ABSTRACT
Mammalian sex chromosomes carry large palindromes that harbor protein-coding gene families with testis-biased expression. However, there are few known examples of sex-chromosome palindromes conserved between species. We identified 26 palindromes on the human X Chromosome, constituting more than 2% of its sequence, and characterized orthologous palindromes in the chimpanzee and the rhesus macaque using a clone-based sequencing approach that incorporates full-length nanopore reads. Many of these palindromes are missing or misassembled in the current reference assemblies of these species' genomes. We find that 12 human X palindromes have been conserved for at least 25 million years, with orthologs in both chimpanzee and rhesus macaque. Insertions and deletions between species are significantly depleted within the X palindromes' protein-coding genes compared to their noncoding sequence, demonstrating that natural selection has preserved these gene families. The spacers that separate the left and right arms of palindromes are a site of localized structural instability, with seven of 12 conserved palindromes showing no spacer orthology between human and rhesus macaque. Analysis of the 1000 Genomes Project data set revealed that human X-palindrome spacers are enriched for deletions relative to arms and flanking sequence, including a common spacer deletion that affects 13% of human X Chromosomes. This work reveals an abundance of conserved palindromes on primate X Chromosomes and suggests that protein-coding gene families in palindromes (most of which remain poorly characterized) promote X-palindrome survival in the face of ongoing structural instability.
Subject(s)
Selection, Genetic , X Chromosome , Animals , Macaca mulatta/genetics , Male , Pan troglodytes/genetics , Sex Chromosomes , X Chromosome/geneticsABSTRACT
RESEARCH QUESTION: What are the views and experiences of patient and expert stakeholders on the positive and negative impacts of commercial influences on the provision of assisted reproductive technology (ART) services, and what are their suggestions for governance reforms? DESIGN: Semi-structured interviews were conducted with 31 ART industry experts from across Australia and New Zealand and 25 patients undergoing ART from metropolitan and regional Australia, between September 2020 and September 2021. Data were analysed using thematic analysis. RESULTS: Expert and patient participants considered that commercial forces influence the provision of ART in a number of positive ways - increasing sustainability, ensuring consistency in standards and providing patients with greater choice. Participants also considered commercial forces to have a number of negative impacts, including increased costs to government and patients; the excessive use of interventions that lack sufficient evidence to be considered part of standard care; inadequately informed consent (particularly with regard to financial information); and threats to patient-provider relationships and patient-centred care. Participants varied in whether they believed that professional self-regulation is sufficient. While recognizing the benefits of commercial investment in healthcare, many considered that regulatory reforms, as well as organizational cultural initiatives, are needed as means to ensure the primacy of patient well-being. CONCLUSIONS: The views expressed in this study should be systematically and critically examined to derive insights into how best to govern ART. These insights may also inform the design and delivery of other types of healthcare that are provided in the private sector.
Subject(s)
Reproductive Techniques, Assisted , Humans , Reproductive Techniques, Assisted/economics , Australia , Female , New Zealand , Male , Adult , Attitude of Health PersonnelABSTRACT
INTRODUCTION: In order to be positioned to address the increasing strain of burnout and worsening nurse shortage, a better understanding of factors that contribute to nursing workload is required. This study aims to examine the difference between order-based and clinically perceived nursing workloads and to quantify factors that contribute to a higher clinically perceived workload. DESIGN: A retrospective cohort study was used on an observational dataset. METHODS: We combined patient flow, nurse staffing and assignment, and workload intensity data and used multivariate linear regression to analyze how various shift, patient, and nurse-level factors, beyond order-based workload, affect nurses' clinically perceived workload. RESULTS: Among 53% of our samples, the clinically perceived workload is higher than the order-based workload. Factors associated with a higher clinically perceived workload include weekend or night shifts, shifts with a higher census, patients within the first 24 h of admission, and male patients. CONCLUSIONS: The order-based workload measures tended to underestimate nurses' clinically perceived workload. We identified and quantified factors that contribute to a higher clinically perceived workload, discussed the potential mechanisms as to how these factors affect the clinically perceived workload, and proposed targeted interventions to better manage nursing workload. CLINICAL RELEVANCE: By identifying factors associated with a high clinically perceived workload, the nurse manager can provide appropriate interventions to lighten nursing workload, which may further reduce the risk of nurse burnout and shortage.
ABSTRACT
In Australia and the UK, commercialization and corporatization of assisted reproductive technologies have created a marketplace of clinics, products, and services. While this has arguably increased choice for patients, 'choice', shaped by commercial imperatives may not mean better-quality care. At present, regulation of clinics (including clinic-corporations) and clinicians focuses on the doctor-patient dyad and the clinic-consumer dyad. Scant attention has been paid to the conflicts between the clinic-corporation's duty to its shareholders and investors, the medical profession's duty to the corporations within which they practice, and the obligations of both clinicians and corporations to patients and to health systems. Frameworks of regulation based in corporate governance and business ethics, such as stakeholder models and 'corporate social responsibility', have well-recognized limits and may not translate well into healthcare settings. This means that existing governance frameworks may not meet the needs of patients or health systems. We argue for the development of novel regulatory approaches that more explicitly characterize the obligations that both corporations and clinicians in corporate environments have to patients and to society, and that promote fulfilment of these obligations. We consider mechanisms for application in the multi-jurisdictional setting of Australia, and the single jurisdictional settings of the UK.
ABSTRACT
OBJECTIVES: To develop a model of family-based psychosocial care for congenital heart disease (CHD). DESIGN: Qualitative study using crowdsourced data collected from parents of young children with CHD who received care across 42 hospitals. SETTING: Yammer, a social networking platform used to facilitate online crowdsourcing and qualitative data collection. SUBJECTS: Geographically diverse sample of 100 parents (72 mothers and 28 fathers) of young children with CHD. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Parents joined a private group on Yammer and responded to 37 open-ended study questions over a 6-month period. Qualitative data were coded and analyzed using an iterative process. Three broad themes corresponding to pillars of family-based psychosocial care were identified: pillar 1) parent partnership in family-integrated medical care, pillar 2) supportive interactions focused on parent and family wellbeing, and pillar 3) integrated psychosocial care and peer support for parents and families. Each pillar was supported by subthemes corresponding to specific intervention strategies. Most parents described the need for intervention strategies across multiple pillars, with almost half reporting needs across all three pillars of psychosocial care. Parents' preferences for psychosocial support changed over time with changes to their child's medical status and across care settings (e.g., hospital, outpatient clinic). CONCLUSIONS: Results support a model of family-based psychosocial care that is multidimensional and flexible to meet the needs of families affected by CHD. All members of the healthcare team play an important role in providing psychosocial support. Future research incorporating components of implementation science is needed to promote uptake of these findings, with the goal of optimizing family-based psychosocial support in the hospital setting and beyond.
Subject(s)
Heart Defects, Congenital , Psychiatric Rehabilitation , Child , Female , Humans , Child, Preschool , Parents/psychology , Mothers , Psychosocial Support Systems , Heart Defects, Congenital/therapy , Heart Defects, Congenital/psychologyABSTRACT
Species identification and growth rates for a collection of Cronobacter strains from clinical and non-clinical sources have been previously reported. However, advancements in DNA sequencing-based identification methods now allow for more accurate identification. Here we report the sequence types (STs) for 24 strains of Cronobacter sakazakii and examine any possible correlation between sequence type and growth rate, which could influence risk through greater pathogen multiplication and reach of infectious doses during time between formula preparation and feeding. The most common clonal complexes (CCs) identified were C. sakazakii CC1 and CC4. CC1 strains belonged to ST1 (n = 8) and ST391 (n = 1), while CC4 included ST4 (n = 4), ST255 (n = 1) and ST295 (n = 1). Three strains were found to belong to CC100 and two were found to belong to ST64. The remaining STs identified were represented by single strains. CC4 strains have a slightly not significant tendency for faster growth rates at 25 °C; however, the small sample size suggests that more strains need to be analysed to determine if this is a true result. In conclusion, the growth rates of C. sakazakii strains do not appear to be strongly correlated to ST.
Subject(s)
Cronobacter sakazakii , Cronobacter sakazakii/genetics , Cronobacter sakazakii/growth & development , Infant Formula/microbiology , Sequence Analysis, DNAABSTRACT
BACKGROUND: Public awareness of Developmental Language Disorder (DLD) is lower than other neurodevelopmental disorders, despite its high prevalence of 7.6%. This lower awareness means recruitment for DLD research studies is difficult. DLD is both underfunded and under-researched, resulting in relatively limited research investigating individuals with DLD. Engage with Developmental Language Disorder (E-DLD) is a response to these considerations. E-DLD is the first international participant database of those affected by DLD. Parents of children with DLD under 16 and young people and adults over 16 from anywhere in the world can sign up to be a part of the E-DLD. AIMS: This paper aims to describe the families of children with DLD and adults with DLD in the database thus far. METHODS & PROCEDURES: E-DLD members sign up via our website, reporting demographic characteristics as part of this procedure. We request all E-DLD members subsequently fill in a yearly survey. The content of the yearly survey changes dependent on the age of the child, while the yearly survey for adults remains consistent. We measure a wide range of domains, such as speech and language therapy (SLT) support, school support, socialisation skills, and early developmental milestones for our youngest members, and health care support and mental well-being measurements for our adults. We also collect parent and self-reported reflections on strengths and challenges for the person with DLD using open-ended questions and the Strengths and Difficulties Questionnaire. OUTCOMES & RESULTS: The database currently consists of 196 parents of children with DLD and 20 individuals over the age of 16 with DLD or suspected DLD across a range of socioeconomic status (SES) backgrounds. Our initial results confirm that E-DLD members meet the linguistic profile of DLD in relation to self- or parent-rated language difficulties. Both children and adults show increased rates of psychosocial difficulties compared to established norms, consistent with past research on clinical samples of people with DLD. CONCLUSIONS & IMPLICATIONS: The findings indicate that a participant database for DLD research is feasible and useful. The rates of emotional, behavioural and sleep difficulties among the child probands are higher than reported rates amongst typically developing children. Initial data indicate that adults with DLD have poorer well-being than their peers. The E-DLD is a useful collection of data on those affected by DLD and is a promising method for connecting people with DLD with academic researchers. WHAT THIS PAPER ADDS: What is already known on this subject Developmental Language Disorder (DLD) is characterised by expressive and/or receptive language difficulties in the absence of another biomedical condition that could explain these difficulties. It is critically under-researched and underfunded. As such, there is a lack of public awareness and difficulty recruiting sufficient sample sizes for DLD research studies. What this paper adds to existing knowledge Engage with Developmental Language Disorder (E-DLD) is the first international participant database of individuals with DLD. This paper provides a preliminary report on the profile of linguistic and psychosocial skills among the individuals on the database, adding to current understanding of DLD across age groups. What are the potential or actual clinical implications of this work? Our aim is that the E-DLD will provide much-needed facilitation of research into DLD. E-DLD will enable those with DLD and their families more readily to shape research agendas and to participate in studies that interest them. Families may be recruited into research that could directly translate to better clinical treatment of DLD. We also believe that the E-DLD yearly survey holds potential to provide key information on the development and longitudinal experience of children and adults with DLD.
Subject(s)
Language Development Disorders , Child , Adult , Humans , Adolescent , Language Development Disorders/diagnosis , Language Development Disorders/epidemiology , Language Development Disorders/therapy , Linguistics , Schools , Speech Therapy , EmotionsABSTRACT
Early screening for language problems is a priority given the importance of language for success in school and interpersonal relationships. The paucity of reliable behavioral instruments for this age group prompted the development of a new touchscreen language screener for 2-year-olds that relies on language comprehension. Developmental literature guided selection of age-appropriate markers of language disorder risk that are culturally and dialectally neutral and could be reliably assessed. Items extend beyond products of linguistic knowledge (vocabulary and syntax) and tap the process by which children learn language, also known as fast mapping. After piloting an extensive set of items (139), two phases of testing with over 500 children aged 2; 0-2; 11 were conducted to choose the final 40-item set. Rasch analysis was used to select the best fitting and least redundant items. Norms were created based on 270 children. Sufficient test-retest reliability, Cronbach's alpha, and convergent validity with the MB-CDI and PPVT are reported. This quick behavioral measure of language capabilities could support research studies and facilitate the early detection of language problems.
Subject(s)
Language , Vocabulary , Child , Humans , Child, Preschool , Reproducibility of Results , LearningABSTRACT
Assortative mating is a phenomenon in which romantic partners typically resemble each other at a level greater than chance. There is converging evidence that social behaviours are subject to assortative mating, though less is known regarding social cognition. Social functioning requires the ability to identify and understand the mental states of others, i.e., theory of mind. The present study recruited a sample of 102 heterosexual couples via an online survey to test if theory of mind as measured using facial expressions (Reading the Mind in the Eyes Test) or language (Stiller-Dunbar Stories Task) is associated with assortative mating. Results provide evidence of assortative mating for theory of mind via facial expressions, though there was no such effect for theory of mind via language. Assortative mating for theory of mind via facial expressions was not moderated by length of relationship nor by partner similarity in age, educational attainment, or religiosity, all variables relevant to social stratification. This suggests assortative mating for theory of mind via facial expressions is better explained by partners being alike at the start of their relationship (initial assortment) rather than becoming similar through sustained social interaction (convergence), and by people seeking out partners that are like themselves (active assortment) rather than simply pairing with those from similar demographic backgrounds (social homogamy).
ABSTRACT
Fewer than half of new drugs have data on their comparative benefits and harms against existing treatment options at the time of regulatory approval in Europe and the USA. Even when active-comparator trials exist, they might not produce meaningful data to inform decisions in clinical practice and health policy. The uncertainty associated with the paucity of well designed active-comparator trials has been compounded by legal and regulatory changes in Europe and the USA that have created a complex mix of expedited programmes aimed at facilitating faster access to new drugs. Comparative evidence generation is even sparser for medical devices. Some have argued that the current process for regulatory approval needs to generate more evidence that is useful for patients, clinicians, and payers in health-care systems. We propose a set of five key principles relevant to the European Medicines Agency, European medical device regulatory agencies, US Food and Drug Administration, as well as payers, that we believe will provide the necessary incentives for pharmaceutical and device companies to generate comparative data on drugs and devices and assure timely availability of evidence that is useful for decision making. First, labelling should routinely inform patients and clinicians whether comparative data exist on new products. Second, regulators should be more selective in their use of programmes that facilitate drug and device approvals on the basis of incomplete benefit and harm data. Third, regulators should encourage the conduct of randomised trials with active comparators. Fourth, regulators should use prospectively designed network meta-analyses based on existing and future randomised trials. Last, payers should use their policy levers and negotiating power to incentivise the generation of comparative evidence on new and existing drugs and devices, for example, by explicitly considering proven added benefit in pricing and payment decisions.
Subject(s)
Device Approval/standards , Drug Approval/methods , Equipment Safety , Safety , Biomarkers, Pharmacological/analysis , Drug Tolerance , Evidence-Based Medicine , Humans , United States , United States Food and Drug AdministrationABSTRACT
Genome sequencing has uncovered a new mutational phenomenon in cancer and congenital disorders called chromothripsis. Chromothripsis is characterized by extensive genomic rearrangements and an oscillating pattern of DNA copy number levels, all curiously restricted to one or a few chromosomes. The mechanism for chromothripsis is unknown, but we previously proposed that it could occur through the physical isolation of chromosomes in aberrant nuclear structures called micronuclei. Here, using a combination of live cell imaging and single-cell genome sequencing, we demonstrate that micronucleus formation can indeed generate a spectrum of genomic rearrangements, some of which recapitulate all known features of chromothripsis. These events are restricted to the mis-segregated chromosome and occur within one cell division. We demonstrate that the mechanism for chromothripsis can involve the fragmentation and subsequent reassembly of a single chromatid from a micronucleus. Collectively, these experiments establish a new mutational process of which chromothripsis is one extreme outcome.
Subject(s)
Chromosome Breakage , DNA Damage , Micronuclei, Chromosome-Defective , Cell Line , Cell Survival , Chromosome Segregation/genetics , DNA Copy Number Variations/genetics , Gene Rearrangement/genetics , Genomic Instability/genetics , Humans , Mutation/genetics , Neoplasms/genetics , S Phase/genetics , Single-Cell AnalysisABSTRACT
Diagnosis of CHD substantially affects parent mental health and family functioning, thereby influencing child neurodevelopmental and psychosocial outcomes. Recognition of the need to proactively support parent mental health and family functioning following cardiac diagnosis to promote psychosocial adaptation has increased substantially over recent years. However, significant gaps in knowledge remain and families continue to report critical unmet psychosocial needs. The Parent Mental Health and Family Functioning Working Group of the Cardiac Neurodevelopmental Outcome Collaborative was formed in 2018 through support from an R13 grant from the National Heart, Lung, and Blood Institute to identify significant knowledge gaps related to parent mental health and family functioning, as well as critical questions that must be answered to further knowledge, policy, care, and outcomes. Conceptually driven investigations are needed to identify parent mental health and family functioning factors with the strongest influence on child outcomes, to obtain a deeper understanding of the biomarkers associated with these factors, and to better understand how parent mental health and family functioning influence child outcomes over time. Investigations are also needed to develop, test, and implement sustainable models of mental health screening and assessment, as well as effective interventions to optimise parent mental health and family functioning to promote psychosocial adaptation. The critical questions and investigations outlined in this paper provide a roadmap for future research to close gaps in knowledge, improve care, and promote positive outcomes for families of children with CHD.
Subject(s)
Family , Mental Health , Child , Educational Status , Heart , Humans , ParentsABSTRACT
In Montgomery v Lanarkshire Health Board, Lords Kerr and Reed referred to the increasing tendency to treat patients 'as consumers exercising choices'. The question of whether it is helpful to regard patients as consumers is not a new one, but it arises most frequently in discussions about the commercialisation of healthcare. Comparing patients with consumers in relation to informed consent is an interesting development, especially in the light of the growing body of contract and consumer law scholarship which questions the extent to which information disclosures to consumers produce informed choices. If there is evidence that the duties of disclosure which are imposed on retailers, in order to redress the imbalance of knowledge and power in the consumer-retailer relationship, do not always fulfil their intended purpose, might this have any resonance for the duties of disclosure which are imposed upon healthcare professionals?
Subject(s)
Disclosure , Informed Consent , Delivery of Health Care , Health Personnel , HumansABSTRACT
PURPOSE: To evaluate a single institution's experience with granulocyte colony-stimulating factor after autologous hematopoietic stem cell transplant in myeloma patients to identify populations that benefit most from granulocyte colony-stimulating factor administration. METHODS: Retrospective chart reviews were conducted on patients 18+ years with multiple myeloma that underwent autologous hematopoietic stem cell transplant at UW Health from January 2012 to May 2016. Data collection included demographics, length of stay, time to engraftment, Eastern Cooperative Oncology Group performance status score, and hematopoietic cell transplantation-comorbidity index. The primary outcome was days from transplant to engraftment, defined as absolute neutrophil count > 500/mm3 for two consecutive days or absolute neutrophil count > 1000/mm3 once. A subset analysis was performed on patients whose date of engraftment was known. RESULTS: In total, 216 individual patients were included in the full cohort and 122 patients included in the subset analysis. Median time to engraftment between patients administered granulocyte colony-stimulating factor and the nongranulocyte colony-stimulating factor group was 12 versus 19 days (P < 0.001) in the full cohort and 12 versus 14 days (P < 0.001) in the subset analysis. The average length of stay posthematopoietic stem cell transplant in the granulocyte colony-stimulating factor group was 15 days versus 17 days in the nongranulocyte colony-stimulating factor group (P = 0.026) in the subset analysis. Additionally, no difference in time to engraftment was seen when stratified by age, Eastern Cooperative Oncology Group performance status score, or hematopoietic cell transplantation-comorbidity index. CONCLUSION: Our study supports use of granulocyte colony-stimulating factor posthematopoietic stem cell transplant in myeloma patients to decrease time to engraftment and length of stay. Consideration should be given to utilization in all patients in this population posthematopoietic stem cell transplant. Further research is needed to identify the populations that benefit most from granulocyte colony-stimulating factor administration.
Subject(s)
Granulocyte Colony-Stimulating Factor/administration & dosage , Hematopoietic Stem Cell Transplantation/methods , Multiple Myeloma/therapy , Adult , Aged , Female , Hematopoietic Stem Cell Mobilization , Humans , Leukocyte Count , Male , Middle Aged , Neutrophils , Retrospective Studies , Transplantation, AutologousABSTRACT
BACKGROUND: Patient falls are a major problem in hospitals. The development of a Patient-Centered Fall Prevention Toolkit, Fall TIPS (Tailoring Interventions for Patient Safety), reduced falls by 25% in acute care hospitals by leveraging health information technology to complete the 3-step fall prevention process-(1) conduct fall risk assessments; (2) develop tailored fall prevention plans with the evidence-based interventions; and (3) consistently implement the plan. We learned that Fall TIPS was most effective when patients and family were engaged in all 3 steps of the fall prevention process. Over the past decade, our team developed 3 Fall TIPS modalities-the original electronic health record (EHR) version, a laminated paper version that uses color to provide clinical decision support linking patient-specific risk factors to the interventions, and a bedside display version that automatically populates the bedside monitor with the patients' fall prevention plan based on the clinical documentation in the EHR. However, the relative effectiveness of each Fall TIPS modality for engaging patients and family in the 3-step fall prevention process remains unknown. OBJECTIVE: This study aims to examine if the Fall TIPS modality impacts patient engagement in the 3-step fall prevention process and thus Fall TIPS efficacy. METHODS: To assess patient engagement in the 3-step fall prevention process, we conducted random audits with the question, "Does the patient/family member know their fall prevention plan?" In addition, audits were conducted to measure adherence, defined by the presence of the Fall TIPS poster at the bedside. Champions from 3 hospitals reported data from April to June 2017 on 6 neurology and 7 medical units. Peer-to-peer feedback to reiterate the best practice for patient engagement was central to data collection. RESULTS: Overall, 1209 audits were submitted for the patient engagement measure and 1401 for the presence of the Fall TIPS poster at the bedside. All units reached 80% adherence for both measures. While some units maintained high levels of patient engagement and adherence with the poster protocol, others showed improvement over time, reaching clinically significant adherence (>80%) by the final month of data collection. CONCLUSIONS: Each Fall TIPS modality effectively facilitates patient engagement in the 3-step fall prevention process, suggesting all 3 can be used to integrate evidence-based fall prevention practices into the clinical workflow. The 3 Fall TIPS modalities may prove an effective strategy for the spread, allowing diverse institutions to choose the modality that fits with the organizational culture and health information technology infrastructure.
Subject(s)
Accidental Falls/prevention & control , Implementation Science , Medical Informatics/methods , Patient Participation/methods , HumansABSTRACT
BACKGROUND: The ability to learn new words is critical in the development of oral and written language, and significantly impacts engagement in social, academic and vocational situations. Many studies have evaluated the word-learning process in people with developmental language disorder (DLD). However, methodologies for assessment are heterogeneous, creating difficulties in synthesizing findings and identifying gaps in the knowledge base. AIMS: To scope systematically the literature and identify key methodological parameters considered in evaluations of word learning in people with DLD; and to identify gaps in the literature to guide further research in this area. METHODS & PROCEDURES: Twelve databases were searched and a total of 70 studies that met eligibility criteria were identified. The studies were evaluated according to key parameters that researchers varied in their word-learning methodologies. MAIN CONTRIBUTION: Most research has focused on word learning in the oral modality, and specifically in children with DLD. Fewer studies have explored word learning in adults and adolescents with DLD, and in the written modality. Depending on the research question and theoretical perspective driving the investigation, methodologies for assessing word learning considered a range of parameters, including words being learned, learning context and cues to support learning in the tasks. CONCLUSIONS & IMPLICATIONS: This review aggregates a variety of methods used previously to assess word learning. Findings highlight the need for further research to explore areas such as: the learning of varied word types (e.g., adjectives and adverbs); learning in the written modality; and word learning (both oral and written) in adolescents and adults with DLD.
Subject(s)
Aptitude , Language Development Disorders/psychology , Verbal Learning , Cues , Humans , Outcome Assessment, Health Care/methods , Phonetics , Semantics , VocabularyABSTRACT
This article seeks to challenge the assumption that it is legitimate to consider the costs of premature babies' future social and educational needs when deciding what treatment, if any, to provide in the neonatal intensive care unit (NICU) . It questions the elision that is made between the claim that a particular treatment is insufficiently cost-effective and the claim that a person will be a burden on the state in the future. It discusses a series of common misunderstandings about how treatment decisions are taken in the NICU and concludes by suggesting that the claim that premature babies are too expensive to treat may depend upon regarding a premature infant as if she were not yet a person, with rights and interests of her own.
Subject(s)
Decision Making/ethics , Fetal Viability , Infant, Extremely Premature , Intensive Care Units, Neonatal , Withholding Treatment/economics , Bioethical Issues , Cost of Illness , Cost-Benefit Analysis , Health Care Costs , Health Care Rationing , Humans , Infant, Newborn , Withholding Treatment/ethics , Withholding Treatment/legislation & jurisprudenceABSTRACT
NEW FINDINGS: What is the central question of this study? In sleep apnoea, a putative link between intermittent hypoxia and hypertension is the generation of oxygen radicals by angiotensin II and xanthine oxidase within the chemoreflex arc and vasculature. We tested whether chemoreflex control of sympathetic outflow, hypoxic vasodilatation and blood pressure are altered by angiotensin blockade (losartan) and/or xanthine oxidase inhibition (allopurinol). What is the main finding and its importance? Both drugs lowered blood pressure without altering sympathetic outflow, reducing chemoreflex sensitivity or enhancing hypoxic vasodilatation. Losartan and allopurinol are effective therapies for achieving blood pressure control in sleep apnoea. ABSTRACT: Chemoreflex sensitization produced by chronic intermittent hypoxia in rats is attenuated by angiotensin II type 1 receptor (AT1 R) blockade. Both AT1 R blockade and xanthine oxidase inhibition ameliorate chronic intermittent hypoxia-induced endothelial dysfunction. We hypothesized that treatment with losartan and allopurinol would reduce chemoreflex sensitivity and improve hypoxic vasodilatation in patients with obstructive sleep apnoea. Eighty-six hypertensive patients with apnoea-hypopnoea index ≥25 events h-1 and no other cardiovascular, pulmonary, renal or metabolic disease were randomly assigned to receive allopurinol, losartan or placebo for 6 weeks. Treatment with other medications and/or continuous positive airway pressure remained unchanged. Tests of chemoreflex sensitivity and hypoxic vasodilatation were performed during wakefulness before and after treatment. Ventilation (pneumotachography), muscle sympathetic nerve activity (microneurography), heart rate (electrocardiography), arterial oxygen saturation (pulse oximetry), blood pressure (sphygmomanometry), forearm blood flow (venous occlusion plethysmography) and cerebral flow velocity (transcranial Doppler ultrasound) were measured during eupnoeic breathing and graded reductions in inspired O2 tension. Losartan and allopurinol lowered arterial pressure measured during eupnoeic breathing and exposure to acute hypoxia. Neither drug altered the slopes of ventilatory, sympathetic or cardiovascular responses to acute hypoxia. We conclude that losartan and allopurinol are viable pharmacotherapeutic adjuncts for achieving blood pressure control in hypertensive obstructive sleep apnoea patients, even those who are adequately treated with continuous positive airway pressure.
Subject(s)
Allopurinol/therapeutic use , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Cardiovascular System/drug effects , Hypertension/drug therapy , Losartan/therapeutic use , Sleep Apnea, Obstructive/drug therapy , Adult , Aged , Allopurinol/pharmacology , Antihypertensive Agents/pharmacology , Blood Pressure/physiology , Cardiovascular System/physiopathology , Cerebrovascular Circulation/drug effects , Cerebrovascular Circulation/physiology , Female , Heart Rate/drug effects , Heart Rate/physiology , Humans , Hypertension/complications , Hypertension/physiopathology , Hypoxia/physiopathology , Losartan/pharmacology , Male , Muscle, Skeletal/drug effects , Muscle, Skeletal/physiopathology , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/physiopathology , Treatment Outcome , Young AdultABSTRACT
BACKGROUND: We sought to determine if female community health volunteers (FCHVs) and literate women in Nepal can accurately determine success of medical abortion (MA) using a symptom checklist, compared to experienced abortion providers. METHODS: Women undergoing MA, and FCHVs, independently assessed the success of each woman's abortion using an 8-question symptom checklist. Any answers in a red-shaded box indicated that the abortion may not have been successful. Women's/FCHVs' assessments were compared to experienced abortion providers using standard of care. RESULTS: Women's (n = 1153) self-assessment of MA success agreed with abortion providers' determinations 85% of the time (positive predictive value = 90, 95% CI 88, 92); agreement between FCHVs and providers was 82% (positive predictive value = 90, 95% CI 88, 92). Of the 92 women (8%) requiring uterine evacuation with manual vacuum aspiration (n = 84, 7%) or medications (n = 8, 0.7%), 64% self-identified as needing additional care; FCHVs identified 61%. However, both women and FCHVs had difficulty recognizing that an answer in a red-shaded box indicated that the abortion may not have been successful. Of the 453 women with a red-shaded box marked, only 35% of women and 41% of FCHVs identified the need for additional care. CONCLUSION: Use of a checklist to determine MA success is a promising strategy, however further refinement of such a tool, particularly for low-literacy settings, is needed before widespread use.
Subject(s)
Abortion, Induced/statistics & numerical data , Checklist/methods , Outcome Assessment, Health Care/methods , Symptom Assessment/methods , Abortion, Induced/methods , Adult , Community Health Workers , Diagnostic Self Evaluation , Female , Humans , Nepal , Pregnancy , Reproducibility of Results , Treatment Outcome , Volunteers , Young AdultABSTRACT
Globally, IVF patients are routinely offered and charged for a selection of adjunct treatments and tests or 'add-ons' that they are told may improve their chance of a live birth, despite there being no clinical evidence supporting the efficacy of the add-on. Any new IVF technology claiming to improve live birth rates (LBR) should, in most cases, first be tested in an appropriate animal model, then in clinical trials, to ensure safety, and finally in a randomized controlled trial (RCT) to provide high-quality evidence that the procedure is safe and effective. Only then should the technique be considered as 'routine' and only when applied to the similar patient population as those studied in the RCT. Even then, further pediatric and long-term follow-up studies will need to be undertaken to examine the long-term safety of the procedure. Alarmingly, there are currently numerous examples where adjunct treatments are used in the absence of evidence-based medicine and often at an additional fee. In some cases, when RCTs have shown the technique to be ineffective, it is eventually withdrawn from the clinic. In this paper, we discuss some of the adjunct treatments currently being offered globally in IVF laboratories, including embryo glue and adherence compounds, sperm DNA fragmentation, time-lapse imaging, preimplantation genetic screening, mitochondria DNA load measurement and assisted hatching. We examine the evidence for their safety and efficacy in increasing LBRs. We conclude that robust studies are needed to confirm the safety and efficacy of any adjunct treatment or test before they are offered routinely to IVF patients.