one with unclear outcomes). Thirty-three studies had high ROB (19 positive, 11 negative, and three with both positive and negative outcomes depending on the symptom). CONCLUSION: Acupuncture is an appropriate adjunctive treatment for chemotherapy-induced nausea/vomiting, but additional studies are needed. For other symptoms, efficacy remains undetermined owing to high ROB among studies. Future research should focus on standardizing comparison groups and treatment methods, be at least single-blinded, assess biologic mechanisms, have adequate statistical power, and involve multiple acupuncturists.


Subject(s)
Acupuncture Therapy , Neoplasms/complications , Neoplasms/therapy , Pain Management/methods , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Anxiety/etiology , Anxiety/therapy , Evidence-Based Medicine , Fatigue/etiology , Fatigue/therapy , Hot Flashes/etiology , Hot Flashes/therapy , Humans , Intestinal Pseudo-Obstruction/etiology , Intestinal Pseudo-Obstruction/therapy , Mood Disorders/etiology , Mood Disorders/therapy , Nausea/etiology , Nausea/therapy , Observer Variation , Pain/etiology , Radiotherapy/adverse effects , Randomized Controlled Trials as Topic , Sleep Wake Disorders/etiology , Sleep Wake Disorders/therapy , Treatment Outcome , Xerostomia/etiology , Xerostomia/therapy
11.
Pediatr Transplant ; 16(3): E90-3, 2012 May.
Article in English | MEDLINE | ID: mdl-21226811

ABSTRACT

AdV hepatitis is a rarely reported complication after pediatric liver transplantation that is associated with high rates of morbidity, mortality and graft failure. Successful treatment of AdV relies on early diagnosis of disease by quantitative PCR measurement of adenoviral DNA in blood and histological evidence in tissue biopsy. Pharmacologic treatment largely consists of antiviral therapy with CDV, an acyclic nucleoside phosphonate analog and reduction in immunosuppression. This report describes a case of AdV hepatitis in a pediatric liver transplant recipient successfully treated with a modified, renal sparing dosing of CDV.


Subject(s)
Adenoviridae/metabolism , Cytosine/analogs & derivatives , Hepatitis/drug therapy , Hepatitis/virology , Liver Transplantation/methods , Organophosphonates/pharmacology , Antiviral Agents/pharmacology , Biopsy/methods , Cidofovir , Cytosine/pharmacology , DNA/metabolism , Hepatitis/therapy , Humans , Infant , Kidney/pathology , Kidney/virology , Liver Transplantation/adverse effects , Male , Polymerase Chain Reaction/methods , Retrospective Studies , Risk Factors , Treatment Outcome
12.
J Infect Dis ; 204(4): 562-5, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21791658

ABSTRACT

The 2003-2006 National Health and Nutrition Examination Surveys were used to assess human papillomavirus (HPV) types 6, 11, 16, and 18 DNA detection from females aged 14-59 years who self-collected cervicovaginal swab specimens. Prevalence was 8.8% (95% confidence interval [CI], 7.8%-10.0%) and was highest among women aged 20-24 years (18.5%; 95% CI, 14.9%-22.8%). Age group, education, marital status, and sexual behavior were associated with detection. These data provide baseline information before HPV vaccine introduction. Early impact of vaccine in the United States may be determined by a reduction in the prevalence of HPV 6, 11, 16, and 18 infection among young women.


Subject(s)
Alphapapillomavirus/isolation & purification , Nutrition Surveys , Papillomavirus Infections/epidemiology , Papillomavirus Vaccines/immunology , Adolescent , Adult , Education , Female , Humans , Marriage , Middle Aged , Papillomavirus Infections/prevention & control , Prevalence , Risk Factors , Sexual Behavior , United States/epidemiology , Young Adult
13.
J Infect Dis ; 204(4): 566-73, 2011 Aug 15.
Article in English | MEDLINE | ID: mdl-21791659

ABSTRACT

BACKGROUND: Genital human papillomaviruses (HPV) include >40 sexually transmitted viruses. Most HPV infections do not progress to disease, but infection with certain types of HPV can cause cervical and other anogenital and oropharyngeal cancer, and other types of HPV are associated with anogenital warts. HPV vaccines prevent infection with HPV 16 and 18, which account for 70% of cases of cervical cancer, and HPV 6 and 11, which cause 90% of the cases of anogenital warts. METHODS: Using data and self-collected cervicovaginal specimens from 4150 females, 14-59 years of age, from consecutive National Health and Nutrition Examination Surveys (2003-2006), we estimated the prevalence of type-specific HPV DNA and examined sociodemographic and sexual determinants. RESULTS: The overall prevalence of HPV was 42.5% in females 14-59 years of age and varied significantly by age, race or ethnicity, and number of sex partners. Individual type prevalence was less than 7%, ranging from <0.5% through 6.5%. The most common type was nononcogenic HPV 62 (found in 6.5% of subjects), followed by HPV 53 and HPV 16 (4.7%), both of which are oncogenic types. The most prevalent species was nononcogenic α3. CONCLUSIONS: HPV infection is common among US females, with the highest burden of infection found in young females 20-24 years of age. Monitoring trends in HPV type distribution will contribute to our understanding of the early impact of HPV vaccines.


Subject(s)
Herpes Genitalis/epidemiology , Nutrition Surveys , Adolescent , Adult , Alphapapillomavirus/classification , Alphapapillomavirus/pathogenicity , Female , Herpes Genitalis/virology , Humans , Middle Aged , Prevalence , United States/epidemiology , Uterine Cervical Neoplasms/virology , Young Adult
14.
J Mol Diagn ; 13(4): 377-81, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21704270

ABSTRACT

DNA from archived FFPE can be used for papillomavirus genotyping, but potential problems include paraffin as a physical barrier, DNA cross-linking, and PCR inhibitors. To address these complications, we combined a commercially available DNA isolation kit (Qiagen DNeasy) with a heat treatment and evaluated the resulting DNA with regards to HPV typing. DNA was extracted from 10-µm sections from 150 FFPE cancer samples. One protocol followed the manufacturer's recommendation, including paraffin removal by xylene and tissue lysis at 56°C. A second section was directly incubated at 120°C and subsequently lysed at 65°C. After spin-column purification, both extracts were tested with a linear array HPV genotyping assay. Additionally, cellular DNA yield, HPV16 DNA copies, and PCR inhibitors were assessed by real-time qPCR assays. Inadequate linear array HPV genotyping assay results were significantly more frequent (P = 0.0003) in xylene-treated (29/150, 19.3%) than in heat-treated extracts (8/150, 5.3%). HPV detection also differed, with 94/150 (62.7%) and 110/150 (73.3%) positive results, respectively (P = 0.0026). The heat method also yielded more PCR-amplifiable cellular DNA (8.2-fold; P < 0.001) and HPV16 copies (6.5-fold; P = 0.009), although PCR inhibitors also had a greater effect (P = 0.035). Aggressive heat treatment demonstrated an advantage over traditional xylene purification protocols, resulting in higher DNA yields and increased sensitivity for HPV testing.


Subject(s)
DNA, Viral/isolation & purification , Fixatives/pharmacology , Formaldehyde/pharmacology , Human papillomavirus 16/genetics , Papillomavirus Infections/diagnosis , Paraffin Embedding , Anus Neoplasms/virology , Capsid Proteins/genetics , Carcinoma in Situ/virology , DNA, Viral/genetics , Genotype , Head and Neck Neoplasms/virology , Humans , Neoplasms, Squamous Cell/virology , Oncogene Proteins, Viral/genetics , Urogenital Neoplasms/virology
15.
Diagn Mol Pathol ; 20(2): 101-4, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21532491

ABSTRACT

Type-specific surveillance of human papillomavirus (HPV) has been proposed as an early indicator of vaccine impact. Longitudinal comparison of HPV typing results requires stable assays with high type-specific reproducibility. Assays are evolving and the impact of even minor changes in the assay format may be difficult to anticipate. We initiated a population-based study of HPV with the prototype line blot (PLB) assay. These reagents were replaced by the research use only Linear Array (LA) HPV Genotyping kit. The assays are similar in principle and earlier comparisons found increased sensitivity and detection of more types per sample with LA; however, in samples from women with cervical abnormalities, the overall concordance was good. Slight changes in sensitivity may be more significant in samples from a general population with lower viral loads in the samples. Residual extracts from 3001 self-collected vaginal swabs from women in the general US population originally tested with PLB were retested with LA. With LA, all the samples were hybridized. PLB hybridization was restricted to samples with probable amplicon in gel electrophoresis. For HPV detection, the agreement between the 2 assays was 78.6% (κ=0.55) with a positive concordance of 52.8%. However, this masks the observation that repeat testing with LA led to the detection of HPV in nearly twice as many samples. Agreement improves if comparison was restricted to the samples hybridized. These results emphasize that assay comparisons should consider the clinical-epidemiologic context of sample collection. Studies designed to examine temporal trends in type-specific prevalence should archive residual material to permit retesting if assays change.


Subject(s)
Molecular Typing/methods , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Virology/methods , Female , Genotype , Humans , Prevalence , Sensitivity and Specificity , United States
16.
Crit Care Med ; 39(7): 1773-8, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21423003

ABSTRACT

OBJECTIVE: There is lack of evidence to guide thromboprophylaxis in the pediatric intensive care unit. We aimed to assess current prescribing practice for pharmacologic thromboprophylaxis in critically ill children. SETTING: Pediatric intensive care units in the United States and Canada with at least ten beds. DESIGN: Cross-sectional self-administered survey of pediatric intensivists using adolescent, child, and infant scenarios. PARTICIPANTS: Pediatric intensive care unit clinical directors or section heads. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physician leaders from 97 of 151 (64.2%) pediatric intensive care units or their designees responded to the survey. In mechanically ventilated children, 42.3% of the respondents would usually or always prescribe thromboprophylaxis for the adolescent but only 1.0% would prescribe it for the child and 1.1% for the infant. Considering all pediatric intensive care unit patients, 3.1%, 32.0%, and 44.2% of respondents would never prescribe thromboprophylaxis for the adolescent, child, and infant scenarios, respectively. These findings were significant (p < .001 for the adolescent vs. child and infant; p = .002 for child vs. infant). Other patient factors that increased the likelihood of prescribing prophylaxis to a critically ill child for all three scenarios were the presence of hypercoagulability, prior deep venous thrombosis, or a cavopulmonary anastomosis. Prophylaxis was less likely to be prescribed to patients with major bleeding or an anticipated invasive intervention. Low-molecular-weight heparin was the most commonly prescribed drug. CONCLUSIONS: In these scenarios, physician leaders in pediatric intensive care units were more likely to prescribe thromboprophylaxis to adolescents compared with children or infants, but they prescribed it less often in adolescents than is recommended by evidence-based guidelines for adults. The heterogeneity in practice we documented underscores the need for rigorous randomized trials to determine the need for thromboprophylaxis in critically ill adolescents and children.


Subject(s)
Anticoagulants/therapeutic use , Practice Patterns, Physicians' , Pulmonary Embolism/prevention & control , Venous Thromboembolism/prevention & control , Venous Thrombosis/prevention & control , Adolescent , Child, Preschool , Cross-Sectional Studies , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Infant , Intensive Care Units, Pediatric , Pulmonary Embolism/etiology , Respiration, Artificial/adverse effects , Statistics, Nonparametric , Venous Thromboembolism/etiology , Venous Thrombosis/etiology
17.
Am J Clin Oncol ; 33(2): 125-7, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19675445

ABSTRACT

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a very rare cancer of the skin. It has only been described previously in case reports and small retrospective series. OBJECTIVE: To analyze and summarize data from the National Cancer Institute, Surveillance, Epidemiology, and End Results (SEER) database regarding MAC. METHODS: The SEER 1973 to 2004 database was investigated, and patients with MAC were identified. A statistical analysis was performed. RESULTS: Two hundred twenty-three patients were identified. Predominant site of disease was the head and neck skin (74%). There was only 1 case of recorded metastatic disease. Lymph nodes were pathologically involved in 1%. The 10-year overall survival was 86.4% (Standard Error [SE]: 3.3%). US census population-matched relative survival was 97.7% at 10 years (SE: 5.2%). LIMITATIONS: This study is limited by the retrospective nature of the SEER database. CONCLUSIONS: MAC is locally invasive, and rarely metastasizes to lymph nodes. Overall and population-matched relative survival is excellent.


Subject(s)
Carcinoma, Ductal/pathology , Carcinoma, Skin Appendage/pathology , Skin Neoplasms/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Ductal/epidemiology , Carcinoma, Skin Appendage/epidemiology , Child , Female , Humans , Lymph Nodes/pathology , Lymphatic Metastasis , Male , Middle Aged , Retrospective Studies , SEER Program , Skin Neoplasms/epidemiology , Survival Rate , Treatment Outcome , Young Adult
18.
J Occup Health ; 51(4): 314-22, 2009.
Article in English | MEDLINE | ID: mdl-19491527

ABSTRACT

OBJECTIVES: To determine the one year prevalence of workplace abuse and sexual harassment and to determine the extent of their associations with symptoms of depression. METHODS: A total of 387 female faculty and staff from colleges in Awassa, Ethiopia completed a self-administered questionnaire which collected information about relationships, mood and feelings, thoughts and satisfaction concerning the workplace, and experiences with sexual harassment. Symptoms of depression were evaluated using the Patient Health Questionnaire (PHQ-9). Logistic regression procedures were employed to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The 12 mo prevalence of either workplace abuse or sexual harassment was 86.3%; with 39.5% reporting workplace abuse only, 4.1% of them reporting sexual harassment only, and 42.6% reporting experiences of both sexual harassment and workplace abuse. Overall, the mean depression score for this cohort was 3.7 (standard deviation 4.2, range 0-19), and 9.3% of the cohort were identified as having moderate or moderately severe depression. The proportion of participants with depression were statistically significantly elevated in relation to reported experience of workplace abuse and sexual harassment (p=0.001). Compared with women reporting no experience with workplace abuse or sexual harassment, those who reported experiencing both workplace abuse and sexual harassment had an 8.00 fold increased risk of depression (OR=8.00, 95% CI:1.05-60.85). Inferences from this analysis are limited by our relatively small sample size as reflected by the wide 95% CI. CONCLUSIONS: Workplace abuse and sexual harassment are highly prevalent, and are positively correlated with symptoms of depression among college female faculty and staff in Awassa, Ethiopia. Future policies should include a combination of education, health, and public policy initiatives that clearly outline the problem and consequences of workplace abuse and sexual harassment in educational settings.


Subject(s)
Occupational Exposure , Sexual Harassment , Stress, Psychological/epidemiology , Adolescent , Adult , Depression/epidemiology , Depression/etiology , Ethiopia/epidemiology , Female , Humans , Middle Aged , Sexual Harassment/psychology , Sexual Harassment/statistics & numerical data , Stress, Psychological/etiology , Surveys and Questionnaires , Young Adult
19.
JAMA ; 297(8): 813-9, 2007 Feb 28.
Article in English | MEDLINE | ID: mdl-17327523

ABSTRACT

CONTEXT: Human papillomavirus (HPV) infection is estimated to be the most common sexually transmitted infection. Baseline population prevalence data for HPV infection in the United States before widespread availability of a prophylactic HPV vaccine would be useful. OBJECTIVE: To determine the prevalence of HPV among females in the United States. DESIGN, SETTING, AND PARTICIPANTS: The National Health and Nutrition Examination Survey (NHANES) uses a representative sample of the US noninstitutionalized civilian population. Females aged 14 to 59 years who were interviewed at home for NHANES 2003-2004 were examined in a mobile examination center and provided a self-collected vaginal swab specimen. Swabs were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Demographic and sexual behavior information was obtained from all participants. MAIN OUTCOME MEASURES: HPV prevalence by polymerase chain reaction. RESULTS: The overall HPV prevalence was 26.8% (95% confidence interval [CI], 23.3%-30.9%) among US females aged 14 to 59 years (n = 1921). HPV prevalence was 24.5% (95% CI, 19.6%-30.5%) among females aged 14 to 19 years, 44.8% (95% CI, 36.3%-55.3%) among women aged 20 to 24 years, 27.4% (95% CI, 21.9%-34.2%) among women aged 25 to 29 years, 27.5% (95% CI, 20.8%-36.4%) among women aged 30 to 39 years, 25.2% (95% CI, 19.7%-32.2%) among women aged 40 to 49 years, and 19.6% (95% CI, 14.3%-26.8%) among women aged 50 to 59 years. There was a statistically significant trend for increasing HPV prevalence with each year of age from 14 to 24 years (P<.001), followed by a gradual decline in prevalence through 59 years (P = .06). HPV vaccine types 6 and 11 (low-risk types) and 16 and 18 (high-risk types) were detected in 3.4% of female participants; HPV-6 was detected in 1.3% (95% CI, 0.8%-2.3%), HPV-11 in 0.1% (95% CI, 0.03%-0.3%), HPV-16 in 1.5% (95% CI, 0.9%-2.6%), and HPV-18 in 0.8% (95% CI, 0.4%-1.5%) of female participants. Independent risk factors for HPV detection were age, marital status, and increasing numbers of lifetime and recent sex partners. CONCLUSIONS: HPV is common among females in the United States. Our data indicate that the burden of prevalent HPV infection among females was greater than previous estimates and was highest among those aged 20 to 24 years. However, the prevalence of HPV vaccine types was relatively low.


Subject(s)
Alphapapillomavirus/isolation & purification , Papillomavirus Infections/epidemiology , Sexually Transmitted Diseases, Viral/epidemiology , Adolescent , Adult , Age Distribution , DNA, Viral/analysis , Female , Humans , Middle Aged , Multivariate Analysis , Nutrition Surveys , Papillomavirus Vaccines , Prevalence , Risk Factors , United States/epidemiology
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