Acceptability of HPV Vaccines: A Qualitative Systematic Review and Meta-Summary.

In 2006, the human papillomavirus (HPV) vaccine was approved for use as an effective intervention for reducing the risk of developing cervical cancer; however, its successful implementation is dependent on acceptability. This study aims to provide a comprehensive understanding of the reasons that favor or do not favor the acceptability of HPV vaccines. METHODS: We conducted a systematic review and meta-summary of qualitative research on 16 databases. A total of 32 articles that considered the perspectives of vaccine users, their parents, and the professionals who care for them were reviewed. Synthesis was conducted as described by Sandelowski and Barroso. RESULTS: We used inductive and deductive methods to obtain a total of 22 dimensions, out of which three issues stood out that should be considered to improve acceptability and are formed by three groups of study, namely, information about the vaccine, fears and side effects, and sexuality associated with the vaccine. CONCLUSIONS: Acceptability, as well as adherence to HPV vaccination, is a complex concept. This review highlights the perspectives of the three sets of actors involved in the process (i.e., users, parents, and professionals) and views these factors in relation to acceptability as a guide for new interventions.

Three-Year Follow-up of 2-Dose Versus 3-Dose HPV Vaccine.

BACKGROUND AND OBJECTIVES: Human papillomavirus (HPV) antibody responses to the 9-valent human papillomavirus (9vHPV) vaccine among girls and boys (aged 9-14 years) receiving 2-dose regimens (months 0, 6 or 0, 12) were noninferior to a 3-dose regimen (months 0, 2, 6) in young women (aged 16-26 years) 4 weeks after last vaccination in an international, randomized, open-label trial (NCT01984697). We assessed response durability through month 36. METHODS: Girls received 2 (months 0 and 6 [0, 6]: n = 301; months 0 and 12 [0, 12]: n = 151) or 3 doses (months 0,2, and 6 [0, 2, 6]: n = 301); boys received 2 doses ([0, 6]: n = 301; [0, 12]: n = 150); and young women received 3 doses ([0, 2, 6]: n = 314) of 9vHPV vaccine. Anti-HPV geometric mean titers (GMTs) were assessed by competitive Luminex immunoassay (cLIA) and immunoglobulin G-Luminex immunoassay (IgG-LIA) through month 36. RESULTS: Anti-HPV GMTs were highest 1 month after the last 9vHPV vaccine regimen dose, decreased sharply during the subsequent 12 months, and then decreased more slowly. GMTs 2 to 2.5 years after the last regimen dose in girls and boys given 2 doses were generally similar to or greater than GMTs in young women given 3 doses. Across HPV types, most boys and girls who received 2 doses (cLIA: 81%-100%; IgG-LIA: 91%-100%) and young women who received 3 doses (cLIA: 78%-98%; IgG-LIA: 91%-100%) remained seropositive 2 to 2.5 years after the last regimen dose. CONCLUSIONS: Antibody responses persisted through 2 to 2.5 years after the last dose of a 2-dose 9vHPV vaccine regimen in girls and boys. In girls and boys, antibody responses generated by 2 doses administered 6 to 12 months apart may be sufficient to induce high-level protective efficacy through at least 2 years after the second dose.

Injectable thermoresponsive hydrogels as drug delivery system for the treatment of central nervous system disorders: A review.

The central nervous system (CNS), consisting of the brain, spinal cord, and retina, superintends to the acquisition, integration and processing of peripheral information to properly coordinate the activities of the whole body. Neurodegenerative and neurodevelopmental disorders, trauma, stroke, and brain tumors can dramatically affect CNS functions resulting in serious and life-long disabilities. Globally, the societal and economic burden associated with CNS disorders continues to grow with the ageing of the population thus demanding for more effective and definitive treatments. Despite the variety of clinically available therapeutic molecules, medical interventions on CNS disorders are mostly limited to treat symptoms rather than halting or reversing disease progression. This is attributed to the complexity of the underlying disease mechanisms as well as to the unique biological microenvironment. Given its central importance, multiple barriers, including the blood brain barrier and the blood cerebrospinal fluid barrier, protect the CNS from external agents. This limits the access of drug molecules to the CNS thus contributing to the modest therapeutic successes. Loco-regional therapies based on the deposition of thermoresponsive hydrogels loaded with therapeutic agents and cells are receiving much attention as an alternative and potentially more effective approach to manage CNS disorders. In this work, the current understanding and challenges in the design of thermoresponsive hydrogels for CNS therapy are reviewed. First, the biological barriers that hinder mass and drug transport to the CNS are described, highlighting the distinct features of each barrier. Then, the realization, characterization and biomedical application of natural and synthetic thermoresponsive hydrogels are critically presented. Advantages and limitations of each design and application are discussed with the objective of identifying general rules that could enhance the effective translation of thermoresponsive hydrogel-based therapies for the treatment of CNS disorders.

A thermoresponsive hydrogel system for long-acting corticosteroid delivery into the paranasal sinuses.

Delivering localized treatment to the paranasal sinuses for diseases such as chronic rhinosinusitis (CRS) is particularly challenging because of the small natural openings leading from the sinuses that can be further obstructed by presence of inflammation. As such, oral steroids, topical nasal sprays or irrigation, and surgery can be utilized to treat persistent sinonasal inflammation, but there exists a need for post-operative options for long-term steroid delivery to prevent disease recurrence. In the present study, a Thermogel, Extended-release Microsphere-based-delivery to the Paranasal Sinuses (TEMPS) is developed with the corticosteroid mometasone furoate. Specifically, the bioactive steroid is released for 4 weeks from poly(lactic-co-glycolic acid) (PLGA) microspheres embedded in a poly(N-isopropylacrylamide) (p-NIPAAm)-based hydrogel. The temperature-responsive system undergoes a reversible sol-gel transition at 34-35 °C such that it can be applied as a liquid at ambient temperature, conforming to the sinonasal epithelium as it gels. In a rabbit model of CRS, TEMPS was maintained in rabbit sinuses and effectively reduced sinonasal inflammation as characterized by micro-computed tomography and histopathology analysis. Ultimately, the combination of controlled release microspheres with a thermoresponsive hydrogel provides flexibility for encapsulating therapeutics in a reversible and conforming system for localized delivery to the sinuses.

Quality of life and added value of a tailored palliative care intervention in patients with soft tissue sarcoma undergoing treatment with trabectedin: a multicentre, cluster-randomised trial within the German Interdisciplinary Sarcoma Group (GISG).

OBJECTIVES: The choice of drug treatment in advanced soft tissue sarcoma (STS) continues to be a challenge regarding efficacy, quality of life (QoL) and toxicity. Unlike other cancer types, where integrating patient-reported outcomes (PRO) has proven to be beneficial for QoL, there is no such evidence in patients with STS as of now. The YonLife trial aimed to explore the effect of a tailored multistep intervention on QoL, symptoms and survival in patients with advanced STS undergoing treatment with trabectedin as well as identifying predictors of QoL. DESIGN: YonLife is a cluster-randomised, open-label, proof-of-concept study. The intervention incorporates electronic PRO assessment, a case vignette and expert-consented treatment recommendations. PARTICIPANTS: Six hospitals were randomised to the control arm (CA) or interventional arm (IA). Seventy-nine patients were included of whom 40 were analysed as per-protocol analysis set. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary end point was the change of Functional Assessment for Cancer Therapy (FACT-G) total score after 9 weeks. Secondary outcomes included QoL (FACT-G subscales), anorexia and cachexia (Functional Assessment of Anorexia/Cachexia Therapy (FAACT)), symptoms (MD Anderson Symptom Inventory (MDASI)), anxiety and depression (HADS), pain intensity and interference (Brief Pain Inventory (BPI)) and survival assessment. RESULTS: After 9 weeks of treatment, QoL declined less in the IA (ΔFACT-G total score: -2.4, 95% CI: -9.2 to 4.5) as compared with CA (ΔFACT-G total score: -3.9; 95% CI:-11.3 to 3.5; p=0.765). In almost all FACT-G subscales, average declines were lower in IA, but without reaching statistical significance. Smaller adverse trends between arms were observed for MDASI, FAACT, HADS and BPI scales. These trends failed to reach statistical significance. Overall mean survival was longer in IA (648 days) than in CA (389 days, p=0.110). QoL was predicted by symptom severity, symptom interference, depression and anxiety. CONCLUSION: Our data suggest a potentially favourable effect of an electronic patient-reported outcomes based intervention on QoL that needs to be reappraised in confirmatory studies. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier (NCT02204111).

[Frequently asked questions regarding the human papillomavirus vaccines]. / Preguntas frecuentes respecto a la vacuna contra el virus papiloma humano.

In this practical article, based on questions and answers, the main queries made to specialists are addressed, such as Why vaccinate against HPV? Composition of the vaccine? What are their effectiveness and safety? Should men be vaccinated? and several others.

Preguntas frecuentes respecto a la vacuna contra el virus papiloma humano / Frequently asked questions regarding the human papillomavirus vaccines

Resumen En este artículo práctico, en base a preguntas y respuestas, se abordan las principales consultas formuladas a los especialistas, tales como ¿Porqué vacunar contra VPH? ¿Composición de la vacuna? ¿Cuáles son su eficacia y seguridad? ¿Deben vacunarse varones? y varias otras.

In this practical article, based on questions and answers, the main queries made to specialists are addressed, such as Why vaccinate against HPV? Composition of the vaccine? What are their effectiveness and safety? Should men be vaccinated? and several others.

[Adolescents find it easy to collect their own samples to study sexually transmitted infections]. / Adolescentes encuentran fácil tomar sus propias muestras para estudio de infecciones de transmisión sexual.

BACKGROUND: As alternative for patients that fear genital examination, we assessed adolescent's comfort and ease with self-collected samples for nucleic acid amplification testing for sexually transmitted infections. PATIENTS AND METHODS: Sexually active Chilean adolescents and youth under 25 years (174 males and 117 females) were enrolled. Females used self-collected vaginal swabs and males collected first-stream urine. A satisfaction survey evaluating self-sampling system was applied. RESULTS: Self-collection was considered easy in 99.3% of the interviewees (CI 95% 0.88-0.98). In women, 79.3% preferred vaginal self-collected samples than pelvic exam (CI 95% 0.73-0.85). In men, 80.3% preferred self-collected first-stream urine to urethral swabs (CI 95% 0.73-0.87). Assuming that self-collected sampling were available, 89.6% of women (CI 95% 0.85-0.94) and 93.2% of men (CI 95% 0.89-0.98) would be prone to be tested more often. Ease of self-collected sampling is not associated with age, gender, educational level or poverty. CONCLUSIONS: Chile currently does not have sexually transmitted infections surveillance or screening programs for youth and adolescents. Given self-collected sampling's good acceptability, it could be successfully used when these programs are implemented.

Adolescentes encuentran fácil tomar sus propias muestras para estudio de infecciones de transmisión sexual / Adolescents find it easy to collect their own samples to study sexually transmitted infections

Background: As alternative for patients that fear genital examination, we assessed adolescent's comfort and ease with self-collected samples for nucleic acid amplification testing for sexually transmitted infections. Patients and Methods: Sexually active Chilean adolescents and youth under 25 years (174 males and 117 females) were enrolled. Females used self-collected vaginal swabs and males collected first-stream urine. A satisfaction survey evaluating self-sampling system was applied. Results: Self-collection was considered easy in 99.3% of the interviewees (CI 95% 0.88-0.98). In women, 79.3% preferred vaginal self-collected samples than pelvic exam (CI 95% 0.73-0.85). In men, 80.3% preferred self-collected first-stream urine to urethral swabs (CI 95% 0.73-0.87). Assuming that self-collected sampling were available, 89.6% of women (CI 95% 0.85-0.94) and 93.2% of men (CI 95% 0.89-0.98) would be prone to be tested more often. Ease of self-collected sampling is not associated with age, gender, educational level or poverty. Conclusions: Chile currently does not have sexually transmitted infections surveillance or screening programs for youth and adolescents. Given self-collected sampling's good acceptability, it could be successfully used when these programs are implemented.

Introducción: Como alternativa para pacientes que temen al examen genital o para aquellos asintomáticos, se evaluó la satisfacción de adolescentes con el sistema de autotoma -muestra tomada por el propio paciente- para amplificación de ácidos nucleicos y determinación de infecciones de transmisión sexual (ITS). Material y Método: Se enrolaron 174 mujeres y 117 hombres menores de 25 años sexualmente activos. Las mujeres se realizaron autotoma con tórula vaginal. Los hombres, autotoma de orina de primer chorro. Se aplicó encuesta de satisfacción. Resultados: A 99,3%, le resultó fácil obtener muestras mediante autotoma (IC 95% 0,88-0,98). En mujeres, 79,3% prefirió la autotoma vaginal por sobre el examen pélvico (IC 95% 0,73-0,85). En hombres, 80,3% prefirió la autotoma de orina por sobre el hisopado uretral (IC 95% 0,73-0,87). Si la autotoma estuviera disponible, 89,7% de las mujeres (IC 95% 0,85-0,94) y 93,2% de los hombres (IC 95% 0,89-0,98) estarían dispuestos a someterse a un examen de ITS en forma más seguida. Encontrar fácil la autotoma no se asoció con edad, género, escolaridad ni pobreza. Conclusiones: Chile aún no tiene programas de vigilancia o detección de ITS para jóvenes y adolescentes. Dada la buena aceptabilidad de la autotoma, se podría emplear exitosamente cuando estos programas se implementen.

Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials.

OBJECTIVES: The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. METHODS: Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6. More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. RESULTS: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients were injection-site AEs (pain, swelling, erythema) and vaccine-related systemic AEs (headache, pyrexia). Injection-site AEs were more common in 9vHPV vaccine than qHPV vaccine recipients; most were mild-to-moderate in intensity. Discontinuations and vaccine-related serious AEs were rare (0.1% and <0.1%, respectively). Seven deaths were reported; none were considered vaccine related. The proportions of pregnancies with adverse outcome were within ranges reported in the general population. CONCLUSIONS: The 9vHPV vaccine was generally well tolerated in subjects aged 9 to 26 years with an AE profile similar to that of the qHPV vaccine; injection-site AEs were more common with 9vHPV vaccine. Its additional coverage and safety profile support widespread 9vHPV vaccination.

Coadministration of a 9-Valent Human Papillomavirus Vaccine With Meningococcal and Tdap Vaccines.

BACKGROUND: This study in 11- to 15-year-old boys and girls compared the immunogenicity and safety of GARDASIL 9 (9-valent human papillomavirus [9vHPV] vaccine) administered either concomitantly or nonconcomitantly with 2 vaccines routinely administered in this age group (Menactra [MCV4; Neisseria meningitidis serotypes A/C/Y/W-135] or Adacel [Tdap; diphtheria/tetanus/acellular pertussis]). METHODS: Participants received 9vHPV vaccine at day 1 and months 2 and 6; the concomitant group (n = 621) received MCV4/Tdap concomitantly with 9vHPV vaccine at day 1; the nonconcomitant group (n = 620) received MCV4/Tdap at month 1. Antibodies to HPV-, MCV4-, and Tdap-relevant antigens were determined. Injection-site and systemic adverse events (AEs) were monitored for 15 days after any vaccination; serious AEs were monitored throughout the study. RESULTS: The geometric mean titers for all HPV types in 9vHPV vaccine 4 weeks after dose 3, proportion of subjects with a fourfold rise or greater in titers for 4 N meningitidis serotypes 4 weeks after injection with MCV4, proportion of subjects with antibody titers to diphtheria and tetanus ≥0.1 IU/mL, and geometric mean titers for pertussis antigens 4 weeks after injection with Tdap were all noninferior in the concomitant group compared with the nonconcomitant group. Injection-site swelling occurred more frequently in the concomitant group. There were no vaccine-related serious AEs. CONCLUSIONS: Concomitant administration of 9vHPV vaccine with MCV4/Tdap was generally well tolerated and did not interfere with the antibody response to any of these vaccines. This strategy would minimize the number of visits required to deliver each vaccine individually.

Prevalencia de Chlamydia trachomatis y Neisseria gonorrhoeae en adolescentes chilenas / Rates of Chlamydia trachomatis and Neisseria gonorrhoeae in Chilean adolescents

Background: Chlamydia trachomatis and Neisseria gonorrhoeae are common sexually transmitted diseases among young women and little has been doing to study them in Chilean adolescents. Aim: Determine the rates of C trachomatis and N gonorrhoeae in Chilean young women. Material and methods: Urine samples were obtained from 203 sexually active females under 25 year-old, who attended hospitals from either high or low-income areas in Chile's capital, Santiago. C trachomatis and Ngonorrhoeae were detected by nucleic acid amplification testing. Results: Seven percent of samples were positive for C trachomatis. AU samples were negative for N gonorrhoeae. Among pregnant women, 19 percent of samples were positive for C trachomatis, while non-pregnant women were positive on 5.5 percent (p =0.04). Systematic use of barrier contraception was referring by 12 percent of women. AU of the latter was free of C trachomatis. No association was observing between age, number of sexual partners, age of first sexual intercourse, and presence of uro-gynecological symptoms, socioeconomic status and the rate of C trachomatis. Conclusions: Seven percent of this group of Chilean young women was infected with C trachomatis. The figure rises to 19 percent if pregnant. Surveillance and screening programs should been implemented to prevent sequels on this vulnerable population.

Retroareolar cysts in the adolescent.

BACKGROUND: Retroareolar cysts present in female adolescents with palpable subareolar masses that can have concomitant inflammatory changes. The purpose of this study was to report our cases of retroareolar cysts and thus to contribute to a better knowledge and understanding of this entity. METHODS: Forty-six girls were diagnosed with retroareolar cysts between December 2000 and July 2002. A retrospective chart review is presented with the clinical and ultrasonographic findings. RESULTS: Age at presentation was 10 to 20 years. The reason for consultation was acute mastalgia and inflammation in 31 cases and palpable nodule in 15 cases. Two patients had areolar discharge. Ultrasonographic imaging in the 46 girls showed retroareolar simple cysts, either multiple or bilateral. The cysts had thin walls and were round, oval, or elongated with a variable diameter always less than 20 mm. They had liquid content with an echogenic or calcific sediment. When retroareolar cysts presented with inflammatory changes, antibiotics and nonsteroidal anti-inflammatory drugs were used. Inflammatory changes disappeared in approximately seven days. All patients experienced favorable outcomes. CONCLUSIONS: Retroareolar cysts are a benign form of breast disease in the adolescent. Further investigation is needed to completely understand the pathophysiology, epidemiology, and natural history of this diagnosis.