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Despite novel therapeutic strategies, advanced-stage prostate cancer (PCa) remains highly lethal, pointing out the urgent need for effective therapeutic strategies. While dysregulation of the splicing process is considered a cancer hallmark, the role of certain splicing factors remains unknown in PCa. This study focuses on characterizing the levels and role of SRSF6 in this disease. Comprehensive analyses of SRSF6 alterations (copy number/mRNA/protein) were conducted across eight well-characterized PCa cohorts and the Hi-MYC transgenic model. SRSF6 was up-regulated in PCa samples, correlating with adverse clinical parameters. Functional assays, both in vitro (cell proliferation, migration, colony, and tumorsphere formation) and in vivo (xenograft tumors), demonstrated the impact of SRSF6 modulation on critical cancer hallmarks. Mechanistically, SRSF6 regulates the splicing pattern of the histone-chaperone HIRA, consequently affecting the activity of H3.3 in PCa and breast cancer cell models and disrupting pivotal oncogenic pathways (AR and E2F) in PCa cells. These findings underscore SRSF6 as a promising therapeutic target for PCa/advanced-stage PCa.
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Chaperonas de Histonas , Neoplasias da Próstata , Fatores de Processamento de Serina-Arginina , Humanos , Fatores de Processamento de Serina-Arginina/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Animais , Linhagem Celular Tumoral , Chaperonas de Histonas/metabolismo , Chaperonas de Histonas/genética , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Regulação Neoplásica da Expressão Gênica , Camundongos , Splicing de RNA , Proliferação de Células , Histonas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , FosfoproteínasRESUMO
PURPOSE: Cancer Immunotherapy Trials Network 12 demonstrated safety of pembrolizumab in treating advanced cancer in people with HIV. Here, we report results of the Kaposi sarcoma (KS) cohort. METHODS: In this multicenter phase I trial, we enrolled participants with HIV-associated KS on antiretroviral therapy with CD4+ ≥50 cells/µL and HIV plasma RNA <200 copies/mL. Pembrolizumab 200 mg intravenously was administered once every 3 weeks for up to 35 cycles. The primary end point was safety, and the secondary end point was KS response by modified AIDS Clinical Trials Group Criteria. RESULTS: Thirty-two cisgender men enrolled with baseline median CD4+ T-cell count of 274 cells/µL. All but nine participants had received previous systemic KS therapy. Participants received a median of 11 cycles of pembrolizumab (range, 1-35). Sixty-six percent had grade ≥1 treatment-emergent adverse events, including one death from polyclonal KS herpesvirus-related B-cell lymphoproliferation. Thirty-one percent had ≥one immune-mediated AEs (imAEs) with 25% requiring systemic steroids. In 29 participants with evaluable KS, the overall response rate (ORR) was 62.1% (95% CI, 42.3 to 79.3) and did not differ by CD4+ T-cell count. ORR in the eight participants with evaluable disease without previous KS therapy was 87.5% (95% CI, 47.3 to 99.7). Median duration of response (DOR) was not reached, and the Kaplan-Meier estimate of DOR of ≥12 months was 92.3% (95% CI, 56.6 to 98.8). Median progression-free survival was 28.2 months (95% CI, 4.2 to noncalculable). CONCLUSION: Pembrolizumab yielded a high rate of durable responses in HIV-associated KS. imAEs were successfully managed with standard guidelines.
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OBJECTIVES: To describe the proportion of patients with liver fibrosis in at-risk populations in primary care (PC). To know the agreement between FIB-4 and transitional elastography (TE), interobserver agreement between PC and hospital care (HC) in TE, and associated risk Factors (RF). METHODS: Observational, descriptive, cross-sectional study in ≥16 years of age with RF for chronic liver disease. Sex and age, RF (alteration of liver tests [LT], metabolic syndrome, diabetes, obesity, alcohol consumption, hepatic steatosis), and FIB-4, controlled attenuation parameter and TE in PC and in HC, were collected. According to a consensus algorithm, vibration-controlled TE was performed in PC in patients with FIB-4≥1,3, and those with measurement ≥8kPa were referred to HC. RESULTS: 326 patients were studied. 71% were not referred to HC, due to liver stiffness <8kPa. 83 of the 95 derivations did TE in HC. 45 (54%) had TE ≥8, and 25 (30%) ≥12. The proportion of patients with stiffness ≥8kPa was 13,8% (45/326) and ≥12kPa, 7,6% (25/326). The predictive values of the FIB-4 were low. The interobserver correlation coefficient between TE in PC and HC was 0,433. Variables associated with TE ≥8 in PC: LT alteration, diabetes and steatosis. With TE ≥12: LT alteration, diabetes and obesity. PREDICTOR VARIABLES: LT alteration and obesity. CONCLUSIONS: The study supports the sequential performance of serum indices and TE as a screening for fibrosis in the at-risk population in PC, which allows a reduction in the percentage of patients referred to AH, and a better stratification of risk patients.
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For patients with metastatic castration-resistant prostate cancer whose tumors harbor BRCA1/2 alterations, the potential benefits of combining a PARP inhibitor and an androgen receptor pathway inhibitor for first-line treatment outweigh the potential side effects. Further research is required to identify patients without detectable BRCA1/2 defects who would benefit from this approach.
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BACKGROUND AND OBJECTIVE: The phase 3 MAGNITUDE trial assessed the efficacy and safety of niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC) and alterations in homologous recombination repair (HRR) genes. Here we report final analysis results for patient-reported outcomes (PROs) in the HRR+ cohort with a focus on BRCA1/2 alterations (BRCA+). METHODS: Protocol-specified endpoints evaluated patient-reported symptoms, health-related quality of life (HRQoL), and tolerability (side-effect bother) using the Brief Pain Inventory-Short Form (BPI-SF), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EQ-5D-5L questionnaires. Evaluations were completed on day 1 of designated treatment cycles and during follow-up. KEY FINDINGS AND LIMITATIONS: All patients with BRCA+ mCRPC (n = 225) were included in the PRO analyses with average on-treatment PRO compliance >80% when completed on-site. Time to deterioration in pain according to BPI-SF and FACT-P scores did not significantly differ between niraparib + AAP and placebo + AAP. During treatment, EQ-5D-5L revealed no clinically meaningful differences in overall HRQoL between treatment arms in the BRCA+ subgroup. Finally, tolerability was similar between arms; side effect bother rated as "not at all" or "a little bit" ranged from 79.8% to 95.9% during treatment. Limitations include a sample size that may not have been powered to detect a difference in PROs. CONCLUSIONS AND CLINICAL IMPLICATIONS: Treatment with niraparib + AAP maintained HRQoL with minimal side-effect bother reported by most patients with BRCA+ mCRPC. Differences between treatment groups in time to pain deterioration did not meet conventional levels of statistical significance. The MAGNITUDE trial is registered on ClinicalTrials.gov as NCT03748641.
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BACKGROUND AND OBJECTIVE: Recently, research on treatment intensification has gathered momentum, and three novel therapy combinations were approved for metastatic castration-resistant prostate cancer (mCRPC). This systematic review summarizes the current and emerging evidence around intensified strategies for mCRPC and provides guidance for an ideal therapeutic sequencing. METHODS: Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidelines were followed to perform this review. PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials.gov, and major international societies' online proceedings were searched comprehensively until May 15, 2024, for terms related to treatment intensification and sequencing for mCRPC. KEY FINDINGS AND LIMITATIONS: Overall, 28 clinical trials and 24 ongoing studies of intensification treatments were included in this review. Algorithms of optimal sequencing of approved treatments for mCRPC were outlined according to the use of androgen receptor pathway inhibitors (ARPIs) with or without docetaxel for earlier disease states. In first line, poly(ADP-ribose) polymerase inhibitor + ARPI combinations improve radiographical progression-free survival (rPFS), particularly for those with BRCA1/2 alterations. The AKT inhibitor combination of ipatasertib + abiraterone extends rPFS in those with PTEN loss or PIK3CA/AKT1/PTEN alterations. In those with two or more risk factors for early progression on enzalutamide, radionuclide 177-Lu-PSMA-617 + enzalutamide prolongs progression-free survival. Ongoing research of intensified approaches for mCRPC, and available and potential predictive and prognostic biomarkers are discussed. CONCLUSIONS AND CLINICAL IMPLICATIONS: Recent approvals and ongoing investigations of single agents and intensification approaches will keep transforming the mCRPC treatment landscape. Improvement of patient profiling applying recognized genomic, molecular, and clinical predictive and prognostic indicators is fundamental to optimize sequential use of available therapies.
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OBJECTIVE: To examine whether socioeconomic status is associated with prognosis after the diagnosis of hypertension (HTN), in a population older than 65 years, in the community setting. DESIGN: Retrospective cohort study. SETTING: All the primary care centres of the Community of Madrid (n=392). PARTICIPANTS: All patients (>65 years) with a new diagnosis of HTN in 2007-08, without previous kidney or cardiovascular (K/CV) events (n=21 754).Patient records from primary care electronic health records and Spanish mortality database were analysed from January 2007 through December 2018. Sociodemographic data such as age, gender, Area Deprivation Index (MEDEA-Mortalidad en áreas pequeñas Españolas y Desigualdades Socioeconómicas y Ambientales-Index in quintiles), and characteristics, such as smoking, type 2 diabetes mellitus and hypercholesterolaemia, were collected at the time of enrolment. PRIMARY AND SECONDARY OUTCOME MEASURES: The occurrence of K/CV events (including mortality from these causes) and total mortality were evaluated using Cox regression. RESULTS: Patients had a mean age of 73.5 (SD 6.5) years, and 63.5% were women. The median follow-up was 128.7 months (IQR: 110.6-136.7 months). There were 10 648 first K/CV events, including 1508 deaths from these causes and 4273 deaths from other causes. Adjusted for age, gender, smoking, diabetes and hypercholesterolaemia, when comparing the third, fourth and last quintiles (less affluent) of the Deprivation Index with respect to the first quintile, the hazard of K/CV events increased by 14.8% (95% CI: 3.3 to 27.6%), 16.0% (95% CI: 6.4 to 26.4%) and 19.1% (95% CI: 8.9 to 30.2%), respectively. The MEDEA Index was not associated with differences in adjusted total mortality. CONCLUSION: Living in a low socioeconomic status area is associated with an increase in kidney or cardiovascular events in hypertensive patients diagnosed after age 65 years, which will result in a significant increase in disease burden even if not related to an increase in total mortality.
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Hipertensão , Classe Social , Humanos , Feminino , Masculino , Hipertensão/epidemiologia , Idoso , Estudos Retrospectivos , Espanha/epidemiologia , Prognóstico , Idoso de 80 Anos ou mais , Fatores de Risco , Modelos de Riscos ProporcionaisRESUMO
DNA repair genomic aberrations in the Homologous Recombination pathway are identifiable in up to 25% of patients with advanced prostate cancer, making them more likely to benefit from treatment with poly (ADP-ribose) polymerase inhibitors (PARPi) alone or in combination with other therapies, particularly when BRCA driver genomic aberrations are documented. Although several clinical trials have demonstrated the efficacy of this approach, the validation of reliable biomarkers predictive of response still needs further improvement to refine patient selection. In this setting, the characterization of resistance mechanisms and the validation of novel biomarkers are critical to maximize clinical benefit and to develop novel treatment combinations to improve outcomes. In this review, we summarize the development of PARPi in prostate cancer as single agent as well as the efficacy of their combination with other drugs, and the future directions for their implementation in the management of advanced prostate cancer.
New treatment strategies for patients with metastatic prostate cancer Prostate cancer is the most common cancer in men worldwide. Alterations in the genes responsible for repairing damaged DNA are found in up to 25% of advanced prostate cancer patients. This inability of cells to repair damaged DNA allows tumours to grow, but it is also exploited by new treatments. An example of such therapies are the inhibitors of the Poly-ADP ribose polymerase, known as PARP inhibitors. PARP inhibitors are being developed alone and in combination with other drugs for the treatment of prostate cancer. In this manuscript, we provide an overview of the studies conducted in prostate cancer, as well as the future directions of PARP inhibitors for the management of the disease.
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Surrogate endpoints are becoming increasingly important in health technology assessment, where decisions are based on complex cost-effectiveness models (CEMs) that require numerous input parameters. Daniels and Hughes Surrogate Model was used to predict missing effect estimates in randomized controlled trials (RCTs) evaluating first-line treatments in metastatic castration-resistant prostate cancer (mCRPC) patients. Network meta-analyses (NMAs) were conducted to assess the comparative efficacy of these treatments. Databases were searched (inception to October 2022) using Ovid®. Several grey literature searches were also conducted (PROSPERO: CRD42021283512). Available trial data for radiographic progression-free survival (rPFS) and overall survival (OS) were used to predict the unreported effect of rPFS or OS for relevant comparator treatments. Bayesian NMAs were conducted using observed and predicted treatment effects. Effect estimates and 95% credible intervals were calculated for each comparison. Mean ranks and the probability of being best (p-best) were obtained. Twenty-five RCTs met the eligibility criteria and of these, 8 reported jointly rPFS and OS; while rPFS was predicted for 12 RCTs and 10 comparators, and OS was predicted for 5 RCTs and 6 comparators. A nonstandard dose of docetaxel (docetaxel 50 mg/m2 every 2 weeks) had the highest probability of being the most effective for rPFS (p-best: 59%) and OS (p-best: 48%), followed by talazoparib plus enzalutamide (13% and 19%, respectively). Advanced surrogate modelling techniques allowed obtaining relevant parameter and indirect estimates of previously unavailable data and may be used to populate future CEMs requiring rPFS and OS in first-line mCRPC.
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Neoplasias de Próstata Resistentes à Castração , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Masculino , Teorema de Bayes , Análise de Custo-Efetividade , Docetaxel/administração & dosagem , Docetaxel/economia , Metanálise em Rede , Intervalo Livre de Progressão , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/economia , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do TratamentoRESUMO
Importance: Half of all carriers of inherited cancer-predisposing variants in BRCA1 and BRCA2 are male, but the implications for their health are underrecognized compared to female individuals. Germline variants in BRCA1 and BRCA2 (also known as pathogenic or likely pathogenic variants, referred to here as BRCA1/2 PVs) are well known to significantly increase the risk of breast and ovarian cancers in female carriers, and knowledge of BRCA1/2 PVs informs established cancer screening and options for risk reduction. While risks to male carriers of BRCA1/2 PVs are less characterized, there is convincing evidence of increased risk for prostate cancer, pancreatic cancer, and breast cancer in males. There has also been a rapid expansion of US Food and Drug Administration-approved targeted cancer therapies, including poly ADP ribose polymerase (PARP) inhibitors, for breast, pancreatic, and prostate cancers associated with BRCA1/2 PVs. Observations: This narrative review summarized the data that inform cancer risks, targeted cancer therapy options, and guidelines for early cancer detection. It also highlighted areas of emerging research and clinical trial opportunities for male BRCA1/2 PV carriers. These developments, along with the continued relevance to family cancer risk and reproductive options, have informed changes to guideline recommendations for genetic testing and strengthened the case for increased genetic testing for males. Conclusions and Relevance: Despite increasing clinical actionability for male carriers of BRCA1/2 PVs, far fewer males than female individuals undergo cancer genetic testing. Oncologists, internists, and primary care clinicians should be vigilant about offering appropriate genetic testing to males. Identifying more male carriers of BRCA1/2 PVs will maximize opportunities for cancer early detection, targeted risk management, and cancer treatment for males, along with facilitating opportunities for risk reduction and prevention in their family members, thereby decreasing the burden of hereditary cancer.
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Proteína BRCA1 , Proteína BRCA2 , Predisposição Genética para Doença , Humanos , Masculino , Proteína BRCA2/genética , Proteína BRCA1/genética , Fatores de Risco , Testes Genéticos , Neoplasias/genética , Neoplasias/epidemiologia , Neoplasias da Mama Masculina/genética , Neoplasias da Mama Masculina/terapia , Detecção Precoce de Câncer , Mutação em Linhagem Germinativa , Medição de RiscoRESUMO
The Zika virus (ZIKV) epidemic had a sanitary, psychosocial, and economic impact on individuals of reproductive age. The primary concern revolved around infection during pregnancy due to possible vertical transmission and its association with adverse fetal and infant outcomes, known as Congenital Zika Syndrome (CZS). This qualitative study employs phenomenology and grounded theory. This study includes interviews with 98 women, some pregnant during the ZIKV epidemic in Brazil, Colombia, and Puerto Rico, who had children with CZS or without diagnosed neurological impairment. Additionally, the study included a group of women who were pregnant during the COVID-19 pandemic in these same countries. In both groups, interviewees had varying levels of knowledge about ZIKV. The study found that messages conveyed through the media tended to be alarmist, in contrast to the information provided by healthcare professionals, which was considered more trustworthy. Pregnant women during the ZIKV epidemic reported receiving their ZIKV and CSZ infection diagnoses late, either during or after childbirth. The study underscores the needs of pregnant women in high-risk scenarios, the importance of health education processes, and the necessity to reinforce communication and continuing education.
A epidemia do vírus Zika (ZIKV) teve impacto sanitário, psicossocial e econômico sobre pessoas em idade reprodutiva. A principal preocupação foi a infecção durante a gravidez devido a possível transmissão vertical e sua associação com resultados fetais e infantis adversos, conhecida como síndrome congênita associada à infecção pelo Vírus Zika (SCZ). Este estudo qualitativo utiliza a fenomenologia e a teoria fundamentada. O estudo inclui entrevistas com 98 mulheres, parte grávida durante a epidemia de ZIKV no Brasil, Colômbia e Porto Rico e que tiveram filhos com SCZ ou sem comprometimento neurológico diagnosticado. Além disso, o estudo inclui um grupo de mulheres grávidas durante a pandemia de COVID-19 nos mesmos países. Em ambos os grupos, as entrevistadas tinham diferentes níveis de conhecimento sobre ZIKV. O estudo constatou que as mensagens veiculadas por meio da mídia eram alarmistas; em contraste com as informações fornecidas por profissionais de saúde, consideradas mais confiáveis. Mulheres gestantes durante a epidemia do ZIKV relataram ter recebido seu diagnóstico de infecção por ZIKV e SCZ tardiamente ou após o parto. O estudo destaca as necessidades das mulheres grávidas em cenários de alto risco, a importância de processos de educação em saúde e a necessidade de reforçar a comunicação e a educação continuada.
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Recently published near full-length KSHV genomes from a Cameroon Kaposi sarcoma case-control study showed strong evidence of viral recombination and mixed infections, but no sequence variations associated with disease. Using the same methodology, an additional 102 KSHV genomes from 76 individuals with KSHV-associated diseases have been sequenced. Diagnoses comprise all KSHV-associated diseases (KAD): Kaposi sarcoma (KS), primary effusion lymphoma (PEL), KSHV-associated large cell lymphoma (KSHV-LCL), a type of multicentric Castleman disease (KSHV-MCD), and KSHV inflammatory cytokine syndrome (KICS). Participants originated from 22 different countries, providing the opportunity to obtain new near full-length sequences of a wide diversity of KSHV genomes. These include near full-length sequence of genomes with KSHV K1 subtypes A, B, C, and F as well as subtype E, for which no full sequence was previously available. High levels of recombination were observed. Fourteen individuals (18%) showed evidence of infection with multiple KSHV variants (from two to four unique genomes). Twenty-six comparisons of sequences, obtained from various sampling sites including PBMC, tissue biopsies, oral fluids, and effusions in the same participants, identified near complete genome conservation between different biological compartments. Polymorphisms were identified in coding and non-coding regions, including indels in the K3 and K15 genes and sequence inversions here reported for the first time. One such polymorphism in KSHV ORF46, specific to the KSHV K1 subtype E2, encoded a mutation in the leucine loop extension of the uracil DNA glycosylase that results in alteration of biochemical functions of this protein. This confirms that KSHV sequence variations can have functional consequences warranting further investigation. This study represents the largest and most diverse analysis of KSHV genome sequences to date among individuals with KAD and provides important new information on global KSHV genomics.
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Genoma Viral , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/genética , Sarcoma de Kaposi/virologia , Sarcoma de Kaposi/genética , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Polimorfismo Genético , Idoso , Infecções por Herpesviridae/genética , Infecções por Herpesviridae/virologia , Etnicidade/genética , Hiperplasia do Linfonodo Gigante/virologia , Hiperplasia do Linfonodo Gigante/genética , FilogeniaRESUMO
COVID-19 self-testing is essential for enabling individuals to self-care, screen themselves and, if positive, isolate themselves. Since 2021, COVID-19 self-tests have been extensively used in high-income countries, however, their programmatic implementation in low- and middle-income countries has been delayed. An implementation pilot, mixed-methods study, was conducted in four industrial manufacturing companies, in Kedah State between November 2022 and May 2023. Participants were asked to take COVID-19 self-tests home for themselves and their household members and to use the tests according to national guidelines. At enrolment and at the end of the study, participants completed an online sociodemographic, knowledge and satisfaction survey. Data were cleaned and analysed using SPSS Statistics V28.0. Qualitative data were collected through semi-structured interviews and focus group discussions. Thematic analysis was conducted. A total of 1768 employees from four manufacturing industries enrolled in the pilot, representing 60% of the total employees and more than 50% of employees at each site. There were 40 COVID-19-positive cases detected in participants from the manufacturing industries, and 100 positive household members. Participants reported 27 invalid test results. Individuals aged 30 or less [adjusted odds ratio (AOR): 2.65; 95% CI: 1.63 to 4.31; p<0.001] and males (AOR: 1.54; 95% CI: 1.09 to 2.17; p = 0.014) showed a significant higher likelihood of self-testing compared to older and female participants. Additionally, individuals who received three or more doses of a COVID-19 vaccine had higher odds of using self-tests (OR 1.56 (95% CI: 1.03 to 2.36, p = 0.037)). There was a significant increase in participants' knowledge on how to correctly collect a self-sample using a nasal swab from 36,9% at baseline to 43,6% post-implementation (p = 0.004) and correct interpretation of a positive result from 80,5% at baseline to 87,6% post-implementation (p<0.001). Furthermore, there was a notable increase in the correct understanding of actions following a positive result, especially regarding self-isolation, which rose from 59.1% to 71.9% (p<0.001). A total of 44 SSIs, and 4 FGDs with a total of 14 participants, were performed. The five main themes explored were: 1) previous experiences with COVID-19, 2) COVID-19 ST experiences during the pilot study, 3) advantages of COVID-19 ST, 4) feelings related to COVID-19 ST, 5) willingness to use COVID-19 ST again, and 6) ST for other diseases. This research shows the feasibility of a self-testing model in the community through workplaces due to participants' high acceptability to enrol and high self-tests' uptake. Lessons learnt can inform operational aspects of the introduction and scale-up of self-care strategies in low- and middle-income countries, in particular the South-East Asia region.
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Providing accurate, evidence-based information to women with Zika infection during pregnancy was problematic because of the high degree of uncertainty in the diagnosis of the infection and the associated risk. The 2015-17 Zika virus epidemic overwhelmingly affected women in countries with limited access to safe abortion. Understanding women's perspectives on risk communication during pregnancy in the context of an emerging pathogen can help inform risk communication in response to future outbreaks that affect fetal or child development. We conducted a cross-sectional qualitative interview study with 73 women from 7 locations in Brazil, Colombia, and Puerto Rico to understand women's experiences of Zika virus (ZIKV) test and outcome-related communication during the ZIKV pandemic. We used thematic analysis to analyze the in-depth interviews. Participants in Brazil and Colombia reported that the healthcare system's lack of preparation and organization in communicating ZIKV test results and associated adverse outcomes led to their feeling abandoned and alone in confronting the challenges of a ZIKV-affected pregnancy. In contrast, participants in Puerto Rico reported that the regular testing schedules and clear, well-planned communication between the care team and between providers and pregnant women helped them to feel they could prepare for a ZIKV-affected pregnancy. Communication of the risk associated with an emerging pathogen suspected to affect pregnancy and developmental outcomes is a fraught issue. Public health authorities and healthcare providers should work together in the interpandemic period to understand families' preferences for risk communication during pregnancy in the presence of uncertainty and develop a community-informed plan for risk communication.
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BACKGROUND: Performing cardiovascular and cancer screenings in target populations can reduce mortality. Visiting a General Practitioner (GP) once a year is related to an increased likelihood of preventive care. The aim of this study was to analyse the influence of visiting a GP in the last year on the delivery of preventive services based on sex and household income. METHODS: Cross-sectional study using data collected from the European Health Interview Survey 2013-2015 of individuals aged 40-74 years from 29 European countries. The variables included: sociodemographic factors (age, sex, and household income (HHI) quintiles [HHI 1: lowest income, HHI 5: more affluent]), lifestyle factors, comorbidities, and preventive care services (cardiometabolic, influenza vaccination, and cancer screening). Descriptive statistics, bivariate analyses and multilevel models (level 1: citizen, level 2: country) were performed. RESULTS: 242,212 subjects were included, 53.7% were female. The proportion of subjects who received any cardiometabolic screening (92.4%) was greater than cancer screening (colorectal cancer: 44.1%, gynaecologic cancer: 40.0%) and influenza vaccination. Individuals who visited a GP in the last year were more prone to receive preventive care services (cardiometabolic screening: adjusted OR (aOR): 7.78, 95% CI: 7.43-8.15; colorectal screening aOR: 1.87, 95% CI: 1.80-1.95; mammography aOR: 1.76, 95% CI: 1.69-1.83 and Pap smear test: aOR: 1.89, 95% CI:1.85-1.94). Among those who visited a GP in the last year, the highest ratios of cardiometabolic screening and cancer screening benefited those who were more affluent. Women underwent more blood pressure measurements than men regardless of the HHI. Men were more likely to undergo influenza vaccination than women regardless of the HHI. The highest differences between countries were observed for influenza vaccination, with a median odds ratio (MOR) of 6.36 (under 65 years with comorbidities) and 4.30 (over 65 years with comorbidities), followed by colorectal cancer screening with an MOR of 2.26. CONCLUSIONS: Greater adherence to preventive services was linked to individuals who had visited a GP at least once in the past year. Disparities were evident among those with lower household incomes who visited a GP. The most significant variability among countries was observed in influenza vaccination and colorectal cancer screening.
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Detecção Precoce de Câncer , Serviços Preventivos de Saúde , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Masculino , Europa (Continente)/epidemiologia , Adulto , Idoso , Serviços Preventivos de Saúde/estatística & dados numéricos , Detecção Precoce de Câncer/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Vacinas contra Influenza/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/epidemiologia , Clínicos Gerais/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Fatores SexuaisRESUMO
BACKGROUND: Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. METHODS: This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). DISCUSSION: This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. TRIAL REGISTRATION: NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023.
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Diabetes Mellitus Tipo 1 , Hemoglobinas Glicadas , Humanos , Glicemia/análise , Monitoramento Contínuo da Glicose/instrumentação , Análise Custo-Benefício , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas/análise , Controle Glicêmico/instrumentação , Hipoglicemiantes/uso terapêutico , Ciência da Implementação , Insulina/uso terapêutico , Quênia , Estudos Multicêntricos como Assunto , Ensaios Clínicos Pragmáticos como Assunto , Qualidade de Vida , África do Sul , Resultado do TratamentoRESUMO
Background: The COVID-19 pandemic imposed lockdown measures that affected caregiving. Understanding caregivers' context provides reveals their adaptive strategies to continue caring in this situation of uncertainty and isolation. Objective: To better understand the caregiving experiences of caregivers looking after dependent individuals living in the community during the pandemic. Design: Qualitative research, phenomenological approach. Setting: Primary healthcare centers in Madrid region (Spain). Participants: 21 family caregivers. Methods: Purposive and theoretical sampling was used to recruit caregivers across nurses from primary healthcare centers. Participants were interviewed using a semi-structured interview guide to explore the caring experience. Interview transcripts were evaluated using thematic analysis. Results: The findings were categorized into two themes: "Caregivers during lockdown-providing care in a time of adversity" and "Caregiving toward normality". The sub-themes identified were the re-structuring of before-care services and the introduction of new care approaches, managing the dependent person's health problems, looking after oneself, and dealing with adversity. To adapt to the new normal, strategies were put in place designed to recover confidence and trust, reincorporate assistance, and reconnect with others. Conclusions: Care intensified during the pandemic. Caregivers took on the task without assistance, focusing on preventing contagion and protecting themselves to be able to continue giving care.
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OBJECTIVE: Diagnostic testing is an important tool to combat the COVID-19 pandemic, yet access to and uptake of testing vary widely 3 years into the pandemic. The WHO recommends the use of COVID-19 self-testing as an option to help expand testing access. We aimed to calculate the cost of providing COVID-19 self-testing across countries and distribution modalities. DESIGN: We estimated economic costs from the provider perspective to calculate the total cost and the cost per self-test kit distributed for three scenarios that differed by costing period (pilot, annual), the number of tests distributed (actual, planned, scaled assuming an epidemic peak) and self-test kit costs (pilot purchase price, 50% reduction). SETTING: We used data collected between August and December 2022 in Brazil, Georgia, Malaysia, Ethiopia and the Philippines from pilot implementation studies designed to provide COVID-19 self-tests in a variety of settings-namely, workplace and healthcare facilities. RESULTS: Across all five countries, 173 000 kits were distributed during pilot implementation with the cost/test distributed ranging from $2.44 to $12.78. The cost/self-test kit distributed was lowest in the scenario that assumed implementation over a longer period (year), with higher test demand (peak) and a test kit price reduction of 50% ($1.04-3.07). Across all countries and scenarios, test procurement occupied the greatest proportion of costs: 58-87% for countries with off-site self-testing (outside the workplace, for example, home) and 15-50% for countries with on-site self-testing (at the workplace). Staffing was the next key cost driver, particularly for distribution modalities that had on-site self-testing (29-35%) versus off-site self-testing (7-27%). CONCLUSIONS: Our results indicate that it is likely to cost between $2.44 and $12.78 per test to distribute COVID-19 self-tests across common settings in five heterogeneous countries. Cost-effectiveness analyses using these results will allow policymakers to make informed decisions on optimally scaling up COVID-19 self-test distribution programmes across diverse settings and evolving needs.
Assuntos
COVID-19 , Infecções por HIV , Humanos , SARS-CoV-2 , Etiópia , Infecções por HIV/epidemiologia , Georgia , Malásia , Pandemias , Brasil , Filipinas , Autoteste , COVID-19/epidemiologiaRESUMO
OBJECTIVE: Kaposi sarcoma is a vascular tumor that affects the pulmonary system. However, the diagnosis of airway lesions suggestive of pulmonary Kaposi sarcoma (pKS) is reliant on bronchoscopic visualization. We evaluated the role of Kaposi sarcoma herpesvirus (KSHV) viral load in bronchoalveolar lavage (BAL) as a diagnostic biomarker in patients with bronchoscopic evidence of pKS and evaluated inflammatory cytokine profiles in BAL and blood samples. DESIGN: In this retrospective study, we evaluated KSHV viral load and cytokine profiles within BAL and blood samples in patients who underwent bronchoscopy for suspected pKS between 2016 and 2021. METHODS: KSHV viral load and cytokine profiles were obtained from both the circulation and BAL samples collected at the time of bronchoscopy to evaluate compartment-specific characteristics. BAL was centrifuged and stored as cell pellets and KSHV viral load was measured using primers for the KSHV K6 gene regions. RESULTS: We evaluated 38 BAL samples from 32 patients (30 with HIV co-infection) of whom 23 had pKS. In patients with airway lesions suggestive of pKS, there was higher KSHV viral load (median 3188 vs. 0âcopies/10 6 cell equivalent; P â=â0.0047). A BAL KSHV viral load cutoff of 526âcopies/10 6 cells had a sensitivity of 72% and specificity of 89% in determining lesions consistent with pKS. Those with pKS also had higher IL-1ß and IL-8 levels in BAL. The 3-year survival rate for pKS patients was 55%. CONCLUSION: KSHV viral load in BAL shows potential for aiding in pKS diagnosis. Patients with pKS also have evidence of cytokine dysregulation in BAL.
Assuntos
Líquido da Lavagem Broncoalveolar , Citocinas , Herpesvirus Humano 8 , Sarcoma de Kaposi , Carga Viral , Humanos , Sarcoma de Kaposi/virologia , Sarcoma de Kaposi/diagnóstico , Herpesvirus Humano 8/isolamento & purificação , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Líquido da Lavagem Broncoalveolar/virologia , Líquido da Lavagem Broncoalveolar/citologia , Adulto , Citocinas/análise , Broncoscopia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/virologia , Neoplasias Pulmonares/patologia , Biomarcadores/análise , Infecções por HIV/complicações , Infecções por HIV/diagnóstico , Idoso , Lavagem BroncoalveolarRESUMO
Objetivo: identificar barreras y facilitadores para el uso de las guías de práctica clínica (GPC) por residentes de Medicina Familiar y Comunitaria.Métodos: metodología cualitativa. Se formaron tres grupos focales, total 28 residentes de tercer y cuarto año de las siete unidades docentes multiprofesionales de Atención Familiar y Comunitaria de Madrid. Los temas explorados fueron: conocimiento, comprensión, utilidad y uso de GPC. Las categorías elegidas para agrupar el discurso se elaboraron siguiendo el Manual metodológico de GuíaSalud. Análisis sociológico bajo la perspectiva fenomenológica.Resultados: las barreras relacionadas con la formación fueron el modelo de formación recibida para adquirir las habilidades necesarias, la falta de conocimientos para evaluar la calidad de las guías y un limitado conocimiento de los buscadores. Entre las barreras del contexto social y del sistema sanitario, se identificaron el conflicto con las expectativas del paciente, con las recomendaciones de otros especialistas, las características de los pacientes que consultan en Atención Primaria (AP) y la limitación de tiempo en las consultas. Como facilitadores se identificaron la motivación personal, los conocimientos y el modelo de práctica profesional del tutor y que las GPC fueran claras, breves y en diversos formatos.Conclusiones: los residentes dan valor a las GPC como herramientas docentes, de ayuda a la toma de decisiones y para desempeñar un mejor ejercicio profesional, aunque encuentran dificultades y limitaciones en su uso. El papel del tutor se identifica como clave; la formación, motivación y el modelo de práctica del tutor son considerados como los mayores facilitadores.(AU)
Aim: to identify barriers and facilitators for the use of Clinical Practice Guidelines (CPG) by Family and Community Medicine residents.Method: qualitative methodology. Three focus groups were set up, with a total of 28 participants, 3rd and 4th year residents of the 7 Multiprofessional Family and Community Care Teaching Units of Madrid. The topics explored were based on knowledge, understanding, usefulness and use of CPG. The categories chosen for discussion were drawn up according to the GuiaSalud Methodological Manual. Sociological analysis was performed using a phenomenological approach.Results: the barriers related to training were the training model received to acquire the necessary skills, the lack of knowledge to evaluate the quality of guidelines and a limited knowledge of the search engines. Among the barriers related to social context and health system, conflict with the patient's expectations or with the recommendations of other specialists, the characteristics of patients who consult in primary care and the limited time available for consultations were all identified. Personal motivation, the tutors knowledge and professional practice model and clear, brief CPGs and in various formats were all identified as facilitators. Conclusions: residents value CPGs as teaching and decision-making tools, as well as a tool to improve their professional practice. However, they detect difficulties and limitations in their use. Training, motivation and the tutor's practice model are considered to be among the greatest facilitators.(AU)