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BACKGROUND: Virological failure, drug resistance, toxicities, and other issues make it difficult for ART to maintain long-term sustainability. These issues would force a modification in the patient's treatment plan. The aim of this research was to determine whether first-line antiretroviral therapy is durable and to identify the factors that lead to patients on HAART changing their first highly active antiretroviral therapy regimen. METHODS: A retrospective cohort study was conducted from October, 2019-March, 2020 across all regional states including Addis Ababa and Dire Dawa administrative cities. The target population is from all health facilities that have been providing ART service for at least the past 6 months as of October 2019. Multi-stage clustered sampling method was used to select study facilities and participants. Simple random selected ART medical records of patients ever enrolled in ART treatment services. We adopted a multi-state survival modelling (msm) approach assuming each treatment regimen as state. We estimate the transition probability of patients to move from one regimen to another for time to treatment change/switch. We estimated the transition probability, prediction probabilities and length of stay and factor associated with treatment modification of patients to move from one regimen to another. RESULTS: Any of the six therapy combinations (14.4%) altered their treatment at least once during the follow-up period for a variety of reasons. Of the patients, 4,834 (13.26%) changed their treatments just once, while 371 (1.1%) changed it more than once. For 38.6% of the time, a treatment change was undertaken due to toxicity, another infection or comorbidity, or another factor, followed by New drugs were then made accessible and other factors 18.3% of the time, a drug was out of supply; 2.6% of those instances involved pregnancy; and 43.1% involved something else. Highly active anti-retroviral therapy (HAART) combinations TDF + 3TC + NVP, d4T + 3TC + NVP, and TDF + 3TC + EFV were high to treatment alterations in all reasons of treatment modifications, with 29.74%, 26.52%, and 19.52% treatment changes, respectively. Early treatment modification or regime change is one of the treatment combinations that include the d4T medication that creates major concern. The likelihood of staying and moving at the the start of s = 0 and 30-month transitions increased, but the likelihood of staying were declined. For this cohort dataset, the presence of opportunistic disease, low body weight, baseline CD4 count, and baseline TB positive were risk factors for therapy adjustment. CONCLUSION: Given that the current study took into account a national dataset, it provides a solid basis for ART drug status and management. The patient had a higher likelihood of adjusting their treatment at some point during the follow-up period due to drug toxicity, comorbidity, drug not being available, and other factors, according to the prediction probability once more. Baseline TB positivity, low CD4 count, opportunistic disease, and low body weight were risk factors for therapy adjustment in this cohort dataset.
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Fármacos Anti-HIV , Terapia Antirretroviral de Alta Atividade , Infecções por HIV , Cadeias de Markov , Tempo para o Tratamento , Humanos , Etiópia/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Adulto , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Fármacos Anti-HIV/uso terapêutico , Tempo para o Tratamento/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto Jovem , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Síndrome da Imunodeficiência Adquirida/epidemiologia , AdolescenteRESUMO
STUDY QUESTION: Which actively translated maternal transcripts are differentially regulated between clinically relevant in vitro and in vivo maturation (IVM) conditions in mouse oocytes and zygotes? SUMMARY ANSWER: Our findings uncovered significant differences in the global transcriptome as well as alterations in the translation of specific transcripts encoding components of energy production, cell cycle regulation, and protein synthesis in oocytes and RNA metabolism in zygotes. WHAT IS KNOWN ALREADY: Properly regulated translation of stored maternal transcripts is a crucial factor for successful development of oocytes and early embryos, particularly due to the transcriptionally silent phase of meiosis. STUDY DESIGN, SIZE, DURATION: This is a basic science study utilizing an ICR mouse model, best suited for studying in vivo maturation. In the treatment group, fully grown germinal vesicle oocytes from stimulated ovaries were in vitro matured to the metaphase II (MII) stage either as denuded without gonadotropins (IVM DO), or as cumulus-oocyte complexes (IVM COC) in the presence of 0.075 IU/ml recombinant FSH (rFSH) and 0.075 IU/ml recombinant hCG (rhCG). To account for changes in developmental competence, IVM COC from non-stimulated ovaries (IVM COC-) were included. In vivo matured MII oocytes (IVO) from stimulated ovaries were used as a control after ovulation triggering with rhCG. To simulate standard IVM conditions, we supplemented media with amino acids, vitamins, and bovine serum albumin. Accordingly, in vitro pronuclear zygotes (IMZ) were generated by IVF from IVM DO, and were compared to in vivo pronuclear zygotes (IVZ). All experiments were performed in quadruplicates with samples collected for both polyribosome fractionation and total transcriptome analysis. Samples were collected over three consecutive months. PARTICIPANTS/MATERIALS, SETTING, METHODS: All ICR mice were bred under legal permission for animal experimentation (no. MZE-24154/2021-18134) obtained from the Ministry of Agriculture of the Czech Republic. Actively translated (polyribosome occupied) maternal transcripts were detected in in vitro and in vivo matured mouse oocytes and zygotes by density gradient ultracentrifugation, followed by RNA isolation and high-throughput RNA sequencing. Bioinformatic analysis was performed and subsequent data validation was done by western blotting, radioactive isotope, and mitotracker dye labelling. MAIN RESULTS AND THE ROLE OF CHANCE: Gene expression analysis of acquired polysome-derived high-throughput RNA sequencing data revealed significant changes (RPKM ≥ 0.2; P ≤ 0.005) in translation between in vitro and in vivo matured oocytes and respectively produced pronuclear zygotes. Surprisingly, the comparison between IVM DO and IVM COC RNA-seq data of both fractionated and total transcriptome showed very few transcripts with more than a 2-fold difference. Data validation by radioactive isotope labelling revealed a decrease in global translation bof20% in IVM DO and COC samples in comparison to IVO samples. Moreover, IVM conditions compromised oocyte energy metabolism, which was demonstrated by both changes in polysome recruitment of each of 13 mt-protein-coding transcripts as well as by validation using mitotracker red staining. LARGE SCALE DATA: The data discussed in this publication have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO Series accession number GSE241633 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE241633). LIMITATIONS, REASONS FOR CAUTION: It is extremely complicated to achieve in vivo consistency in animal model systems such as porcine or bovine. To achieve a high reproducibility of in vivo stimulations, the ICR mouse model was selected. However, careful interpretation of our findings with regard to assisted reproductive techniques has to be made by taking into consideration intra-species differences between the mouse model and humans. Also, the sole effect of the cumulus cells' contribution could not be adequately addressed by comparing IVM COC and IVM DO, because the IVM DO were matured without gonadotropin supplementation. WIDER IMPLICATIONS OF THE FINDINGS: Our findings confirmed the inferiority of standard IVM technology compared with the in vivo approach. It also pointed at compromised biological processes employed in the critical translational regulation of in vitro matured MII oocytes and pronuclear zygotes. By highlighting the importance of proper translational regulation during in vitro oocyte maturation, this study should prompt further clinical investigations in the context of translation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Czech Grant Agency (22-27301S), Charles University Grant Agency (372621), Ministry of Education, Youth and Sports (EXCELLENCE CZ.02.1.01/0.0/0.0/15_003/0000460 OP RDE), and Institutional Research Concept RVO67985904. No competing interest is declared.
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Células do Cúmulo , Desenvolvimento Embrionário , Técnicas de Maturação in Vitro de Oócitos , Camundongos Endogâmicos ICR , Oócitos , Animais , Oócitos/metabolismo , Feminino , Camundongos , Desenvolvimento Embrionário/fisiologia , Células do Cúmulo/metabolismo , Biossíntese de Proteínas , Transcriptoma , Zigoto/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Gonadotropina Coriônica/farmacologiaRESUMO
Infertility represents a significant global health challenge impacting millions of couples worldwide. Approximately half of all infertile couples exhibit compromised semen quality, indicative of diminished male fertility. While the diagnosis of male infertility traditionally relies on semen analysis, its limitations in providing a comprehensive assessment of male reproductive health have spurred efforts to identify novel biomarkers. Seminal plasma, a complex fluid containing proteins, lipids, and metabolites, has emerged as a rich source of such indicators. Reproduction depends heavily on seminal plasma, the primary transporter of chemicals from male reproductive glands. It provides a non-invasive sample for urogenital diagnostics and has demonstrated potential in the identification of biomarkers linked to illnesses of the male reproductive system. The abundance of seminal proteins has enabled a deeper understanding of their biological functions, origins, and differential expression in various conditions associated with male infertility, including azoospermia, asthenozoospermia, oligozoospermia, teratozoospermia, among others. The true prevalence of male infertility is understated due to the limitations of the current diagnostic techniques. This review critically evaluates the current landscape of seminal plasma biomarkers and their utility in assessing male infertility. Βy bridging the gap between research and clinical practice, the integrative assessment of seminal plasma biomarkers offers a multimodal approach to comprehensively evaluate male infertility.
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Antiretroviral therapy (ART) is needed across the lifetime to maintain viral suppression for people living with HIV. In South Africa, obstacles to reliable access to ART persist and are magnified in rural areas, where HIV services are also typically costlier to deliver. A recent pilot randomized study (the Deliver Health Study) found that home-delivered ART refills, provided at a low user fee, effectively overcame logistical barriers to access and improved clinical outcomes in rural South Africa. In the present costing study using the payer perspective, we conducted retrospective activity-based micro-costing of home-delivered ART within the Deliver Health Study and when provided at-scale (in a rural setting), and compared to facility-based costs using provincial expenditure data (covering both rural and urban settings). Within the context of the pilot Deliver Health Study which had an average of three deliveries per day for three days a week, home-delivered ART cost (in 2022 USD) $794 in the first year and $714 for subsequent years per client after subtracting client fees, compared with $167 per client in provincial clinic-based care. We estimated that home-delivered ART can reasonably be scaled up to 12 home deliveries per day for five days per week in the rural setting. When delivered at scale, home-delivered ART cost $267 in the first year and $183 for subsequent years per client. Average costs of home delivery further decreased when increasing the duration of refills from three-months to six- and 12-month scripts (from $183 to $177 and $135 per client, respectively). Personnel costs were the largest cost for home-delivered refills while ART drug costs were the largest cost of clinic-based refills. When provided at scale, home-delivered ART in a rural setting not only offers clinical benefits for a hard-to-reach population but is also comparable in cost to the provincial standard of care.
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STUDY QUESTION: Does the use of frozen sperm affect live birth rate (LBR) and cumulative LBR (CLBR) compared to fresh sperm samples in oocyte donation ICSI cycles? SUMMARY ANSWER: Although there were slight decreases in pregnancy rates (PRs) and LBR, as well as CLBR per embryo replaced and per embryo transfer (ET), when frozen sperm samples were used compared to fresh ejaculates, their clinical impact was limited. WHAT IS KNOWN ALREADY: Sperm cryopreservation is part of the daily routine in reproduction clinics worldwide because of its many advantages in cycle planning. Nonetheless, there is a lack of agreement in terms of its impact on the outcomes of ICSI cycles. Previous studies showed conflicting conclusions and focused on different populations, which makes reaching consensus on the impact of sperm freezing-thawing complicated. Moreover, classical parameters are used to assess cycle success: pregnancy, live birth and miscarriage rates per ET. This study reports those measurements plus CLBR, which more accurately reflects the impact of the technique on the likelihood of achieving a newborn. STUDY DESIGN, SIZE, DURATION: A retrospective multicenter observational cohort study, including data from 37 041 couples and 44 423 ICSI procedures from January 2008 to June 2022, was carried out. The group using frozen sperm included 23 852 transferred embryos and 108 661 inseminated oocytes, whereas the fresh sample group comprised 73 953 embryos replaced and 381 509 injected oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS: Outcomes measured per first ET and per ET were compared between groups using Fisher's exact test and Chi-squared test, as appropriate. Binary-logistics regression models were used to adjust the analyses according to clinically relevant co-variables. Kaplan-Meier curves plotted the CLBR per oocyte inseminated, per embryo replaced and per ET, and compared between groups using the Mantel-Cox test. Cox regressions were employed for the multivariate analyses of CLBR. MAIN RESULTS AND THE ROLE OF CHANCE: The frozen sperm group showed a slightly lower biochemical (3.55% and 2.56%), clinical (3.68% and 3.54%) and ongoing (3.63% and 3.15%) PR compared to the cycles using fresh sperm, respectively, both per first ET and per ET. LBR was 4.57% lower per first ET and 3.95% lower per ET in the frozen sperm group than the fresh sperm group. There was also a subtle increase of 2.66% in biochemical miscarriage rate per ET when using frozen versus fresh sperm. All these differences remained statistically significant after the multivariate analysis (adjusted P ≤ 0.001). There were statistically significant differences in CLBR per embryo replaced and per ET but not per oocyte used (adjusted P = 0.071). Despite the statistical significance of the differences between the groups, those using frozen sperm required only 0.54 more oocytes injected, 0.45 more embryos transferred and 0.41 more ET procedures, on average, to achieve a live birth compared to the fresh samples. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study subjects the data to biases or potential errors during annotation on the source clinical and cycle records. This study uses multivariate analyses to control biases as much as possible. Using the oocyte donation model also contributes to reducing heterogeneity in the oocyte quality factor. WIDER IMPLICATIONS OF THE FINDINGS: The large sample sizes included in this study allowed for the detection of small changes in cycle success rates between groups. Although statistically significant, the decrease in PRs, LBR, and CLBR when using frozen sperm can be clinically overlooked in favor of the many benefits of sperm cryopreservation. STUDY FUNDING/COMPETING INTEREST(S): None declared. TRIAL REGISTRATION NUMBER: Not applicable.
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Antiretroviral medications have substantially improved life expectancy for people with HIV. These medications are also highly effective in preventing HIV acquisition in people who do not have HIV, a strategy known as HIV preexposure prophylaxis (PrEP). Despite these advances, some life and disability insurers continue to deny or limit coverage for people with HIV, and some have even refused to cover people who are using PrEP to protect themselves. These policies unfairly deny people with HIV, PrEP users, and their families the peace of mind and financial protection that can come with life and disability insurance coverage. This article summarizes the current evidence on HIV treatment and prevention, arguing that underwriting decisions by life and disability insurers should not be made based on HIV status or use of PrEP.
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Infecções por HIV , Seguro por Deficiência , Seguro de Vida , Humanos , Infecções por HIV/prevenção & controle , Profilaxia Pré-Exposição/economia , Cobertura do Seguro , Política de Saúde , Fármacos Anti-HIV/uso terapêutico , Estados Unidos/epidemiologiaRESUMO
Introduction: The current study builds on the expertise of National Gallery Singapore and Nanyang Technological University Singapore (NTU) in developing and piloting an enhanced version of the Slow Art program, namely "Slow Art Plus" for mental health promotion. Methods: A single-site, open-label, waitlist Randomized Control Trial (RCT) design comprising of a treatment group and waitlist control group was adopted (ClinicalTrials.gov ID: NCT05803226). Participants (N = 196) completed three online questionnaires at three timepoints: baseline [T1], immediately post-intervention/s baseline [T2], post-intervention follow-up/immediately post-intervention [T3]. Qualitative focus groups were conducted to evaluate program acceptability. Results: A mixed model ANOVA was performed to understand intervention effectiveness between the immediate intervention group and waitlist control group. The analyses revealed a significant interaction effect where intervention group participants reported an improvement in spiritual well-being (p = 0.001), describing their thoughts and experiences (p = 0.02), and nonreacting to inner experiences (p = 0.01) immediately after Slow Art Plus as compared to the control group. Additionally, one-way repeated measure ANOVAs were conducted for the intervention group to evaluate maintenance effects of the intervention. The analyses indicated significant improvements in perceived stress (p < 0.001), mindfulness (p < 0.001) as well as multiple mindfulness subscales, active engagement with the world (p = 0.003), and self-compassion (p = 0.02) 1 day after the completion of Slow Art Plus. Results from framework analysis of focus group data revealed a total of two themes (1: Experiences of Slow Art Plus, 2: Insights to Effective Implementation) and six subthemes (1a: Peaceful relaxation, 1b: Self-Compassion, 1c: Widened Perspective, 2a: Valuable Components, 2b: Execution Requisites, 2c: Suggested Enhancements), providing valuable insights to the overall experience and implementation of the intervention. Discussion: Slow Art Plus represents a unique approach, offering a standardized, multimodal, single-session program that integrates mindfulness and self-compassion practices, as well as reflective and creative expressions with Southeast Asian art. It demonstrates potential in meeting the mental health needs of a wide range of individuals and could be readily incorporated into social prescribing initiatives for diverse populations.
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Grupos Focais , Promoção da Saúde , Saúde Mental , Humanos , Feminino , Masculino , Adulto , Promoção da Saúde/métodos , Singapura , Inquéritos e Questionários , Listas de Espera , Pessoa de Meia-Idade , Arteterapia/métodos , Projetos PilotoRESUMO
Reduced susceptibility to ART, the first-line treatment against malaria, is common in South East Asia (SEA). It is associated with point mutations, mostly in kelch13 (k13) but also in other genes, like ubp1. K13 and its compartment neighbors (KICs), including UBP1, are involved in endocytosis of host cell cytosol. We tested 135 mutations in KICs but none conferred ART resistance. Double mutations of k13C580Y with k13R539T or k13C580Y with ubp1R3138H, did also not increase resistance. In contrast, k13C580Y parasites subjected to consecutive RSAs did, but the k13 sequence was not altered. Using isogenic parasites with different k13 mutations, we found correlations between K13 protein amount, resistance, and fitness cost. Titration of K13 and KIC7 indicated that the cellular levels of these proteins determined resistance through the rate of endocytosis. While fitness cost of k13 mutations correlated with ART resistance, ubp1R3138H caused a disproportionately higher fitness cost. IMPORTANCE: Parasites with lowered sensitivity to artemisinin-based drugs are becoming widespread. However, even in these "resistant" parasites not all parasites survive treatment. We found that the proportion of surviving parasites correlates with the fitness cost of resistance-inducing mutations which might indicate that the growth disadvantages prevents resistance levels where all parasites survive treatment. We also found that combining two common resistance mutations did not increase resistance levels. However, selection through repeated ART-exposure did, even-though the known resistance genes, including k13, were not further altered, suggesting other causes of increased resistance. We also observed a disproportionally high fitness cost of a resistance mutation in resistance gene ubp1. Such high fitness costs may explain why mutations in ubp1 and other genes functioning in the same pathway as k13 are rare. This highlights that k13 mutations are unique in their ability to cause resistance at a comparably low fitness cost.
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Antimaláricos , Artemisininas , Resistência a Medicamentos , Plasmodium falciparum , Proteínas de Protozoários , Plasmodium falciparum/genética , Plasmodium falciparum/efeitos dos fármacos , Resistência a Medicamentos/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Antimaláricos/farmacologia , Artemisininas/farmacologia , Mutação , Humanos , Malária Falciparum/parasitologia , Aptidão Genética , Sudeste Asiático , EndocitoseRESUMO
Despite the effectiveness of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection remains a global public health concern. However, weaknesses in its management regarding access to integrated HIV care include treatment gaps and loss to follow-up (LTFU) from antiretroviral treatment (ART). This study aimed to characterize the epidemiological and clinical profiles of people living with HIV/AIDS (PLHA) in LTFU from HIV care in Campo Grande, Central Brazil. This retrospective cross-sectional study was conducted between January 2021 and April 2022 using secondary data from PLHA who had LTFU in Campo Grande. A total of 852 patients with PLHA were included in this study. The majority of participants in LTFU were male (63.1%), had a CD4 cell count > 200 cells/mm3 (68.2%), and had been treated for ≥ 3 months (86.4%). Only 287 (33.7%) participants had undetectable HIV viral load. Of the total number of patients who returned to treatment during the study period, 448 (54.3%) were LTFU-positive. The tracking strategy was not applied to 556 (65.26%) patients, and 44.4% of the participants had been in spontaneous demand. These results highlight the relevance of patient-centered interventions and the need to ensure early treatment and promote retention in care systems with consequent viral suppression, impacting the healthcare indicators of the population, with emphasis on health managers and stakeholders in HIV care.
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Infecções por HIV , Perda de Seguimento , Carga Viral , Humanos , Masculino , Brasil/epidemiologia , Feminino , Estudos Transversais , Estudos Retrospectivos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Adulto , Pessoa de Meia-Idade , Contagem de Linfócito CD4 , Fármacos Anti-HIV/uso terapêutico , Acessibilidade aos Serviços de Saúde , Adesão à Medicação/estatística & dados numéricosRESUMO
Measurement-based verification is impossible for the patient-specific quality assurance (QA) of online adaptive magnetic resonance imaging-guided radiotherapy (oMRgRT) because the patient remains on the couch throughout the session. We assessed a deep learning (DL) system for oMRgRT to predict the gamma passing rate (GPR). This study collected 125 verification plans [reference plan (RP), 100; adapted plan (AP), 25] from patients with prostate cancer treated using Elekta Unity. Based on our previous study, we employed a convolutional neural network that predicted the GPRs of nine pairs of gamma criteria from 1%/1 mm to 3%/3 mm. First, we trained and tested the DL model using RPs (n = 75 and n = 25 for training and testing, respectively) for its optimization. Second, we tested the GPR prediction accuracy using APs to determine whether the DL model could be applied to APs. The mean absolute error (MAE) and correlation coefficient (r) of the RPs were 1.22 ± 0.27% and 0.29 ± 0.10 in 3%/2 mm, 1.35 ± 0.16% and 0.37 ± 0.15 in 2%/2 mm, and 3.62 ± 0.55% and 0.32 ± 0.14 in 1%/1 mm, respectively. The MAE and r of the APs were 1.13 ± 0.33% and 0.35 ± 0.22 in 3%/2 mm, 1.68 ± 0.47% and 0.30 ± 0.11 in 2%/2 mm, and 5.08 ± 0.29% and 0.15 ± 0.10 in 1%/1 mm, respectively. The time cost was within 3 s for the prediction. The results suggest the DL-based model has the potential for rapid GPR prediction in Elekta Unity.
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Aprendizado Profundo , Imageamento por Ressonância Magnética , Aceleradores de Partículas , Neoplasias da Próstata , Radioterapia Guiada por Imagem , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Masculino , Planejamento da Radioterapia Assistida por Computador/métodos , Raios gamaRESUMO
STUDY QUESTION: Which assited reproductive technology (ART) interventions in high-income countries are cost-effective and which are not? SUMMARY ANSWER: Among all ART interventions assessed in economic evaluations, most high-cost interventions, including preimplantation genetic testing for aneuploidy (PGT-A) for a general population and ICSI for unexplained infertility, are unlikely to be cost-effective owing to minimal or no increase in effectiveness. WHAT IS KNOWN ALREADY: Approaches to reduce costs in order to increase access have been identified as a research priority for future infertility research. There has been an increasing number of ART interventions implemented in routine clinical practice globally, before robust assessments of evidence on economic evaluations. The extent of clinical effectiveness of some studied comparisons has been evaluated in high-quality research, allowing more informative decision making around cost-effectiveness. STUDY DESIGN, SIZE, DURATION: We performed a systematic review and searched seven databases (MEDLINE, PUBMED, EMBASE, COCHRANE, ECONLIT, SCOPUS, and CINAHL) for studies examining ART interventions for infertility together with an economic evaluation component (cost-effectiveness, cost-benefit, cost-utility, or cost-minimization assessment), in high-income countries, published since January 2011. The last search was 22 June 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Two independent reviewers assessed publications and included those fulfilling the eligibility criteria. Studies were examined to assess the cost-effectiveness of the studied intervention, as well as the reporting quality of the study. The chosen outcome measure and payer perspective were also noted. Completeness of reporting was assessed against the Consolidated Health Economic Evaluation Reporting Standard. Results are presented and summarized based on the intervention studied. MAIN RESULTS AND THE ROLE OF CHANCE: The review included 40 studies which were conducted in 11 high-income countries. Most studies (n = 34) included a cost-effectiveness analysis. ART interventions included medication or strategies for controlled ovarian stimulation (n = 15), IVF (n = 9), PGT-A (n = 7), single embryo transfer (n = 5), ICSI (n = 3), and freeze-all embryo transfer (n = 1). Live birth was the mostly commonly reported primary outcome (n = 27), and quality-adjusted life years was reported in three studies. The health funder perspective was used in 85% (n = 34) of studies. None of the included studies measured patient preference for treatment. It remains uncertain whether PGT-A improves pregnancy rates compared to IVF cycles managed without PGT-A, and therefore cost-effectiveness could not be demonstrated for this intervention. Similarly, ICSI in non-male factor infertility appears not to be clinically effective compared to standard fertilization in an IVF cycle and is therefore not cost-effective. Interventions such as use of biosimilars or HMG for ovarian stimulation are cheaper but compromise clinical effectiveness. LIMITATIONS, REASONS FOR CAUTION: Lack of both preference-based and standardized outcomes limits the comparability of results across studies. The selection of efficacy evidence offered for some interventions for economic evaluations is not always based on high-quality randomized trials and systematic reviews. In addition, there is insufficient knowledge of the willingness to pay thresholds of individuals and state funders for treatment of infertility. There is variable quality of reporting scores, which might increase uncertainty around the cost-effectiveness results. WIDER IMPLICATIONS OF THE FINDINGS: Investment in strategies to help infertile people who utilize ART is justifiable at both personal and population levels. This systematic review may assist ART funders decide how to best invest to maximize the likelihood of delivery of a healthy child. STUDY FUNDING/COMPETING INTEREST(S): There was no funding for this study. E.C. and R.W. receive salary support from the National Health and Medical Research Council (NHMRC) through their fellowship scheme (EC GNT1159536, RW 2021/GNT2009767). M.D.-T. reports consulting fees from King Fahad Medical School. All other authors have no competing interests to declare. REGISTRATION NUMBER: Prospero CRD42021261537.
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Análise Custo-Benefício , Países Desenvolvidos , Técnicas de Reprodução Assistida , Humanos , Técnicas de Reprodução Assistida/economia , Feminino , Gravidez , Países Desenvolvidos/economia , Infertilidade/terapia , Infertilidade/economia , Injeções de Esperma Intracitoplásmicas/economia , Injeções de Esperma Intracitoplásmicas/métodos , Diagnóstico Pré-Implantação/economia , Diagnóstico Pré-Implantação/métodos , Taxa de GravidezRESUMO
Background: Dust generated during the processing of building materials enterprises can pose a serious health risk. The study aimed to compare and analyze the results of ART and the Monte Carlo model for the dust exposure assessment in building materials enterprises, to derive the application scope of the two models. Methods: First, ART and the Monte Carlo model were used to assess the exposure to dust in each of the 15 building materials enterprises. Then, a comparative analysis of the exposure assessment results was conducted. Finally, the model factors were analyzed using correlation analysis and the scope of application of the models was determined. Results: The results show that ART is mainly influenced by four factors, namely, localized controls, segregation, dispersion, surface contamination, and fugitive emissions, and applies to scenarios where the workplace information of the building materials enterprises is specific and the average dust concentration is greater than or equal to 1.5 mg/m3. The Monte Carlo model is mainly influenced by the dust concentration in the workplace of building materials enterprises and is suitable for scenarios where the dust concentration in the workplace of the building materials enterprises is relatively uniform and the average dust concentration is less than or equal to 6mg/m3. Conclusion: ART is most accurate when workplace information is specific and average dust concentration is > 1.5 mg/m3; whereas, The Monte Carlo model is the best when dust concentration is homogeneous and average dust concentration is < 6 mg/m3.
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INTRODUCTION: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures. RESULTS: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m2 (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m2, and CD4 counts <200 cells/µL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/µL were independent risk factors for lower weight gain after TLD switch. CONCLUSIONS: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen.
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Alcinos , Benzoxazinas , Ciclopropanos , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piridonas , Aumento de Peso , Humanos , Masculino , Feminino , Aumento de Peso/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Adulto , África do Sul , Estudos Retrospectivos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Oxazinas/uso terapêutico , Benzoxazinas/uso terapêutico , Benzoxazinas/efeitos adversos , Benzoxazinas/administração & dosagem , Pessoa de Meia-Idade , Piperazinas , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Estudos Longitudinais , Índice de Massa Corporal , Lamivudina/uso terapêutico , Lamivudina/efeitos adversos , Lamivudina/administração & dosagem , Tenofovir/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/administração & dosagem , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagemRESUMO
Advanced oxidation processes (AOPs) are wastewater treatment technologies that stand out for their ability to degrade Contaminants of Emerging Concern (CECs). The literature has extensively investigated these removal processes for different aqueous matrices. Once technically mature, some of these systems have become accredited to be applied on a large scale, and therefore, their systemic performances in the environmental and cost spheres have also become essential requirements. This study proposed corroborating this trend, analyzing the available literature on the subject to verify how experts in the AOP area investigated this integration during 2015-2023. For this purpose, a sample of publications was treated by applying the Systematic Review (SR) methodology. This resulted in an extract of 83 studies that adopted life-cycle logic to estimate environmental impacts and process costs or evaluated them as complementary to the technical dimension of each treatment technology. This analysis found that both dimensions can be used for selecting or sizing AOPs at the design scale. However, the appropriate choice of the impact categories for the environmental assessment and establishing a methodology for cost analysis can make the approach still more effective. In addition, a staggering number of processes would broaden the reality and applicability of the estimates, and adopting multicriteria analysis methodologies could address essential aspects of decision-making processes during the design of the arrangements. By meeting the original purposes, the study broadened the requirements for designing AOPs and disseminating their use in mitigating the discharge of CECs.
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Bibliometria , Oxirredução , Águas Residuárias/química , Purificação da Água/métodos , Eliminação de Resíduos Líquidos/métodosRESUMO
BACKGROUND: ART differs in effectiveness, side-effects, administration, and costs. To improve the decision-making process, we need to understand what factors patients consider to be most important. OBJECTIVE AND RATIONALE: We conducted this systematic review to assess which aspects of ART treatment (effectiveness, safety, burden, costs, patient-centeredness, and genetic parenthood) are most important in the decision-making of patients with an unfulfilled wish to have a child. SEARCH METHODS: We searched studies indexed in Embase, PubMed, PsycINFO, and CINAHL prior to November 2023. Discrete choice experiments (DCEs), surveys, interviews, and conjoint analyses (CAs) about ART were included. Studies were included if they described two or more of the following attributes: effectiveness, safety, burden, costs, patient-centeredness, and genetic parenthood.Participants were men and women with an unfulfilled wish to have a child. From each DCE/CA study, we extracted the beta-coefficients and calculated the relative importance of treatment attributes or, in case of survey studies, extracted results. We assessed the risk of bias using the rating developed by the Grading of Recommendations Assessment, Development and Evaluation working group. Attributes were classified into effectiveness, safety, burden, costs, patient-centeredness, genetic parenthood, and others. OUTCOMES: The search identified 938 studies of which 20 were included: 13 DCEs, three survey studies, three interview studies, and one conjoint analysis, with a total of 12â452 patients. Per study, 47-100% of the participants were women. Studies were assessed as having moderate to high risk of bias (critical: six studies, serious: four studies, moderate: nine studies, low: one study). The main limitation was the heterogeneity in the questionnaires and methodology utilized. Studies varied in the number and types of assessed attributes. Patients' treatment decision-making was mostly driven by effectiveness, followed by safety, burden, costs, and patient-centeredness. Effectiveness was rated as the first or second most important factor in 10 of the 12 DCE studies (83%) and the relative importance of effectiveness varied between 17% and 63%, with a median of 34% (moderate certainty of evidence). Of eight studies evaluating safety, five studies valued safety as the first or second most important factor (63%), and the relative importance ranged from 8% to 35% (median 23%) (moderate certainty of evidence). Cost was rated as first or second most important in five of 10 studies, and the importance relative to the other attributes varied between 5% and 47% (median 23%) (moderate certainty of evidence). Burden was rated as first or second by three of 10 studies (30%) and the relative importance varied between 1% and 43% (median 13%) (low certainty of evidence). Patient-centeredness was second most important in one of five studies (20%) and had a relative importance between 7% and 24% (median 14%) (low certainty of evidence). Results suggest that patients are prepared to trade-off some effectiveness for more safety, or less burden and patient-centeredness. When safety was evaluated, the safety of the child was considered more important than the mother's safety. Greater burden (cycle cancellations, number of injections, number of hospital visits, time) was more likely to be accepted by patients if they gained effectiveness, safety, or lower costs. Concerning patient-centeredness, information provision and physician attitude were considered most important, followed by involvement in decision-making, and treatment continuity by the same medical professional. Non-genetic parenthood did not have a clear impact on decision-making. WIDER IMPLICATIONS: The findings of this review can be used in future preference studies and can help healthcare professionals in guiding patients' decision-making and enable a more patient-centered approach.
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Tomada de Decisões , Infertilidade , Técnicas de Reprodução Assistida , Humanos , Técnicas de Reprodução Assistida/economia , Infertilidade/terapia , Infertilidade/economia , Feminino , MasculinoRESUMO
Significant ethnic and racial disparities exist in the utilization and outcomes of assisted reproductive technology (ART) in the United States. The popularity of fertility preservation (FP) procedures, a specific application of ART for those desiring to delay childbearing, has increased; however, many minority populations have seen a less rapid uptake of these services. Minority patients pursuing ART are more likely to have poorer in vitro fertilization (IVF) and pregnancy outcomes. These outcomes are used to predict success after FP and may lessen the appeal of such procedures in these populations. Suboptimal outcomes are further compounded by challenges with receiving referrals to, accessing, and paying for FP services. Resolving these disparities in minority populations will require culturally appropriate education surrounding the benefits of ART and FP, the demonstration of favorable outcomes in ART and FP through continued research engaging minority participants, and continued advocacy for expanded access to care for patients.
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Today, technology and sustainability are two strategic axes for the development of any industry. Art is no exception and embodies both principles. Artificial intelligence (AI) is driving the art world forwards with its applications and algorithms. Additionally, the circular economy (CE) is concerned with resources and the environment in this context. The objective of the present work is to provide an overview of the current state of research on the application of AI in the art world and an analysis of how CE principles are being incorporated, considering the interactions between AI and the CE. To this end, a systematic review of the literature is carried out in which 60 articles related to the subject are selected, analysed, and classified, highlighting the lines of research addressed. The assessment of the current state of research on the subject concludes with the four main axes of classification of works. The first line is related to AI generative content in art, addressing issues of content creation, image and painting, video, and theatre. The second line is related to AI applications for art industry production, considering the sustainability of the supply chain. The third line focuses on how the CE is being applied to art, while the fourth line focuses on other relevant aspects analysed, such as training and design. The topic is still incipient, mandating further research to study the full potential of AI and the CE in the world of art.
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In this article, we reflect on our teaching practices that include the development of an artist-in-residency program in one teacher education course and one graduate course in the Fall of 2022 at The University of British Columbia. During these residencies, Carrier Wit'at artist and printmaker Whess Harman and Indigenous scholar and a/r/tographer Jocelyne Robinson of the Algonquin Timiskaming First Nation demonstrate through their art practices how love and land are central tenets to relational ethics. We engage with Cherrie Moraga and Gloria Anzaldua's theory in the flesh alongside the artists-in-residencies as we consider an anti-colonial future in art education. We propose the concept of relational ethics through the flesh as a reflexive, embodied, social justice-oriented way of being in the world.
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In this article, I examine 'underground memories' to demonstrate how they serve as resources for resistance in the margins of Colombia. I focus on their relations with the urban fabric, looking at the ways the walls of Bogota and Medellin are used as canvases for spreading images and narratives about the conflict. I suggest that murals representing the violence serve as a repository for memories; they challenge hegemonic narratives and contribute to the recovery of public space. This analysis draws on three case studies. In the first one, I examine the impact of a mural in Bogota that denounced extrajudicial killings involving the Colombian army. The second case focuses on a community initiative aimed at collecting testimonies from residents in a marginalized district of Medellin. Finally, the last case study analyses the touristification of some of the many murals depicting the violence in Medellin. I argue that, to different degrees, all the memorial projects presented in this study challenge state narratives. Through representations of murdered teenagers, suspect military officers and even drug cartel bosses, they raise questions of social justice, impunity, illegality and the dramatic banalization of violence in the country. They broaden the narrative on the recent past, through histories and images that the Colombian state is still reluctant to unearth.