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This study is a qualitative case series of lifestyle medicine practitioners’ protocols for medication de-escalation in the context of reduced need for glucose-lowering medications due to lifestyle modifications. Increasing numbers of lifestyle medicine practitioners report achieving reductions in medications among patients with type 2 diabetes, and in some cases remission, but limited data exist on the clinical decision-making process used to determine when and how medications are deprescribed. Practitioners interviewed here provide accounts of their deprescribing protocols. This information can serve as pilot data for other practitioners seeking examples of how deprescribing in the context of lifestyle medicine treatment is conducted.

Objective: The objective of this Expert Consensus Statement is to assist clinicians in achieving remission of type 2 diabetes (T2D) in adults using diet as a primary intervention. Evidence-informed statements agreed upon by a multi-disciplinary panel of expert healthcare professionals were used. Methods: Panel members with expertise in diabetes treatment, research, and remission followed an established methodology for developing consensus statements using a modified Delphi process. A search strategist systematically reviewed the literature, and the best available evidence was used to compose statements regarding dietary interventions in adults 18 years and older diagnosed with T2D. Topics with significant practice variation and those that would result in remission of T2D were prioritized. Using an iterative, online process, panel members expressed levels of agreement with the statements, resulting in classification as consensus, near-consensus, or non-consensus based on mean responses and the number of outliers. Results: The expert panel identified 131 candidate consensus statements that focused on addressing the following high-yield topics: (1) definitions and basic concepts; (2) diet and remission of T2D; (3) dietary specifics and types of diets; (4) adjuvant and alternative interventions; (5) support, monitoring, and adherence to therapy; (6) weight loss; and (7) payment and policy. After 4 iterations of the Delphi survey and removal of duplicative statements, 69 statements met the criteria for consensus, 5 were designated as near consensus, and 60 were designated as no consensus. In addition, the consensus was reached on the following key issues: (a) Remission of T2D should be defined as HbA1c Conclusion: Expert consensus was achieved for 69 statements pertaining to diet and remission of T2D, dietary specifics and types of diets, adjuvant and alternative interventions, support, monitoring, adherence to therapy, weight loss, and payment and policy. Clinicians can use these statements to improve quality of care, inform policy and protocols, and identify areas of uncertainty.

Data sharing: The PHOSP-COVID study protocol, consent form, definition, and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online. UK Biobank information can be released once necessary approvals have been obtained. Other data (eg, the R code and protocol) will be made available on reasonable request to the corresponding author. Copyright © 2023 The Author(s). Background: Sleep disturbance is common following hospital admission both for COVID-19 and other causes. The clinical associations of this for recovery after hospital admission are poorly understood despite sleep disturbance contributing to morbidity in other scenarios. We aimed to investigate the prevalence and nature of sleep disturbance after discharge following hospital admission for COVID-19 and to assess whether this was associated with dyspnoea. Methods: CircCOVID was a prospective multicentre cohort substudy designed to investigate the effects of circadian disruption and sleep disturbance on recovery after COVID-19 in a cohort of participants aged 18 years or older, admitted to hospital for COVID-19 in the UK, and discharged between March, 2020, and October, 2021. Participants were recruited from the Post-hospitalisation COVID-19 study (PHOSP-COVID). Follow-up data were collected at two timepoints: an early time point 2–7 months after hospital discharge and a later time point 10–14 months after hospital discharge. Sleep quality was assessed subjectively using the Pittsburgh Sleep Quality Index questionnaire and a numerical rating scale. Sleep quality was also assessed with an accelerometer worn on the wrist (actigraphy) for 14 days. Participants were also clinically phenotyped, including assessment of symptoms (ie, anxiety [Generalised Anxiety Disorder 7-item scale questionnaire], muscle function [SARC-F questionnaire], dyspnoea [Dyspnoea-12 questionnaire] and measurement of lung function), at the early timepoint after discharge. Actigraphy results were also compared to a matched UK Biobank cohort (non-hospitalised individuals and recently hospitalised individuals). Multivariable linear regression was used to define associations of sleep disturbance with the primary outcome of breathlessness and the other clinical symptoms. PHOSP-COVID is registered on the ISRCTN Registry (ISRCTN10980107). Findings: 2320 of 2468 participants in the PHOSP-COVID study attended an early timepoint research visit a median of 5 months (IQR 4–6) following discharge from 83 hospitals in the UK. Data for sleep quality were assessed by subjective measures (the Pittsburgh Sleep Quality Index questionnaire and the numerical rating scale) for 638 participants at the early time point. Sleep quality was also assessed using device-based measures (actigraphy) a median of 7 months (IQR 5–8 months) after discharge from hospital for 729 participants. After discharge from hospital, the majority (396 [62%] of 638) of participants who had been admitted to hospital for COVID-19 reported poor sleep quality in response to the Pittsburgh Sleep Quality Index questionnaire. A comparable proportion (338 [53%] of 638) of participants felt their sleep quality had deteriorated following discharge after COVID-19 admission, as assessed by the numerical rating scale. Device-based measurements were compared to an age-matched, sex-matched, BMI-matched, and time from discharge-matched UK Biobank cohort who had recently been admitted to hospital. Compared to the recently hospitalised matched UK Biobank cohort, participants in our study slept on average 65 min (95% CI 59 to 71) longer, had a lower sleep regularity index (–19%; 95% CI –20 to –16), and a lower sleep efficiency (3·83 percentage points; 95% CI 3·40 to 4·26). Similar results were obtained when comparisons were made with the non-hospitalised UK Biobank cohort. Overall sleep quality (unadjusted effect estimate 3·94; 95% CI 2·78 to 5·10), deterioration in sleep quality following hospital admission (3·00; 1·82 to 4·28), and sleep regularity (4·38; 2·10 to 6·65) were associated with higher dyspnoea scores. Poor sleep quality, deterioration in sleep quality, and sleep regularity were also associated with impaired lung function, as assessed by forced vital capacity. Depending on the sleep metric, anxiety mediated 18–39% of the effect of sleep disturbance on dyspnoea, while muscle weakness mediated 27–41% of this effect. Interpretation: Sleep disturbance following hospital admission for COVID-19 is associated with dyspnoea, anxiety, and muscle weakness. Due to the association with multiple symptoms, targeting sleep disturbance might be beneficial in treating the post-COVID-19 condition. Funding: UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council. UK Research and Innovation, National Institute for Health Research, and Engineering and Physical Sciences Research Council.

Data sharing statement This is an Open Access article under the CC BY 4.0 license The ISARIC4C protocol, data sharing and publication policy are available at https://isaric4c.net. ISARIC4C's Independent Data and Material Access Committee welcomes applications for access to data and materials (https://isaric4c.net). The PHOSP-COVID protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, information about requests for data access, and other relevant study materials are available online: https://phosp.org/resource/. Access to these materials can be granted by contacting phosp@leicester.ac.uk and Phospcontracts@leicester.ac.uk. All data used in this study is available within ODAP and accessible under reasonable request. Data access criteria and information about how to request access is available online: https://phosp.org/resource/. If criteria are met and a request is made, access can be gained by signing the eDRIS user agreement. Supplementary data are available online at https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00584-9/fulltext#supplementaryMaterial . Copyright © 2022 The Author(s). Background: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. Methods: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. Findings: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. Interpretation: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. Funding: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript. This work is supported by the following grants: The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute for Health and Care Research (grant references: MR/V027859/1 and COV0319). ISARIC4C is supported by grants from the National Institute for Health and Care Research (award CO-CIN-01) and the Medical Research Council (grant MC_PC_19059) Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research (grant reference: C18616/A25153). Other grants which have supported this work include: the UK Coronavirus Immunology Consortium [funder reference:1257927], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant IS-BRC-1215-20013), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], Health Data Research UK (HDR UK) [grant code: 2021.0155], Medical Research Council [grant code: MC_UU_12014/12], and NIHR Clinical Research Network for providing infrastructure support for this research. FL is supported by an MRC clinical training fellowship [award MR/W000970/1]. LPH is supported by Oxford NIHR Biomedical Research Centre. AART is supported by a BHF Intermediate Clinical Fellowship (FS/18/13/33281). SLRJ receives support from UKRI, GCRF, Rosetrees Trust, BHIVA, EDCTP, Globvac. JDC has grants from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Gilead Sciences, Grifols, Novartis and Insmed. RAE holds a NIHR Clinician Scientist Fellowship (CS-2016-16-020). AH is currently supported by UK Research and Innovation. NIHR and NIHR Manchester BRC. BR receives support from BHF Oxford Centre of Research Excellence, NIHR Oxford BRC and MRC. SJD is funded by an NIHR Global Research Professorship [NIHR300791]. DW is supported by an NIHR Advanced Fellowship. AH has received support from MRC and the Coronavirus Immunology Consortium (MR/V028448/1). LVW has received support from UKRI, GSK/Asthma + Lung UK and NIHR for this study. MGS has received support from NIHR UK, MRC UK and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. JKB is supported by the Wellcome Trust (223164/Z/21/Z) and UKRI (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1, and MC_PC_20029). PJMO is supported by a NIHR Senior Investigator Award [award 201385]. LT is supported by the Wellcome Trust [clinical career development fellowship grant number 205228/Z/16/Z], the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity.

Data sharing statement: PHOSP-COVID: The protocol, consent form, definition and derivation of clinical characteristics and outcomes, training materials, regulatory documents, requests for data access and other relevant study materials are available online at https://www.phosp.org. COVIDENCE UK: De-identified participant data will be made available upon reasonable request to the corresponding author. Supplementary data is available online at: https://www.sciencedirect.com/science/article/pii/S2666776223000546?via%3Dihub#appsec1 . Copyright © 2023 The Author(s). Background: The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods: We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings: We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation: Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding: PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders. PHOSP-COVID: This study would not be possible without all the participants who have given their time and support. We thank all the participants and their families. We thank the many research administrators, health-care and social-care professionals who contributed to setting up and delivering the study at all of the 65 NHS trusts/Health boards and 25 research institutions across the UK, as well as all the supporting staff at the NIHR Clinical Research Network, Health Research Authority, Research Ethics Committee, Department of Health and Social Care, Public Health Scotland, and Public Health England, and support from the ISARIC Coronavirus Clinical Characterisation Consortium. We thank Kate Holmes at the NIHR Office for Clinical Research Infrastructure (NOCRI) for her support in coordinating the charities group. The PHOSP-COVID industry framework was formed to provide advice and support in commercial discussions, and we thank the Association of the British Pharmaceutical Industry as well NOCRI for coordinating this. We are very grateful to all the charities that have provided insight to the study: Action Pulmonary Fibrosis, Alzheimer's Research UK, Asthma + Lung UK, British Heart Foundation, Diabetes UK, Cystic Fibrosis Trust, Kidney Research UK, MQ Mental Health, Muscular Dystrophy UK, Stroke Association Blood Cancer UK, McPin Foundations, and Versus Arthritis. We thank the NIHR Leicester Biomedical Research Centre patient and public involvement group and Long Covid Support. COVIDENCE UK: We thank all participants of COVIDENCE UK, and the following organisations who supported study recruitment: Asthma UK/British Lung Foundation, the British Heart Foundation, the British Obesity Society, Cancer Research UK, Diabetes UK, Future Publishing, Kidney Care UK, Kidney Wales, Mumsnet, the National Kidney Federation, the National Rheumatoid Arthritis Society, the North West London Health Research Register (DISCOVER), Primary Immunodeficiency UK, the Race Equality Foundation, SWM Health, the Terence Higgins Trust, and Vasculitis UK.

Palladium-catalyzed N-arylations of amino acid tert-butyl esters using 4-bromo-N,N-dimethylaniline as a coupling partner are reported. The resulting N-aryl amino acid esters are suitable building blocks for the synthesis of electron-rich N-aryl peptides, which undergo oxidative couplings to aminooxy groups to afford ketoxime peptides under mild conditions. N-aryl amino acid tert-butyl esters possessing unnatural side chains were also accessed via glycine Schiff base alkylation, further increasing the scope of Cα-substitution in ketoxime peptides.

Chemoselective ligation methods that preserve or introduce side chain diversity are critical for chemical synthesis of peptides and proteins. Starting from ketone substrates instead of aldehydes in oxime ligation reactions would allow substitution at the site of ligation; however, synthetic challenges to readily access ketone derivatives from common amino acid building blocks have precluded the widespread use of ketoxime peptide ligation reactions thus far. Moreover, ketones are typically much slower to react in condensation reactions compared to aldehydes. Here, one-pot catalyst-free oxidative couplings of α-substituted N-aryl peptides with alkoxyamines provide access to oxime linkages with diverse side chains. Electron-rich N-(p-Me2N-phenyl)-amino acids possessing substituents at the α-carbon were found to be uniquely capable of undergoing site-selective α-C–H oxidations in situ under an O2 atmosphere at neutral pH. Comparative studies with N-arylglycinyl peptides revealed that substitution at the α-carbon caused notable changes in reactivity, with greater sensitivity to solvent and buffer salt composition.

uncorrected proof article, Purpose: A survey in 2015 identified a high level of eye care practitioner concern about myopia with a reported moderately high level of activity, but the vast majority still prescribed single vision interventions to young myopes. This research aimed to update these findings 4 years later.Methods: A self-administrated, internet-based questionnaire was distributed in eight languages, through professional bodies to eye care practitioners globally. The questions examined: awareness of increasing myopia prevalence, perceived efficacy of available strategies and adoption levels of such strategies, and reasons for not adopting specific strategies.Results: Of the 1336 respondents, concern was highest (9.0 +/- 1.6; p < 0.001) in Asia and lowest (7.6 +/- 2.2; p < 0.001) in Australasia. Practitioners from Asia also considered their clinical practice of myopia control to be the most active (7.7 +/- 2.3; p < 0.001), the North American practitioners being the least active (6.3 +/- 2.9; p < 0.001). Orthokeratology was perceived to be the most effective method of myopia control, followed by pharmaceutical approaches and approved myopia control soft contact lenses (p < 0.001). Although significant infra-regional differences existed, overall, most practitioners did not consider single-vision distance under-correction to be an effective strategy for attenuating myopia progression (79.6 %), but prescribed single vision spectacles or contact lenses as the primary mode of correction for myopic patients (63.6 +/- 21.8 %). The main justifications for their reluctance to prescribe alternatives to single vision refractive corrections were increased cost (20.6 %) and inadequate information (17.6 %).Conclusions: While practitioner concern about myopia and the reported level of activity have increased over the last 4 years, the vast majority of eye care clinicians still prescribe single vision interventions to young myopes. With recent global consensus evidence-based guidelines having been published, it is hoped that this will inform the pr, This project was supported by many eye care organisations and individuals across the globe, in particular the Association of Malaysia Optometrists, British Contact Lens Association, College of Optometrists (UK), International Association of Contact Lens Educators, Optometry Today, Spanish General Council of the Colleges of Opticians-Optometrists, Contact Lens Spectrum and Caroline Christie.

Quality medical care requires clinicians to have expertise in many areas of practice; one essential area is communication with patients, families, and surrogates. This expertise is especially important when the patient is critically ill in an intensive care unit (ICU), where information exchange occurs more commonly with families and surrogates. Communication challenges in the ICU are greater because critically ill patients frequently are unable to speak for themselves and the clinician is dependent on surrogate decision-makers, friends, or family members, to understand the patient’s goals and values regarding life and health care.

Non-drug therapy should be foundational to our treatment plans. These should be evidence-based. Drug based therapies rely heavily on randomized controlled trials while the evidence many lifestyle interventions relies more heavily on epidemiological studies. Both have weaknesses and strengths. Medicine needs a system for evaluating evidence that recognizes the strengths of both types of studies and includes some common measure such as Number Needed to Treat (NNT) and Number Needed to Harm (NNH).

Finding the truth is important. In the field of lifestyle medicine the randomized controlled trial has significant limitations. Physicians and patients need to know the truth about the healthy lifestyle changes and their ability to prevent and reverse disease. To meet this challenge, the American College of Lifestyle Medicine has established a committee of experts (HEaLM), under the leadership of David Katz to create a level of evidence construct for ranking lifestyle medicine evidence that includes evidence from basic science and epidemiologic trials. This tool will be used by the new Expert Lifestyle Medicine Panel to create guidelines and standards of practice.

Mild conditions for oxime ligations via in situ generation of α-imino amide intermediates are reported. The evaluation of a variety of N-terminal N-phenylglycine residues revealed that a metal-free, chemoselective oxidation was possible using oxygen as the only oxidant in buffer at pH 7.0. Moreover, selective unmasking of an inert residue by addition of potassium ferricyanide is demonstrated. These simple and mild conditions, which can be fine-tuned by the electronic properties of the N-phenylglycine residue, offer unique advantages over conventional approaches for oxime ligations.

Patients are often not aware of the reversibility of chronic lifestyle-related diseases and most physicians are not telling them. The present practice of communicating treatment effectiveness with relative risk reductions does not allow clinicians or patients to evaluate the relative effectiveness of our technotherapies or lifestyle interventions. Clinicians should use the clarity of “number needed to treat,” “number needed to harm,” and absolute risk in communicating with patients about all available therapies and then empower the patient to make the choices that fit their needs best.

A new president is stepping into leadership at the American College of Lifestyle Medicine (ACLM). Opportunities abound. The fact that both diabetes and heart disease are reversible is a message that is not reaching the majority of the general public. But times are changing and lifestyle treatment is on the cusp of being accepted as the self-evident best treatment for chronic medical conditions. ACLM is poised to be the leader in this area. Our members passion and experience are our richest resources. Each member is encouraged to be involved with the different committees of ACLM. Choices include Conference Planning, Education, Research, practice Models, Publications, Awards, Business Development, Membership Development, Strategic Partnerships, Marketing and Communications.

The effective integration of lifestyle medicine into allopathic practices is an evolving necessity driven by limited resources and escalating costs. Efforts in the Florida Hospital system graduate medical education (GME) department to meet this challenge may be instructive to others. Efforts include the hiring of an experienced dietician with a focus on a whole food plant based diet and a patient engagement tool to identify areas where patients are ready to make change. Billing is done using existing finance structure with the goal of decreasing the overall cost of providing care within a Clinically Integrated Network (CIN) context. Additionally, one GME clinician’s experience in clinical lifestyle based intervention identifies and comments on several practical clinical factors for bringing effective behavior change to individual patients: patient readiness, a knowledgeable health care provider, adequate time, as well as the effectiveness of the intervention.

Lifestyle Medicine is still being defined. The ACLM is making significant progress in defining it within the house of medicine. The new American and International Boards of Lifestyle Medicine go a long way in identifying the clinical parameters for this new specialty. The board review course defines the academic corpus in a clear way. Now that Lifestyle Medicine has clear borders it needs to be spread throughout the cultures of the world. People in all walks of life and levels of responsibility need to hear stories of individuals and communities that have their health improved by following the principles of Lietyle Medicine.

Compared to the background population, people with epilepsy tend to have lower rates of education and employment, lower rates of marriage and childbearing, and lower overall socioeconomic status (SES). Disparities in epilepsy care based on sociodemographic factors have been observed in the literature, but it is not known whether any such disparities exist in the UK. The UK Epilepsy and Pregnancy Register is a prospective, observational, registration and follow-up study that was set up to determine the relative safety of all AEDs taken in pregnancy. Here, we report outcomes of registered pregnancies to women with epilepsy living in Scotland from December 1996 to June 2012, based on the degree of socioeconomic deprivation of their postcode area. The Scottish Index of Multiple Deprivation (SIMD) quintile scores from 2006 were used to determine degree of socioeconomic deprivation, and group 1 (most deprived) and group 5 (least deprived) were compared. There were 1526 pregnancies with complete outcome data to women living in Scotland. Of these, 1453 (95.1%) resulted in a live birth and 68 (4.7%) had a major congenital malformation (MCM). Postcodes could not be reliably identified or verified for an additional three women, who have been excluded from SIMD group analysis. Of all women included in this study, 32.4% were in group 1 and 13.2% in group 5. No difference in MCM rate was observed between the two groups (4.4% in group 1 compared to 4.7% in group 5, p=0.84). Women in group 5 were more likely to take preconceptual folic acid (56.8% compared to 14.0%, relative risk: 4.1; 95% CI: 3.1-5.2) and less likely to have generalized tonic-clonic seizures in pregnancy (13.0% compared to 29.2%, relative risk: 0.4; 95% CI: 0.3-0.7) than those in group 1. Women in group 5 were more likely to be on monotherapy regimens (80.2% compared to 65.9%, relative risk: 1.2; 95% CI: 1.1-1.3), less likely to be on valproate (19.5% compared to 28.0%, p=0.05), and more likely to be on lower doses of the drug (825.9mg/day compared to 1012.0mg/day, p=0.05) compared to those in group 1. Although no change in MCM rate was seen based on SES, differences in treatment between socioeconomic groups do exist, particularly for preconceptual folic acid consumption, AED regimen, and seizure frequency. Greater emphasis on the importance of preconceptual counseling, both to discuss AED choice and folic acid intake, would be of benefit, particularly to those living in areas of high socioeconomic deprivation, to improve equity of healthcare delivery for women with epilepsy in Scotland.

The cost of providing medical care is increasing. The driving forces include inherent health care system conflicts of interest and financial incentives for procedures and technology. Effective lifestyle medicine principles are not easily adopted and rewarded in the present environment. Recent moves toward outcomes-based pay systems offer the potential to demonstrate the effectiveness of lifestyle medicine principles while bypassing many of the biases, application delays, and political machinations of the traditional randomized control trial methodology. The American College of Lifestyle Medicine is uniquely positioned to be a leading organization in improving health, enhancing patient experience, and reducing the cost of care.

ErnieJ, a cluster C mycobacteriophage that infects Mycobacterium smegmatis mc 2 155, was recovered from soil in Washington, DC. Its genome is 153,243 bp in size and encodes 227 predicted proteins, 30 tRNAs, and one transfer-messenger RNA (tmRNA). Ten percent of the predicted proteins have homologs in phages that infect nonmycobacterial Actinobacteria .

Purpose: Reducing 30-day unplanned hospital readmissions is a national policy priority. We examined the impact of a quality improvement project focused on reducing oncology readmissions among patients with cancer who were admitted to palliative and general medical oncology services at the Cleveland Clinic. Methods: Baseline rates of readmissions were gathered during the period from January 2013 to April 2014. A quality improvement project designed to improve outpatient care transitions was initiated during the period leading to April 1, 2014, including: (1) provider education, (2) postdischarge nursing phone calls within 48 hours, and (3) postdischarge provider follow-up appointments within 5 business days. Nursing callback components included symptom management, education, medication review/compliance, and follow-up appointment reminder. Results: During the baseline period, there were 2,638 admissions and 722 unplanned 30-day readmissions for an overall readmission rate of 27.4%. Callbacks and 5-day follow-up appointment monitoring revealed a mean monthly compliance of 72% and 78%, respectively, improving over time during the study period. Readmission rates declined by 4.5% to 22.9% (P < .01; relative risk reduction, 18%) during the study period. The mean direct cost of one readmission was $10,884, suggesting an annualized cost savings of $1.04 million with the observed reduction in unplanned readmissions. Conclusion: Modest readmission reductions can be achieved through better systematic transitions to outpatient care (including follow-up calls and early provider visits), thereby leading to a reduction in use of inpatient resources. These data suggest that efforts focused on improving outpatient care transition were effective in reducing unplanned oncology readmissions.

SUMMARY * Hospitals can create an environment that supports patients, families, and healthcare professionals so that they are better able to recognize the best way to care for each patient during times of transition. This article highlights some of the supports intentionally put into place to assist patients, family, and staff through difficult transitions at Oregon Health & Science University. These supports include an expert inpatient and outpatient palliative care team to coach patients, families, and staff at the bedside; statewide efforts to raise the skill level of all healthcare professionals through education; and the Physician Orders for Life-Sustaining Treatment (POLST) program, which helps ensure that care decisions made in one setting are respected as the patient moves to another care setting. INTRODUCTION In his August 2010 article for the New Yorker, "Letting Go: What Should Medicine Do When It Can't Save Your Life?," surgeon and author Atul Gawande discusses the dilemma that patients, families, healthcare professionals, hospital administrators, payers, and legislators find themselves in when faced with the reality of death. Our medical system is excellent at trying to stave off death with eight-thousand-dollar-amonth chemotherapy, three-thousand-dollar-aday intensive care, five-thousand-dollar-anhour surgery. But, ultimately, death comes, and no one is good at knowing when to stop. The subject seems to reach national awareness mainly as a question of who should "win" when the expensive decisions are made: the insurers and the taxpayers footing the bill or the patient battling for his or her life. Budget hawks urge us to face the fact that we can't afford everything. Demagogues shout about rationing and death panels. Market purists blame the existence of insurance: if patients and families paid the bills themselves, those expensive therapies would all come down in price. But they're debating the wrong question. The failure of our system of medical care for people facing the end of their life runs much deeper. To see this, you have to get close enough to grapple with the way decisions about care are actually made. Throughout his article, Gawande never defines letting go, perhaps in deference to the mystery and sacredness that surround the struggle to survive and to accept life's end. Instead, he focuses on the decisions made by patients, families, healthcare professionals, healthcare institutions, and health insurers and the very real challenges that these decisions pose. Let go too soon and risk missing the chance to have a longer or better life. Let go too late and risk enduring burdensome and costly care that contributes to suffering rather than relieving it. While letting go is something that happens internally in an individual, in hospital care the outward manifestations of letting go are more commonly called transitions. Transition is a broad term that can refer to moving from one care setting to the next, changing goals of care, changing both care setting and goals (as happens with the transition to hospice care), or even death. Nothing can reliably tell a patient when is the right time to let go, but hospitals can create an environment that supports patients, families, and healthcare professionals so that they are more able to recognize the best way to care for each patient during times of transition. As Oregon's only academic medical center, Oregon Health & Science University (OHSU) serves an independentminded citizenry that has high expectations for palliative and end-of-life care (Fromme et al. 2004). This article highlights some of the supports that have been intentionally put into place to assist patients, family, and staff during times of difficult transition. These supports include an expert inpatient and outpatient palliative care team to coach patients, families, and staff at the bedside and in doctors' offices; statewide efforts to educate health professionals and raise the skill level of all practitioners; and the Physician Orders for Life- Sustaining Treatment program that helps ensure that the goals of "letting go" or continued "pushing on" that arise in one setting are identified and respected as the patient transitions to another care setting. …

zeitz k., kitson a., gibb h., bagley e., chester m., davy c., frankham j., guthrie s., roney f. & shanks a. (2010) Working together to improve the care of older people: a new framework for collaboration. Journal of Advanced Nursing 67(1), 43–55. Abstract Aim. This paper is a report of a study identifying the care issues experienced by older people in the acute setting that could be improved through a collaborative approach to action. Background. Actively involving consumers in the governance of healthcare organizations is viewed positively, although there is less agreement on how to do this. Co-operative inquiry is a useful approach to involve consumers and clinicians in structured dialogue about understanding and changing care, whereas traditional quality improvement methodologies are often singular in their dimensions of change. Method. Using a co-operative inquiry approach, five workshops were facilitated over a 4-month period in 2008 with four volunteer older people, four clinicians and three facilitators (n = 11). All participants were actively involved in generating ideas and actions using a range of facilitation techniques and data collection methods. Findings. There was increased awareness, understanding and acceptance of clinicians’ and consumers’ experiences and expectations of care. The complexity behind changing so-called simple care (providing warm drinks, appetizing food), which were the key concerns for consumers, relied on the active management and broader transformation of the system, including teamwork, communication processes and organizational and individual values and beliefs. Conclusion. Consumers and clinicians put different emphasis on perspectives related to improving care of older people in the acute hospital setting. The disconnect between what consumers viewed as ‘simple’ organizational behaviours to change and what the clinicians viewed as complex, led to a recognition that the approach to organizational change needs to be reconceptualized.

Topiramate (Topamax) is licensed to be used, either in monotherapy or as adjunctive treatment, for generalized tonic clonic seizures or partial seizures with or without secondary generalization and for prevention of migraine. The safety of topiramate in human pregnancy is largely unknown. Here we report on our experience of pregnancies exposed to topiramate.This study is part of a prospective, observational, registration and follow-up study. Suitable cases are women with epilepsy who become pregnant while taking topiramate either singly or along with other antiepileptic drugs (AEDs), and who are referred before outcome of the pregnancy is known. The main outcome measure is the major congenital malformation (MCM) rate. Secondary outcomes include risk of specific MCM, minor malformation rate, birthweight, and gestational age at delivery.Full outcome data are available on 203 pregnancies. Of these, 178 resulted in live birth; 16 had an MCM (9.0%; 95% CI 5.6% to 14.1%). Three MCMs were observed in 70 monotherapy exposures (4.8%; 95% CI 1.7% to 13.3%) and 13 in cases exposed to topiramate as part of a polytherapy regimen (11.2%; 95% CI 6.7% to 18.2%). Four of the MCMs were oral clefts (2.2%; 95% CI 0.9% to 5.6%). Four cases of hypospadias were reported (5.1%; 95% CI 0.2% to 10.1%) among 78 known live male births of which two were classified as major malformations.The number of outcomes of human pregnancies exposed to topiramate is low, but the major congenital malformation rate for topiramate polytherapy raises some concerns. Overall, the rate of oral clefts observed was 11 times the background rate. Although the present data provide new information, they should be interpreted with caution due to the sample size and wide confidence intervals.

Purpose: Routine prophylactic pegylated granulocyte colony-stimulating factor (pGCSF) administration for patients receiving chemotherapy regimens associated with low risk (< 10%) for neutropenic fever (LRNF) is not recommended. Inappropriate use of pGCSF increases patient morbidity and health care costs. Methods: A multidisciplinary team reviewed the charts of patients with non–small-cell lung cancer (NSCLC) at the Taussig Cancer Institute in whom a new chemotherapy regimen was initiated from April through November 2013. pGCSF use was identified and deemed appropriate if prescribed for chemotherapy associated with high risk of neutropenic fever (> 20%) or intermediate risk (10% to 20%) if other risk factors for neutropenic fever were present. Use with LRNF chemotherapy was recorded as inappropriate. Results: One hundred eighty patients with NSCLC received a new chemotherapy regimen during the specified time period. Thirty-four of 119 patients (28%) treated with LRNF chemotherapy received pGCSF. Each patient received an average of 2.6 doses of pGCSF (total, 89 doses). We implemented three plan-do-study-act cycles: education of providers, development of Taussig Cancer Institute consensus guidelines for pGCSF in NSCLC, and removal of standing pGCSF orders from LRNF chemotherapy in the electronic medical record. Analysis during the change period revealed 4% of patients with NSCLC treated with LRNF chemotherapy received pGCSF. Cost analysis showed an 84% decrease in billed charges per month. No increase in neutropenic fever admissions was found. Conclusion: pGCSF was excessively prescribed for patients with NSCLC. Factors contributing to inappropriate use included provider lack of familiarity with guidelines and knowledge with regard to the risk of neutropenic fever for individual chemotherapy regimens, and electronic medical record chemotherapy templates that contain standing GCSF orders. Interventions to address these gaps quickly produced improved compliance with guidelines and led to significant cost savings.

We propose a conceptual model to explain the quantitative data from synchrotron X-ray diffraction experiments on the shear-induced phase behavior of cocoa butter, the main structural component of chocolate. We captured two-dimensional diffraction patterns from cocoa butter at crystallization temperatures of 17.5, 20.0, and 22.5 °C under shear rates from 45 to 1440 s-1 and under static conditions. From the simultaneous analysis of the integrated intensity, correlation length, lamellar thickness, and crystalline orientation, we postulate a conceptual model to provide an explanation for the distribution of phases II, IV, V, and X and the kinetics of the process. As previously proposed in the literature, we assume that the crystallites grow layer upon layer of slightly different composition. The shear rate and temperature applied define these compositions. Simultaneously, the shear and temperature define the crystalline interface area available for secondary nucleation by promoting segregation and affecting t...

The purpose of this study was to determine the clinical impact of using SYSTANE BALANCE Lubricant Eye Drops (Alcon, Fort Worth, TX), an oil-in-water emulsion, as a rewetting eye drop in symptomatic contact lens wearers.Subjects who had previously experienced contact lens discomfort (CLD), with a mean lens wearing history of 18.6±12.8 years, were randomly assigned to use a Test (SYSTANE BALANCE Lubricant Eye Drops; n=76) or control (habitual nonlipid contact lens rewetting eye drop; n=30) drop over their contact lenses within 5 min of lens insertion and then subsequently at 2 hr intervals up to a maximum of 4 drops per eye daily for a 1-month period. Assessments of subjective comfort, comfortable wearing time, lid wiper epitheliopathy (LWE), and corneal staining were conducted at baseline and after 1 month, after 6 hr of lens wear.Comfort, wearing time, LWE, and corneal staining all showed statistically significant improvements in the test group using SYSTANE BALANCE Lubricant Eye Drops at the 1-month visit compared with baseline data (all P0.01) and compared with the control group at the 1-month visit (P0.01, P=0.01, P0.01, and P=0.03, respectively).The use of SYSTANE BALANCE Lubricant Eye Drops as a rewetting drop in a group of wearers who experienced symptoms of CLD improved subjective comfort scores, increased comfortable wearing time, and reduced signs of LWE and corneal staining, when compared with the use of non-lipid-containing contact lens rewetting eye drops.

When examining chocolate samples by means of X-ray diffraction, it has become common practice for any sugar to be removed through repeated rinsing in cold water. While necessary in some cases, we show that it is possible to determine the phase of certain dark chocolate samples without sugar removal, through examination of distinctive X-ray diffraction peaks corresponding to lattice spacings of 3.98 and 3.70 Angstroms.

Time-resolved synchrotron X-ray diffraction techniques were used to study the effect of cooling rates and temperature on the crystallization dynamics and polymorphism of anhydrous milk fat (AMF) and milk fat triacylglycerols (MFTs). The crystallization of AMF at fast cooling rates and low final temperatures proceeded through the metastable phase a and resulted in the formation of a mixture of phases β' and β. Slow cooling rates and high final temperatures resulted in the formation of phase β' only, with no formation of phase a nor phase β. Moreover, in the absence of polar lipids, MFTs had a decreased tendency to form the a and β phases. The formation of the β phase was largely dependent on the initial amount of a phase formed. At high cooling rates and low crystallization temperatures, polar lipids may have initiated the crystallization process together with a high melting fraction of milk fat in the a phase. In time, this metastable phase transformed to the β phase. When no a phase was initially formed (high temperatures and/or slow cooling rates), no β phase was formed either. Small-angle X-ray diffraction could be used to monitor compositional variation of crystals over time, and demonstrated that minor polar lipids present in the milk fat delayed the onset of crystallization and reduced the rate of crystal growth.

We report on an x-ray diffraction investigation of the nucleation and growth of wax crystals and the evolution of the resulting wax-gel deposit in mixtures of paraffin wax and dodecane under pipe flow. This work is an in situ x-ray diffraction study of wax crystallization in oil-wax mixtures under flow and is completely noninvasive. This technique is shown to be consistent with other methods.

Crystalline orientation and phase transition acceleration induced by shear are demonstrated to occur in different edible fats using synchrotron X-ray diffraction. Cocoa butter, milk fat, stripped milk fat, and palm oil were crystallized statically and under shear (90 s-1 and 1400 s-1) from the melt (50 °C) to 18 °C at a constant rate of 3 °C min-1. The 2D diffraction patterns clearly showed crystallite orientation imposed by the flow in the different phases. A dramatic reduction in phase transition times was also evident. These effects of shear on crystallizing fats are of great importance for the industrial processes carried out in chocolate, dairy, margarine, and shortening production, since temperature and shear treatments are the tools for tailoring the desired crystalline structures.

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The prognosis for congenital esotropia remains guarded. Monofixation syndrome currently is the best widely reported result following surgery. The reoperation rate in congenital esotropia (including reoperations for horizontal misalignment, dissociated vertical deulation, and inferior oblique overaction) also is high, approaching 50%. The role of very early surgical intervention needs to be examined further and could result in dramatic improvement in the long-term outcomes associated with congenital esotropia.

We have selected the Streptoalloteichus hindustanus bleomycin-resistance protein ShBle, a 28-kDa homodimer, as a scaffold for the display of bioactive peptides and other peptide epitopes. To create a monomeric scaffold, we investigated the effect of mutating residue proline 9 to glycine. This residue plays a critical role in ShBle dimerization by affecting the position of the eight N-terminal residues which secure the interaction between the monomeric subunits. We demonstrate that this mutation weakens the dimerization interaction, resulting in establishment of a stable equilibrium between monomeric and dimeric ShBle species in solution. Circular dichroism and SDS-PAGE data indicate that the Pro9Gly mutation does not disrupt the structure of the molecule. Production of a fully monomeric form of ShBle required complete removal of the eight-residue N-terminal peptide, and the interaction across the now solvent-exposed hydrophobic interface of the ShBle monomer was insufficient to drive dimerization. To demonstrate efficient display of epitope tags on the ShBle protein, we displayed dual-octapeptide FLAG tags at the protein C-terminus. These additions did not interfere with protein folding or activity. The resulting ShBle scaffold was used to compare the efficiency of two commercial FLAG-specific antibodies by biosensor.

In the Gulf of California, Paracerceis sculpta (Holmes), a sphaeromatid isopod, feeds on coralline algae and breeds in the spongocoels of calcareous sponges (Leucetta losangelensis de Laubenfels). Near Puerto Penasco, Sonora, sea surface temperature and algal abundance fluctuate throughout the year. To investigate how these factors influence isopod growth, we plotted the body lengths of field-collected isopods against monthly sea surface temperatures, as well as against the relative abundance of coralline algae (Corallina; Amphiroa), over a 26-month period (1983–1985). We found that average body lengths of the four adult morphs in this species (α-, β-, γ-males and females), were larger in cool months and smaller in warm months. Our records of female reproductive condition at capture allowed identification of the approximate dates on which females matured, thus the effect of temperature on growth was most clearly seen in females. Monthly average body lengths correlated negatively with temperature for all adult morphotypes, with different slopes and intercepts; morphotypes undergoing more molts had steeper slopes. Coralline algae abundance showed no seasonal patterns, and we found no significant relationships between relative algal abundance and isopod body length for any adult morph. In the laboratory, animals reared at lower temperature (21°C) matured at larger body lengths than individuals reared at higher temperatures (27–30°C). However, well-fed individuals grew no more rapidly than poorly-fed individuals. Thus, variation in food availability had no recognizable effect on isopod growth in either the laboratory or in the field, whereas variation in temperature significantly influenced growth in both locations, with effects proportional to the number of pre-adult molts.