PARP inhibitors alone or in combination for prostate cancer.

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.

Pregnant women's perceptions on Information Sources on Zika Virus: a qualitative study.

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.

Predicting Treatment Effects from Surrogate Endpoints in Historical Trials in First-Line Metastatic Castration-Resistant Prostate Cancer.

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.

BRCA1, BRCA2, and Associated Cancer Risks and Management for Male Patients: A Review.

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.

Sequencing of Kaposi's Sarcoma Herpesvirus (KSHV) genomes from persons of diverse ethnicities and provenances with KSHV-associated diseases demonstrate multiple infections, novel polymorphisms, and low intra-host variance.

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.

"I found out about Zika virus after she was born." Women's experiences of risk communication during the Zika virus epidemic in Brazil, Colombia, and Puerto Rico.

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.

Implementation pilot study of community self-testing for COVID-19 among employees of manufacturing industries and their household members in 2022 to 2023.

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.

Family Caregivers' Experiences during the COVID-19 Pandemic: Qualitative Study.

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.

Effect of GP visits in the compliance of preventive services: a cross-sectional study in Europe.

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.

Implementation research: a protocol for two three-arm pragmatic randomised controlled trials on continuous glucose monitoring devices in people with type 1 diabetes in South Africa and Kenya.

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.

Cost of SARS-CoV-2 self-test distribution programmes by different modalities: a micro-costing study in five countries (Brazil, Georgia, Malaysia, Ethiopia and the Philippines).

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.

Kaposi sarcoma herpesvirus viral load in bronchoalveolar lavage as a diagnostic marker for pulmonary Kaposi sarcoma.

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. 0 copies/10 6 cell equivalent; P  = 0.0047). A BAL KSHV viral load cutoff of 526 copies/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.

Barreras y facilitadores para el uso de las guías de práctica clínica por residentes de Medicina Familiar y Comunitaria: estudio cualitativo con grupos focales / Barriers and facilitators for the use of clinical practice guidelines by Family and Community Medicine residents: qualitative study with focus groups

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 tutor’s 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)

Implementing a pilot study of COVID-19 self-testing in high-risk populations and remote locations: results and lessons learnt.

BACKGROUND: Rapid antigen-detection tests for SARS-CoV-2 self-testing represent a useful tool for pandemic control and expanding access to community-level case screening. COVID-19 self-tests have been extensively used in high-income countries since 2021; however, their introduction and programmatic implementation in low- and middle-income countries was delayed. We aimed to identify and continuously improve a weekly COVID-19 self-testing model among staff at healthcare facilities and schools. METHODS: This mixed-methods, observational prospective study was conducted in 5 healthcare centres and 24 schools in Georgia, between June and December 2022. The study comprised the integration of COVID-19 self-testing into the national mandatory testing programme for high-risk groups, with primary distribution of self-tests among staff performed weekly, plus secondary distribution to their household members. These use cases were selected because NCDC was seeking to strengthen their already strong weekly testing programme, by investigating self-testing to ease the burden of testing in the healthcare system. Online surveys and semi-structured interviews were used for data collection. RESULTS: In total, 2156 participants were enrolled (1963 female, 72%). At baseline and mid- and end-points, 88%, 97% and 99%, respectively, of participants agreed/strongly agreed they would self-test. Similarly, the majority were willing to report their self-testing results (88%, 98% and 96% at baseline and mid- and end-points, respectively). Weekly reporting of test results to the national COVID-19 database was high during all the implementation. There were 622 COVID-19 positive results reported, and linked to care, from 601 individuals (282 participants and 319 household members). Findings from qualitative interviews showed great satisfaction with self-testing for its convenience, ease of use, trust in the results, no need to travel for diagnostics, and increased perception of safety. CONCLUSIONS: Our findings contribute to the evidence-base regarding self-testing strategies conducted via workplaces and secondary distribution to households. Willingness to perform a COVID-19 self-test increased after implementation. This pilot enhanced pandemic preparedness through expansion of the national self-testing reporting system, development of communications materials, changes in the national legal framework and coordination mechanisms, and improved perceptions around self-care in the community. The lessons learnt can inform operational aspects of the introduction and scale-up of self-care strategies.

Inherited Mutations in DNA Damage Repair Genes in Italian Men with Metastatic Prostate Cancer: Results from the Meet-URO 10 Study.

Background: The prevalence of pathogenic germline mutations in DNA damage repair (gDDR) genes in the Italian population is unknown. Objective: In this prospective multicenter cohort study, we evaluated the prevalence of gDDR alterations in the Italian population affected by metastatic prostate cancer (mPCa) and analyzed the impact on response to therapy, survival, and time to castration resistance. Design setting and participants: In an observational prospective trial, 300 consecutive Italian mPCa patients, enrolled in the Meet-Uro-10 trial from three academic Italian centers, were recruited between 2017 and 2019 and were screened for gDDR mutations in 107 genes. Outcome measurements and statistical analysis: The primary endpoint was to assess the prevalence of gDDR mutations in the Italian population of patients with mPCa. The secondary endpoints included the association of gDDR subgroups with metastatic onset, Gleason score, and time to castration resistance. Results and limitations: We identified 297 valuable patients. Forty-six patients had a pathogenic/likely pathogenic variant (15.5%, 95% confidence interval: 11.4-19.6): the more frequent was gBRCA2 found in nine cases (3%), followed by gATM in five cases (1.7%). In patients without mutations, longer median overall survival was observed with the sequence docetaxel-androgen receptor signaling inhibitor (ARSI) than with the sequence ARSI-docetaxel (87.9 vs 42 mo, p = 0.0001). In a univariate analysis, the median time to castration resistance in gDDR mutated patients was 19.8 mo, versus 23.7 mo in no mutated patients (p = 0.024). There were no associations of gDDR subgroups with metastatic onset and Gleason score ≥8. In our cohort, variants of unknown significance in gDDR genes were found in 80 patients and might have a prognostic relevance. Conclusions: The study reported the prevalence of gDDR in the Italian population. The presence of gBRCA2 mutations correlates with a shorter time to the onset of castration resistance disease. Patient summary: The prevalence of gBRCA2 in the Italian population is 3%, which is similar to that in the Spanish population, identifying similarities between people of the Western Mediterranean area.

Health service and psychotropic medication use for mental health conditions among healthcare workers active during the Spain Covid-19 Pandemic - A prospective cohort study using web-based surveys.

Little is known about healthcare workers' (HCW) use of healthcare services for mental disorders. This study presents data from a 16-month prospective cohort study of Spanish HCW (n = 4,809), recruited shortly after the COVID-19 pandemic onset, and assessed at four timepoints using web-based surveys. Use of health services among HCW with mental health conditions (i.e., those having a positive screen for mental disorders and/or suicidal thoughts and behaviours [STB]) was initially low (i.e., 18.2 %) but increased to 29.6 % at 16-month follow-up. Service use was positively associated with pre-pandemic mental health treatment (OR=1.99), a positive screen for major depressive disorder (OR=1.50), panic attacks (OR=1.74), suicidal thoughts and behaviours (OR=1.22), and experiencing severe role impairment (OR=1.33), and negatively associated with being female (OR = 0.69) and a higher daily number of work hours (OR=0.95). Around 30 % of HCW with mental health conditions used anxiolytics (benzodiazepines), especially medical doctors. Four out of ten HCW (39.0 %) with mental health conditions indicated a need for (additional) help, with most important barriers for service use being too ashamed, long waiting lists, and professional treatment not being available. Our findings delineate a clear mental health treatment gap among Spanish HCW.

Development of PARP inhibitors in advanced prostate cancer.

The relatively high prevalence of alterations in the homologous recombination repair (HRR) pathway described in advanced prostate cancer provides a unique opportunity to develop therapeutic strategies that take advantage of the decreased tumor ability to repair DNA damage. Poly ADP-ribose polymerase (PARP) inhibitors have been demonstrated to improve the outcomes of metastatic castration-resistant prostate cancer (mCRPC) patients with HRR defects, particularly in those with BRCA1/2 alterations. To expand the benefit of PARPi to patients without detectable HRR alterations, multiple studies are addressing potential synergies between PARP inhibition (PARPi) and androgen receptor pathway inhibitors (ARSi), radiation, radioligand therapy, chemotherapy, or immunotherapy, and these strategies are also being evaluated in the hormone-sensitive setting. In this review, we summarize the development of PARPi in prostate cancer, the potential synergies, and combinations being investigated as well as the future directions of PARPi for the management of the disease.

Development of PARP inhibitors in advanced prostate cancer Alterations in the mechanisms responsible for repairing damaged DNA are frequently altered in advanced prostate cancer. This provides a unique opportunity to develop therapies that exploit the decreased ability of these prostate tumours to repair DNA. Poly ADP-ribose polymerase (PARP) inhibitors have been successfully used to treat other tumor types with similar deficiencies and recently, multiple studies have demonstrated its efficacy also in prostate cancer, particularly in tumors with BRCA1/2 alterations. To expand the benefit of PARPi to patients without detectable DNA repair alterations, multiple studies are addressing potential synergies between PARP inhibition (PARPi) and androgen receptor pathway inhibitors (ARSi), radiation, radiopharmaceuticals, chemotherapy and immunotherapy in different disease stages. In this review, we summarize the development of PARPi in prostate cancer, the potential synergies and combinations being evaluated as well as the future directions of PARPi for the management of the disease.

Percepções das mulheres grávidas sobre as fontes de informação relativas ao vírus Zika: um estudo qualitativo / Pregnant women's perceptions on information sources on Zika virus: a qualitative study

Resumo 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.

Abstract 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.

Prospective Assessment of Bone Metabolism Biomarkers and Survival in Metastatic Castration-resistant Prostate Cancer Patients Treated with Radium-223: The PRORADIUM Study.

BACKGROUND: Radium-223 is an active therapy option for bone metastatic castration-resistant prostate cancer (mCRPC). The lack of adequate biomarkers for patient selection and response assessment are major drawbacks for its use. OBJECTIVE: To assess the prognostic value of bone metabolism biomarkers (BMBs) in ra-223-treated mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of mCRPC patients treated with Ra-223 (PRORADIUM study: NCT02925702) was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main objective of the study was to evaluate the association between high (≥median) baseline values in at least three bone formation (bone alkaline phosphatase [BAP] and C-terminal type-I collagen propeptide) and bone resorption (N-terminal telopeptide and pyridinoline) biomarkers, and survival. The independent prognostic value of each BMB was also assessed. The association with time to radiographic, clinical, and prostate-specific antigen (PSA) progression; time to skeletal-related events; and PSA response were secondary objectives. Multivariable (MV) Cox-regression models were evaluated. RESULTS AND LIMITATIONS: A total of 169 patients were included. Of the patients, 70.4% received Ra-223 in second/third line; 144 (85.2%) were Eastern Cooperative Oncology Group 0-1, 126 (74.6%) were in pain, and 80 (47.5%) had more than ten bone metastases. Sixty-seven (39.6%) patients had elevation in at least three BMBs. The median overall survival was 12.1 mo (95% confidence interval [CI]: 10-14.7). No association was observed with other treatment-related secondary outcome parameters. Patients with high values in three or more BMBs had significantly worse survival (9.9 vs 15.2 mo; hazard ratio [HR]: 1.8 [95% CI: 1.3-2.5]; p < 0.001) in the univariate analysis, but not independent in the MV analysis (HR: 1.33; 95% CI: 0.89-2; p = 0.181). High baseline BAP was the only biomarker associated with survival in the MV model (HR: 1.89; 95% CI: 1.28-2.79; p = 0.001). Addition of BAP to the MV clinical model increased the area under the receiver operating characteristic curve 2-yr value from 0.667 to 0.755 (p = 0.003). CONCLUSIONS: Biomarkers of bone formation, especially BAP, have prognostic value in mCRPC patients treated with radium-223. Its predictive value remains to be assessed, ideally in prospective, adequately powered, randomised clinical trials. PATIENT SUMMARY: In this study, we evaluate the role of bone metabolism biomarkers to help improve the use of radium-223 as therapy for advanced prostate cancer. We found that bone alkaline phosphatase may be a suitable tool.

Prevalencia de síntomas mentales entre los refugiados saharauis en Tinduf, Argelia, utilizando el Cuestionario de Salud General Goldberg 28 / Prevalence of mental symptoms in the Sahrawi refugees in Tindouf camps, Algeria, determined using the Goldberg General Health Questionnaire 28

Objetivo: Estimar la prevalencia de síntomas psicopatológicos entre los refugiados saharauis y la influencia de factores sociodemográficos en la expresión fenotípica de los trastornos mentales. Diseño: Estudio descriptivo transversal. Emplazamiento: Atención primaria y hospitalaria de salud. Participantes: Trescientos ochenta y tres (383) participantes mayores de 18 años, 59,8% mujeres y 40,2% hombres, con una media de edad del 37,2 (DE = 13,0), del campamento del Aaiún y del Hospital Nacional de Rabuni. Método: Se llevó a cabo un estudio descriptivo transversal y analítico entre enero y agosto de 2017. Los participantes se seleccionaron por muestreo consecutivo. La variable principal fue la presencia de síntomas mentales, medida con el Cuestionario General de Salud de Goldberg-28. Se hizo un análisis descriptivo de cada variable sociodemográfica (edad, sexo, nivel de estudios, ocupación) y su asociación con la variable principal mediante regresión logística. Resultados: El 43,3%, IC 95% (38,4-48,3) obtuvo puntuación que sugiere la presencia de síntomas mentales. Las mujeres presentaron una puntuación media superior a los hombres, en las subescalas A (síntomas somáticos) y en la subescala B (ansiedad). Se asociaron con mayor probabilidad de tener síntomas mentales la edad mayor de 50 años y no tener nivel de estudios. Conclusiones: El estudio pone de manifiesto que la prevalencia de síntomas mentales entre los refugiados saharauis es alta, y refuerza la necesidad de más investigaciones científicas en el campo de la salud mental para poner la prevención de los trastornos mentales y la promoción de la salud mental en el foco de las políticas sanitarias.(AU)

Objective: To assess the prevalence of psychopathological symptoms among Saharawi refugees and the influence of sociodemographic factors on the phenotypic expression of mental disorders.Design: Cross-sectional descriptive study. Location: Primary and hospital health care. Participants: 383 participants over 18 years of age, 59.8% women and 40.2% men, with a mean age of 37.2 (SD = 13.0), from the Laayoune camp, and from the Rabuni National Hospital. Methodology: A descriptive, cross-sectional and analytical study was carried out between January and August 2017. Participants were selected by consecutive sampling. The main variable was the presence of mental symptoms, measured with the Goldberg General Health Questionnaire - 28. A descriptive analysis of each sociodemographic variable (age, sex, educational level, occupation) and its association with the main variable was carried out using Logistic regression. Results: 43.3%, 95%CI (38.4-48.3) obtained a score that suggests the presence of mental symptoms. Women presented a mean score higher than men, in subscales A (somatic symptoms) and in subscale B (anxiety). Age over 50 years and having no educational level were associated with a higher probability of having mental symptoms. Conclusions: The study shows that the prevalence of mental symptoms among Saharawi refugees is high, and reinforces the need for more scientific research in the field of mental health to put the prevention of mental disorders and the promotion of mental health in the focus of health policy.(AU)