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To further explore the role of different antipsychotic treatments for cardio-cerebrovascular mortality, we performed several subgroup, sensitivity and meta-regression analyses based on a large previous meta-analysis focusing on cohort studies assessing mortality relative risk (RR) for cardio-cerebrovascular disorders in people with schizophrenia, comparing antipsychotic treatment versus no antipsychotic. Quality assessment through the Newcastle-Ottawa Scale (NOS) and publication bias was measured. We meta-analyzed 53 different studies (schizophrenia patients: n = 2,513,359; controls: n = 360,504,484) to highlight the differential effects of antipsychotic treatment regimens on cardio-cerebrovascular-related mortality in incident and prevalent samples of patients with schizophrenia. We found first generation antipsychotics (FGA) to be associated with higher mortality in incident samples of schizophrenia (oral FGA [RR=2.20, 95 %CI=1.29-3.77, k = 1] and any FGA [RR=1.70, 95 %CI=1.20-2.41, k = 1]). Conversely, second generation antipsychotics (SGAs) and clozapine were associated with reduced cardio-cerebrovascular-related mortality, in prevalent samples of schizophrenia. Subgroup analyses with NOS score ≥7 (higher quality) demonstrated a significantly increased cardio-cerebrovascular disorder-related mortality, among those exposed to FGAs vs SGAs. Meta-regression analyses demonstrated a larger association between antipsychotics and decreased risk of mortality with longer follow-up, recent study year, and higher number of adjustment variables. Overall, this subanalysis of a systematic review contributes to the evolving understanding of the complex role of antipsychotic treatment for cardio-cerebrovascular mortality in schizophrenia, paving the way for more targeted interventions and improved patient outcomes.
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INTRODUCTION: Severe osteogenesis imperfecta (OI) is a debilitating disease with no cure or sufficiently effective treatment. Mesenchymal stem cells (MSCs) have good safety profile, show promising effects and can form bone. The Boost Brittle Bones Before Birth (BOOSTB4) trial evaluates administration of allogeneic expanded human first trimester fetal liver MSCs (BOOST cells) for OI type 3 or severe type 4. METHODS AND ANALYSIS: BOOSTB4 is an exploratory, open-label, multiple dose, phase I/II clinical trial evaluating safety and efficacy of postnatal (n=15) or prenatal and postnatal (n=3, originally n=15) administration of BOOST cells for the treatment of severe OI compared with a combination of historical (1-5/subject) and untreated prospective controls (≤30). Infants<18 months of age (originally<12 months) and singleton pregnant women whose fetus has severe OI with confirmed glycine substitution in COL1A1 or COL1A2 can be included in the trial.Each subject receives four intravenous doses of 3×106/kg BOOST cells at 4 month intervals, with 48 (doses 1-2) or 24 (doses 3-4) hours in-patient follow-up, primary follow-up at 6 and 12 months after the last dose and long-term follow-up yearly until 10 years after the first dose. Prenatal subjects receive the first dose via ultrasound-guided injection into the umbilical vein within the fetal liver (16+0 to 35+6 weeks), and three doses postnatally.The primary outcome measures are safety and tolerability of repeated BOOST cell administration. The secondary outcome measures are number of fractures from baseline to primary and long-term follow-up, growth, change in bone mineral density, clinical OI status and biochemical bone turnover. ETHICS AND DISSEMINATION: The trial is approved by Competent Authorities in Sweden, the UK and the Netherlands (postnatal only). Results from the trial will be disseminated via CTIS, ClinicalTrials.gov and in scientific open-access scientific journals. TRIAL REGISTRATION NUMBERS: EudraCT 2015-003699-60, EUCT: 2023-504593-38-00, NCT03706482.
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Trasplante de Células Madre Mesenquimatosas , Osteogénesis Imperfecta , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Embarazo , Ensayos Clínicos Fase I como Asunto , Ensayos Clínicos Fase II como Asunto , Células Madre Fetales/trasplante , Trasplante de Células Madre Mesenquimatosas/métodos , Células Madre Mesenquimatosas , Estudios Multicéntricos como Asunto , Osteogénesis Imperfecta/terapia , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVES: Despite advances in the prevention of rhesus (Rh)(D) alloimmunization, alloantibodies to Rh(D) and non-Rh(D) red blood cell antigens continue to be detected in â¼4% of US pregnancies and can result in hemolytic disease of the fetus and newborn (HDFN). Recent reports on HDFN lack granularity and are unable to provide antibody-specific outcomes. The objective of this study was to calculate the frequency of alloimmunization in our large hospital system and summarize the outcomes based on antibody specificity, titer, and other clinical factors. METHODS: We identified all births in a 6-year period after a positive red blood cell antibody screen result during pregnancy and summarized their characteristics and outcomes. RESULTS: A total of 707 neonates were born after a positive maternal antibody screen result (3.0/1000 live births). In 31 (4%), the positive screen result was due to rhesus immune globulin alone. Of the 676 neonates exposed to alloantibodies, the direct antibody test (DAT) result was positive, showing antigen-positivity and evidence of HDFN in 37% of those tested. Neonatal disease was most severe with DAT-positive anti-Rh antibodies (c, C, D, e, E). All neonatal red blood cell transfusions (15) and exchange transfusions (6) were due to anti-Rh alloimmunization. No neonates born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis required NICU admission for hyperbilirubinemia or transfusion. CONCLUSIONS: Alloimmunization to Rh-group antibodies continues to cause a majority of the severe HDFN cases in our hospital system. In neonates born to alloimmunized mothers, a positive DAT result revealing antigen-positivity is the best predictor of anemia and hyperbilirubinemia.
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Eritroblastosis Fetal , Isoanticuerpos , Isoinmunización Rh , Humanos , Femenino , Embarazo , Recién Nacido , Isoanticuerpos/inmunología , Isoanticuerpos/sangre , Isoinmunización Rh/inmunología , Isoinmunización Rh/epidemiología , Eritroblastosis Fetal/inmunología , Eritroblastosis Fetal/epidemiología , Eritroblastosis Fetal/diagnóstico , Resultado del Embarazo/epidemiología , Sistema del Grupo Sanguíneo Rh-Hr/inmunología , Masculino , Globulina Inmune rho(D)/inmunología , Adulto , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVE: In Europe, prostate cancer (PCa) is the most common cancer in men. Screening may therefore be crucial to lower health care costs, morbidity, and mortality. This systematic review aimed to provide a contemporary overview of the costs and benefits of PCa screening programmes. METHODS: A peer-reviewed literature search was conducted, using the PICO method. A detailed search strategy was developed in four databases based on the following key search terms: "PCa", "screening", and "cost effectiveness". Any type of economic evaluation was included. The search strategy was restricted to European countries, but no restrictions were set on the year of publication. KEY FINDINGS AND LIMITATIONS: A total of 7484 studies were identified initially. Of these, 19 studies described the cost effectiveness of PCa screening in Europe. Among the studies using an initially healthy study population, most focussed on risk- and/or age- and/or magnetic resonance imaging (MRI)-based screening in addition to prostate-specific antigen (PSA) testing and compared this with no screening. Incremental cost ratios (ICERs) varied from 5872 per quality-adjusted life year (QALY) to 372 948/QALY, with a median of 56 487/QALY. Risk-based screening followed by MRI testing seemed to be a more cost-effective strategy than no screening. CONCLUSIONS AND CLINICAL IMPLICATIONS: This systematic review indicates that screening programmes incorporating a risk-based approach and MRI have the potential to be cost effective. PATIENT SUMMARY: In this review, we looked at the cost effectiveness of prostate cancer screening in Europe. We found that a risk-based approach and incorporation of magnetic resonance imaging has the potential to be cost effective. However, there remains a knowledge gap regarding cost effectiveness of prostate cancer screening. Therefore, determinants of cost effectiveness require further investigation.
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People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020-compliant systematic review/random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) versus any control group, and moderators, in people with ICD/DSM-defined schizophrenia, comparing countries and continents. We conducted subgroup, meta-regression analyses, and quality assessment. The primary outcome was all-cause mortality. Secondary outcomes were suicide-, /natural-cause- and other-cause-related mortality. We included 135 studies from Europe (n = 70), North-America (n = 29), Asia (n = 33), Oceania (n = 2), Africa (n = 1). In incident plus prevalent schizophrenia, differences across continents emerged for all-cause mortality (highest in Africa, RR=5.98, 95 %C.I.=4.09-8.74, k = 1, lowest in North-America, RR=2.14, 95 %C.I.=1.92-2.38, k = 16), suicide (highest in Oceania, RR=13.5, 95 %C.I.=10.08-18.07, k = 1, lowest in North-America, RR=4.4, 95 %C.I.=4.07-4.76, k = 6), but not for natural-cause mortality. Europe had the largest association between antipsychotics and lower all-cause mortality/suicide (Asia had the smallest or no significant association, respectively), without differences for natural-cause mortality. Higher country socio-demographic index significantly moderated larger suicide-related and smaller natural-cause-related mortality risk in incident schizophrenia, with reversed associations in prevalent schizophrenia. Antipsychotics had a larger/smaller protective association in incident/prevalent schizophrenia regarding all-cause mortality, and smaller protective association for suicide-related mortality in prevalent schizophrenia. Additional regional differences emerged in incident schizophrenia, across countries, and secondary outcomes. Significant regional differences emerged for all-cause, cause-specific and suicide-related mortality. Natural-cause death was homogeneously increased globally. Moderators differed across countries. Global initiatives are needed to improve physical health in people with schizophrenia, local studies to identify actionable moderators.
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Esquizofrenia , Humanos , Esquizofrenia/mortalidad , Esquizofrenia/epidemiología , Europa (Continente)/epidemiología , Factores de Riesgo , Asia/epidemiología , Suicidio/estadística & datos numéricos , Causas de Muerte/tendencias , Oceanía/epidemiología , África/epidemiología , Mortalidad/tendenciasRESUMEN
Neurodegenerative diseases are one of the most important contributors to morbidity and mortality in the elderly. In Europe, over 14 million people are currently living with dementia, at a cost of over 400 billion EUR annually. Recent advances in diagnostics and approval for new pharmaceutical treatments for Alzheimer's disease (AD), the most common etiology of dementia, heralds the beginning of precision medicine in this field. However, their implementation will challenge an already over-burdened healthcare systems. There is a need for innovative digital solutions that can drive the related clinical pathways and optimize and personalize care delivery. Public-private partnerships are ideal vehicles to tackle these challenges. Here we describe the Innovative Health Initiative (IHI) public-private partnership project PROMINENT that has been initiated by connecting leading dementia researchers, medical professionals, dementia patients and their care partners with the latest innovative health technologies using a precision medicine based digital platform. The project builds upon the knowledge and already implemented digital tools from several collaborative initiatives that address new models for early detection, diagnosis, and monitoring of AD and other neurodegenerative disorders. The project aims to provide support to improvement efforts to each aspect of the care pathway including diagnosis, prognosis, treatment, and data collection for real world evidence and cost effectiveness studies. Ultimately the PROMINENT project is expected to lead to cost-effective care and improved health outcomes.
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INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy. MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific. RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4). CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.
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Preeclampsia , Proteínas Gestacionales , Femenino , Humanos , Embarazo , Biomarcadores , Inmunoensayo , Factor de Crecimiento Placentario , Preeclampsia/diagnóstico , Primer Trimestre del Embarazo , Suecia , Receptor 1 de Factores de Crecimiento Endotelial VascularRESUMEN
OBJECTIVES: The objective of this study was to characterize the epidemiological development of cancer in the Middle East and Africa since 2000 and to quantify its current economic impact. METHODS: Nine countries were studied: Algeria, Egypt, Jordan, Kuwait, Lebanon, Morocco, Saudi Arabia, South Africa, and the United Arab Emirates. Information on causes of death and disability-adjusted life-years (DALYs) was obtained from the World Health Organization. Information on cancer incidence was collected from local cancer registries and estimations by the World Health Organization. The economic burden of cancer was estimated from local health expenditure data and from age-specific mortality data. RESULTS: Between 2000 and 2019, cancer went from third-leading to second-leading cause of death (10% to 13% of all deaths) across these 9 countries. It also climbed from the sixth-leading to third-leading cause of DALYs (6% to 8% of all DALYs). New cancer cases per 100 000 inhabitants increased by 10% to 100% between 2000 and 2019, whereas future increases until 2040 range from 27% in Egypt to 208% in the United Arab Emirates, solely because of expected demographic changes. The economic burden of cancer ranged from around USD 15 per capita in the 4 African countries to USD 79 in Kuwait in 2019. CONCLUSIONS: Cancer is becoming one of the leading causes of disease burden in the Middle East and Africa. Patient numbers are expected to rise strongly in the coming decades. Increasing healthcare expenditure on appropriate cancer care is important to improve patient outcomes and can attenuate the economic impact of cancer on society.
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Estrés Financiero , Neoplasias , Humanos , Egipto , Costo de Enfermedad , Líbano , Marruecos , Neoplasias/epidemiologíaRESUMEN
Objectives: Biomarker testing is indispensable for the implementation of precision medicine (PM) in oncology. The aim of this study was to assess the value of biomarker testing from a holistic perspective based on the example of advanced non-small cell lung cancer (aNSCLC). Materials and methods: A partitioned survival model was populated with data from pivotal clinical trials of first-line treatments in aNSCLC. Three testing scenarios were considered; "no biomarker testing" encompassing chemotherapy treatment, "sequential testing" for EGFR and ALK encompassing treatment with targeted- or chemotherapy, and "multigene testing" covering EGFR, ALK, ROS1, BRAF, NTRK, MET, RET and encompassing treatment with targeted- or immuno(chemo)therapy. Analyses of health outcomes and costs were run for nine countries (Australia, Brazil, China, Germany, Japan, Poland, South Africa, Turkey, United States). A 1-year and 5-year time horizon was applied. Information on test accuracy was combined with country-specific information on epidemiology and unit costs. Results: Compared to the no-testing scenario, survival improved and treatment-related adverse events decreased with increased testing. Five-year survival increased from 2% to 5-7% and to 13-19% with sequential testing and multigene testing, respectively. The highest survival gains were observed in East Asia due to a higher local prevalence of targetable mutations. Overall costs increased with increased testing in all countries. Although costs for testing and medicines increased, costs for treatment of adverse events and end-of-life care decreased throughout all years. Non-health care costs (sick leave and disability pension payments) decreased during the first year but increased over a 5-year horizon. Conclusion: The broad use of biomarker testing and PM in aNSCLC leads to more efficient treatment assignment and improves health outcomes for patients globally, in particular prolonged progression-free disease phase and overall survival. These health gains require investment in biomarker testing and medicines. While costs for testing and medicines would initially increase, cost decreases for other medical services and non-health care costs may partly offset the cost increases.
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OBJECTIVE: This article estimates the life-cycle value of risperidone as representative of second-generation antipsychotics (SGA) relative to haloperidol (first-generation antipsychotics). METHODS: We estimated the number of patients treated with risperidone in Sweden and the United Kingdom, from 1994 to 2017, using data of usage and volume sales. We collected data from the literature on the effectiveness (quality-adjusted life-years per patient per year), direct costs (health services), and indirect costs (productivity) of risperidone and haloperidol. We proxied the incremental value added by the new class (SGA) using a comparator from the inferior class. Next, we modeled the life-cycle uptake of risperidone to estimate the life-cycle incremental cost (ie, direct, indirect, and medicine costs), incremental quality-adjusted life-years, and net monetary benefit of risperidone. We also assessed the life-cycle distribution of the social surplus between the payer (consumer surplus) and the innovator (producer surplus). RESULTS: For the United Kingdom, consumer surplus represents around 72% of the total surplus before patent expiration and around 95% after patent expiration. For Sweden, the consumer surplus represents around 94% of the total surplus before patent expiration and around 99% after generic competition. CONCLUSION: These results suggest that the value added by SGAs to the system is higher than the expected value estimated using cost-effectiveness analysis at launch. Pricing and reimbursement decisions could recognize the full life cycle of value of innovative medicines. This not only presents a challenge of estimation but also of assessing the appropriate division of shares of social value.
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Antipsicóticos , Risperidona , Humanos , Antipsicóticos/uso terapéutico , Análisis Costo-Beneficio , Haloperidol , Risperidona/uso terapéutico , Suecia , Reino UnidoRESUMEN
PURPOSE: Hypertension is a leading causeof premature death worldwide and a major public health problem. This study investigated the long-term effects (>1 year) of digital hypertension monitoring by home blood pressure (HBP) measurements in combination with individualized remote treatment via a Swedish Digital Therapeutics platform in a large patient population. METHODS: The primary endpoint, HBP, and exploratory endpoints, BMI, alcohol consumption, stress level, physical activity, and smoking, were assessed every 3 months for 540 and 360 days, respectively, in 7752 Swedish primary hypertension patients. Patients received individualized medical treatments and lifestyle advice via asynchronous text-based communication in an app. Changes from baseline in endpoints were calculated for the whole population and for subgroups defined by baseline SBP ≥135 (high SBP), 125-135 (suboptimal SBP), 115-125 (optimal SBP), and <115 mmHg (low SBP). RESULTS: After 360 days of treatment, the whole population showed a significant increase of 57% (from 37 to 58%) in the proportion of patients with controlled SBP (i.e. SBP of 115-135 mmHg). The largest reduction in SBP of 13.8 mmHg was observed for the high SBP subgroup, whereas for the low SBP subgroup, SBP increased by 13.4 mmHg. BP improved most in the first three months, and for both the high and low BP subgroups, the improvement continued during the 540-day study period. Significant beneficial changes were also observed for some exploratory endpoints including BMI and smoking. CONCLUSIONS: In conclusion, the digital therapeutics platform was associated with significant improvement in BP control and associated risk factors, which were maintained over a longer period.
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Enfermedades Cardiovasculares , Hipertensión , Humanos , Presión Sanguínea , Enfermedades Cardiovasculares/etiología , Factores de Riesgo , Factores de Riesgo de Enfermedad Cardiaca , Antihipertensivos/uso terapéuticoRESUMEN
OBJECTIVES: This study aimed to describe the role of real-world data (RWD) and real-world evidence (RWE) in health technology assessment (HTA) in 5 European countries and to identify the hurdles to the acceptance of RWE and suggest directions toward its more effective use. METHODS: Authors from France, Germany, Italy, and Sweden used a common template to extract evidence. For England, the Cancer Drugs Fund was described and analyzed as a particular model for the use of RWD to provide evidence for coverage decisions and managed entry agreements. RESULTS: In all countries except Germany, HTA bodies acknowledged the relevance of RWD/RWE to address postlaunch uncertainties. In Germany, evidence from randomized controlled trials remains the gold standard, and evidence based on RWD is generally rejected. Multiple sources of RWD exist, but the quality, the immediate relevance of existing sources, and their interoperability limit their adaptation to the specifics of a given drug. This leads to skepticism about the validity of the evidence. Timing is also a key issue: the production of evidence may not be synchronized with the HTA and pricing bodies' agendas. The Cancer Drugs Fund case emphasizes that a strong partnership among all stakeholders and a pragmatic use of existing data, alongside clinical evidence provided by companies, are key success factors. CONCLUSIONS: A continuous investment in national health information systems is a key issue for providing valid RWE. Processes and aids to guide the acceptability and usage of RWE derived from pairing between sources and questions are essential.
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Evaluación de la Tecnología Biomédica , Humanos , Europa (Continente) , Francia , Alemania , Italia , SueciaRESUMEN
OBJECTIVE: To evaluate the effectiveness of Tobacco Cessation on Prescription (TCP) compared to standard treatment in socioeconomically disadvantaged areas in Swedish primary healthcare (PHC). STUDY DESIGN: A pragmatic cluster randomized controlled trial, where randomization was conducted at the PHC center level using a computer-generated random allocation sequence. SETTING: 18 PHC centers in socioeconomically disadvantaged areas in Stockholm. PARTICIPANTS: 250 adult daily tobacco users (56% female, 41% foreign born) with Swedish social security numbers and permanent resident permits, fluent in Swedish or Arabic, of which 140 responded to the follow-up at 6 months and 139 to the follow-up at 12 months. No blinding was applied. INTERVENTIONS: TCP (tobacco cessation counseling for ≥10 minutes, an individualized prescription for tobacco cessation treatment and follow-up on ≥1 occasion) compared to standard treatment. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was self-reported 7-day abstinence at 6 months and the secondary outcomes included self-reported 7-day abstinence at 12 months and 3-month continued abstinence at 6 and 12 months follow-up. RESULTS: PHC centers were randomized to the intervention group (n = 8) and control group (n = 10). At the PHC centers, 250 patients (TCP n = 188, standard treatment n = 62) were recruited. There was a statistically significant effect of TCP compared to standard treatment for the outcomes 7-day abstinence at 6 months (OR adjusted 5.4, 95% CI 1.57 to 18.93) and 3-month continued abstinence at 6 (OR adjusted 6.4, 95% CI 1.30 to 31.27) and 12 months follow-up (OR adjusted 7.8, 95% CI 1.25 to 48.82). CONCLUSIONS: TCP may be effective in achieving abstinence from tobacco use compared to standard treatment in the given setting but due to several limitations, resulting in high attrition rates and a low statistical power in the study, more research is needed to evaluate this. TRIAL REGISTRATION: ISRCTN 11498135.
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Cese del Uso de Tabaco , Adulto , Humanos , Femenino , Masculino , Motivación , Suecia , Prescripciones , Atención Primaria de SaludRESUMEN
BACKGROUND: Intrauterine infection and inflammation caused by microbial transfer from the vagina are believed to be important factors causing spontaneous preterm delivery (PTD). Multiple studies have examined the relationship between the cervicovaginal microbiome and spontaneous PTD with divergent results. Most studies have applied a DNA-based assessment, providing information on the microbial composition but not transcriptional activity. A transcriptomic approach was applied to investigate differences in the active vaginal microbiome and human transcriptome at midgestation between women delivering spontaneously preterm versus those delivering at term. METHODS: Vaginal swabs were collected in women with a singleton pregnancy at 18 + 0 to 20 + 6 gestational weeks. For each case of spontaneous PTD (delivery <37 + 0 weeks) two term controls were randomized (39 + 0 to 40 + 6 weeks). Vaginal specimens were subject to sequencing of both human and microbial RNA. Microbial reads were taxonomically classified using Kraken2 and RefSeq as a reference. Statistical analyses were performed using DESeq2. GSEA and HUMAnN3 were used for pathway analyses. RESULTS: We found 17 human genes to be differentially expressed (false discovery rate, FDR < 0.05) in the preterm group (n = 48) compared to the term group (n = 96). Gene expression of kallikrein-2 (KLK2), KLK3 and four isoforms of metallothioneins 1 (MT1s) was higher in the preterm group (FDR < 0.05). We found 11 individual bacterial species to be differentially expressed (FDR < 0.05), most with a low occurrence. No statistically significant differences in bacterial load, diversity or microbial community state types were found between the groups. CONCLUSIONS: In our mainly white population, primarily bacterial species of low occurrence were differentially expressed at midgestation in women who delivered preterm versus at term. However, the expression of specific human transcripts including KLK2, KLK3 and several isoforms of MT1s was higher in preterm cases. This is of interest, because these genes may be involved in critical inflammatory pathways associated with spontaneous PTD.
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Líquidos Corporales , Nacimiento Prematuro , Bacterias , Secreciones Corporales , Femenino , Humanos , Recién Nacido , Embarazo , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/genética , Transcriptoma/genética , Vagina/microbiologíaRESUMEN
BACKGROUND: Systemic anti-cancer therapy (SACT) is the recommended treatment modality in patients with advanced non-small cell lung cancer (aNSCLC) in clinical guidelines. SACT options in aNSCLC have multiplied in recent years with the introduction of immunotherapy and targeted therapy. This article presents findings from the first comparative analysis of SACT patterns in Europe. METHODS: SACT rates in aNSCLC were estimated as the ratio between the number of patients treated with SACT (chemotherapy, immunotherapy, targeted therapy) and the number of potentially eligible patients for SACT in 11 countries (Belgium, Bulgaria, Finland, Hungary, Ireland, Netherlands, Norway, Poland, Portugal, Romania, UK) between 2014 and 2020. Treated patients were estimated by combining national sales volume data of cancer drugs and average drug use per patient based on clinical trials. Potentially eligible patients were estimated from national epidemiological data. RESULTS: SACT rates in aNSCLC differed greatly, ranging from around 30 % in Hungary, Poland, and the UK to almost 60 % in Ireland, Norway, and Portugal in 2014. SACT rates seemed to increase over time in most countries, but differences were still large by 2020, ranging from around 40 % in the UK to 75 % or more in Belgium, Norway, and Portugal. Even in countries with the highest SACT rates, far from all patients seemed to receive guideline-recommended SACT options, as underuse of immunotherapy and targeted therapy was common. CONCLUSION: Up to 35 % of eligible patients with aNSCLC receives no SACT in certain European countries, although improvements have been achieved over time. The use of immunotherapy and targeted therapy is suboptimal even in countries with high SACT rates, indicating room to improve the quality of care and patient outcomes. POLICY SUMMARY: Measuring if and what kind of therapy cancer patients have access to is vital to assess quality of care. The care of aNSCLC patients seems to be suboptimal in Europe, due to factors such as exclusion of patients with moderate performance status from SACT, limited resources for diagnostic testing, long reimbursement timelines and slow adoption of new medicines in clinical practice.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inmunoterapia , Europa (Continente)/epidemiología , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: The rate of events such as recurrent heart failure (HF) hospitalization and death are known to dramatically increase directly after HF hospitalization. Furthermore, the number of HF hospitalizations is associated with irreversible long-term disease progression, which is in turn associated with increased event rates. However, cost-effectiveness models of HF treatments commonly fail to capture both the short- and long-term association between HF hospitalization and events. OBJECTIVE: The aim of this study was to provide a decision-analytic model that reflects the short- and long-term association between HF hospitalization and event rates. Furthermore, we assess the impact of omitting these associations. METHODS: We developed a life-time Markov cohort model to evaluate HF treatments, and modeled the short-term impact of HF hospitalization on event rates via a sequence of tunnel states, with transition probabilities following a parametric survival curve. The corresponding long-term impact was modeled via hazard ratios per HF hospitalization. We obtained baseline event rates and utilities from published literature. Subsequently, we assessed, for a hypothetical HF treatment, how omitting the modeled associations (through a simple two-state model) affects incremental quality-adjusted life-years (QALYs). RESULTS: We developed a model that incorporates both short- and long-term impacts of HF hospitalizations. Based on an assumed treatment effect of a 20% risk reduction for HF hospitalization (and associated reductions in all-cause mortality of 15%), omitting the short-term, the long-term, or both associations resulted in a 5%, 1%, and 22% decrease in QALYs gained, respectively. CONCLUSION: For both modeling components, i.e., the short- and long-term implications of HF hospitalization, the impact on incremental outcomes associated with treatment was substantial. Considering these aspects as proposed within this modeling approach better reflects the natural course of this progressive condition and will enhance the evaluation of future HF treatments.
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Insuficiencia Cardíaca , Análisis Costo-Beneficio , Insuficiencia Cardíaca/terapia , Hospitalización , Humanos , Modelos de Riesgos Proporcionales , Años de Vida Ajustados por Calidad de VidaRESUMEN
INTRODUCTION: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years. METHODS AND ANALYSIS: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (≥4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire. ETHICS AND DISSEMINATION: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy. TRIAL REGISTRATION NUMBER: Main sponsor: Imperial College London, Reference: 19QC5491. Funders: NIHR HTA, Reference: 127 976. Study coordination centre: Imperial College Healthcare NHS Trust, Du Cane Road, London, W12 0HS with Centre for Trials Research, College of Biomedical & Life Sciences, Cardiff University. IRAS Project ID: 266 400. REC reference: 20/LO/0031. ISRCTN registry: 76 016 200.
Asunto(s)
Nacimiento Prematuro , Ultrasonografía Prenatal , Cardiotocografía , Niño , Femenino , Retardo del Crecimiento Fetal , Peso Fetal , Frecuencia Cardíaca Fetal/fisiología , Humanos , Lactante , Recién Nacido , Embarazo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Today our life without smart gadgets is beyond imagination. In fact, smart apps are now the inseparable part of a human life. The use of technology has provided more comfortable and easier life than ancient times, but the overuse of social media and mobile devices may lead to numerous Psychological, Physical and Psychosomatic (P3) disorders, such as eyestrain, anxiety, fatigue, and difficulty focusing on important tasks. They may also create serious health malfunctions, such as depression and hypertension. Social media may be the first solution that comes to mind when we are lonely; it seems to be a quick and easy access to number of people. However, many studies have shown that our online networks, although they may offer an illusion of connectedness, rather make us even lonelier and more segregated. The overuse of technology may have a significant impact on developing children and teenagers. Mind is the powerhouse of a human body, and the activity level determines the overall health of a person. Hyperactive or hypoactive minds, both are the signs of abnormality and to avoid such conditions C5 (Creativity, Contentment, Confidence, Calmness, Concentration) concept is being practiced. In this paper, we present a novel idea of using C5 concept for overall harmonical holistic development. A good relationship is established between C5 growth along with HEALTH (Harmony, Energy, Aesthetics, Limberness, Tranquility & Happiness). The convenience of C5 concept to assess anxiousness and stressed mental state of a person through empathetic intelligence by applying haptic Aps via tactile internet makes our world smarter than present times to dwell in with a proper care of ourselves and our related people giving better outcomes in our personal and professional fronts.