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ObjectivesTo develop a physiotherapist-led consensus statement on the definition and provision of high-value care for people with musculoskeletal conditions.DesignWe performed a three-stage study using Research And Development/University of California Los Angeles Appropriateness Method methodology. We reviewed evidence about current definitions through a rapid literature review and then performed a survey and interviews with network members to gather consensus. Consensus was finalised in a face-to-face meeting.SettingAustralian primary care.ParticipantsRegistered physiotherapists who are members of a practice-based research network (n=31).ResultsThe rapid review revealed two definitions, four domains of high value care and seven themes of high-quality care. Online survey responses (n=26) and interviews (n=9) generated two additional high-quality care themes, a definition of low-value care, and 21 statements on the application of high value care. Consensus was reached for three working definitions (high value, high-quality and low value care), a final model of four high value care domains (high-quality care, patient values, cost-effectiveness, reducing waste), nine high-quality care themes and 15 statements on application.ConclusionHigh value care for musculoskeletal conditions delivers most value for the patient, and the clinical benefits outweigh the costs to the individual or system providing the care. High-quality care is evidence based, effective and safe care that is patient-centred, consistent, accountable, timely, equitable and allows easy interaction with healthcare providers and healthcare systems.

The report draws on world-class expertise from climate scientists, ecologists, mathematicians, geographers, engineers, energy, food, livestock, and transport experts, economists, social and political scientists, public health professionals, and doctors. The Lancet Countdown's work builds on decades of research in this field, and was first proposed in the 2015 Lancet Commission on health and climate change,1 which documented the human impacts of climate change and provided ten global recommendations to respond to this public health emergency and secure the public health benefits available (panel 1). The following four key messages derive from the Lancet Countdown's 2018 report Present day changes in heat waves, labour capacity, vector-borne disease, and food security provide early warning of the compounded and overwhelming impact on public health that are expected if temperatures continue to rise. Correspondingly, global subsidies for fossil fuels continued to decrease, and carbon pricing only covers 13·1% of global greenhouse-gas emissions, a number that is expected to increase to more than 20% when planned legislation in China is implemented in late 2018 (indicators 4.6 and 4.7).

Background Novel, rapid blood culture diagnostics can provide faster antibiotic susceptibility results (AST) compared to standard methods but their impact on clinical outcomes is unclear and not assessed in many prospective clinical trials. Methods This study is a two-arm, multicenter, multinational, prospective randomized controlled clinical trial conducted in countries with high antibiotic resistance rates including Greece, India, Israel, and Spain. Nine hundred hospitalized subjects who have blood cultures collected as part of routine clinical care with growth of Gram-negative bacilli (GNB) will be randomized 1:1 to blood culture evaluation using standard of care (SOC) AST vs. a rapid phenotypic AST method, VITEK REVEAL™ in addition to SOC AST. Subjects in both study arms will be reviewed by antibiotic stewardship clinicians who will recommend changes to antibiotic therapy, if indicated. The primary outcome is a composite three-category Desirability of Outcome Ranking (DOOR) defined using three ordered levels: alive without deleterious events, alive with at least one deleterious event, and death. Key secondary outcomes include mortality, length of stay, and time to antibiotic escalation or de-escalation within 3 days of randomization. Exploratory outcomes include a five-category DOOR, categorial agreement between VITEK REVEAL™ and SOC testing, clinician compliance with antibiotic stewardship recommendations, and desirability of treatment selection based on antibiotic spectrum, activity, and bloodstream isolate susceptibility profile (DOOR MAT). The primary analysis will be conducted on the modified intention-to-treat population. Discussion This trial will evaluate whether use of a rapid phenotypic AST method improves outcomes compared to use of conventional methods for patients with Gram-negative bloodstream infections in clinical settings with high antibiotic resistance rates. Trial registration ClinicalTrials.gov ID NCT06174649. Registered on Dec 18 2023. Protocol version Number 20-0021, version 5.0, 11-April-2024.

Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P  < 10 −8 , which together explain 4–9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster . Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function. A series of genetic studies have led to the discovery of novel independent loci and candidate genes associated with red blood cell phenotype; for a proportion of these genes potential single-nucleotide genetic variants are also identified, providing new insights into genetic pathways controlling red blood cell formation, function and pathology. The genetics of red blood cell biology This genome-wide association study of more than 135,000 individuals identifies 75 independent genetic loci influencing red blood cell phenotypes, enriched for genes involved in cell cycle control, transcriptional regulation, growth factor and cytokine signalling, haemoglobin synthesis, iron handling and cytoskeletal function, as well as a number of genes of uncertain or unknown function. Further analyses identified 121 candidate genes related to red blood cell biology, one-third of which have haematopoietic phenotypes in mouse and Drosophila .

The rationale for fetal surveillance in monochorionic twin pregnancies is timely intervention to prevent the increased fetal/perinatal morbidity and mortality attributed to twin-twin transfusion syndrome and intrauterine growth restriction. We investigated the residual risk of fetal death after viability in otherwise uncomplicated monochorionic diamniotic twin pregnancies. We searched an electronic database of 480 completed monochorionic pregnancies that underwent fortnightly ultrasound surveillance in our tertiary referral fetal medicine service between 1992 and 2004. After excluding pregnancies with twin-twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence, and monoamniotic and high-order multiple pregnancies, we identified 151 uncomplicated monochorionic diamniotic twin pregnancies with normal growth, normal liquor volume, and normal Doppler studies on fortnightly ultrasound scans. Ten unexpected intrauterine deaths occurred in seven (4.6%) of 151 previously uncomplicated monochorionic diamniotic pregnancies, within 2 wk of a normal scan, at a median gestational age of 34(+1) wk (weeks(+days); range 28(+0) to 36(+3)). Two of the five cases that underwent autopsy had features suggestive of acute late onset twin-twin transfusion syndrome, but no antenatal indicators of transfusional imbalance or growth restriction, either empirically or in a 1:3 gestation-matched case-control comparison. The prospective risk of unexpected antepartum stillbirth after 32 wk was 1/23 monochorionic diamniotic pregnancies (95% confidence interval 1/11 to 1/63). Despite intensive fetal surveillance, structurally normal monochorionic diamniotic twin pregnancies without TTTS or IUGR are complicated by a high rate of unexpected intrauterine death. This prospective risk of fetal death in otherwise uncomplicated monochorionic diamniotic pregnancies after 32 wk of gestation might be obviated by a policy of elective preterm delivery, which now warrants evaluation.

Background Enhanced Recovery After Surgery (ERAS) guidelines have been widely promoted and supported largely due to several studies showing decreased post-operative complications and length of stay. The objective of this study was to review the emergency room (ER) visits and readmission rates and reasons for both in patients who were part of the Implementation of an Enhanced Recovery After Surgery (iERAS) program for colorectal surgery. Methods All patients having elective colorectal surgery at 15 academic hospitals were enrolled in the iERAS program. All patients were prospectively followed until 30 days post-discharge. Data were analyzed using descriptive statistics and multivariable analysis. Results A total of 2876 patients (48% female; mean 60 years old) were enrolled. Cancer was the most frequent indication (68.2%) for surgery. Overall, the median length of stay (LOS) was 5 days. Post-discharge, 359 (11.6%) of patients had a visit to the ER not requiring admission. The most common reasons for visiting the ER were surgical site infections (SSI) (34.5%), other wound complications (10.0%), and urinary tract infections (UTI) (8.6%). In addition, a smaller proportion of patients, 260 (8.2%) required readmission. The most common reasons for readmission were ileus and nausea/vomiting (26.1%), intra-abdominal abscess (23.9%), and SSI (11.5%). Patient and disease factors associated with ER visits, on multivariable analysis, included extremes of BMI (RR 1.02, 95%CI 1.01–1.04, p  = 0.002), rectal surgery versus colon surgery (RR 1.34, 95%CI 1.14–1.58, p  < 0.001), and open operative approach (RR 1.63, 95%CI 1.28–2.09, p  < 0.001). Independent factors associated with hospital readmissions included rectal surgery (RR 1.89, 95%CI 1.34–2.77, p  < 0.001), formation of a stoma (RR 1.34, 95%CI 1.04–1.74, p  = 0.026), and reoperation during first admission (RR 4.60, 95%CI 3.50–6.05, p  < 0.001). Length of stay of 5 days or less was not associated with ER visits or readmission (RR 0.99, 95%CI 0.72–1.35 and RR 0.91, 95%CI 0.71–1.18, respectively). Conclusion Following colorectal surgery using an ERAS pathway, shortened length of stay is not associated with an increased return to the ER or hospital readmission. The majority of return visits to the hospital are ER visits not requiring readmission and the predominant reason for return are surgical site infections and wound complications.

BACKGROUND: The rationale for fetal surveillance in monochorionic twin pregnancies is timely intervention to prevent the increased fetal/perinatal morbidity and mortality attributed to twin-twin transfusion syndrome and intrauterine growth restriction. We investigated the residual risk of fetal death after viability in otherwise uncomplicated monochorionic diamniotic twin pregnancies. METHODS AND FINDINGS: We searched an electronic database of 480 completed monochorionic pregnancies that underwent fortnightly ultrasound surveillance in our tertiary referral fetal medicine service between 1992 and 2004. After excluding pregnancies with twin-twin transfusion syndrome, growth restriction, structural abnormalities, or twin reversed arterial perfusion sequence, and monoamniotic and high-order multiple pregnancies, we identified 151 uncomplicated monochorionic diamniotic twin pregnancies with normal growth, normal liquor volume, and normal Doppler studies on fortnightly ultrasound scans. Ten unexpected intrauterine deaths occurred in seven (4.6%) of 151 previously uncomplicated monochorionic diamniotic pregnancies, within 2 wk of a normal scan, at a median gestational age of 34(+1) wk (weeks(+days); range 28(+0) to 36(+3)). Two of the five cases that underwent autopsy had features suggestive of acute late onset twin-twin transfusion syndrome, but no antenatal indicators of transfusional imbalance or growth restriction, either empirically or in a 1:3 gestation-matched case-control comparison. The prospective risk of unexpected antepartum stillbirth after 32 wk was 1/23 monochorionic diamniotic pregnancies (95% confidence interval 1/11 to 1/63). CONCLUSION: Despite intensive fetal surveillance, structurally normal monochorionic diamniotic twin pregnancies without TTTS or IUGR are complicated by a high rate of unexpected intrauterine death. This prospective risk of fetal death in otherwise uncomplicated monochorionic diamniotic pregnancies after 32 wk of gestation might be obviated by a policy of elective preterm delivery, which now warrants evaluation.

The natural killer (NK) and non-cytotoxic innate lymphoid cells (ILC) lineages play vital role in the regulation of the immune system. Yet understanding of mechanisms controlling NK/ILC development remains incomplete. The evolutionary conserved FOXO family of forkhead transcription factors are critical regulators of cellular processes. We found that the loss of FOXO1 and FOXO3 together caused impaired activation of the NK gene expression program and reduced ETS binding already at the common lymphoid progenitor (CLP) level and a block at the ILC progenitor (ILCP) to NK progenitor transition. FOXO controlled NK cell maturation in organ specific manner and their ability to respond to IL-15. At the ILCP level, disruption of the ILC lineage specific gene programs was associated with broad perturbation of the generation of the non-cytotoxic ILC subsets. We concluded that FOXO1 and FOXO3 cooperatively regulate ILC lineage specification at the progenitor level as well as the generation of mature ILCs.

Marks and Spencer is always a good source - it is selling a terracotta pot filled with narcissi or amaryllis. The Conran Shop, 81 Fulham Road, London SW3, has coloured glass tumblers at £2.95, glass candlesticks at £4.95, coloured glass flower pots at £2.95, or coloured cotton napkins for £1.75. At Manguette, 40 Gordon Place, London W8, there are delicious rock-shaped soaps, for £9.95, at Next, splendid notebooks for the same price, while Johnny Loves Rosie hair slides are £8.95, and Aromatherapy of Roma candles (available from Space NK apothecary shops) are just £7.95. Here, on the rest of the page, are what our guinea pigs chose. Zeev Aram, founder and owner of Aram Designs \"I would like a good bottle of cold-pressed first pressing extra virgin olive oil because it is very enjoyable while it lasts, you are not stuck with it forever like a sweater or a tie, and it is good for you and your health. Try a simple Olio Sasso from Camisa in Old Compton Street, or half a litre of Il Pad-rone from Carluccio's in Covent Garden. Don't use it for cooking, keep it for salad.\"