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Aim: To investigate changes in treatment patterns in extensive-stage small-cell lung cancer (ES-SCLC) in France, Germany, Italy, Spain and the UK (EU5) between 2018 and 2021. Methods: Cross-sectional data from an oncology database were analyzed retrospectively. Results: Of 5832 eligible patients, 88.4% had stage IV disease at diagnosis. Among patients receiving first-line treatment, 91.8% (1079 /1176) received the platinum-etoposide (PE) combination in 2018 which decreased to 42.3% (509/1203) by 2021. Usage of the PE-atezolizumab combination increased from 0 to 41.2% during the same timeframe. Topotecan monotherapy remained the most widely used second-line treatment regardless of patients' platinum sensitivity. Conclusion: The first-line standard of care for ES-SCLC has evolved in EU5 with the PE-atezolizumab/durvalumab combination gradually superseding PE usage.
Lung cancer is the leading cause of cancer-related deaths. Small-cell lung cancer (SCLC) is fast-growing type of lung cancer. New treatments for SCLC using medicines that stimulate the immune system to kill cancer cells (called immunotherapies) have recently been approved for use in Europe. The purpose of the study was to describe the type of treatments that patients received in five European countries before and after the introduction of these new treatments to determine how quickly these new treatments were adopted in a real-world setting. This study found that most patients treated between 2018 and 2020 still received a platinum-based chemotherapy as their first anticancer therapy, but immunotherapies were used more often in later years and became the most common first treatment in 2021 for patients who had never been treated for their cancer. Topotecan, a type of chemotherapy, was the most used treatment for patients whose cancer came back after treatment. There is still a clear unmet need for new, safe and effective therapies for the treatment of patients with SCLC whose cancer comes back again after treatment.
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Awareness of the link between human papillomavirus (HPV) and oral cancer varies across populations. Levels of awareness and factors may impact HPV vaccine uptake in women and the intent to obtain the vaccine in men if it becomes available. A cross-sectional survey of 1415 UK university students (495 men and 920 women) aged 18-25 years was conducted. Women who had and had not received the HPV vaccine were included. Vaccination was not available for men at the time of the survey. Seventy percent of participants had heard of oral cancer but only 25% were aware of the link between HPV and oral cancer. Women who ever engaged in sexual activity (adjusted odds ratio, aOR = 1.74; 95% CI: 1.12-2.72) or had at least one dose of the HPV vaccine (aOR = 1.71; 95% CI: 1.24-2.37) were more likely to be aware. Men who intend to receive the HPV vaccine in the future were more likely to be aware (aOR = 1.62; 95% CI: 1.04-2.53). Non-white women were less likely to be vaccinated (aOR = 0.56; 95% CI: 0.41-0.77). However, being aware was associated with HPV vaccine uptake in women (aOR = 1.65; 95% CI: 1.19-2.28) and borderline associated with the intent to obtain the HPV vaccine in men (aOR = 1.52; 95% CI: 0.99-2.35). Non-heterosexual men were more willing than heterosexuals to receive the vaccine. Following the UK gender-neutral HPV vaccination programme, there is an opportunity to increase awareness about the link between HPV and oral cancers aside from the cervical cancer link to influence HPV vaccine uptake.
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Alphapapillomavirus , Neoplasias de la Boca , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Adolescente , Adulto , Estudios Transversales , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Neoplasias de la Boca/prevención & control , Papillomaviridae , Infecciones por Papillomavirus/prevención & control , Estudiantes , Encuestas y Cuestionarios , Reino Unido/epidemiología , Universidades , Vacunación , Adulto JovenRESUMEN
Aim: There is a growing body of data on real-world use of talimogene laherparepvec (T-VEC). We aimed to characterize real-world T-VEC use using a nationally representative German prescription database covering 60% of prescriptions reimbursed. Patients & methods: A retrospective analysis was conducted using the German IMS® LRx prescription database, analyzing patients aged ≥18 years with an initial T-VEC prescription at 106 plaque-forming units (PFU)/ml and ≥1 subsequent prescription at 108 PFU/ml. Median time on T-VEC treatment, patient characteristics and patterns of T-VEC use were described. Results: Of 127 patients prescribed T-VEC, 72 patients (57%) met study criteria. About two-thirds of these patients initiated T-VEC in 2017. Median age at T-VEC initiation was 74 years (range: 44 to 91). Most prescriptions (88%) were dispensed from hospitals. At study end, 26 (36%) patients remained on T-VEC; 46 (64%) had ended treatment. Median duration of T-VEC treatment for all patients was 18.7 weeks (95% CI: 15.3-26.9) and was longer among those who initiated treatment in 2017 versus 2016 (26.7 vs 15.6 weeks, respectively). Median volume administered for the first 106 PFU/ml and second 108 PFU/ml was 4 ml; the volume decreased for subsequent administrations (2 ml by the eighth administration and 1 ml by the 16th administration). Conclusion: This real-world prescription database study showed that patients who initiated treatment in 2017 had a treatment duration in clinical practice that corresponded with the European Summary of Product Characteristics guideline of continuing T-VEC for ≥6 months. Additional long-term data linking drug use with clinical outcomes are needed.
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Productos Biológicos , Herpesvirus Humano 1 , Viroterapia Oncolítica/métodos , Viroterapia Oncolítica/estadística & datos numéricos , Virus Oncolíticos , Adulto , Anciano , Anciano de 80 o más Años , Productos Biológicos/uso terapéutico , Terapia Combinada , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Estimación de Kaplan-Meier , Masculino , Melanoma/epidemiología , Melanoma/terapia , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Oropharyngeal cancer incidence is rapidly rising due to human papillomavirus (HPV) type 16 infection. The dearth of data on effectiveness of national female-only vaccination programs in preventing oral HPV infection and potential herd immunity in unvaccinated males has resulted in considerable controversy regarding the need to vaccinate males, especially in countries with high female vaccination coverage. METHODS: Subjects aged 0-65 years undergoing tonsillectomy for nonmalignant indications were recruited in 6 hospitals in the United Kingdom. Oral samples were collected as follows: oral rinse, tongue base, and pharyngeal wall brushes, then tonsil tissue (tonsillectomy). Vaccination data were obtained from regional health authorities. All samples were centrally tested for HPV DNA by polymerase chain reaction. RESULTS: Of 940 subjects, 243 females and 69 males were aged 12-24 years (median age, 18.6 years), with 189 (78%) females and no males vaccinated against HPV. Overall, oropharyngeal HPV-16 prevalence was significantly lower in vaccinated versus unvaccinated females (0.5% vs 5.6%, P = .04). In contrast, prevalence of any oropharyngeal HPV type was similar in vaccinated and unvaccinated females (19% vs 20%, P = .76). Oropharyngeal HPV-16 prevalence in unvaccinated males was similar to vaccinated females (0% vs 0.5%, P > .99), and lower than unvaccinated females (0% vs 5.6%, P = .08). CONCLUSIONS: Our findings indicate that the UK female-only vaccination program is associated with significant reductions in oropharyngeal HPV-16 infections. These are also the first data to suggest potential herd immunity from female-only vaccination against oropharyngeal HPV infection in contemporaneously aged males.
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Papillomavirus Humano 16/inmunología , Inmunidad Colectiva , Programas de Inmunización , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/inmunología , Vacunación , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/virología , Prevalencia , Reino Unido/epidemiología , Adulto JovenRESUMEN
Monitoring therapy response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with novel hormonal therapies, taxanes, and newly approved therapies is crucial for optimizing treatment. [68Ga]Ga-prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computed tomography (PSMA PET/CT) is a promising target for managing treatment in patients with prostate cancer. PSMA is overexpressed in patients with mCRPC; understanding how expression might change in patients undergoing treatment could determine its potential for guiding clinical decisions. We examined PSMA expression in patients with CRPC and compared PET/CT response with prostate-specific antigen (PSA) variation as a prognostic factor for progression-free survival and overall survival (PFS and OS, respectively). Methods: This was a single-center, retrospective observational cohort study in patients with CRPC enrolled in the PSMA-PROSTATA registry study (EudraCT: 2015-004589-27). A first and second (if applicable) PSMA PET/CT were performed to determine PSMA expression (absence or presence). PET/CT response was assessed as responders (patients with stable disease, partial or complete response) versus nonresponders (patients with progressive disease) by comparing the first with the second PET/CT. PSA variation (increase or decrease from baseline) was assessed across the same time period. PFS was defined as the time between second PET/CT and PSA recurrence or evidence of radiologic progression. Results: Overall, 160 patients with CRPC were included in the analysis. At first PET/CT, nearly all (n = 152; 95.0%) patients had PSMA expression (classified as mCRPC), irrespective of prior systemic therapy. SUVmax was positively associated with baseline PSA levels and velocity (both P < 0.001). According to PET/CT response, median SUVmax on first PET/CT was numerically lower in nonresponders than in responders (17.5 vs. 20.4; P = 0.127). Similarly, patients with a PSA increase had significantly lower median SUVmax on first PET/CT (15.8) than did those with a PSA decrease (30.4; P = 0.018). PSA change was, on average, 146% in nonresponders and -57% in responders between first and second PET/CT (P < 0.001). Agreement between PET/CT and PSA response was 79% (k = 0.553, P < 0.001). Among the 63 patients included in PFS/OS analyses, 76.2% had a relapse and 36.5% died before 24-mo follow-up; median PFS and OS were 6.1 and 24 mo, respectively. PET/CT response, independent of PSA variation, was a significant prognostic factor for PFS. OS was not significantly different between PET/CT responders and nonresponders. Conclusion: PSMA PET/CT may be a useful imaging method predictive of treatment response in patients with mCRPC, regardless of ongoing systemic therapy. Data also suggest that response assessed by PET/CT is a potentially more significant prognostic factor than PSA for PFS. Further studies are needed to understand the potential involvement of PSMA expression on survival.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Antígeno Prostático Específico/metabolismo , Estudios Retrospectivos , Próstata/patología , Recurrencia Local de Neoplasia , Resultado del Tratamiento , Radioisótopos de Galio/uso terapéuticoRESUMEN
OBJECTIVES: We aimed to characterize the advanced NSCLC population in terms of KRAS G12C prevalence, patient characteristics, and survival outcomes after the introduction of immunotherapies. MATERIALS AND METHODS: We identified adult patients diagnosed with advanced NSCLC between January 1, 2018 and June 30, 2021 using the Danish health registries. Patients were grouped by mutational status (any KRAS mutation, KRAS G12C, and KRAS/EGFR/ALK wildtype [Triple WT]). We analyzed KRAS G12C prevalence, patient and tumor characteristics, treatment history, time-to-next-treatment (TTNT), and overall survival (OS). RESULTS: We identified 7,440 patients of whom 40% (n = 2,969) were KRAS tested prior to the first line of therapy (LOT1). Among the KRAS tested, 11% (n = 328) harbored KRAS G12C. More KRAS G12C patients were women (67%), smokers (86%), had a high (≥50%) level of PD-L1 expression (54%), and more frequently received anti-PD-L1 treatment than any other group. From the date of the mutational test result, OS (7.1-7.3 months) was similar between the groups. OS from LOT1 (14.0 months) and LOT2 (10.8 months), and TTNT from LOT1 (6.9 months) and LOT2 (6.3 months) was numerically longer for the KRAS G12C mutated group compared to any other group. However, from LOT1 and LOT2, the OS and TTNT were comparable when stratifying the groups by PD-L1 expression level. Regardless of the mutational group, OS was markedly longer for patients with high PD-L1 expression. CONCLUSION: In patients diagnosed with advanced NSCLC after the implementation of anti-PD-1/L1 therapies, the survival in KRAS G12C mutated patients is comparable to patients with any KRAS mutation, Triple WT, and all NSCLC patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Adulto , Humanos , Femenino , Masculino , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Mutación , Dinamarca/epidemiología , Antígeno B7-H1/metabolismoRESUMEN
BACKGROUND: Real-world data on demographics related to KRAS mutation subtypes are crucial as targeted drugs against the p.G12C variant have been approved. METHOD: We identified 6183 NSCLC patients with reported NGS-based KRAS status in the Swedish national lung cancer registry between 2016 and 2019. Following exclusion of other targetable drivers, three cohorts were studied: KRAS-G12C (n = 848), KRAS-other (n = 1161), and driver negative KRAS-wild-type (wt) (n = 3349). RESULTS: The prevalence of KRAS mutations and the p.G12C variant respectively was 38%/16% in adenocarcinoma, 28%/13% in NSCLC-NOS and 6%/2% in squamous cell carcinoma. Women were enriched in the KRAS-G12C (65%) and KRAS-other (59%) cohorts versus KRAS-wt (48%). A high proportion of KRAS-G12C patients in stage IV (28%) presented with CNS metastasis (vs. KRAS-other [19%] and KRAS-wt [18%]). No difference in survival between the mutation cohorts was seen in stage I-IIIA. In stage IV, median overall survival (mOS) from date of diagnosis was shorter for KRAS-G12C and KRAS-other (5.8 months/5.2 months) vs. KRAS wt (6.4 months). Women had better outcome in the stage IV cohorts, except in KRAS-G12C subgroup where mOS was similar between men and women. Notably, CNS metastasis did not impact survival in stage IV KRAS-G12C, but was associated with poorer survival, as expected, in KRAS-other and KRAS-wt. CONCLUSION: The KRAS p.G12C variant is a prevalent targetable driver in Sweden and significantly associated with female sex and presence of CNS metastasis. We show novel survival effects linked to KRAS p.G12C mutations in these subgroups with implications for clinical practice.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Masculino , Femenino , Humanos , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Suecia/epidemiología , Proteínas Proto-Oncogénicas p21(ras)/genética , Mutación/genética , Sistema de Registros , DemografíaRESUMEN
BACKGROUND: Chronic hepatitis C (HCV) disease can be complicated with comorbid conditions that may impact treatment eligibility and outcomes. The aim of the study was to systematically review comorbidities and symptoms in an HCV infected population, specifically assessing comorbidities associated with HCV anti-viral treatment and disease, as well as comparing comorbidities between an HCV infected and uninfected control population. METHODS: This was a retrospective cohort study within a United States medical claims database among patients with chronic HCV designed to estimate the two-year period prevalence of comorbidities. Patients with two HCV diagnosis codes, 24 months of continuous health insurance coverage, and full medical and pharmacy benefits were included. RESULTS: Among a chronic HCV cohort of 7411 patients, at least one comorbid condition was seen in almost all patients (> 99%) during the study period. HCV-infected patients reported almost double the number of comorbidities compared to uninfected controls. Of the 25 most common comorbidities, the majority of the comorbidities (n = 22) were known to be associated with either HCV antiviral treatment or disease. The five most frequent comorbidities were liver disease [other] (37.5%), connective tissue disease (37.5%), abdominal pain (36.1%), upper respiratory infections (35.6%), and lower respiratory disease (33.7%). Three notable comorbidities not known to be associated with antiviral treatment or disease were benign neoplasms (24.3%), genitourinary symptoms & ill-defined conditions (14.8%), and viral infections (13.8%). CONCLUSIONS: This US medically insured HCV population is highly comorbid. Effective strategies to manage these comorbidities are necessary to allow wider access to HCV treatment and reduce the future burden of HCV disease and its manifestations.
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Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Malaria is the leading cause of morbidity and mortality in post-conflict Burundi. To counter the increasing challenge of anti-malarial drug resistance and improve highly effective treatment Burundi adopted artesunate-amodiaquine (AS-AQ) as first-line treatment for uncomplicated Plasmodium falciparum malaria and oral quinine as second-line treatment in its national treatment policy in 2003. Uptake of this policy in the public, private and non-governmental (NGO) retail market sectors of Burundi is relatively unknown. This study was conducted to evaluate access to national policy recommended anti-malarials. METHODS: Adapting a standardized methodology developed by Health Action International/World Health Organization (HAI/WHO), a cross-sectional survey of 70 (24 public, 36 private, and 10 NGO) medicine outlets was conducted in three regions of Burundi, representing different levels of transmission of malaria. The availability on day of the survey, the median prices, and affordability (in terms of number of days' wages to purchase treatment) of AS-AQ, quinine and other anti-malarials were calculated. RESULTS: Anti-malarials were stocked in all outlets surveyed. AS-AQ was available in 87.5%, 33.3%, and 90% of public, private, and NGO retail outlets, respectively. Quinine was the most common anti-malarial found in all outlet types. Non-policy recommended anti-malarials were mainly found in the private outlets (38.9%) compared to public (4.2%) and NGO (0%) outlets. The median price of a course of AS-AQ was US$0.16 (200 Burundi Francs, FBu) for the public and NGO markets, and 3.5-fold higher in the private sector (US$0.56 or 700 FBu). Quinine tablets were similarly priced in the public (US$1.53 or 1,892.50 FBu), private and NGO sectors (both US$1.61 or 2,000 FBu). Non-policy anti-malarials were priced 50-fold higher than the price of AS-AQ in the public sector. A course of AS-AQ was affordable at 0.4 of a day's wage in the public and NGO sectors, whereas, it was equivalent to 1.5 days worth of wages in the private sector. CONCLUSIONS: AS-AQ was widely available and affordable in the public and NGO markets of hard-to-reach post-conflict communities in Burundi. However greater accessibility and affordability of policy recommended anti-malarials in the private market sector is needed to improve country-wide policy uptake.
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Amodiaquina/uso terapéutico , Antimaláricos/uso terapéutico , Artemisininas/uso terapéutico , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/epidemiología , Quinina/uso terapéutico , Burundi/epidemiología , Estudios Transversales , Combinación de Medicamentos , Utilización de Medicamentos/estadística & datos numéricos , Política de Salud , HumanosRESUMEN
INTRODUCTION: Talimogene laherparepvec (T-VEC; IMLYGIC®, Amgen Inc.) is an oncolytic immunotherapy approved in Europe for the treatment of unresectable metastatic melanoma (stage IIIB-IVM1a). This study characterised real-world use of T-VEC in four European countries. METHODS: Data on demographics, treatment pattern, safety, and clinical effectiveness were examined in a retrospective chart review of patients with stage IIIB-IVM1a unresectable melanoma treated with T-VEC in surgical (the Netherlands) and medical (Austria, Germany, UK) oncology settings. RESULTS: Overall, 66 patients were included (the Netherlands: n = 31; Austria, Germany, UK: n = 35). The median age was 69 years and 59.1% were female. At the time of T-VEC initiation, 47 patients (71.2%) had stage IIIB/C disease; of these, 30 were from the Netherlands. Although 72.7% patients overall received T-VEC as first-line therapy, this was higher in the Netherlands than the other countries (93.5% vs 54.3%). Of the 47 patients who discontinued T-VEC, 26 (55.3%) had no remaining injectable lesions (potentially indicating complete response); 20/26 of these patients were from the Netherlands. One patient discontinued T-VEC due to toxicity. CONCLUSION: This study is the first comprehensive multinational evaluation of the use of T-VEC to treat unresectable stage IIIB/C-IVM1a melanoma in real-world clinical practice in Europe. The differences between European countries were apparent, with physicians in the Netherlands using T-VEC in patients with earlier advanced disease stage and in the first-line setting compared with other countries.
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Melanoma , Viroterapia Oncolítica , Anciano , Productos Biológicos , Europa (Continente) , Femenino , Alemania , Herpesvirus Humano 1 , Humanos , Masculino , Melanoma/terapia , Países Bajos , Estudios RetrospectivosRESUMEN
BACKGROUND: Calcimimetic treatment of secondary hyperparathyroidism in chronic dialysis patients is often followed by hypocalcemia. METHODS: We investigated the frequency, predictors, consequences and therapeutic responses following cinacalcet-induced hypocalcemia in an incident European hemodialysis cohort of 1068 patients with a cinacalcet prescription. RESULTS: Of 905 normocalcemic patients initiating cinacalcet, 67% developed hypocalcemia within 12 months: 68% mild, 23% moderate, 9% severe. Compared to persistently normocalcemic patients, those with severe hypocalcemia were more often diabetic, overweight, had cardiovascular disease, shorter dialysis vintage, used a catheter dialysis access, had fewer active vitamin-D sterols, and exhibited higher CRP and iPTH and lower calcium levels. Multivariate predictors of hypocalcemia included a catheter for vascular access, low albumin and high iPTH. Generally, no therapeutic intervention to prevent hypocalcemia was taken prior to cinacalcet initiation. After the hypocalcemic event, the most common clinical response was no change of the dialysis or medical regimen. Following the hypocalcemic event, iPTH remained low even in those with severe hypocalcemia. The number of deaths and cardiovascular events did not differ between patients with and without hypocalcemia within six months following cinacalcet initiation. CONCLUSION: Two-thirds of cinacalcet initiated patients experienced hypocalcaemia with 9% being severe. Hypocalcemia was mostly asymptomatic, transient (with and without targeted intervention to correct it) and not associated with an increase in cardiovascular events or deaths.
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Cinacalcet , Hiperparatiroidismo Secundario , Hipocalcemia , Diálisis Renal , Anciano , Calcio/sangre , Cinacalcet/administración & dosificación , Cinacalcet/efectos adversos , Europa (Continente)/epidemiología , Femenino , Humanos , Hiperparatiroidismo Secundario/sangre , Hiperparatiroidismo Secundario/tratamiento farmacológico , Hipocalcemia/inducido químicamente , Hipocalcemia/epidemiología , Masculino , Persona de Mediana Edad , Hormona Paratiroidea , Diálisis Renal/estadística & datos numéricosRESUMEN
OBJECTIVES: To identify the gaps of knowledge and highlight the challenges and opportunities for controlling cervical cancer in sub-Saharan Africa (SSA). METHODS: A comprehensive review of peer-reviewed literature to summarize the epidemiological data on human papillomavirus (HPV) and invasive cervical cancer (ICC) by HIV status, to review feasible and effective cervical screening strategies, and to identify barriers in the introduction of HPV vaccination in SSA. RESULTS: ICC incidence in SSA is one of the highest in the world with an age-standardized incidence rate of 31.0 per 100,000 women. The prevalence of HPV16/18, the two vaccine preventable-types, among women with ICC, does not appear to differ by HIV status on a small case series. However, there are limited data on the role of HIV in the natural history of HPV infection in SSA. Cervical screening coverage ranges from 2.0% to 20.2% in urban areas and 0.4% to 14.0% in rural areas. There are few large scale initiatives to introduce population-based screening using cytology, visual inspection or HPV testing. Only one vaccine safety and immunogenicity study is being conducted in Senegal and Tanzania. Few data are available on vaccine acceptability, health systems preparedness and vaccine cost-effectiveness and long-term impact. CONCLUSIONS: Additional data are needed to strengthen ICC as a public health priority to introduce, implement and sustain effective cervical cancer control in Africa.
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Infecciones por VIH/complicaciones , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Adolescente , Adulto , África del Sur del Sahara/epidemiología , Anciano , Niño , Femenino , Conductas Relacionadas con la Salud , Humanos , Incidencia , Tamizaje Masivo , Persona de Mediana Edad , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/virología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Adulto JovenRESUMEN
INTRODUCTION: Talimogene laherparepvec is a first-in-class oncolytic immunotherapy for intratumoral injection with proven efficacy and tolerability in patients with unresectable early metastatic melanoma (stage IIIB-IVM1a) in the pivotal phase III OPTiM study. The objective was to characterize melanoma patients treated with talimogene laherparepvec in routine clinical practice in Germany. METHODS: A retrospective chart review was conducted in unresectable stage IIIB-IVM1a melanoma patients. Data on demographics, disease and medical history, and use of talimogene laherparepvec were collected. A survey was also conducted to understand physician treatment decisions. RESULTS: Data for 27 patients who initiated talimogene laherparepvec between June 2016 and July 2017 were analyzed (median age 68; stage IIIB/C disease 56%). All patients had prior surgery, and over half had repeated resections for recurrent disease (median 3). Overall, 48% of patients received at least one prior local treatment, mainly radiation therapy or electrochemotherapy. Talimogene laherparepvec was first-line systemic therapy in 63% of patients. The most frequent prior systemic treatment was immunotherapy (7/27 patients). At end of follow-up, 13 patients were still on talimogene laherparepvec and 14 patients had discontinued treatment. Among those who discontinued, 8 (57%) did not receive subsequent systemic therapy. Only one patient receiving first-line talimogene laherparepvec received a subsequent systemic therapy. Three patients stopped treatment because of no remaining injectable lesions. Median treatment duration was 22.1 weeks overall and 27.9 weeks in stage IIIB/C disease patients. Nearly all cutaneous lesions (93%) were injected with talimogene laherparepvec compared to subcutaneous (83%) and nodal lesions (77%). No new safety signals were reported. The main reasons given in the physician survey for treating with talimogene laherparepvec were good tolerability, overall efficacy, and lack of contraindications. CONCLUSION: Talimogene laherparepvec is now included as a routine treatment option for unresectable early metastatic melanoma in Germany. This study characterizes the first patients treated with talimogene laherparepvec in Europe and confirms the good tolerability observed in clinical trials. TRIAL REGISTRATION: EUPAS registry, EUPAS17410. FUNDING: Amgen Inc.
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Antineoplásicos Inmunológicos/uso terapéutico , Productos Biológicos/uso terapéutico , Melanoma/tratamiento farmacológico , Viroterapia Oncolítica/métodos , Anciano , Femenino , Estudios de Seguimiento , Alemania , Herpesvirus Humano 1 , Humanos , Inmunoterapia/métodos , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
In 2012, Colombia implemented a school-based HPV vaccination program of a 3-dose series for nine year old girls. Following a mass psychogenic response after vaccination in a Colombian town, vaccination rates dropped from 80% in 2012-2013 to 5% in 2016. The study aimed to identify barriers and facilitators of HPV vaccine uptake among girls eligible for vaccination in the initial years of vaccine implementation from 2012 to 2014, and their parents. We conducted 19 individual qualitative interviews and 18 focus groups with an average of 5 girls, in Manizales, Colombia between 2016 and 2017. In total, 49 girls from six schools and 58 of their parents participated in the study. Participants had some degree of awareness about cervical cancer, especially among those of middle and upper socioeconomic level. However, the vaccine was known as a prevention measure only after pap-smears and condoms. The main facilitator for vaccine uptake for parents was the desire to prevent diseases in general and for girls, it was facilitated by receiving positive information about the vaccine. The main barriers for vaccine uptake or for three doses completion were the event in Carmen de Bolivar, fear of adverse effects and fear of needles. Girls and parents stated that they received little or no information from schools or health care services about the HPV vaccine prior to vaccination. Our results suggest that improving HPV vaccination rates in Colombia will require a comprehensive education program including mass media information about HPV vaccine.
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BACKGROUND & AIMS: Complications of HCV infection are primarily related to the development of advanced fibrosis and whether cannabis use is a risk factor for more severe fibrosis is controversial. METHODS: Baseline data from a prospective cohort study of 204 persons with chronic HCV infection were used for analysis. The outcome was fibrosis score on biopsy, and the primary predictor evaluated was daily cannabis use. RESULTS: The median age of the cohort was 46.8 years, 69.1% were male, 49.0% were white, and the presumed route of infection was injection drug use in 70.1%. The median lifetime duration and average daily use of alcohol were 29.1 years and 1.94 drink equivalents per day, respectively. Cannabis use frequency (within prior 12 months) was daily in 13.7%, occasional in 45.1%, and never in 41.2%. Fibrosis stage, assessed by the Ishak method, was F0, F1-2, and F3-6 in 27.5%, 55.4%, and 17.2% of subjects, respectively. Daily compared with non-daily cannabis use was significantly associated with moderate to severe fibrosis (F3-6 vs F1-2) in univariate (odds ratio [OR], 3.21; 95% confidence interval [CI], 1.20-8.56, P = .020) and multivariate analyses (OR, 6.78; 95% CI, 1.89-24.31, P = .003). Other independent predictors of F3-6 were >or=11 portal tracts (compared with <5, OR, 6.92; 95% CI, 1.34-35.7, P = .021) and lifetime duration of moderate to heavy alcohol use (OR per decade, 1.72; 95% CI, 1.02-2.90, P = .044). CONCLUSIONS: Daily cannabis use is strongly associated with moderate to severe fibrosis, and HCV-infected individuals should be counseled to reduce or abstain from cannabis use.
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Hepatitis C Crónica/epidemiología , Cirrosis Hepática/patología , Fumar Marihuana/epidemiología , Índice de Severidad de la Enfermedad , Adulto , Consumo de Bebidas Alcohólicas/epidemiología , Biopsia , California/epidemiología , Femenino , Humanos , Hígado/patología , Cirrosis Hepática/epidemiología , Masculino , Fumar Marihuana/efectos adversos , Persona de Mediana Edad , Análisis Multivariante , Estudios ProspectivosRESUMEN
BACKGROUND: Health equality is increasingly being considered alongside overall health gain when assessing public health interventions. However, the trade-off between the direct effects of vaccination and herd immunity could lead to unintuitive consequences for the distribution of disease burden within a population. We used a transmission dynamic model of human papillomavirus (HPV) to investigate the effect of ethnic disparities in vaccine and cervical screening uptake on inequality in disease incidence in England. METHODS: We developed an individual-based model of HPV transmission and disease, parameterising it with the latest data for sexual behaviour (from National Survey of Sexual Attitudes and Lifestyles [Natsal-3]) and vaccine and screening uptake by ethnicity (from Public Health England [PHE]) and fitting it to data for HPV prevalence (from ARTISTIC, PHE, Natsal-3) and HPV-related disease incidence (from National Cancer Registry [ONS]). The outcome of interest was the age-adjusted incidence of HPV-related cancer (both cervical and non-cervical) in all women in England in view of differences and changes in vaccination and screening uptake by ethnicity in England, over time. We also studied three potential public health interventions aimed at reducing inequality in HPV-related disease incidence: increasing uptake in black and Asian females to match that in whites for vaccination; cervical screening in women who turn 25 in 2018 or later; and cervical screening in all ages. FINDINGS: In the pre-vaccination era, before 2008, women from ethnic minorities in England reported a disproportionate share of cervical disease. Our model suggests that Asian women were 1·7 times (95% credibility interval [CI] 1·1-2·7) more likely to be diagnosed with cervical cancer than white women (22·8 vs 13·4 cases per 100â000 women). Because HPV vaccination uptake is lower in ethnic minorities, we predict an initial widening of this gap, with cervical cancer incidence in Asian women up to 2·5 times higher (95% CI 1·3-4·8) than in white women 20 years after vaccine introduction (corresponding to an additional 10·8 [95% CI 10·1-11·5] cases every year). In time, we predict that herd immunity benefits will diffuse from the larger white sub-population and the disparity will narrow. Increased cervical screening uptake in vaccinated women from ethnic minorities would lead to rapid improvement in equality with parity in incidence after 20 years of HPV vaccination. INTERPRETATION: Our study suggests that the introduction of HPV vaccination in England will initially widen a pre-existing disparity in the incidence of HPV-related cancer by ethnicity, partly due to herd immunity disproportionately benefiting subgroups with high vaccination rates. Although in time this induced disparity will narrow, increasing cervical screening uptake in girls from ethnic minorities should be encouraged to eliminate the inequality in cervical cancer incidence in the medium term. We recommend that dynamic effects should be considered when estimating the effect of public health programmes on equality. FUNDING: Cancer Research UK.
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Detección Precoz del Cáncer/estadística & datos numéricos , Etnicidad/estadística & datos numéricos , Disparidades en el Estado de Salud , Vacunas contra Papillomavirus/administración & dosificación , Neoplasias del Cuello Uterino/etnología , Adolescente , Adulto , Niño , Inglaterra/epidemiología , Femenino , Humanos , Programas de Inmunización , Incidencia , Persona de Mediana Edad , Modelos Estadísticos , Evaluación de Programas y Proyectos de Salud , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
Human papillomavirus (HPV) vaccination elicits high-titer genotype-specific antibody responses that are associated with a reduced risk of cervical disease caused by vaccine-incorporated genotypes. Our objective was to evaluate dried blood spots (DBSs) and oral mucosal transudate (OMT) as alternative samples to serum to confirm HPV vaccine antibody status. A study was carried out to evaluate the feasibility of detecting HPV16 and HPV18 antibodies in OMT, DBSs, and sera among women who self-reported being unvaccinated or fully vaccinated with the HPV vaccine. Serum had the highest sensitivity (100%) for detection of antibodies against both HPV16 and HPV18 but the lowest specificity, due to the detection of natural infection antibodies in 16% of unvaccinated women. Conversely, DBSs and OMT had lower sensitivity (96% and 82%, respectively) but high specificity (98%). We confirmed that these antibodies were functional (i.e., neutralizing) and that their detection was quantitatively reproducible and well correlated between sample types when normalized to IgG content. DBSs and OMT are appropriate alternative sample types for HPV vaccine surveillance. These alternative sample types warrant consideration for the purposes of cervical screening, diagnosis, and management, but more work will be needed to establish the stringent parameters required for such application.IMPORTANCE Human papillomavirus (HPV) is the causative agent of cervical and other anogenital cancers. HPV vaccination, primarily targeted at young girls before the age of sexual debut, is starting to demonstrate population-level declines in HPV infection and early disease associated with vaccine-incorporated genotypes. Monitoring young women for vaccine-specific antibody is important for vaccine surveillance and may be useful as an adjunct test within a cervical screening context. We evaluated serum, dried blood spots, and oral fluid as potential samples for such applications and report robust measures of diagnostic accuracy. This is the first time a direct comparison of alternative sample types has been made between vaccinated and unvaccinated women for the detection and quantitation of HPV antibodies.
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Anticuerpos Antivirales/análisis , Anticuerpos Antivirales/sangre , Desecación , Mucosa Bucal/inmunología , Infecciones por Papillomavirus/diagnóstico , Manejo de Especímenes/métodos , Monitoreo Epidemiológico , Humanos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The magnitude of the growing burden of oropharyngeal cancers (OPC), a sub-set of head and neck cancers (HNC), is unknown in England. METHODS: Data were extracted from population-based cancer registries in England. The burden of HNC overall and by anatomic site was described from 1995 to 2011. Projections of future rates up to 2025 were estimated using flexible age-period-cohort modelling. RESULTS: HNC increased by 59% between 1995 and 2011 in England. Projections indicate that the number of HNC cases will increase by 55% from 2011, totalling 11,748 new cases in 2025, ranking HNC as the sixth most common cancer. Of the anatomic sites, OPC is projected to account for 35% of HNC with the largest rate increase (annual percentage change, +7.3% for men and +6.2% for women between 2011 and 2025), predominantly affecting males <60years. This projected burden is equivalent to a 239% increase in number of OPC cases. Incidence of the oral cavity, salivary glands and palate are projected to rise at lower rates, whereas rates of the nasopharynx, hypopharynx and larynx remain relatively stable or decreasing. CONCLUSION: The substantial recent and predicted future significant increase in OPC highlights the need for prioritising the provision of cancer services for the considerable burden of OPC patients and survivors and cancer control strategies.
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Neoplasias Orofaríngeas/epidemiología , Inglaterra/epidemiología , Predicción , Humanos , Sistema de RegistrosRESUMEN
Malaria remains the leading burden of disease in post-conflict Sierra Leone. To overcome the challenge of anti-malarial drug resistance and improve effective treatment, Sierra Leone adopted artemisinin-combination therapy artesunate-amodiaquine (AS+AQ) as first-line treatment for uncomplicated P. falciparum malaria. Other national policy anti-malarials include artemether-lumefantrine (AL) as an alternative to AS+AQ, quinine and artemether for treatment of complicated malaria; and sulphadoxine-pyrimethamine (SP) for intermittent preventive treatment (IPTp). This study was conducted to evaluate access to national policy recommended anti-malarials. A cross-sectional survey of 127 medicine outlets (public, private and NGO) was conducted in urban and rural areas. The availability on the day of the survey, median prices, and affordability policy and available non-policy anti-malarials were calculated. Anti-malarials were stocked in 79% of all outlets surveyed. AS+AQ was widely available in public medicine outlets; AL was only available in the private and NGO sectors. Quinine was available in nearly two-thirds of public and NGO outlets and over one-third of private outlets. SP was widely available in all outlets. Non-policy anti-malarials were predominantly available in the private outlets. AS+AQ in the public sector was widely offered for free. Among the anti-malarials sold at a cost, the same median price of a course of AS+AQ (US$1.56), quinine tablets (US$0.63), were found in both the public and private sectors. Quinine injection had a median cost of US$0.31 in the public sector and US$0.47 in the private sector, while SP had a median cost of US$0.31 in the public sector compared to US$ 0.63 in the private sector. Non-policy anti-malarials were more affordable than first-line AS+AQ in all sectors. A course of AS+AQ was affordable at nearly two days' worth of wages in both the public and private sectors.
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Antimaláricos/uso terapéutico , Malaria/tratamiento farmacológico , Amodiaquina/administración & dosificación , Antimaláricos/economía , Artemisininas/administración & dosificación , Artesunato , Costos de los Medicamentos , Geografía , Política de Salud , Accesibilidad a los Servicios de Salud , Humanos , Malaria/prevención & control , Organizaciones sin Fines de Lucro , Farmacias , Pobreza , Sector Privado , Sector Público , Sierra LeonaRESUMEN
BACKGROUND: The independent role of tobacco smoking in invasive cervical cancer (ICC) has been established. We evaluated the potential impact of passive smoking (PS). METHODS: A pooled analysis of 1,919 couples enrolled in one of seven case-control studies involving cervical carcinoma in situ (CIS) or ICC was investigated. Information on smoking and sexual behavior was collected from interviews. Specimens were taken from the cervix and penis for human papillomavirus (HPV) DNA testing. Three PS risk models were constructed with all couples, couples with monogamous women, and couples with lifetime nonsmoking monogamous women. For the third model, the analysis considered potential misclassification of smoking status and was restricted to the risk period for which the woman was exposed to both HPV, a necessary cause of ICC, and PS. Multivariable unconditional logistic regression was used to estimate associations between CIS or ICC and PS. RESULTS: An increased risk was found among couples with both ever smoking men and women (OR = 2.26; 95% CI: 1.40-3.64). No statistically increased risk of CIS was found with PS in the models analyzed. Similar significant increased risks of ICC with PS was found among all couples (OR = 1.57; 95% CI: 1.15-2.15) and couples with monogamous women (OR = 1.55; 95% CI: 1.07-2.23) but not among lifetime nonsmoking monogamous women married to ever smoking men. CONCLUSION: PS could not be detected as an independent risk factor of ICC in the absence of active smoking. IMPACT: The combined effects of exposure to active and PS suggest its potential adverse role in cervical carcinogenesis.