Echocardiogram by apical-subcostal protocol in prone position during invasive mechanical ventilation in cardiovascular intensive care unit.

AIMS: To evaluate the feasibility of a transthoracic echocardiogram using an apical-subcostal protocol in invasive mechanical ventilation (IMV) and prone position. METHODS: Prospective study of adults who required a prone position during IMV. A pillow was placed only under the left hemithorax in the prone position to elevate and ease the apical and subcostal windows. A critical care cardiologist (prone group) acquired and evaluated the images using the apical-subcostal protocol. Besides, we used ambulatory echocardiograms performed as a comparative group (supine group). RESULTS: 86 patients were included, 43 in the prone and 43 in the supine. In the prone group, the indication to perform an echocardiogram was hemodynamic monitoring. All patients were ventilated with protective parameters, and the mean end-expiratory pressure was 10.6 cmH2O. The protocol was performed entirely in 42 of 43 patients in the prone group because one patient did not have any acoustic window. In the 43 patients in the prone group analyzed and compared to the supine group, global biventricular function was assessed in 97.7% (p = 1.0), severe heart valve disease in 88.4% (p = 0.055), ruled out of the presence of pulmonary hypertension in 76.7% (p = 0.80), pericardial effusion in 93% (p = 0.12), and volume status by inferior vena cava in 93% (p = 0.48). Comparing prone versus supine position, a statistical difference was found when evaluating the left ventricle apical 2-chamber view (65.1 versus 100%, p < 0.01) and its segmental function (53.4 versus 100%, p < 0.01). CONCLUSION: The echocardiogram using an apical-subcostal protocol is feasible in patients in the IMV and prone position.

Performance of Cervical Screening a Decade Following HPV Vaccination: The Costa Rica Vaccine Trial.

BACKGROUND: We investigated the impact of human papillomavirus (HPV) vaccination on the performance of cytology-based and HPV-based screening for detection of cervical precancer among women vaccinated as young adults and reaching screening age. METHODS: A total of 4632 women aged 25-36 years from the Costa Rica HPV Vaccine Trial were included (2418 HPV-vaccinated as young adults and 2214 unvaccinated). We assessed the performance of cytology- and HPV-based cervical screening modalities in vaccinated and unvaccinated women to detect high-grade cervical precancers diagnosed over 4 years and the absolute risk of cumulative cervical precancers by screening results at entry. RESULTS: We detected 95 cervical intraepithelial neoplasia grade 3 or worse (52 in unvaccinated and 43 in vaccinated women). HPV16/18/31/33/45 was predominant (69%) among unvaccinated participants, and HPV35/52/58/39/51/56/59/66/68 predominated (65%) among vaccinated participants. Sensitivity and specificity of cervical screening approaches were comparable between women vaccinated as young adults and unvaccinated women. Colposcopy referral rates were lower in the vaccinated group for HPV-based screening modalities, but the positive predictive value was comparable between the 2 groups. CONCLUSIONS: Among women approaching screening ages, vaccinated as young adults, and with a history of intensive screening, the expected reduction in the positive predictive value of HPV testing, associated with dropping prevalence of HPV-associated lesions, was not observed. This is likely due to the presence of high-grade lesions associated with nonvaccine HPV types, which may be less likely to progress to cancer.

Resultados clínicos del reemplazo valvular aórtico percutáneo con dispositivo balón expandible MyVal en estenosis aórtica severa de alto riesgo / Clinical results of percutaneous aortic valve replacement using the MyVal prosthesis in patients with severe aortice stenosis and hisgh surgical risk

INTRODUCCIÓN: El dispositivo MyVal balón-expandible (Meril Life Sciences, India) fue recientemente aprobado en Chile y la Unión Europea para uso comercial. El objetivo del presente estudio fue proveer datos de eficacia y seguridad temprana y de mediano plazo en pacientes portadores de estenosis aórtica (EA) severa de alto riesgo quirúrgico sometidos a reemplazo valvular aórtico percutáneo (RVAP) con dispositivo MyVal. MATERIAL Y MÉTODOS: Se enrolaron retrospectivamente todos los pacientes con EA severa sintomática de alto riesgo según criterio del ´heart team´ local, sometidos a RVAP usando prótesis MyVal en Hospital San Borja Arriarán. RESULTADOS: La población quedó compuesta por 14 sujetos tratados entre Octubre 2018 y Noviembre 2019. La población tuvo una edad media de 82,5±7,8 años y elevado perfil de riesgo (puntaje STS promedio 11,6±5,1% de mortalidad a 30 días). Se logró éxito de dispositivo y procedimiento en 12 pacientes (86%) con caída sustancial de la gradiente aórtica media, persistente a 6 meses de seguimiento sin insuficiencia aórtica más que leve. Ocurrió falla de dispositivo en 2 pacientes, una debida a falla de entrega y otra por embolización a ventrículo, esta última con resultado de muerte. En términos de complicaciones, ocurrió una muerte precoz atribuida a disección/ruptura de aorta y 2 hemorragias mayores. La tasa de marcapasos ascendió a 3 pacientes, 23% considerando todos quienes recibieron implante. CONCLUSIÓN: El presente registro cuestiona la seguridad de MyVal en el tratamiento percutáneo de la EA severa de alto riesgo. Sin embargo, una vez logrado un implante exitoso MyVal muestra adecuados parámetros de funcionamiento, persistentes a un plazo mediano de seguimiento.

BACKGROUND: The recently approved balloon expandable MyVal (Meril Life Sciences, India) transcatheter aortic valve replacement (TAVR) prosthesis is available for commercial use in Chile and the European Union. The aim of this study is to provide early and mid-term data on the safety and efficacy of patients with severe aortic stenosis (AS) at high surgical risk undergoing TAVR using the MyVal device. METHODS: All patients with symptomatic severe AS at high surgical risk undergoing intended TAVR with MyVal prosthesis at San Borja-Arriarán Hospital entered to a retrospective registry. RESULTS: Between October 2018 and November 2019, 14 patients entered to the registry. The mean age was 82.5±7.8 years-old with a high-surgical riskprofile (mean STS score of 11.6±5.1% for 30-day mortality). Device and procedural success were achieved in 12 patients (86%) with substantial decrease in the mean aortic gradient, persistent at 6 months follow-up, all with mild or trace aortic regurgitation. Device failure occurred in 2 patients, one due to failed delivery and other due to device embolization into the left ventricle, which resulted in patient death. There were one death attributed aortic dissection/rupture and two major bleeding episodes. Three patients receiving MyVal implant required the implantation of a permanent pacemaker (23%). CONCLUSION: The present registry rises a question upon the safety of the MyVal TAVR device in high-risk AS. However, once a successfully implant was achieved the MyVal prosthesis showed an adequate performance to mid-term follow-up.

Single trans-septal access technique for left atrial intracardiac echocardiography to guide left atrial appendage closure.

OBJECTIVE: This registry aimed to describe the safety and feasibility of a single trans-septal (TS) access technique for left intracardiac echocardiography (ICE) guidance of left-atrial appendage (LAA) closure procedure. BACKGROUND: LAA closure is currently accepted as an alternative to oral anticoagulation (OAC) in patients with non-valvular atrial fibrillation (NVAF) who are at high-risk for bleeding. Currently, LAA closure procedure is typically performed under trans-esophageal echocardiogram (TEE) guidance. Although, ICE has the advantage of not requiring profound sedation/anesthesia, ICE-LAA imaging quality is often limited from the right atrium requiring double TS access. METHODS: Twenty-two patients with NVAF underwent LAA closure using the Amplatzer Amulet™ device (St Jude Medical) under ICE guidance from the left atrium. The ICE AcuNav catheter (Biosense Webster) and the Amulet delivery sheath were advanced into the LA through single TS puncture technique. RESULTS: The population was predominately male (59.1%) with a mean age of 74 ± 9.3 years, at high-risk for stroke (mean CHADS2 score of 3.8 ± 1.1) and bleeding (mean HAS BLED score of 3.5 ± 1.3). The Amplatzer AmuletTM device was successfully implanted in all patients. No procedural related complications including device embolization were noted. No major cardiovascular events occurred and all patients were discharged alive. At 30-day follow-up all patients remained alive, free of ischemic stroke and with no residual leak or device thrombus on TEE. CONCLUSIONS: This initial experience suggests that LAA occlusion with the Amplatzer Amulet device using ICE guidance from the left atrium via a single trans-septal technique is feasible and safe.

Cervical cancer incidence after screening with HPV, cytology, and visual methods: 18-Year follow-up of the Guanacaste cohort.

Testing negative for human papillomavirus (HPV) predicts long-term reassurance against invasive cervical cancer (ICC). To provide realistic estimates of effectiveness for new screening programs, we studied ICC risk after a 7-year repeated multimethod screening effort. In 1993-1994, 10,049 women aged 18-97 years were enrolled into a population-based cohort study of cervical HPV in Guanacaste, Costa Rica. Women were screened at different intervals according to enrollment results. Each visit (mean 3.2, 90% attendance) included split-sample conventional, automated, and liquid-based cytology, visual inspection, cervicography, and PCR-based HPV testing. Abnormal screening led to colposcopy and excisional treatment as appropriate during the study. Referral to colposcopy for HPV in the absence of other findings was introduced only at the last visit. Population-based Costa Rica Cancer Registry linkage identified cohort women diagnosed with ICC in the 18 years following cohort enrollment. The ICC cumulative risk was 0.4% (n = 38); 18 were diagnosed with ICC after study participation. Of these, 9 were missed at the screening step (negative screening or below the referral threshold, refused screening or colposcopy), 5 attended colposcopy but were not diagnosed as CIN2+, and 4 were treated for CIN2/3 but progressed to ICC nonetheless. Decreasing age-standardized ICC rates for the 1993-2011 period were observed in Guanacaste; cohort women showed additional 31% ICC incidence reduction with apparent downstaging of cancers that occurred. ICC risk following negative HPV testing in the optimal age range 30-50 years was extremely low. Real-life screening effectiveness following introduction is lower than the potential near-complete efficacy predicted by HPV natural history.

Costo-efectividad de reemplazo valvular aórtico percutáneo vs terapia conservadora en la estenosis aórtica de muy alto riesgo en un centro terciario chileno / Cost-effectiveness of trans aortic valve replacement vs. conservative treatment in high-risk patients with severe aortic stenosis in a referral hospital center in Santiago, Chile

Introducción: El objetivo fue evaluar la costo-efectividad del reemplazo valvular aórtico percutáneo (RVAP) contra terapia conservadora (TC) en pacientes con estenosis aórtica (EA) severa de muy alto riesgo, en un centro de derivación. Métodos: Los pacientes derivados entre Enero 2013 y Septiembre 2014, considerados de muy alto riesgo y candidatos a RVAP fueron incluidos. El costo de los recursos usados, de las readmisiones y la sobrevida fueron obtenidos para determinar el tiempo de vida ganado y la relación incremental de costo-efectividad (RICE) del RVAP Resultados: El grupo estudiado quedó compuesto por 39 pacientes, con edad promedio 82±7 años, más frecuentemente mujeres (74.4%), con elevado perfil de riesgo (STS score 11.4±5.6). Diecisiete pacientes (43.6%) fueron sometidos a RVAP y 22 (56.4%) a TC. Durante el seguimiento se registraron 25 rehospitalizaciones en el grupo de TC, a un costo promedio de $4.195.073 por paciente (7,027 dólares). Todos los pacientes sometidos a RAVP recibieron con éxito una prótesis Sapien XT y fueron egresados vivos. El costo promedio estimado del RVAP fue $20.000.000 (33,500 dólares). La sobrevida media fue de 54.5% (10 eventos) en grupo TC contra 94.1% (una muerte) en el grupo RVAP [285±204 días/seguimiento] (p<0.001). Así se pudo estimar que RVAP se asoció a un incremento de vida de al menos un año, lo cual resultó en una RICE de 26,470 dólares/año de vida ganado. Conclusión: El RAVP resultó costo-efectivo comparado con la TC en pacientes portadores de EA severa de muy alto riego tratados en la realidad de un centro de derivación nacional.

Aim: to evaluate cost-effectiveness of Transcatheter Aortic Valve Replacement (TAVR) compared to conservative treatment in patients with very high risk severe aortic stenosis (AS) referred to a tertiary center in Santiago, Chile Methods: Patients with high surgical risk and severe AS referred between January 2013 and September 2014 were included. Cost of resources, readdmissions, life-years gained and incremental cost-effectiveness of TAVI were calculated Results: Thirty-nine patients were finally included. Mean age was 82±7 years old, more commonly women (74%) with a mean STS score of 11.4±5.6 that confirmed their high-risk. Seventeen patients (43.6%) had TAVR and 22 (56.4%) underwent conventional medical therapy. All patients in the TAVR group - treated with Sapien XT® device - survived the procedure and were discharged alive. Mean cost of the procedure was approximately US$ 33,500. After a mean follow-up period of 285±204 days, mean survival rate in the control group was 54.5% (10 deaths) as compared to 94.1% in the TAVR group (1 death, p<0.001). Therefore, a gain of al least one year was obtained with TAVR resulting in an incremental cost effectiveness of US$ 26.470 per year of life gained. Conclusion: TAVR resulted costly-effective compared to conventional therapy in patients with severe AS and high surgical risk in a Chilean referral center.

Views on sex and sex education among gang-involved Latino youth in the United States.

Although gang-involved Latino youth in the United States are uniquely at risk of adverse consequences from sexual behavior, little research is available that can guide those who wish to develop interventions to reduce sexual risk among these youth. To facilitate the development of effective interventions, we identified cultural and contextual factors that influence sexual behavior and sex education among gang-involved Latino youth in one U.S. community. By analyzing transcripts from interviews and focus groups with three different groups of key stakeholders--gang-experienced Latino youth, the parents of gang-experienced Latino youth, and the personnel of a program providing comprehensive human services for gang-involved Latino youth--we identified three domains to be considered in developing sexual risk-reduction interventions for gang-involved U.S. Latino youth. The focus of our discussion is on the implications of these findings for future development or adaptation of interventions.

Experiencia con Ecocardiograma de estrés dipiridamol y Reserva coronaria no invasiva: Comunicación preliminar / Dipyridamol Stress Echocardiography and Non-invasive Coronary Reserve: Preliminary report

Antecedentes: El Ecocardiograma de Estrés (EE) es una técnica ampliamente utilizada en el estudio de pacientes con Enfermedad Coronaria conocida o sospechada Recientemente se ha preconizado efectuar el test vasodilatador, método recomendado para evaluar no invasivamente la reserva de flujo coronario (RFC). Objetivos: Mostrar la experiencia preliminar con el EE Dipiridamol, con un seguimiento inicial, así como el estudio de la RFC en la porción distal de la arteria Descendente Anterior (ADA). Métodos: Se analizaron 164 pacientes (101 hombres, edad promedio 65 años) a los que se les efectuó un EE Dipiridamol entre Julio 2011 y Septiembre 2012, con una dosis de 0.84mg/kg en 6 minutos, que incluyó el estudio de RFC. Todos los pacientes completaron la prueba sin efectos secundarios significativos, y en un tiempo menor a 25 minutos. El seguimiento se hizo con miras a la aparición de eventos cardiovasculares mayores (revascularización, infarto al miocardio y muerte cardíaca). Resultados: EE resultó positivo para isquemia en 19 (21 por ciento) pacientes. En 19 (12 por ciento) el EE resultó alterado por motilidad parietal; 29 (15 por ciento) presentaron respuesta anormal en la RFC, con una coincidencia de 12 pacientes (7 por ciento) con ambos tipo de alteración; En 142 (88 por ciento) pacientes se logró medir la RFC en ADA. En 151 pacientes se obtuvo datos confiables del seguimiento, que fue en promedio 10 meses (6 a 18); entre estos, 10 pacientes tuvieron alguna revascularización. No hubo infartos ni fallecidos por causa cardio-vascular. Dado el corto período de seguimiento y baja incidencia de eventos, no se pudo establecer el valor predictivo del resultado de la prueba en esta muestra. Conclusiones: Esta experiencia permitió familiarizarse con la técnica del EE con Dipiridamol y estudiar en un alto porcentaje la RFC en la ADA. La técnica es segura y consume muy poco tiempo. Queda pendiente la determinación del valor predictivo de estos resultados en nuestras manos.

Background: Stress Echocardiography is a common technique in the study of patients with known or suspected Coronary artery disease (CAD). Recently the vasodilation test has been recommended for the non invasive study of Coronary Flow Reserve (CFR). Aim: to report our preliminary experience with Di-pyridamol Stress Echocardiography (DSE), an initial follow-up, and the study of CFR in the distal portion of the left anterior descending coronary artery (LAD). Methods: 164 consecutive patients (101 men, mean age 65) with suspected or known CAD underwent a high-dose DSE (0.84 mg/kg over 6 min) between July 2011 and September 2012. The test included a study of CFR. All patients completed the test within 25 min. Prospective follow-up regarding major adverse cardiovascular events(revascularization, cardiac mortality and infarction) was conducted for a mean of 10 months (range 6-18) Results: DSE was positive for ischemia in 34 (21 percent) patients, showed abnormal wall motion in 19 (12 percent), abnormal CFR in 29 (15 percent) , and both abnormalities in12 (7 percent). 142 patients (88 percent) had a normal CFR in the LAD. 151 patients were followed for a mean of 10 months (6 to 18). Ten of these patients required some type of revascularization. There were no myocardial infarctions or cardiac deaths. Due to the short follow up period and the low incidence of events, it was not possible to estimate the predictive value of abnormal CFR. Conclusion: The dipyridamol echo stress test with a study of coronary flow reserve is safe and brief. The predictive value for cardiac events remains to be determined.

Low risk of type-specific carcinogenic HPV re-appearance with subsequent cervical intraepithelial neoplasia grade 2/3.

Carcinogenic human papillomavirus (HPV) infections are very common after sexual debut and nearly all become undetectable ("clear") within a few years. Following clearance, the long-term risks of type-specific HPV re-appearance and subsequent risk of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) are not well defined. In the 7-year, population-based cohort study in Guanacaste, Costa Rica, we studied how often type-specific carcinogenic HPV infections re-appeared after clearance and how often re-appearance led to CIN2+. We considered 1,740 carcinogenic HPV infections detected by MY09/11 PCR among 2,805 women (18-91 years old, median 34) who were actively followed at 6- or 12-month intervals. We identified women with one or more type-specific HPV infections that cleared and re-appeared and further defined a subgroup of "definite clearance and re-appearance" (≥2 intervening negative results over a period of ≥1 year). We determined the absolute risk of CIN2+ among the different groups. p values are two-sided. Only 7.7% (81/1,052) of HPV-infected women had intervening negative results. Very few (3.7%, 39/1,052) had "definite clearance and re-appearance", of which 5.1% (2/39) subsequently persisted to a diagnosis of CIN2. There were zero CIN3+ lesions. Extremely few women (2/2,805 of women in our cohort) had a type-specific carcinogenic HPV infection clear, re-appear and lead to CIN2+. If confirmed, this argues against vaccination to avoid re-appearance that leads to precursor lesions and against the need of frequent HPV screening after initial negative results.

Switch from cytology-based to human papillomavirus test-based cervical screening: implications for colposcopy.

Human papillomavirus (HPV) testing is more sensitive than cytology; some cervical cancer prevention programs will switch from cytology to carcinogenic HPV test-based screening. The objective of our study is to evaluate the clinical implications of a switch to HPV test-based screening on performance and workload of colposcopy. Women in the population-based, 7-year Guanacaste cohort study were screened at enrollment using cytology. We also took another specimen for HPV DNA testing and collected magnified cervical photographic images (cervigrams). A final case diagnosis (≥cervical intraepithelial neoplasia [CIN] grade 3, CIN2,

A competitive serological assay shows naturally acquired immunity to human papillomavirus infections in the Guanacaste Natural History Study.

BACKGROUND: A competitive Luminex Immunoassay (cLIA) has been developed to measure neutralizing antibodies against human papillomavirus (HPV) types 6, 11, 16 and 18. METHODS: In a cohort of 974 women from the Guanacaste Natural History Study, we studied the relationship of baseline cLIA and virus-like particle (VLP) enzyme-linked immunosorbent assay (ELISA) (HPV16 and HPV18 only) seropositivity to measures of HPV exposure, HPV DNA positivity, number of sexual partners, cytology findings, and age. We then studied immunity against subsequent infection with HPV6, 11, 16, 18 and related types over a 7-year period. RESULTS: cLIA seroprevalence varied with previous exposure; the prevalence of cLIA results positive for HPV16 and HPV18 was lower than the prevalence of positive VLP ELISA responses. cLIA and VLP ELISA positivity predicted protection from subsequent infections with concordant types. The combined odds ratio for HPV16 and HPV18 cLIA positivity was 0.41 (95% confidence interval [CI], 0.21-0.80), and the combined odds ratio for the HPV16 and HPV18 VLP ELISA positivity was 0.65 (95% CI, 0.46-0.93). Of individual types, statistical significance was only reached for HPV16 cLIA positivity (odds ratio, 0.44; 95% CI, 0.15-0.94). CONCLUSIONS: Both assays showed an association between positive results and significant protection from subsequent infections for HPV16 and HPV18 combined. cLIA seroprevalence was lower than VLP ELISA, suggesting that the assay detects a subset of antibodies following natural infection that are specifically linked to immunity against subsequent HPV infection.

A population-based prospective study of carcinogenic human papillomavirus variant lineages, viral persistence, and cervical neoplasia.

Human papillomavirus (HPV) types differ profoundly in cervical carcinogenicity. For the most carcinogenic type HPV16, variant lineages representing further evolutionary divergence also differ in cancer risk. Variants of the remaining 10 to 15 carcinogenic HPV types have not been well studied. In the first prospective, population-based study of HPV variants, we explored whether, on average, the oldest evolutionary branches within each carcinogenic type predicted different risks of >2-year viral persistence and/or precancer and cancer [cervical intraepithelial neoplasia grade 3+ (CIN3+)]. We examined the natural history of HPV variants in the 7-year, 10,049-woman Guanacaste Cohort Study, using a nested case-control design. Infections were assigned to a variant lineage determined by phylogenetic parsimony methods based on URR/E6 sequences. We used the Fisher's combination test to evaluate significance of the risk associations, cumulating evidence across types. Globally, for HPV types including HPV16, the P value was 0.01 for persistence and 0.07 for CIN3+. Excluding HPV16, the P values were 0.04 and 0.37, respectively. For HPV16, non-European viral variants were significantly more likely than European variants to cause persistence [odds ratio (OR), 2.6; P = 0.01] and CIN3+ (OR, 2.4; P = 0.004). HPV35 and HPV51 variant lineages also predicted CIN3+. HPV variants generally differ in risk of persistence. For some HPV types, especially HPV16, variant lineages differ in risk of CIN3+. The findings indicate that continued evolution of HPV types has led to even finer genetic discrimination linked to HPV natural history and cervical cancer risk. Larger viral genomic studies are warranted, especially to identify the genetic basis for HPV16's unique carcinogenicity.

Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection.

BACKGROUND: The natural history of human papillomavirus (HPV) infections in older women is critical for preventive strategies, including vaccination and screening intervals, but is poorly understood. In a 7-year population-based cohort study in Guanacaste, Costa Rica, we examined whether women's age and the duration of carcinogenic HPV infections influenced subsequent persistence of infection and risk of cervical intraepithelial neoplasia grade 2 (CIN 2) or worse disease. METHODS: At enrollment, of the 9466 participants eligible for pelvic examination, 9175 were screened for cervical neoplasia using multiple methods; those with CIN 2 or worse disease were censored and treated. Participants at low risk of CIN 2 or worse (n = 6029) were rescreened at 5-7 years (passively followed), whereas higher-risk participants (n = 2115) and subsets of low-risk women (n = 540) and initially sexually inactive women (n = 410) were rescreened annually or semiannually (actively followed) for up to 7 years. HPV testing was done using a polymerase chain reaction-based method. We determined, by four age groups (18-25, 26-33, 34-41, and > or =42 years), the proportion of prevalent infections (found at baseline) and newly detected infections (first found during follow-up) that persisted at successive 1-year time points and calculated absolute risks of CIN 2 and CIN grade 3 (CIN 3) or worse during follow-up. P values are two-sided. RESULTS: Regardless of the woman's age, newly detected infections were associated with very low absolute risks of persistence, CIN 2, or worse disease. For newly detected infections, the rate of progression to CIN 2+ (or CIN 3+), after 3 years of follow-up, was not higher for women aged 34 years and older than for younger women. Moreover, rates of newly detected infections declined sharply with age (in the actively followed group, at ages 18-25, 26-33, 34-41, and > or =42 years, rates were 35.9%, 30.6%, 18.1%, and 13.5%, respectively; P < .001). Among prevalent infections, persistent infections among older women (> or =42 years) was higher than that among younger age groups or new infections at any age (P < .01 for comparison of eight groups). Most (66 of 85) CIN 2 or worse detected during follow-up was associated with prevalent infections. Only a small subset (25 of 1128) of prevalent infections persisted throughout follow-up without apparent CIN 2 or worse. CONCLUSIONS: The rate of new infections declines with age, and new infections typically do not progress to CIN 2 or worse disease in older women; thus, overall potential benefit of prophylactic vaccination or frequent HPV screening to prevent or detect new carcinogenic HPV infections at older ages is low.

Activation of calcitonin gene-related peptide receptor during ozone inhalation contributes to airway epithelial injury and repair.

The authors investigated the importance of the neuropeptide, calcitonin gene-related peptide (CGRP), in epithelial injury, repair, and neutrophil emigration after ozone exposure. Wistar rats were administered either a CGRP-receptor antagonist (CGRP(8-37)) or saline and exposed to 8 hours of 1-ppm ozone or filtered air with an 8-hour postexposure period. Immediately after exposure, ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, airway dissected lung lobes were stained for 5'-bromo-2'-deoxyuridine, a marker of epithelial proliferation. Positive epithelial cells were quantified in specific airway generations. Rats treated with CGRP(8-37) had significantly reduced epithelial injury in terminal bronchioles and reduced epithelial proliferation in proximal airways and terminal bronchioles. Bronchoalveolar lavage and sections of terminal bronchioles showed no significant difference in the number of neutrophils emigrating into airways in CGRP(8-37)-treated rats. The airway epithelial cell line, HBE-1, showed no difference in the number of oxidant stress positive cells during exposure to hydrogen peroxide and a range of CGRP(8-37) doses, demonstrating no antioxidant effect of CGRP(8-37). We conclude that activation of CGRP receptors during ozone inhalation contributes to airway epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

Neither one-time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer.

A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993-1994. At the enrollment visit, we applied multiple state-of-the-art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more than one pathologist), visual inspection and cervicography. Any positive screening test led to colposcopic referral and biopsy and/or excisional treatment of CIN2 or worse. We retrospectively tested stored specimens with an early HPV test (hybrid capture tube test) and for >40 HPV genotypes using a research PCR assay. We followed women typically 5-7 years and some up to 11 years. Nonetheless, 16 cases of invasive cervical cancer were diagnosed during follow-up. Six cancer cases were failures at enrollment to detect abnormalities by cytology screening; 3 of the 6 were also negative at enrollment by sensitive HPV DNA testing. Seven cancers represent failures of colposcopy to diagnose cancer or a precancerous lesion in screen-positive women. Finally, 3 cases arose despite attempted excisional treatment of precancerous lesions. Based on this evidence, we suggest that no current secondary cervical cancer prevention technologies applied once in a previously under-screened population is likely to be 100% efficacious in preventing incident diagnoses of invasive cervical cancer.

Short term persistence of human papillomavirus and risk of cervical precancer and cancer: population based cohort study.

OBJECTIVE: To evaluate the cumulative incidence of cervical intraepithelial neoplasia II or worse (grade II+) or cervical intraepithelial neoplasia grade III+ after short term persistence of prevalently detected carcinogenic human papillomavirus (HPV). DESIGN: Population based cohort study. SETTING: Guanacaste, Costa Rica. PARTICIPANTS: 2282 sexually active women actively followed after enrolment. MAIN OUTCOME MEASURES: Primary end points: three year and five year cumulative incidence of histologically confirmed cervical intraepithelial neoplasia grade II+ (n=70). Cervical specimens collected at each visit tested for more than 40 HPV genotypes. HPV 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 73, and 82 were considered the primary carcinogenic genotypes. RESULTS: Women who tested positive for a carcinogenic HPV at enrolment and after about one year (9-21 months) (positive/positive) had a three year cumulative incidence of cervical intraepithelial neoplasia grade II+ of 17.0% (95% confidence interval 12.1% to 22.0%). Those who tested negative/positive (3.4%, 0.1% to 6.8%), positive/negative (1.2%, -0.2% to 2.5%), and negative/negative (0.5%, 0.1% to 0.9%) were at a significantly lower risk. There was little difference in the cumulative incidence of cervical intraepithelial neoplasia grade II+ between testing positive twice for any carcinogenic HPV genotype (same genotype or different genotypes) v testing positive twice for the same carcinogenic genotype (17.0% v 21.3%, respectively). Short term persistence of HPV 16 strongly predicted cervical intraepithelial neoplasia grade II+, with a three year cumulative incidence of 40.8% (26.4% to 55.1%). Similar patterns were observed for the five year cumulative incidence of grade II+ and for three year and five year cumulative incidence of grade III+. CONCLUSIONS: Short term persistence of a prevalently detected carcinogenic HPV infection, especially HPV 16, strongly predicts a subsequent diagnosis of cervical intraepithelial neoplasia II+ over the next few years.

Rationale and design of a community-based double-blind randomized clinical trial of an HPV 16 and 18 vaccine in Guanacaste, Costa Rica.

We report the rationale, design, methods and details of participation of a community-based, double-blind, randomized clinical trial of an HPV 16 and 18 vaccine conducted in two provinces of Costa Rica to investigate the efficacy and population impact of the vaccine in the prevention of cervical cancer precursors. More than 24,000 women between 18 and 25 years of age were invited to participate and pre-screened for eligibility, with recruitment of 7466 women (30% of those pre-screened, 59% of those eligible) who were randomized to receive 3 doses of the HPV vaccine or hepatitis A vaccine as control. A complex protocol of data and specimen collection was applied, including an interview, pelvic exam for sexually active women, blood for serology and cell-mediated immunity, cervical secretions for local immunity and cells for HPV, Chlamydia trachomatis and gonorrhea testing. Eighty percent of the women received three doses, 12.4% two doses and 7.4% one dose. At visits, compliance with data and specimen collection was close to 100%. Baseline characteristics and age-specific prevalence of HPV and cervical neoplasia are reported. Overall prevalence of HPV was high (50%), with 8.3% of women having HPV 16 and 3.2% HPV 18. LSIL was detected in 12.7% of women at baseline and HSIL in 1.9%. Prevalence of Chlamydia was 14.2%. There was very good agreement in HPV detection between clinician-collected and self- collected specimens (89.4% agreement for all types, kappa 0.59). Follow up will continue with yearly or more frequent examinations for at least 4 years for each participant.

Activation of neurokinin-1 receptors during ozone inhalation contributes to epithelial injury and repair.

We investigated the importance of neurokinin (NK)-1 receptors in epithelial injury and repair and neutrophil function. Conscious Wistar rats were exposed to 1 ppm ozone or filtered air for 8 hours, followed by an 8-hour postexposure period. Before exposure, we administered either the NK-1 receptor antagonist, SR140333, or saline as a control. Ethidium homodimer was instilled into lungs as a marker of necrotic airway epithelial cells. After fixation, whole mounts of airway dissected lung lobes were immunostained for 5-bromo-2'-deoxyuridine, a marker of epithelial proliferation. Both ethidium homodimer and 5-bromo-2'-deoxyuridine-positive epithelial cells were quantified in specific airway generations. Rats treated with the NK-1 receptor antagonist had significantly reduced epithelial injury and epithelial proliferation compared with control rats. Sections of terminal bronchioles showed no significant difference in the number of neutrophils in airways between groups. In addition, staining ozone-exposed lung sections for active caspase 3 showed no apoptotic cells, but ethidium-positive cells colocalized with the orphan nuclear receptor, Nur77, a marker of nonapoptotic, programmed cell death mediated by the NK-1 receptor. An immortalized human airway epithelial cell line, human bronchial epithelial-1, showed no significant difference in the number of oxidant stress-positive cells during exposure to hydrogen peroxide and a range of SR140333 doses, demonstrating no antioxidant effect of the receptor antagonist. We conclude that activation of the NK-1 receptor during acute ozone inhalation contributes to epithelial injury and subsequent epithelial proliferation, a critical component of repair, but does not influence neutrophil emigration into airways.

Monitoreo inalámbrico de presión arterial pulmonar en pacientes con insuficiencia cardíaca / Wireless pulmonary artery pressure monitoring in patients with congestive heart failure

Antecedentes: El monitoreo continuo y remoto de presiones intracardiacas ha sido reportado de utilidad en el manejo y prevención de hospitalización en pacientes con Insuficiencia Cardíaca (IC). Objetivos: Describir la técnica y las complicaciones en el seguimiento a mediano plazo de un sensor inalámbrico(Sensor CardioMEMS Heart Sure®) pulmonar; evaluar la exactitud de la determinación de la presión en arteriapulmonar (PAP) después de un año de implante y su correlación con la presión estimada por cateterismo cardíaco convencional (catéter de Swan-Ganz).Método: Fueron incluidos en el estudio pacientes con IC avanzada con al menos una hospitalización en el año previo al implante de este sensor. Se realizaron mediciones simultáneas con catéter de Swan-Ganz (SG) durante el implante y a los 60, 180 días y un año de seguimiento. Se empleó análisis de regresión lineal como una medida de la correlación entre los métodos. La variabilidad entre las técnicas se evaluó mediante análisis del Bland-Altman.Resultados: En este reporte fueron incluidos 27 pacientes, 24 hombres con edad promedio de 64+/-14.1 años y FE promedio de 25 por ciento, la gran mayoría en clase funcional III de la NYHA. Un paciente falleció 190 días post implante por causa extra cardíaca y otro falleció 45 días post implante por shock cardiogénico. La PAP sistólica, diastólica y media cuantificada a 60 días, 6 meses y un año post implante tuvo una correlación adecuada cuando se comparó con el cateterismo de SG preservando la calidad de la curva de presión obtenida desde el sensor. La calidad de la señal se ha mantenido hasta más de un año de seguimiento. Conclusión: Existió muy buena correlación entre las presiones obtenidas con el sensor y las mediciones del catéter de SG. Es necesario validar este sistema en un número mayor de enfermos y establecer su papel en el manejo de la IC crónica.

Background: Continuous and remote intracardiac pressure monitoring has been reported to be useful to manage patients with congestive heart failure (CHF) and to prevent rehospitalization. Aim: To describe the technical aspects and complications in the use of a wireless pulmonary artery pressure sensor (CardioMEMS Heart Sure© ) in a medium term follow up. Also, to evaluate de precision of pulmonary artery pressure (PAP) measurement one year after implantation of the device. Methods: Patients with advanced CHF with at least one hospitalization in the preceding year were included. PAP was measured through Swan Ganz catheterization at the time of device implantation and after 60 days, 6 months and one year of follow up. Linear regression was used to estimate inter method correlation and Bland-Altman analysis to estimate variability among methods Results: Twenty-seven patients (24 men) aged 64 +/-14.1 (SD) years, most of them in functional class III were included. The mean ejection fraction was 25 percent. One patient died 190 days after implant due to non cardiac causes and another 45 days post implant from cardiogenic shock. Systolic, diastolic and mean PAP was measured 60 days, 6 months and 1 year post implant. The correlation with Swan Ganz catheter measurement was adequate. The quality of the signal obtained from the PAP sensor was maintained at one year of follow up. Conclusion: A very good correlation between wireless and Swan Ganz measurements of PAP was observed. More extensive assessment of this method is needed to establish its usefulness in the management of patients with chronic CHF.

Comparison of a radiofrequency-based wireless pressure sensor to swan-ganz catheter and echocardiography for ambulatory assessment of pulmonary artery pressure in heart failure.

OBJECTIVES: The goal of this work was to evaluate the accuracy of a new heart failure (HF) sensor (HFS) (Heart Failure Sensor, CardioMEMS Inc., Atlanta, Georgia) pulmonary artery pressure (PAP) monitoring compared with Swan-Ganz (SG) (Hospira, Inc., Lake Forest, Illinois) catheterization and echocardiography (ECHO) in ambulatory HF patients. BACKGROUND: There is an increasing interest in the development of ambulatory monitoring devices aiming to adjust therapy and prevent hospitalizations in HF patients. METHODS: Twelve patients with HF and New York Heart Association functional class II to IV were included in this study. The HFS was deployed into the pulmonary artery under angiography, allowing wireless PAP measurement. Two independent blind operators performed 3 HFS measurements at each visit, with simultaneous ECHO at 2, 14, 30, 60, and 90 days. Swan-Ganz catheterization was performed at 0 and 60 days. Linear regression was used as a measure of agreement. Variability between methods and interobserver variability were evaluated by Bland-Altman analysis. RESULTS: Mean age was 63 +/- 14.6 years. Systolic PAP was 64 +/- 22 mm Hg and 58 +/- 22 mm Hg for HFS and SG, respectively (p < 0.01). Both methods showed a significant correlation (r2 = 0.96 baseline, r2 = 0.90 follow-up, p < 0.01), with a mean difference of 6.2 +/- 4.5 mm Hg. Diastolic PAP was 23 +/- 14 mm Hg and 28 +/- 16 mm Hg for HFS and SG, respectively (r2 = 0.88 baseline, r2 = 0.48 follow-up, p < 0.01), with a mean difference of -1.6 +/- 6.8 mm Hg. Systolic PAP was 60 +/- 20 mm Hg and 62 +/- 12 mm Hg for HFS and ECHO, respectively (r2 = 0.75, p < 0.01), with a mean difference of -2.6 +/- 11 mm Hg. There was no significant interobserver difference. CONCLUSIONS: The HFS provides an accurate method for PAP assessment in the intermediate follow-up of HF patients.