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Haemochromatosis (HC) encompasses a range of genetic disorders. HFE-HC is by far the most common in adults, while non-HFE types are rare due to mutations of HJV, HAMP, TFR2 and gain-of-function mutations of SLC40A1. HC is often unknown to paediatricians as it is usually asymptomatic in childhood. We report clinical and biochemical data from 24 paediatric cases of HC (10 cases of HFE-, 5 TFR2-, 9 HJV-HC), with a median follow-up of 9.6 years. Unlike in the adult population, non-HFE-HC constitutes 58% (14/24) of the population in our series. Transferrin saturation was significantly higher in TFR2- and HJV-HC compared to HFE-HC, and serum ferritin and LIC were higher in HJV-HC compared to TFR2- and HFE-HC. Most HFE-HC subjects had relatively low ferritin and LIC at the time of diagnosis, so therapy could be postponed for most of them after the age of 18. Our results confirm that HJV-HC is a severe form already in childhood, emphasizing the importance of early diagnosis and treatment to avoid the development of organ damage and reduce morbidity and mortality. Although phlebotomies were tolerated by most patients, oral iron chelators could be a valid option in early-onset HC.
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Hemocromatose , Sobrecarga de Ferro , Adulto , Humanos , Criança , Hemocromatose/diagnóstico , Hemocromatose/genética , Hemocromatose/terapia , Estudos Retrospectivos , Proteína da Hemocromatose/genética , Mutação , Ferritinas , Antígenos de Histocompatibilidade Classe I/genética , Sobrecarga de Ferro/genéticaRESUMO
PURPOSE: The aim was to evaluate the safety and effectiveness of a computed tomography-guided surgery implant placement with a flapless technique and immediate functional loading in an American Society of Anesthesiology-III patient. METHODS: This technical note involved a 64-year-old American Society of Anesthesiology-III patient. Her hopeless teeth were extracted and a restorative evaluation was provided as a prosthetic reference. The surgical procedure was based on the flapless technique that let us to use local anesthesia. The authors used an All-on-4 concept restoration for maxilla and conventional fixed prosthesis procedures for jaw rehabilitation. The authors placed 4 tilted implants in the upper maxilla and 6 right implants in the jaw. Implants were loaded with a provisional prosthesis on the same day of surgery. Five months later, provisional restoration was removed; the authors placed into the ceramic crowns 2 Procera Implant Bridge (Nobel Biocare) frameworks, developed through computer-aided design/computer-aided manufacturing technology. CONCLUSIONS: Computed tomography-guided surgery is a minimally invasive technique that allows, through a flapless approach, safer and more predictable procedures. In this technical note, the authors achieved accurate implant placement and precise fit of restoration with natural looking appearance; this patient-oriented-treatment led to a reduced healing time with better compliance.
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Anestesiologia , Implantes Dentários , Carga Imediata em Implante Dentário , Arcada Edêntula , Cirurgia Assistida por Computador , Humanos , Feminino , Pessoa de Meia-Idade , Implantação Dentária Endóssea/métodos , Tomografia Computadorizada por Raios X , Carga Imediata em Implante Dentário/métodos , Prótese Dentária Fixada por Implante , Maxila/cirurgia , Arcada Edêntula/cirurgia , Resultado do TratamentoRESUMO
Since the discovery of cisplatin's antitumoral activity and its approval as an anticancer drug, significant efforts have been made to enhance its physiological stability and anticancer efficacy and to reduce its side effects. With the rapid development of targeted and personalized therapies, and the promising theranostic approach, platinum drugs have found new opportunities in more sophisticated systems. Theranostic agents combine diagnostic and therapeutic moieties in one scaffold, enabling simultaneous disease monitoring, therapy delivery, response tracking, and treatment efficacy evaluation. In these systems, the platinum core serves as the therapeutic agent, while the functionalized ligand provides diagnostic tools using various imaging techniques. This review aims to highlight the significant role of platinum-based complexes in theranostic applications, and, to the best of our knowledge, this is the first focused contribution on this type of platinum compounds. This review presents a brief introduction to the development of platinum chemotherapeutic drugs, their limitations, and resistance mechanisms. It then describes recent advancements in integrating platinum complexes with diagnostic agents for both tumor treatment and monitoring. The main body is organized into three categories based on imaging techniques: fluorescence, positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). Finally, this review outlines promising strategies and future perspectives in this evolving field.
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Antineoplásicos , Neoplasias , Nanomedicina Teranóstica , Humanos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/química , Neoplasias/tratamento farmacológico , Neoplasias/diagnóstico por imagem , Animais , Tomografia por Emissão de Pósitrons/métodos , Imageamento por Ressonância Magnética , Compostos de Platina/química , Compostos de Platina/uso terapêutico , Compostos de Platina/farmacologia , Medicina de Precisão/métodosRESUMO
In addition to progressive muscular degeneration due to dystrophin mutations, 1/3 of Duchenne muscular dystrophy (DMD) patients present cognitive deficits. However, there is currently an incomplete understanding about the function of the multiple dystrophin isoforms in human brains. Here, we tested the hypothesis that dystrophin deficiency affects glial function in DMD and could therefore contribute to neural impairment. We investigated human dystrophin isoform expression with development and differentiation and response to damage in human astrocytes from control and induced pluripotent stem cells from DMD patients. In control cells, short dystrophin isoforms were up-regulated with development and their expression levels changed differently upon neuronal and astrocytic differentiation, as well as in 2-dimensional versus 3-dimensional astrocyte cultures. All DMD-astrocytes tested displayed altered morphology, proliferative activity and AQP4 expression. Furthermore, they did not show any morphological change in response to inflammatory stimuli and their number was significantly lower as compared to stimulated healthy astrocytes. Finally, DMD-astrocytes appeared to be more sensitive than controls to oxidative damage as shown by their increased cell death. Behavioral and metabolic defects in DMD-astrocytes were consistent with gene pathway dysregulation shared by lines with different mutations as demonstrated by bulk RNA-seq analysis. Together, our DMD model provides evidence for altered astrocyte function in DMD suggesting that defective astrocyte responses may contribute to neural impairment and might provide additional potential therapeutic targets.
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Células-Tronco Pluripotentes Induzidas , Distrofia Muscular de Duchenne , Astrócitos/metabolismo , Diferenciação Celular , Distrofina/genética , Distrofina/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismoRESUMO
BACKGROUND: Violence against women and girls (VAWG) is a human rights violation with social, economic, and health consequences for survivors, perpetrators, and society. Robust evidence on economic, social, and health impact, plus the cost of delivery of VAWG prevention, is critical to making the case for investment, particularly in low- and middle-income countries (LMICs) where health sector resources are highly constrained. We report on the costs and health impact of VAWG prevention in 6 countries. METHODS AND FINDINGS: We conducted a trial-based cost-effectiveness analysis of VAWG prevention interventions using primary data from 5 randomised controlled trials (RCTs) in sub-Saharan Africa and 1 in South Asia. We evaluated 2 school-based interventions aimed at adolescents (11 to 14 years old) and 2 workshop-based (small group or one to one) interventions, 1 community-based intervention, and 1 combined small group and community-based programme all aimed at adult men and women (18+ years old). All interventions were delivered between 2015 and 2018 and were compared to a do-nothing scenario, except for one of the school-based interventions (government-mandated programme) and for the combined intervention (access to financial services in small groups). We computed the health burden from VAWG with disability-adjusted life year (DALY). We estimated per capita DALYs averted using statistical models that reflect each trial's design and any baseline imbalances. We report cost-effectiveness as cost per DALY averted and characterise uncertainty in the estimates with probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEACs), which show the probability of cost-effectiveness at different thresholds. We report a subgroup analysis of the small group component of the combined intervention and no other subgroup analysis. We also report an impact inventory to illustrate interventions' socioeconomic impact beyond health. We use a 3% discount rate for investment costs and a 1-year time horizon, assuming no effects post the intervention period. From a health sector perspective, the cost per DALY averted varies between US$222 (2018), for an established gender attitudes and harmful social norms change community-based intervention in Ghana, to US$17,548 (2018) for a livelihoods intervention in South Africa. Taking a societal perspective and including wider economic impact improves the cost-effectiveness of some interventions but reduces others. For example, interventions with positive economic impacts, often those with explicit economic goals, offset implementation costs and achieve more favourable cost-effectiveness ratios. Results are robust to sensitivity analyses. Our DALYs include a subset of the health consequences of VAWG exposure; we assume no mortality impact from any of the health consequences included in the DALYs calculations. In both cases, we may be underestimating overall health impact. We also do not report on participants' health costs. CONCLUSIONS: We demonstrate that investment in established community-based VAWG prevention interventions can improve population health in LMICs, even within highly constrained health budgets. However, several VAWG prevention interventions require further modification to achieve affordability and cost-effectiveness at scale. Broadening the range of social, health, and economic outcomes captured in future cost-effectiveness assessments remains critical to justifying the investment urgently required to prevent VAWG globally.
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Países em Desenvolvimento , Pobreza , Adolescente , Adulto , Criança , Análise Custo-Benefício , Feminino , Humanos , Masculino , África do Sul , Violência/prevenção & controleRESUMO
AIM: To evaluate the cumulative prevalence of coeliac disease, systemic lupus erythematosus, autoimmune hyperthyroidism and primary immunodeficiencies in children with either newly diagnosed/persistent or chronic immune thrombocytopenia (ITP). METHODS: Monocentric retrospective analysis of the clinical and biochemical features of 330 consecutive patients with ITP referred to our Pediatric Hematology Unit between January 2009 and December 2018. RESULTS: The prevalence of systemic lupus erythematosus (0.3%), coeliac disease (0.3%) and autoimmune hyperthyroidism (0.6%) was not increased compared to general paediatric population. Of note, the prevalence of underlying primary immunodeficiencies was 2.4%, remarkably higher than the general paediatric population (P = .005). All the patients diagnosed with immunodeficiency developed either bi-/trilinear cytopenia or splenomegaly. CONCLUSION: Whilst autoimmune and immunological screening is already recommended at the onset of immune thrombocytopenia, we recommend that primary immunodeficiencies be regularly screened during follow-up, especially in case of additional cytopenia or lymphoproliferation.
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Doença Celíaca , Hipertireoidismo , Lúpus Eritematoso Sistêmico , Púrpura Trombocitopênica Idiopática , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Criança , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/etiologia , Estudos RetrospectivosRESUMO
Young people living with HIV (YPLHIV) in sub-Saharan Africa (SSA) are at high risk of having a poor quality of life. Addressing wellbeing explicitly within HIV/AIDS policies could assist mitigation efforts. However, guidance on wellbeing measures to evaluate policies for YPLHIV is scarce. The aims of this mixed-methods review were to identify: i) key dimensions of wellbeing and ii) wellbeing measures that align to these dimensions among YPLHIV (15-24 years) in SSA. We searched six social science and medical databases, including grey literature. We included studies that examined correlates and lived experiences of wellbeing, among YPLHIV in SSA, from January 2000 to May 2019. Two reviewers independently screened abstracts and full texts and assessed methodological quality of included articles. We analysed quantitative and qualitative data using descriptive and meta-ethnographic approaches, respectively. Thereafter, we integrated findings using a framework approach. We identified 6527 citations. Of these, 10 quantitative and 30 qualitative studies were included. Being male, higher educational status, less stigma and more social support were likely correlates of wellbeing. Themes that shaped experiences suggestive of wellbeing were: 1) acceptance and belonging- stigma, social support; 2) coping; 3) standard of living. Our final synthesis found that the following dimensions potentially characterise wellbeing: self-acceptance, belonging, autonomy; positive relations, environmental mastery, purpose in life. Wellbeing for YPLHIV is multi-dimensional and relational. Relevant measures include the Personal Wellbeing Index, Ryff's Psychological Wellbeing Scale and Mental Health Continuum Short Form. However, psychometric evaluations of these scales among YPLHIV in SSA are needed.
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Infecções por HIV/psicologia , Qualidade de Vida , Adaptação Psicológica , Adolescente , Adulto , África Subsaariana , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Estigma Social , Apoio Social , Adulto JovemRESUMO
While recent decades have seen considerable research on cohabitation without marriage, the study of marriage without cohabitation has not fared as well. Prior work on the latter has emphasized the importance of occupational stratification, but ignored the social context around occupation, particularly regarding labour mobility and economic development. In this paper, we outline the significance of contemporary labour mobility and concomitant occupational stratification for the risk of non-cohabiting marriage, and use data from the IPUMS-International project to provide a cross-national accounting of non-cohabiting marriage. We focus on two issues: first, how does prevalence vary across countries, across time, and with respect to economic development? Second, how do the core dynamics of labour mobility-including migration, occupational status, and economic development-influence the probability of non-cohabiting marriage? Results indicate broad cross-national differences in prevalence, increasing risk over time, and a pattern of accumulating risk associated with multifaceted social disadvantage.
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Emigração e Imigração/estatística & dados numéricos , Emprego/estatística & dados numéricos , Casamento/estatística & dados numéricos , Desenvolvimento Econômico/estatística & dados numéricos , Feminino , Humanos , Masculino , Fatores de Risco , Fatores Sexuais , Classe Social , Fatores SocioeconômicosRESUMO
The prognostic value of minimal residual disease (MRD) in Philadelphia-chromosome-positive (Ph+) childhood acute lymphoblastic leukemia (ALL) treated with tyrosine kinase inhibitors is not fully established. We detected MRD by real-time quantitative polymerase chain reaction (RQ-PCR) of rearranged immunoglobulin/T-cell receptor genes (IG/TR) and/or BCR/ABL1 fusion transcript to investigate its predictive value in patients receiving Berlin-Frankfurt-Münster (BFM) high-risk (HR) therapy and post-induction intermittent imatinib (the European intergroup study of post-induction treatment of Philadelphia-chromosome-positive acute lymphoblastic leukemia (EsPhALL) study). MRD was monitored after induction (time point (TP)1), consolidation Phase IB (TP2), HR Blocks, reinductions, and at the end of therapy. MRD negativity progressively increased over time, both by IG/TR and BCR/ABL1. Of 90 patients with IG/TR MRD at TP1, nine were negative and none relapsed, while 11 with MRD<5×10-4 and 70 with MRD≥5×10-4 had a comparable 5-year cumulative incidence of relapse of 36.4 (15.4) and 35.2 (5.9), respectively. Patients who achieved MRD negativity at TP2 had a low relapse risk (5-yr cumulative incidence of relapse (CIR)=14.3[9.8]), whereas those who attained MRD negativity at a later date showed higher CIR, comparable to patients with positive MRD at any level. BCR/ABL1 MRD negative patients at TP1 had a relapse risk similar to those who were IG/TR MRD negative (1/8 relapses). The overall concordance between the two methods is 69%, with significantly higher positivity by BCR/ABL1. In conclusion, MRD monitoring by both methods may be functional not only for measuring response but also for guiding biological studies aimed at investigating causes for discrepancies, although from our data IG/TR MRD monitoring appears to be more reliable. Early MRD negativity is highly predictive of favorable outcome. The earlier MRD negativity is achieved, the better the prognosis.
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Proteínas de Fusão bcr-abl/genética , Imunoglobulinas/genética , Neoplasia Residual/diagnóstico , Neoplasia Residual/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Receptores de Antígenos de Linfócitos T/genética , Biomarcadores Tumorais , Terapia Combinada , Feminino , Humanos , Mesilato de Imatinib/uso terapêutico , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Recidiva , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: Transcribed-ultraconserved regions (T-UCR) are long non-coding RNAs which are conserved across species and are involved in carcinogenesis. We studied T-UCRs downstream of the Wnt/ß-catenin pathway in liver cancer. DESIGN: Hypomorphic Apc mice (Apcfl/fl) and thiocetamide (TAA)-treated rats developed Wnt/ß-catenin dependent hepatocarcinoma (HCC) and cholangiocarcinoma (CCA), respectively. T-UCR expression was assessed by microarray, real-time PCR and in situ hybridisation. RESULTS: Overexpression of the T-UCR uc.158- could differentiate Wnt/ß-catenin dependent HCC from normal liver and from ß-catenin negative diethylnitrosamine (DEN)-induced HCC. uc.158- was overexpressed in human HepG2 versus Huh7 cells in line with activation of the Wnt pathway. In vitro modulation of ß-catenin altered uc.158- expression in human malignant hepatocytes. uc.158- expression was increased in CTNNB1-mutated human HCCs compared with non-mutated human HCCs, and in human HCC with nuclear localisation of ß-catenin. uc.158- was increased in TAA rat CCA and reduced after treatment with Wnt/ß-catenin inhibitors. uc.158- expression was negative in human normal liver and biliary epithelia, while it was increased in human CCA in two different cohorts. Locked nucleic acid-mediated inhibition of uc.158- reduced anchorage cell growth, 3D-spheroid formation and spheroid-based cell migration, and increased apoptosis in HepG2 and SW1 cells. miR-193b was predicted to have binding sites within the uc.158- sequence. Modulation of uc.158- changed miR-193b expression in human malignant hepatocytes. Co-transfection of uc.158- inhibitor and anti-miR-193b rescued the effect of uc.158- inhibition on cell viability. CONCLUSIONS: We showed that uc.158- is activated by the Wnt pathway in liver cancers and drives their growth. Thus, it may represent a promising target for the development of novel therapeutics.
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Neoplasias dos Ductos Biliares/metabolismo , Carcinoma Hepatocelular/metabolismo , Colangiocarcinoma/metabolismo , Sequência Conservada/genética , Neoplasias Hepáticas/metabolismo , RNA não Traduzido/genética , Via de Sinalização Wnt , Animais , Neoplasias dos Ductos Biliares/genética , Carcinoma Hepatocelular/genética , Colangiocarcinoma/genética , Regulação Neoplásica da Expressão Gênica/genética , Hepatócitos/metabolismo , Humanos , Neoplasias Hepáticas/genética , Camundongos Knockout , MicroRNAs/metabolismo , Neoplasias Experimentais , Transfecção , beta Catenina/genética , beta Catenina/metabolismoRESUMO
BACKGROUND: Preventing intimate partner violence (IPV) remains a global public health challenge. Studies suggest urban informal settlements have particularly high levels of IPV and HIV-prevalence and these settlements are rapidly growing. The current evidence base of effective approaches to preventing IPV recognizes the potential of combining economic strengthening and gender transformative interventions. However, few of these interventions have been done in urban informal settlements, and almost none have included men as direct recipients of these interventions. METHODS: Stepping Stones and Creating Futures intervention is a participatory gender transformative and livelihoods strengthening intervention. It is being evaluated through a cluster randomized control trial amongst young women and men (18-30) living in urban informal settlements in eThekwini Municipality, South Africa. The evaluation includes a qualitative process evaluation and cost-effectiveness analysis. A comparison of baseline characteristics of participants is also included. DISCUSSION: This is one of the first large trials to prevent IPV and HIV-vulnerability amongst young women and men in urban informal settlements. Given the mixed methods evaluation, the results of this trial have the ability to develop a stronger understanding of what works to prevent violence against women and the processes of change in interventions. TRIAL REGISTRATION: NCT03022370 . Registered 13 January 2017, retrospectively registered.
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Terapia Comportamental/métodos , Infecções por HIV/prevenção & controle , Infecções por HIV/psicologia , Maus-Tratos Conjugais/prevenção & controle , Maus-Tratos Conjugais/psicologia , Adolescente , Adulto , Cidades , Feminino , Humanos , Masculino , Prevalência , Ensaios Clínicos Controlados Aleatórios como Assunto , Assunção de Riscos , África do Sul , Adulto JovemAssuntos
Hematologia , Oncologia , Betacoronavirus , COVID-19 , Criança , Infecções por Coronavirus , Humanos , Itália , Pandemias , Pneumonia Viral , SARS-CoV-2RESUMO
The paper studies the association between partners' relative incomes and union dissolution among couples in France. With the increase in dual-earner couples and women's educational level, couples in which women earn more than their partners are structurally becoming more widespread. Because female breadwinning challenges long-lived social norms regarding traditional gender roles, scholars have theorized a higher risk of union dissolution among female-breadwinner couples compared to couples in other income arrangements. We estimate the risk of union dissolution using regression analyses on unique longitudinal data from French administrative sources containing an unconventionally high number of couples (4% of the population) and separation events (more than 100,000), as well as precise and reliable income measurement. Female-breadwinner couples face a higher risk of union dissolution compared to other couple types. This result is robust to various definitions of female breadwinning and controls for partners' employment status. Contrary to recent research on other countries, we find no sign of a fading effect among younger cohorts. However, among younger, cohabiting couples and couples in registered partnerships the risk of union dissolution is lowest when both partners are employed and provide a similar share of the total couple's income, suggesting the emergence of a new profile of stable couples. The female-breadwinner penalty in union dissolution is in place; also in France, it holds among married and cohabiting couples and registered partnerships, across all birth cohorts and levels of household income.
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This clinical case report's objective was to describe an alternative technique executed to ensure bone regeneration after removing a cystic lesion in the upper jaw. The bone defect after the cystectomy was filled with autologous fibrin-rich clots containing concentrated growth factor (CGF). A 45-year-old female patient was presumed to have a cystic lesion with massive bone destruction on the vestibular and palatal walls between teeth 2.2 and 2.3. CGF was applied to fill the gap to promote the development of the bone. The tooth was asymptomatic and repair was still increasing steadily after a year, according to the results of the clinical and radiological follow-up assessment. This article describes a different way to treat a two-wall defect involving both the palatal and buccal bone, after removing a cystic lesion, with the use of CGF as an equivalent to the traditional use of autologous or heterologous bone. A promising substance for bone repair is CGF fibrin, which may encourage the growth of new bone in jaw deformities and promote bone tissue healing.
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PURPOSE: Dysgeusia is a common side effect in oncology patients, significantly impacting their quality of life. This systematic review aims to evaluate the effectiveness of non-pharmacological strategies in treating dysgeusia in patients undergoing chemotherapy or radiotherapy. METHODS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search across five databases: PubMed, Embase, Cochrane Library, CINAHL, and the British Nursing Database. We used the Joanna Briggs Institute Critical Appraisal Tools to assess the quality of the included studies. A harvest plot was used to synthesise evidence about the differential effects of population-level interventions. RESULTS: Nine studies of non-pharmacological strategies to manage dysgeusia were included. These studies encompassed a variety of interventions, including oral applications and supplements, instrumental techniques, and educational programs. The review identified promising interventions such as cryotherapy and Miraculine supplementation, which showed potential in mitigating taste alterations. Instrumental techniques like photobiomodulation therapy and complementary and integrative medicine approaches, including acupuncture and herbs, were also found to be beneficial. Educational and self-management strategies emerged as effective interventions for empowering patients to manage dysgeusia. Despite the diversity of interventions and the limitations of the included studies, such as small sample sizes and geographical differences, these findings underscore the potential of non-pharmacological strategies in managing dysgeusia. CONCLUSION: The results support the integration of these strategies into clinical practice, highlighting the importance of multidisciplinary approaches to improve patient care. Further research should prioritize rigorous studies to enhance evidence and explore long-term effects.
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Antineoplásicos , Disgeusia , Neoplasias , Feminino , Humanos , Masculino , Antineoplásicos/efeitos adversos , Terapias Complementares/métodos , Disgeusia/induzido quimicamente , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Qualidade de VidaRESUMO
BACKGROUND/OBJECTIVE: Among the side effects of chemotherapy, there is dysgeusia, which is an alteration or damage to the taste perception that negatively impacts the biopsychosocial sphere of the patient. Therefore, it is important to recognize and manage it appropriately. The objective of this study is to identify clinical pharmacological strategies to reduce dysgeusia in chemotherapy patients. METHODS: A systematic literature review was conducted following the PRISMA guidelines between February and May 2023, utilizing PubMed, Embase, Cochrane Library, CINAHL, and the British Nursing Database. Methodological quality and bias risk assessment were performed using the JBI framework, while evidence certainty was evaluated using the Oxford OCEBM methodology. RESULTS: Out of 1225 consulted records, 12 articles were included. The results underscore the efficacy of diverse pharmacological interventions in mitigating dysgeusia among chemotherapy patients. These include zinc supplementation with a daily dosage ranging between 50 and 220 mg (p ≤ 0.005), lactoferrin at 250 mg thrice daily (p < 0.001), delta-9-tetrahydrocannabinol at 2 mg per day (p < 0.05), and cannabidiol at 150 mg per day (p = 0.04). All studies analysed showed a low risk of bias. The zinc and Delta-9-Tetrahydrocannabinoid treatment proved particularly promising, compared to the other treatments considered, where sample sizes were smaller and the placebo effect was not always clear. CONCLUSION: Among the various pharmacological strategies identified, those that appear most promising concern the integration of zinc and Delta-9-Tetrahydrocannabinoid. Future studies should further explore the treatments identified in this review to expand the evidence base in this relatively underexplored field.
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Background: The natural transmission cycle of tick-borne encephalitis (TBE) virus is enhanced by complex interactions between ticks and key hosts strongly connected to habitat characteristics. The diversity of wildlife host species and their relative abundance is known to affect transmission of tick-borne diseases. Therefore, in the current context of global biodiversity loss, we explored the relationship between habitat richness and the pattern of human TBE cases in Europe to assess biodiversity's role in disease risk mitigation. Methods: We assessed human TBE case distribution across 879 European regions using official epidemiological data reported to The European Surveillance System (TESSy) between 2017 and 2021 from 15 countries. We explored the relationship between TBE presence and the habitat richness index (HRI1) by means of binomial regression. We validated our findings at local scale using data collected between 2017 and 2021 in 227 municipalities located in Trento and Belluno provinces, two known TBE foci in northern Italy. Findings: Our results showed a significant parabolic effect of HRI on the probability of presence of human TBE cases in the European regions included in our dataset, and a significant, negative effect of HRI on the local presence of TBE in northern Italy. At both spatial scales, TBE risk decreases in areas with higher values of HRI. Interpretation: To our knowledge, no efforts have yet been made to explore the relationship between biodiversity and TBE risk, probably due to the scarcity of high-resolution, large-scale data about the abundance or density of critical host species. Hence, in this study we considered habitat richness as proxy for vertebrate host diversity. The results suggest that in highly diverse habitats TBE risk decreases. Hence, biodiversity loss could enhance TBE risk for both humans and wildlife. This association is relevant to support the hypothesis that the maintenance of highly diverse ecosystems mitigates disease risk.
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BACKGROUND: The emerging use of direct oral anticoagulants (DOAC) in the management of cancer-associated venous thromboembolism (CAT) is significantly improving therapeutic adherence and quality of life. Despite this, many conditions can restrict the therapeutic index of these drugs. For all these reasons the latest guidelines recommend the use of heparins in the treatment of CAT as the preferred treatment in some clinical settings. OBJECTIVES: We evaluated the efficacy and the safety of DOAC, in terms of recurrent venous thromboembolism (VTE) and major bleeding (MB), as a composite primary outcome. Mortality and clinically relevant non-major bleeding (CRNMB) were evaluated as secondary outcomes. METHODS: We performed a retrospective study on 209 patients to compare the effects of DOAC versus heparins for the treatment of CAT. 127 patients with a high bleeding risk neoplasia were enrolled. RESULTS: A primary-outcome event occurred in 11.3% of patients treated with heparins and in 10.5% treated with DOAC (Relative Risk 0.92; 95% CI 0.42-2.01, p = 0.84). Recurrent VTE occurred in 6.1% in the heparins group and in 8.4% in the DOAC group (RR 1.37; 95% CI 0.51-3.64, p = 0.52). MB occurred in 5.2% in the heparins group and in 2.1% in the DOAC group (RR 0.40; 95% CI 0.08-1.93, p = 0.25). CONCLUSIONS: DOAC seem to be as effective and safe as heparins in the treatment of CAT. Most bleeding events occurred in patients with high-risk bleeding neoplasms regardless of the type of anticoagulant. Considering the characteristics and satisfaction of patients using DOAC in this setting, this approach should be considered as a first choice.
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Neoplasias , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Estudos Retrospectivos , Qualidade de Vida , Anticoagulantes/efeitos adversos , Heparina/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/complicações , Hemorragia/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Administração OralRESUMO
Human-induced environmental alterations in the Alps may importantly affect small mammal species, but evidence in this sense is limited. We live-trapped small rodents in the Central-Eastern Italian Alps in three close-by habitat types (rocky scree, alpine grassland, and heath) at 2100 m a.s.l. during summer-fall, in 1997 and 2016. We compared small rodent assemblages through a Redundancy Detrended Analysis (RDA). In both surveys, we detected two specialist species, i.e., the common vole (Microtus arvalis) and the snow vole (Chionomys nivalis), and, unexpectedly, the forest generalist bank vole (Myodes glareolus). In 1997, grassland was mainly occupied by the common vole, while the bank vole and the snow vole were sympatric in the other habitats. In 2016, the snow vole was detected only in the scree, while other species did not show distribution changes. We discuss a series of hypotheses that might have driven the differences observed across decades, among which is a species-specific response to abiotic and biotic environmental alterations, with the alpine habitat specialist moving out of sub-optimal habitats. We encourage further research on this topic, e.g., via long-term longitudinal studies.
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Violence against women and girls (VAWG) is a human rights violation with substantial health-related consequences. Interventions to prevent VAWG, often implemented at the community level by volunteers, have been proven effective and cost-effective. One such intervention is the Rural Response System in Ghana, a volunteer-run program which hires community based action teams (COMBATs) to sensitise the community about VAWG and to provide counselling services in rural areas. To increase programmatic impact and maximise the retention of these volunteers, it is important to understand their preferences for incentives. We conducted a discrete choice experiment (DCE) among 107 COMBAT volunteers, in two Ghanaian districts in 2018, to examine their stated preferences for financial and non-financial incentives that could be offered in their roles. Each respondent answered 12 choice tasks, and each task comprised four hypothetical volunteering positions. The first three positions included different levels of five role attributes. The fourth option was to cease volunteering as a COMBAT volunteer (opt-out). We found that, overall, COMBAT volunteers cared most for receiving training in volunteering skills and three-monthly supervisions. These results were consistent between multinomial logit, and mixed multinomial logit models. A three-class latent class model fitted our data best, identifying subgroups of COMBAT workers with distinct preferences for incentives: The younger 'go getters'; older 'veterans', and the 'balanced bunch' encompassing the majority of the sample. The opt-out was chosen only 4 (0.3%) times. Only one other study quantitatively examined the preferences for incentives of VAWG-prevention volunteers using a DCE (Kasteng et al., 2016). Understanding preferences and how they vary between sub-groups can be leveraged by programme managers to improve volunteer motivation and retention. As effective VAWG-prevention programmes are scaled up from small pilots to the national level, data on volunteer preferences may be useful in improving volunteer retention.