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.

"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.

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.

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.

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.

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.

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.

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.

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)

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.

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)

Health-related quality of life in GALAHAD: A multicenter, open-label, phase 2 study of niraparib for patients with metastatic castration-resistant prostate cancer and DNA-repair gene defects.

BACKGROUND: Niraparib is a highly selective poly (adenosine diphosphateribose) polymerase-1 and poly (adenosine diphosphate-ribose) polymerase-2 inhibitor indicated for select patients with ovarian, fallopian tube, and primary peritoneal cancer. The phase 2 GALAHAD trial (NCT02854436) demonstrated that niraparib monotherapy is tolerable and efficacious in patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations, particularly those with breast cancer gene (BRCA) alterations who had progressed on prior androgen signaling inhibitor therapy and taxane-based chemotherapy. OBJECTIVE: To report the prespecified patient-reported outcomes analysis from GALAHAD. METHODS: Eligible patients with alterations to BRCA1 and/or BRCA2 (BRCA cohort) and with pathogenic alterations in other HRR genes (other HRR cohort) were enrolled and received niraparib 300 mg once daily. Patient-reported outcome instruments included the Functional Assessment of Cancer Therapy-Prostate and the Brief Pain Inventory-Short Form. Changes from baseline were compared using a mixed-effect model for repeated measures. RESULTS: On average, health-related quality of life (HRQoL) improved in the BRCA cohort by cycle 3 (mean change = 6.03; 95% CI = 2.76-9.29) and was maintained above baseline until cycle 10 (mean change = 2.84; 95% CI = -1.95 to 7.63), whereas the other HRR cohort showed no early change in HRQoL from baseline (mean change = -0.07; 95% CI = -4.69 to 4.55) and declined by cycle 10 (mean change = -5.10; 95% CI = -15.3 to 5.06). Median time to deterioration in pain intensity and pain interference could not be estimated in either cohort. CONCLUSIONS: Patients with advanced mCRPC and BRCA alterations treated with niraparib experienced more meaningful improvement in overall HRQoL, pain intensity, and pain interference compared with those with other HRR alterations. In this population of castrate, heavily pretreated patients with mCRPC and HRR alterations, stabilization, and improvement in HRQoL may be relevant to consider when making treatment decisions. DISCLOSURES: This work was supported by Janssen Research & Development, LLC (no grant number). Dr Smith has received grants and personal fees from Bayer, Amgen, Janssen, and Lilly; and has received personal fees from Astellas Pharma, Novartis, and Pfizer. Dr Sandhu has received grants from Amgen, Endocyte, and Genentech; has received grants and personal fees from AstraZeneca and Merck; and has received personal fees from Bristol Myers Squibb and Merck Serono. Dr George has received personal fees from the American Association for Cancer Research, Axess Oncology, Capio Biosciences, Constellation Pharma, EMD Serono, Flatiron, Ipsen, Merck Sharp & Dohme, Michael J. Hennessey Association, Millennium Medical Publishing, Modra Pharma, Myovant Sciences, Inc., NCI Genitourinary, Nektar Therapeutics, Physician Education Resource, Propella TX, RevHealth, LLC, and UroGPO; has received grants and personal fees from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, and Pfizer; has received personal fees and nonfinancial support from Bayer and UroToday; has received grants from Calithera and Novartis; and has received grants, personal fees, and nonfinancial support from Exelixis, Inc., Sanofi, and Janssen Pharma. Dr Chi has received grants from Janssen during the conduct of the study; has received grants and personal fees from AstraZeneca, Bayer, Astellas Pharma, Novartis, Pfizer, POINT Biopharma, Roche, and Sanofi; and has received personal fees from Daiichi Sankyo, Merck, and Bristol Myers Squibb. Dr Saad has received grants, personal fees, and nonfinancial support from Janssen during the conduct of the study; and has received grants, personal fees, and nonfinancial support from AstraZeneca, Astellas Pharma, Pfizer, Bayer, Myovant, Sanofi, and Novartis. Dr Thiery-Vuillemin has received grants, personal fees, and nonfinancial support from Pfizer; has received personal fees and nonfinancial support from AstraZeneca, Janssen, Ipsen, Roche/Genentech, Merck Sharp & Dohme, and Astellas Pharma; and has received personal fees from Sanofi, Novartis, and Bristol Myers Squibb. Dr Olmos has received grants, personal fees, and nonfinancial support from AstraZeneca, Bayer, Janssen, and Pfizer; has received personal fees from Clovis, Daiichi Sankyo, and Merck Sharp & Dohme; and has received nonfinancial support from Astellas Pharma, F. Hoffman-LaRoche, Genentech, and Ipsen. Dr Danila has received research support from the US Department of Defense, the American Society of Clinical Oncology, the Prostate Cancer Foundation, Stand Up to Cancer, Janssen Research & Development, Astellas Pharma, Medivation, Agensys, Genentech, and CreaTV. Dr Gafanov has received grants from Janssen during the conduct of the study. Dr Castro has received grants from Janssen during the conduct of the study; has received grants and personal fees from Janssen, Bayer, AstraZeneca, and Pfizer; and has received personal fees from Astellas Pharma, Merck Sharp & Dohme, Roche, and Clovis. Dr Moon has received research funding from SeaGen, HuyaBio, Janssen, BMS, Aveo, Xencor, and has received personal fees from Axess Oncology, MJH, EMD Serono, and Pfizer. Dr Joshua has received nonfinancial support from Janssen; consulted or served in an advisory role for Neoleukin, Janssen Oncology, Ipsen, AstraZeneca, Sanofi, Noxopharm, IQvia, Pfizer, Novartis, Bristol Myers Squibb, Merck Serono, and Eisai; and received research funding from Bristol Myers Squibb, Janssen Oncology, Merck Sharp & Dohme, Mayne Pharma, Roche/Genentech, Bayer, MacroGenics, Lilly, Pfizer, AstraZeneca, and Corvus Pharmaceuticals. Drs Mason, Liu, Bevans, Lopez-Gitlitz, and Francis and Mr Espina are employees of Janssen Research & Development. Dr Mason owns stocks with Janssen. Dr Fizazi has participated in advisory boards and talks for Amgen, Astellas, AstraZeneca, Bayer, Clovis, Daiichi Sankyo, Janssen, MSD, Novartis/AAA, Pfizer, and Sanofi, with honoraria to his institution (Institut Gustave Roussy); has participated in advisory boards for, with personal honoraria from, Arvinas, CureVac, MacroGenics, and Orion. Study registration number: NCT02854436.

Germline DNA Repair Genes Pathogenic Variants Among Mexican Patients With Prostate Cancer.

BACKGROUND: Early identification of germline mutation carriers may be relevant for the optimal management of prostate cancer and to inform cancer risk in relatives. However, population minorities have limited access to genetic testing. The aim of this study was to describe the frequency of DNA repair gene pathogenic variants (PVs) among Mexican men with prostate cancer referred for Genomic Cancer Risk Assessment and testing. METHODS: Patients diagnosed with prostate cancer who meet criteria for genetic testing and enrolled in the Clinical Cancer Genomics Community Research Network at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City were included. Descriptive statistics were performed using frequency and proportions for categorical variables and median and range for quantitative variables. X2 and t test were used for group comparisons. RESULTS: A total of 199 men were enrolled, median age at diagnosis was 66 (range 44-88) years; 45% were de novo metastatic and 44% were high- very high and 10% were intermediate risk group. Four (2%) had a pathogenic germline variant; one each of the following genes: ATM, CHEK2, BRIP1, and MUTYH (all monoallelic). Younger men at diagnosis were more likely to carry a PV than older age at diagnosis (56.7 vs. 66.4 years, P = .01). CONCLUSION: Our results showed a low prevalence of known prostate cancer associated PVs and no BRCA PVs in Mexican men with prostate cancer. This suggests that the genetic and/or epidemiologic risk factors for prostate cancer are not well characterized in this specific population.

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

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.

Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022.

BACKGROUND: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. OBJECTIVE: To present the voting results of the APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. RESULTS AND LIMITATIONS: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. TWITTER SUMMARY: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. TAKE-HOME MESSAGE: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.

Critical Action Among Asian and Hispanic/Latinx Youth: Identifying a Multidimensional Measure and Exploring Within-Group Differences.

Critical action-behaviors aimed at dismantling systems of oppression-must be examined within youths' racialized experiences and should incorporate cultural and sociohistorical factors. We considered an expansive list of items capturing youth behaviors to create a novel four-factor (service, community change, expression, and care) measure of critical action for Asian and Hispanic/Latinx youth. Multiple distinct profiles of critical action were identified within both racial-ethnic groups, and associations between the profiles and sociodemographic and contextual support variables were explored. Gender differences in the type of critical action were found in both racial-ethnic groups, pointing to the potential influence of gender roles on critical action among these populations. Differences in critical action patterns were also found between those born in the U.S. versus those born outside the U.S.; access to critical action may differ within racial-ethnic groups depending on birthplace and associated nuances in familial and cultural contexts. This paper demonstrated a need for attending to variation between and within groups in the study of critical action in order to effectively support racialized youth's coping within and resistance against systems of oppression.

Inhibition of Prolyl Oligopeptidase Restores Prohibitin 2 Levels in Psychosis Models: Relationship to Cognitive Deficits in Schizophrenia.

Cognitive impairment represents one of the core features of schizophrenia. Prolyl Oligopeptidase (POP) inhibition is an emerging strategy for compensating cognitive deficits in hypoglutamatergic states such as schizophrenia, although little is known about how POP inhibitors exert their pharmacological activity. The mitochondrial and nuclear protein Prohibitin 2 (PHB2) could be dysregulated in schizophrenia. However, altered PHB2 levels in schizophrenia linked to N-methyl-D-aspartate receptor (NMDAR) activity and cognitive deficits are still unknown. To shed light on this, we measured the PHB2 levels by immunoblot in a postmortem dorsolateral prefrontal cortex (DLPFC) of schizophrenia subjects, in the frontal pole of mice treated with the NMDAR antagonists phencyclidine and dizocilpine, and in rat cortical astrocytes and neurons treated with dizocilpine. Mice and cells were treated in combination with the POP inhibitor IPR19. The PHB2 levels were also analyzed by immunocytochemistry in rat neurons. The PHB2 levels increased in DLPFC in cases of chronic schizophrenia and were associated with cognitive impairments. NMDAR antagonists increased PHB2 levels in the frontal pole of mice and in rat astrocytes and neurons. High levels of PHB2 were found in the nucleus and cytoplasm of neurons upon NMDAR inhibition. IPR19 restored PHB2 levels in the acute NMDAR inhibition. These results show that IPR19 restores the upregulation of PHB2 in an acute NMDAR hypoactivity stage suggesting that the modulation of PHB2 could compensate NMDAR-dependent cognitive impairments in schizophrenia.