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1.
BMC Public Health ; 24(1): 433, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38347566

ABSTRACT

BACKGROUND: The COVID-19 pandemic restrictions posed challenges to maintaining healthy lifestyles and physical well-being. During the first mobility restrictions from March to mid-July 2020, the German population was advised to stay home, except for work, exercise, and essential shopping. Our objective was to comprehensively assess the impact of these restrictions on changes in physical activity and sedentary behavior to identify the most affected groups. METHODS: Between April 30, 2020, and May 12, 2020, we distributed a COVID-19-specific questionnaire to participants of the German National Cohort (NAKO). This questionnaire gathered information about participants' physical activity and sedentary behavior currently compared to the time before the restrictions. We integrated this new data with existing information on anxiety, depressive symptoms, and physical activity. The analyses focused on sociodemographic factors, social relationships, physical health, and working conditions. RESULTS: Out of 152,421 respondents, a significant proportion reported altered physical activity and sedentary behavioral patterns due to COVID-19 restrictions. Over a third of the participants initially meeting the WHO's physical activity recommendation could no longer meet the guidelines during the restrictions. Participants reported substantial declines in sports activities (mean change (M) = -0.38; 95% CI: -.390; -.378; range from -2 to + 2) and reduced active transportation (M = -0.12; 95% CI: -.126; -.117). However, they also increased recreational physical activities (M = 0.12; 95% CI: .117; .126) while engaging in more sedentary behavior (M = 0.24; 95% CI: .240; .247) compared to pre-restriction levels. Multivariable linear and log-binomial regression models indicated that younger adults were more affected by the restrictions than older adults. The shift to remote work, self-rated health, and depressive symptoms were the factors most strongly associated with changes in all physical activity domains, including sedentary behavior, and the likelihood to continue following the physical activity guidelines. CONCLUSIONS: Mobility patterns shifted towards inactivity or low-intensity activities during the nationwide restrictions in the spring of 2020, potentially leading to considerable and lasting health risks.


Subject(s)
COVID-19 , Running , Humans , Aged , Sedentary Behavior , Pandemics , COVID-19/epidemiology , Exercise , Germany/epidemiology
2.
J Public Health Manag Pract ; 30(3): 336-345, 2024.
Article in English | MEDLINE | ID: mdl-38603742

ABSTRACT

OBJECTIVES: We sought to (1) document how health departments (HDs) developed COVID-19 case investigation and contact tracing (CI/CT) interview scripts and the topics covered, and (2) understand how and why HDs modified those scripts. DESIGN: Qualitative analysis of CI/CT interview scripts and in-depth key informant interviews with public health officials in 14 HDs. Collected scripts represent 3 distinct points (initial, the majority of which were time stamped May 2020; interim, spanning from September 2020 to August 2021; and current, as of April 2022). SETTING: Fourteen state, local, and tribal health jurisdictions and Centers for Disease Control and Prevention (CDC). PARTICIPANTS: Thirty-six public health officials involved in leading CI/CT from 14 state, local, and tribal health jurisdictions (6 states, 3 cities, 4 counties, and 1 tribal area). MAIN OUTCOME MEASURE: Interview script elements included in CI/CT interview scripts over time. RESULTS: Many COVID-19 CI/CT scripts were developed by modifying questions from scripts used for other communicable diseases. Early in the pandemic, scripts included guidance on isolation/quarantine and discussed symptoms of COVID-19. As the pandemic evolved, the length of scripts increased substantially, with significant additions on contact elicitation, vaccinations, isolation/quarantine recommendations, and testing. Drivers of script changes included changes in our understanding of how the virus spreads, risk factors and symptoms, new treatments, new variants, vaccine development, and adjustments to CDC's official isolation and quarantine guidance. CONCLUSIONS: Our findings offer suggestions about components to include in future CI/CT efforts, including educating members of the public about the disease and its symptoms, offering mitigation guidance, and providing sufficient support and resources to help people act on that guidance. Assessing the correlation between script length and number of completed interviews or other quality and performance measures could be an area for future study.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Pandemics/prevention & control , Contact Tracing , SARS-CoV-2 , Quarantine
3.
Wilderness Environ Med ; 34(4): 553-557, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37741729

ABSTRACT

Caving accidents are rare, but when they occur, they represent a unique logistical and medical challenge. Retrieving the patient to the surface often means navigating stretchers through narrow corridors with limited options for monitoring and interventions. Because the patient is usually not fasting, opioids and sedatives should be used with extreme caution. Therefore, alternative analgesic techniques such as locoregional nerve blocks are a promising strategy to improve patient comfort and safety during cave rescues. In this article, we describe 2 cases in which portable point-of-care ultrasound equipment was used to supplement clinical assessment and provide locoregional anesthesia to facilitate patient evacuation and transport. In this context, we discuss the role of portable ultrasound-guided locoregional anesthesia in cave rescue and in the global preclinical context. In summary, our cases demonstrated that the administration of ultrasound-guided prehospital locoregional anesthesia is a safe, rapid, and effective procedure even in extreme situations such as cave rescues. The advent of portable, high-quality ultrasound equipment may open the door for more widespread application of this technique in the global preclinical setting.


Subject(s)
Nerve Block , Operating Rooms , Humans , Ultrasonography , Nerve Block/methods , Caves , Ultrasonography, Interventional/methods
4.
Sex Transm Infect ; 2022 Jul 16.
Article in English | MEDLINE | ID: mdl-35842229

ABSTRACT

INTRODUCTION: Human papillomavirus (HPV) vaccines protect against incident HPV infections, which cause cervical cancer. OBJECTIVES: We estimated the prevalence and incidence of HPV infections in young adult women to understand the impact of an HPV vaccination programme in this population. METHODS: We collected cervical specimens from 6322 unvaccinated women, aged 18-37 years, who participated in the Costa Rica Vaccine Trial and its long-term follow-up. Women were followed for (median) 4.8 years and had (median) 4.0 study visits. Cervical specimens were tested for the presence/absence of 25 HPV genotypes. For each age band, we estimated the percentage of women with 1+ prevalent or 1+ incident HPV infections using generalised estimating equations. We also estimated the prevalence and incidence of HPV as a function of time since first sexual intercourse (FSI). RESULTS: The model estimated HPV incident infections peaked at 28.0% (95% CI 25.3% to 30.9%) at age 20 years then steadily declined to 11.8% (95% CI 7.6% to 17.8%) at age 37 years. Incident oncogenic HPV infections (HPV16/18/31/33/35/39/45/51/52/56/58/59) peaked and then declined from 20.3% (95% CI 17.9% to 22.9%) to 7.7% (95% CI 4.4% to 13.1%); HPV16/18 declined from 6.4% (95% CI 5.1% to 8.1%) to 1.1% (95% CI 0.33% to 3.6%) and HPV31/33/45/52/58 declined from 11.0% (95% CI 9.3% to 13.1%) to 4.5% (95% CI 2.2% to 8.9%) over the same ages. The percentage of women with 1+ incident HPV of any, oncogenic, non-oncogenic and vaccine-preventable (HPV16/18, HPV31/33/45, HPV31/33/45/52/58, and HPV6/11) types peaked <1 year after FSI and steadily declined with increasing time since FSI (p for trends <0.001). We observed similar patterns for model estimated HPV prevalences. CONCLUSION: Young adult women may benefit from HPV vaccination if newly acquired vaccine-preventable oncogenic infections lead to cervical precancer and cancer. HPV vaccination targeting this population may provide additional opportunities for primary prevention. TRIAL REGISTRATION NUMBER: NCT00128661.

5.
J Wound Care ; 31(Sup7): S5-S14, 2022 Jul 01.
Article in English | MEDLINE | ID: mdl-35797250

ABSTRACT

OBJECTIVE: To investigate the role of an adherent soft silicone antimicrobial occlusive foam silver-impregnated dressing for reduction of surgical site infections (SSI) in primary low-transverse caesarean section (1°LTCS) delivery. METHOD: Women aged 18-45 years admitted to the labour and delivery or the antepartum unit undergoing a 1°LTCS were recruited. Exclusion criteria included repeat caesarean, vertical skin incision, intrapartum fever and closure with staples. Consented participants delivered by scheduled or unscheduled 1°LTCS received the silver-impregnated dressing. Those who declined to participate and were delivered by scheduled or unscheduled caesarean received a standard gauze with tape dressing (controls). Surgical preparation and preoperative antibiotics were administered as per hospital policy. RESULTS: A total of 362 participants were consented for use of the silver-impregnated dressing, with 190 participants undergoing 1°LTCS, of whom 185 were included in the final analysis. Of those who declined to participate, 190 ultimately underwent 1°LTCS during the same time period. Cases and controls were similar in demographics, body mass index, diabetes status, labour and procedure length, and tobacco use. The overall incidence of SSI was 3.7%. A 50% reduction in incidence of SSI was observed in the silver-impregnated dressing group compared with control group (2.7% versus 4.7%, respectively), but this was not statistically significant (p=0.08; odds ratio 0.55; 95% confidence interval: 0.18-1.67). CONCLUSION: Among women undergoing 1°LTCS with subcuticular closure of a transverse incision, use of a silver-impregnated dressing reduced the rate of SSI by >50% but was not statistically significant.


Subject(s)
Anti-Infective Agents , Cesarean Section , Anti-Bacterial Agents/therapeutic use , Bandages , Female , Humans , Occlusive Dressings , Pregnancy , Silver/therapeutic use , Surgical Wound Infection/epidemiology
6.
J Vet Pharmacol Ther ; 45(3): 320-324, 2022 May.
Article in English | MEDLINE | ID: mdl-35098559

ABSTRACT

The objective of this study was to determine the pharmacokinetic parameters of oclacitinib maleate as a top dress given to adult horses. Six adult horses with a mean weight of 528 kg were administered a single dose of 0.5 mg/kg oclacitinib maleate. Blood was collected prior to drug administration and at 15 min, 30 min, 45 min, 1, 2, 4, 6, 8, 12, 24, 48, and 72 h after treatment. Oclacitinib maleate plasma concentrations were measured by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were found best to fit a one-compartment model. Mean Cmax was 486 ng/ml (range 423-549 ng/ml), and Tmax was estimated to be 1.7 h (range 0.3-3.1 h). The estimated T1/2 was 7.5-8 h.


Subject(s)
Pyrimidines , Sulfonamides , Administration, Oral , Animals , Area Under Curve , Chromatography, Liquid/veterinary , Horses , Maleates , Pyrimidines/pharmacokinetics , Sulfonamides/pharmacokinetics
7.
Int J Mol Sci ; 23(15)2022 Aug 07.
Article in English | MEDLINE | ID: mdl-35955909

ABSTRACT

Colorectal cancer (CRC) is one of the most lethal cancers worldwide. If detected on time, surgery can expand life expectations of patients up to five more years. However, if metastasis has grown deliberately, the use of chemotherapy can play a crucial role in CRC control. Moreover, the lack of selectivity of current anticancer drugs, plus mutations that occur in cancerous cells, demands the development of new chemotherapeutic agents. Several steroids have shown their potentiality as anticancer agents, while some other compounds, such as Taxol and its derivatives bearing a carbamate functionality, have reached the market. In this article, the synthesis, characterization, and antiproliferative activity of four steroidal carbamates on mouse colon carcinoma CT26WT cells are described. Carbamate synthesis occurred via direct reaction between diosgenin, its B-ring modified derivative, and testosterone with phenyl isocyanate under a Brønsted acid catalysis. All obtained compounds were characterized by 1H and 13C Nuclear Magnetic Resonance (NMR), High Resolution Mass Spectroscopy (HRMS); their melting points are also reported. Results obtained from antiproliferative activity assays indicated that carbamates compounds have inhibitory effects on the growth of this colon cancer cell line. A molecular docking study carried out on Human Prostaglandin E Receptor (EP4) showed a high affinity between carbamates and protein, thus providing a valuable theoretical explanation of the in vitro results.


Subject(s)
Antineoplastic Agents , Carcinoma , Colonic Neoplasms , Animals , Antineoplastic Agents/chemistry , Carbamates/pharmacology , Cell Line, Tumor , Cell Proliferation , Colonic Neoplasms/drug therapy , Drug Screening Assays, Antitumor , Humans , Mice , Molecular Docking Simulation , Molecular Structure , Steroids/chemistry , Structure-Activity Relationship
8.
J Infect Dis ; 224(3): 503-516, 2021 08 02.
Article in English | MEDLINE | ID: mdl-33326576

ABSTRACT

BACKGROUND: Factors that lead human papillomavirus (HPV) infections to persist and progress to cancer are not fully understood. We evaluated co-factors for acquisition, persistence, and progression of non-HPV-16/18 infections among HPV-vaccinated women. METHODS: We analyzed 2153 women aged 18-25 years randomized to the HPV-vaccine arm of the Costa Rica HPV Vaccine Trial. Women were HPV DNA negative for all types at baseline and followed for approximately 11 years. Generalized estimating equation methods were used to account for correlated observations. Time-dependent factors evaluated were age, sexual behavior, marital status, hormonally related factors, number of full-term pregnancies (FTPs), smoking behavior, and baseline body mass index. RESULTS: A total of 1777 incident oncogenic non-HPV-16/18 infections were detected in 12 292 visits (average, 0.14 infections/visit). Age and sexual behavior-related variables were associated with oncogenic non-HPV-16/18 acquisition. Twenty-six percent of incident infections persisted for ≥1 year. None of the factors evaluated were statistically associated with persistence of oncogenic non-HPV-16/18 infections. Risk of progression to Cervical Intraepithelial Neoplasia grade 2 or worst (CIN2+) increased with increasing age (P for trend = .001), injectable contraceptive use (relative risk, 2.61 [95% confidence interval, 1.19-5.73] ever vs never), and increasing FTPs (P for trend = .034). CONCLUSIONS: In a cohort of HPV-16/18-vaccinated women, age and sexual behavior variables are associated with acquisition of oncogenic non-HPV-16/18 infections; no notable factors are associated with persistence of acquired infections; and age, parity, and hormonally related exposures are associated with progression to CIN2+.


Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Adolescent , Adult , Costa Rica/epidemiology , DNA , Female , Human papillomavirus 16/immunology , Human papillomavirus 18/immunology , Humans , Papillomaviridae , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Pregnancy , Risk Factors , Treatment Outcome , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Young Adult , Uterine Cervical Dysplasia
9.
J Vet Pharmacol Ther ; 44(5): 793-798, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33817876

ABSTRACT

The objective of this study was to determine the pharmacokinetics of firocoxib after oral administration in un-weaned calves. Eight Holstein calves with a mean age of 36 days and a mean weight of 55 kg were administered a single oral dose of 227 mg firocoxib. The resulting mean dosage was 4.2 mg/kg (range 3.5-5.0 mg/kg). Blood was collected prior to drug administration and at 2, 4, 6, 8, 24, 48, 72, and 96 h after treatment. Firocoxib concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry. Using computer software, pharmacokinetic parameters were found to fit best with a one-compartment model. Mean Cmax was 0.9 µg/ml (range 0.570-1.254), and Tmax was estimated to be 7 h (range 4-8 h). The estimated T1/2 was 15.3 h. The pharmacokinetics of firocoxib after oral dosing are similar to those in dogs, with the exception of a T1/2 that is approximately twice as long. Based on the similar pharmacokinetics, it is possible that a dose of 227 mg firocoxib orally could provide an analgesic effect in un-weaned calves.


Subject(s)
4-Butyrolactone , Sulfones , 4-Butyrolactone/analogs & derivatives , Administration, Oral , Animals , Cattle , Chromatography, Liquid/veterinary , Dogs
10.
Lancet Oncol ; 21(12): 1643-1652, 2020 12.
Article in English | MEDLINE | ID: mdl-33271093

ABSTRACT

BACKGROUND: Oncogenic human papillomavirus (HPV) infections cause most cases of cervical cancer. Here, we report long-term follow-up results for the Costa Rica Vaccine Trial (publicly funded and initiated before licensure of the HPV vaccines), with the aim of assessing the efficacy of the bivalent HPV vaccine for preventing HPV 16/18-associated cervical intraepithelial neoplasia grade 2 or worse (CIN2+). METHODS: Women aged 18-25 years were enrolled in a randomised, double-blind, controlled trial in Costa Rica, between June 28, 2004, and Dec 21, 2005, designed to assess the efficacy of a bivalent vaccine for the prevention of infection with HPV 16/18 and associated precancerous lesions at the cervix. Participants were randomly assigned (1:1) to receive an HPV 16/18 AS04-adjuvanted vaccine or control hepatitis A vaccine. Vaccines were administered intramuscularly in three 0·5 mL doses at 0, 1, and 6 months and participants were followed up annually for 4 years. After the blinded phase, women in the HPV vaccine group were invited to enrol in the long-term follow-up study, which extended follow-up for 7 additional years. The control group received HPV vaccine and was replaced with a new unvaccinated control group. Women were followed up every 2 years until year 11. Investigators and patients were aware of treatment allocation for the follow-up phase. At each visit, clinicians collected cervical cells from sexually active women for cytology and HPV testing. Women with abnormal cytology were referred to colposcopy, biopsy, and treatment as needed. Women with negative results at the last screening visit (year 11) exited the long-term follow-up study. The analytical cohort for vaccine efficacy included women who were HPV 16/18 DNA-negative at vaccination. The primary outcome of this analysis was defined as histopathologically confirmed CIN2+ or cervical intraepithelial neoplasia grade 3 or worse associated with HPV 16/18 cervical infection detected at colposcopy referral. We calculated vaccine efficacy by year and cumulatively. This long-term follow-up study is registered with ClinicalTrials.gov, NCT00867464. FINDINGS: 7466 women were enrolled in the Costa Rica Vaccine Trial; 3727 received the HPV vaccine and 3739 received the control vaccine. Between March 30, 2009, and July 5, 2012, 2635 women in the HPV vaccine group and 2836 women in the new unvaccinated control group were enrolled in the long-term follow-up study. 2635 women in the HPV vaccine group and 2677 women in the control group were included in the analysis cohort for years 0-4, and 2073 women from the HPV vaccine group and 2530 women from the new unvaccinated control group were included in the analysis cohort for years 7-11. Median follow-up time for the HPV group was 11·1 years (IQR 9·1-11·7), 4·6 years (4·3-5·3) for the original control group, and 6·2 years (5·5-6·9) for the new unvaccinated control group. At year 11, vaccine efficacy against incident HPV 16/18-associated CIN2+ was 100% (95% CI 89·2-100·0); 34 (1·5%) of 2233 unvaccinated women had a CIN2+ outcome compared with none of 1913 women in the HPV group. Cumulative vaccine efficacy against HPV 16/18-associated CIN2+ over the 11-year period was 97·4% (95% CI 88·0-99·6). Similar protection was observed against HPV 16/18-associated CIN3-specifically at year 11, vaccine efficacy was 100% (95% CI 78·8-100·0) and cumulative vaccine efficacy was 94·9% (73·7-99·4). During the long-term follow-up, no serious adverse events occurred that were deemed related to the HPV vaccine. The most common grade 3 or worse serious adverse events were pregnancy, puerperium, and perinatal conditions (in 255 [10%] of 2530 women in the unvaccinated control group and 201 [10%] of 2073 women in the HPV vaccine group). Four women in the unvaccinated control group and three in the HPV vaccine group died; no deaths were deemed to be related to the HPV vaccine. INTERPRETATION: The bivalent HPV vaccine has high efficacy against HPV 16/18-associated precancer for more than a decade after initial vaccination, supporting the notion that invasive cervical cancer is preventable. FUNDING: US National Cancer Institute.


Subject(s)
Human papillomavirus 16/immunology , Human papillomavirus 18/immunology , Papillomavirus Infections/prevention & control , Papillomavirus Vaccines/administration & dosage , Uterine Cervical Dysplasia/prevention & control , Uterine Cervical Neoplasms/prevention & control , Vaccines, Combined/administration & dosage , Adolescent , Adult , Costa Rica , Double-Blind Method , Female , Humans , Immunization , Neoplasm Grading , Papillomavirus Infections/diagnosis , Papillomavirus Infections/virology , Papillomavirus Vaccines/adverse effects , Time Factors , Treatment Outcome , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/virology , Vaccines, Combined/adverse effects , Young Adult , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/virology
12.
BMC Public Health ; 20(1): 782, 2020 May 26.
Article in English | MEDLINE | ID: mdl-32456674

ABSTRACT

BACKGROUND: Transgender women ("trans women"), particularly African-American and Latina trans women, have disproportionately high prevalence of HIV in the United States (U.S.). In order to decrease gender dysphoria and overcome discrimination, trans women affirm their gender through social and medical transition, often in contexts of economic hardship and sexual risk. This study qualitatively examined how gender-affirming behaviors enhance or diminish vulnerability to HIV in light of structural and economic barriers to gender transition. METHODS: We conducted individual interviews with 19 adult trans women in two U.S. cities (Richmond, VA and St. Louis, MO) who reported one or more sexual risk behaviors and recent economic hardship related to employment/income, housing, or food security. Interviews were recorded, transcribed, and analyzed using thematic content analysis. RESULTS: The majority (74%) of trans women were racial/ethnic minorities with mean age of 26.3 years. Gender-affirming behaviors varied with 58% of trans women having legally changed their name and gender marker; 79% having initiated hormone therapy; and 11% having not initiated any medical or legal changes. None had undertaken surgical changes. Findings suggested that the process of gender transitioning resulted in both increasing and decreasing HIV risk. The high need for gender affirmation by male sex partners contributed to trans women's exposure to sexual objectification, sexual risk behaviors, and conflicting interests in HIV prevention messaging. Loss of housing and employment due to transition along with the high costs of transition products and medical visits increased reliance on sex work and created new obstacles in accessing HIV services. Trans women experienced lower HIV risk as they acquired legal and medical transition services, reshaped interactions with sex partners, and received gender-affirming support by others, including health providers, employers, peers, and housing professionals. Sexual abstinence was viewed as a negative consequence of incomplete transition, although characterized as a period of low HIV risk. CONCLUSIONS: Structural and policy initiatives that promote safe gender transition and economic stability in trans women may play a critical role in reducing HIV in this population. Addressing the harmful pressures for U.S. trans women to conform to perceived feminine stereotypes may also serve an important role.


Subject(s)
Gender Identity , HIV Infections/epidemiology , Transgender Persons/psychology , Transgender Persons/statistics & numerical data , Vulnerable Populations , Adolescent , Adult , Cities/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Qualitative Research , Risk Assessment , Risk-Taking , Sexual Behavior/psychology , Sexual Partners/psychology , Socioeconomic Factors , United States/epidemiology , Young Adult
13.
J Infect Dis ; 220(10): 1609-1619, 2019 10 08.
Article in English | MEDLINE | ID: mdl-31536132

ABSTRACT

BACKGROUND: Human papillomaviruses (HPV) cause over 500 000 cervical cancers each year, most of which occur in low-resource settings. Human papillomavirus genotyping is important to study natural history and vaccine efficacy. We evaluated TypeSeq, a novel, next-generation, sequencing-based assay that detects 51 HPV genotypes, in 2 large international epidemiologic studies. METHODS: TypeSeq was evaluated in 2804 cervical specimens from the Study to Understand Cervical Cancer Endpoints and Early Determinants (SUCCEED) and in 2357 specimens from the Costa Rica Vaccine Trial (CVT). Positive agreement and risks of precancer for individual genotypes were calculated for TypeSeq in comparison to Linear Array (SUCCEED). In CVT, positive agreement and vaccine efficacy were calculated for TypeSeq and SPF10-LiPA. RESULTS: We observed high overall and positive agreement for most genotypes between TypeSeq and Linear Array in SUCCEED and SPF10-LiPA in CVT. There was no significant difference in risk of precancer between TypeSeq and Linear Array in SUCCEED or in estimates of vaccine efficacy between TypeSeq and SPF10-LiPA in CVT. CONCLUSIONS: The agreement of TypeSeq with Linear Array and SPF10-LiPA, 2 well established standards for HPV genotyping, demonstrates its high accuracy. TypeSeq provides high-throughput, affordable HPV genotyping for world-wide studies of cervical precancer risk and of HPV vaccine efficacy.


Subject(s)
Genotype , Genotyping Techniques/methods , High-Throughput Nucleotide Sequencing/methods , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adolescent , Adult , Aged , Aged, 80 and over , Costa Rica , Costs and Cost Analysis , Cross-Sectional Studies , Female , Genotyping Techniques/economics , High-Throughput Nucleotide Sequencing/economics , Humans , Middle Aged , Papillomaviridae/genetics , Papillomavirus Infections/prevention & control , Papillomavirus Infections/virology , Papillomavirus Vaccines/immunology , Uterine Cervical Neoplasms/prevention & control , Uterine Cervical Neoplasms/virology , Young Adult
14.
BMC Bioinformatics ; 20(1): 389, 2019 Jul 12.
Article in English | MEDLINE | ID: mdl-31299914

ABSTRACT

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection associated with cervical cancer that frequently occurs as a coinfection of types and subtypes. Highly similar sublineages that show over 100-fold differences in cancer risk are not distinguishable in coinfections with current typing methods. RESULTS: We describe an efficient set of computational tools, rkmh, for analyzing complex mixed infections of related viruses based on sequence data. rkmh makes extensive use of MinHash similarity measures, and includes utilities for removing host DNA and classifying reads by type, lineage, and sublineage. We show that rkmh is capable of assigning reads to their HPV type as well as HPV16 lineage and sublineages. CONCLUSIONS: Accurate read classification enables estimates of percent composition when there are multiple infecting lineages or sublineages. While we demonstrate rkmh for HPV with multiple sequencing technologies, it is also applicable to other mixtures of related sequences.


Subject(s)
Coinfection/diagnosis , Coinfection/virology , Computational Biology/methods , Human papillomavirus 16/physiology , Software , DNA, Viral/genetics , Human papillomavirus 16/classification , Humans , Papillomavirus Infections/virology , Phylogeny , Sequence Analysis, DNA , Time Factors
15.
J Clin Microbiol ; 57(5)2019 05.
Article in English | MEDLINE | ID: mdl-30814267

ABSTRACT

We have developed a new human papillomavirus (HPV) genotyping assay for detection of 51 HPV genotypes by next-generation sequencing (NGS). The TypeSeq assay consists of 3 PCR steps that equalize viral load and each type's amplicon copies prior to genotyping by NGS, thereby maximizing multiple-type sensitivity with minimal sequencing reads. The analytical sensitivity of the TypeSeq assay is 10 copies per reaction for 49 of the 51 types, including 13 high-risk (HR) types. We tested 863 clinical cervical specimens previously evaluated with the Roche Linear Array HPV genotyping test (LA). TypeSeq achieved 94.4% positive agreement with LA for detection of any HR type. Positive agreement was 91.4% and 85.5% for HPV16 and HPV18, respectively. Low-risk (LR) types ranged from 40.0% positive agreement (HPV83) to 90.9% (HPV69). Our unique approach to HPV amplification achieved a multiple-type sensitivity comparable to that of LA, with 83.9% and 84.2% of specimens positive for multiple HPV types by TypeSeq or LA, respectively. A total of 48.2% of specimens showed perfect agreement for all 37 types common to both assays. The simplicity of our open-source TypeSeq assay allows for high-throughput yet scalable processing, with a single technician able to process up to 768 specimens within 3 days. By leveraging NGS sample multiplexing capabilities, the per-sample labor requirements are greatly reduced compared to those of traditional genotyping methods. These features and the broad spectrum of detectable types make TypeSeq highly suitable for a wide range of applications.


Subject(s)
Genotyping Techniques/methods , High-Throughput Nucleotide Sequencing , Papillomaviridae/classification , Papillomaviridae/genetics , Papillomavirus Infections/virology , Cervix Uteri/virology , DNA, Viral/genetics , Female , Genotype , Human papillomavirus 16/genetics , Human papillomavirus 18/genetics , Humans , Nucleic Acid Amplification Techniques , Papillomavirus Infections/diagnosis , Sensitivity and Specificity , Sequence Analysis, DNA , Uterine Cervical Neoplasms/diagnosis , Viral Load
16.
Kidney Blood Press Res ; 44(2): 158-169, 2019.
Article in English | MEDLINE | ID: mdl-31048581

ABSTRACT

BACKGROUND: In Germany, practice patterns of conservative renal care (CRC), dialysis withdrawal (DW), and concomitant palliative care in patients who choose these options are unknown. METHOD: A survey was designed including 13 structured and one open questions on the management and frequency of CRC and DW, local palliative care structure, and fundamentals of the decision-making process, and addressed to the head physicians of all renal centers (n = 193) of a non-profit renal care provider (KfH - Kuratorium für Dialyse und Nierentransplantation, Neu-Isenburg, Germany). RESULTS: Response rate was 62.2% (n = 122 centers) comprising 14,197 prevalent dialysis patients and 159,652 renal outpatients. Two-thirds of the respondents were men (85% in the age group between 45 and 64 years). Mean time of experience in renal medicine was 22.2 years in men, 20.8 years in women. 94% of all centers provided CRC with a different frequency and proportion of patients (mean 8.4% of the center population, median 5%, range 0-50%). Mean proportion of DW was 2.85% per year (median 2%, range 1-15%). Physicians and center features were not significantly associated with utilization of CRC or DW. Palliative care management varied including local palliative teams, support by general physicians, or by the renal team itself. Hospice care was only established in patients undergoing CRC. Fundamentals of the decision-making process were the desire of the patient (90% in CRC, 67% in DW). Patients undergoing CRC changed their opinion towards treatment modality "frequently" in 18% of the cases, "occasionally" in 73%. Physicians' decisions were mostly driven by presumed fatal prognosis and poor physical or mental conditions of the individual patient. Different barriers to provide palliative care for the renal population like lack of education in palliative medicine, shortness of staff, lack of financial resources, and local palliative care structures were reported. CONCLUSION: Compared to international numbers, in Germany, proportion of CRC and DW reported by non-profit renal centers is in the lower range. Center practice of palliative care management varies and is driven by availability of local palliative care resources and presumably by attitudes of the renal teams. Quality of palliative care and the decision-making process need further evaluation.


Subject(s)
Conservative Treatment , Palliative Care , Renal Dialysis/statistics & numerical data , Adult , Aged , Decision Making , Female , Germany , Hospice Care , Humans , Male , Middle Aged , Quality of Health Care , Surveys and Questionnaires
17.
Acta Paediatr ; 108(7): 1350-1356, 2019 07.
Article in English | MEDLINE | ID: mdl-30536480

ABSTRACT

AIM: Children and adolescents with end-stage renal disease face a high morbidity and mortality. Palliative care provides a multidisciplinary approach to reduce disease burden and improve quality of life. This study evaluated concepts and current structures of palliative care from the perspective of a multidisciplinary paediatric nephrology team including physicians, nurses and psychosocial health professionals. METHODS: Evaluation was done by an online survey sent to the members of the German Society of Nephrology and to the nurse managers of German paediatric dialysis centres between April 9, 2018 and May 31, 2018. RESULTS: Out of the 52 respondents, 54% were physicians, 21% nurses and 25% psychosocial health professionals. The quality of actual palliative care service was rated as moderate (3.3 on a scale from one to six). Specialised palliative care teams (54%) and the caring paediatric nephrologist (50%) were considered as primarily responsible for palliative care. Two thirds wished for training in palliative care. In only 15% of the respondents' centres, palliative care specialisation existed. CONCLUSION: Palliative care structures in paediatric nephrology were not sufficient in the view of the multidisciplinary healthcare team. Therefore, efforts should be taken to integrate palliative care into the routine treatment of children and adolescents with chronic kidney diseases.


Subject(s)
Attitude of Health Personnel , Nephrology , Palliative Care/statistics & numerical data , Pediatrics , Adult , Aged , Female , Humans , Male , Middle Aged , Palliative Care/psychology , Surveys and Questionnaires
18.
Matern Child Health J ; 23(12): 1604-1612, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31541375

ABSTRACT

INTRODUCTION: Nearly half of all women gain above gestational weight gain (GWG) recommendations. This study assessed the feasibility and efficacy of a pilot behavioral intervention on GWG and physical activity behaviors. METHODS: Women (n = 45) 14-20 weeks gestation enrolled in a behavioral intervention. Physicians 'prescribed' the intervention to low risk patients. The intervention included self-monitoring, support, and optional walking groups. Process evaluation measures regarding usage and acceptability of study components were obtained. Physical activity was objectively measured at baseline and 35 weeks. The percentage of participants with appropriate GWG was calculated. Control data was obtained from the same clinic where participants were recruited. RESULTS: Overall, the intervention was acceptable to participants; attrition was low (6.7%), weekly contact was high (87%), and self-monitoring was high (Fitbit worn on 82% of intervention weeks; weekly weighing on 81%). Facebook (40% of weeks) and study website use (19%) was low, as was walking group attendance (7% attended a single group). Participants reported a lack of discussions about the study with their physician. Results showed no significant difference between intervention and control participants in the percentage who gained excess weight (p = 0.37). There was a significant decrease in moderate-to-vigorous physical activity in intervention participants (p < 0.0001). DISCUSSION: Continued efforts for promoting physical activity and appropriate GWG are needed. Although acceptable, the intervention was not efficacious. Trainings for, or input from prenatal healthcare providers on how to best encourage and support patients' engagement in healthy behaviors, such as PA, are warranted.


Subject(s)
Behavior Therapy/methods , Exercise , Gestational Weight Gain , Health Behavior , Obesity/prevention & control , Adolescent , Adult , Body Mass Index , Feasibility Studies , Female , Health Knowledge, Attitudes, Practice , Humans , Obesity/therapy , Pilot Projects , Pregnancy , Pregnancy Complications/prevention & control , Pregnancy Complications/therapy , Prenatal Care/methods , Public Health , Risk Factors , Weight Gain , Young Adult
19.
BMC Cancer ; 18(1): 562, 2018 05 15.
Article in English | MEDLINE | ID: mdl-29764400

ABSTRACT

BACKGROUND: A low cost and accurate method for detecting high-risk (HR) human papillomavirus (HPV) is important to permit HPV testing for cervical cancer prevention. We used a commercially available HPV method (H13, Hybribio) which was documented to function accurately in a reduced volume of cervical specimen to determine the most prevalent HPV types and the distribution of HPV infections in over 1795 cancer-free women in Guatemala undergoing primary screening for cervical cancer by cytology. METHODS: HR-HPV detection was attempted in cervical samples from 1795 cancer-free women receiving Pap smears using the Hybribio™ real-time PCR assay of 13 HR types. The test includes a globin gene internal control. HPV positive samples were sequenced to determine viral type. Age-specific prevalence of HPV was also assessed in the study population. RESULTS: A total of 13% (226/1717) of women tested HPV+, with 78 samples (4.3%) failing to amplify the internal control. The highest prevalence was found in younger women (< 30 years, 22%) and older ones (≥60 years, 15%). The six most common HR-HPV types among the 148 HPV+ typed were HPV16 (22%), HPV18 (11%), HPV39 (11%), HPV58 (10%), HPV52 (8%), and HPV45 (8%). CONCLUSIONS: In this sample of cancer free women in Guatemala, HPV16 was the most prevalent HR type in Guatemala and the age-specific prevalence curve peaked in younger ages. Women in the 30-59-year age groups had a prevalence of HR-HPV of 8%, however, larger studies to better describe the epidemiology of HPV in Guatemala are needed.


Subject(s)
Asymptomatic Infections/epidemiology , Early Detection of Cancer/economics , Papillomaviridae/isolation & purification , Papillomavirus Infections/diagnosis , Uterine Cervical Neoplasms/prevention & control , Adolescent , Adult , Age Factors , Aged , Cervix Uteri/virology , Early Detection of Cancer/methods , Female , Genotype , Guatemala/epidemiology , Humans , Mass Screening , Middle Aged , Papillomaviridae/genetics , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , Prevalence , Uterine Cervical Neoplasms/virology , Vaginal Smears , Young Adult , Uterine Cervical Dysplasia
20.
Am J Respir Cell Mol Biol ; 56(6): 708-715, 2017 06.
Article in English | MEDLINE | ID: mdl-28118023

ABSTRACT

Obliterative bronchiolitis (OB), characterized by fibrous obliteration of the small airways, is a major impediment to long-term survival in lung allograft recipients. We found previously that IL-17A is produced primarily by CD4+ T cells and γδ T cells after lung transplant in a mouse model of orthotopic lung transplant. The absence of either subset of T cells was compensated for by expansion of the other subset, which suggested that systemic blockade of IL-17A was necessary. To determine the specific role of IL-17A in the development of OB, we treated lung allograft recipients with an IL-17A antagonistic antibody. After IL-17A blockade, the incidence of OB was significantly reduced in lung allografts. IL-17A blockade also significantly attenuated the severity of acute rejection and overall lung fibrosis. The decreased OB incidence was associated with reduced lymphocyte recruitment, particularly CD8+ T cells and other IFN-γ-producing lymphocytes, to the lung allograft. Interestingly, IL-17A blockade led to an increase in the frequency of IL-17A-producing T-helper cell type 17 cells and γδ T cells in lung allografts, suggesting that IL-17A is a negative regulator of these T cells. Our data suggest that blocking IL-17A after lung transplant reduces the overall IFN-γ-mediated lymphocyte response and decreases the development of OB.


Subject(s)
Allografts/immunology , Bronchiolitis Obliterans/immunology , Immunity, Cellular/immunology , Interferon-gamma/metabolism , Interleukin-17/metabolism , Lung Transplantation , Animals , Bronchiolitis Obliterans/complications , Bronchiolitis Obliterans/pathology , Chemokines/metabolism , Inflammation Mediators/metabolism , Male , Mice, Inbred C57BL , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/immunology , Pulmonary Fibrosis/pathology , Th17 Cells/immunology
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