Negative impact of the first COVID-19 lockdown upon health-related behaviours and psychological wellbeing in people living with severe and complex obesity in the UK

BACKGROUND: Coronavirus disease 2019 (COVID-19) has led to unprecedented changes in the way we live, particularly for people at higher risk of severe illness from COVID-19. People with pre-existing health conditions have been markedly impacted and, in some instances, left unsupported due to reduced provision of routine healthcare services. People living with obesity (PLWO) are identified as at higher risk of severe illness from COVID-19 infection. Currently, there is a paucity of evidence about the impact of the first COVID-19 lockdown on PLWO, including those accessing weight management and bariatric surgery services (WMS). METHODS: 543 adults (16–80 years) with obesity (BMI ≥ 30 kg/m2) were recruited between 14th May and 9th July 2020 through social media advertisements, professional and patient obesity organisations and WMS. Participants completed an online survey regarding the impact of the first COVID-19 lockdown upon, mental health, well-being, health-related behaviours, risk mitigating behaviours, access to WMS and weight stigma. FINDINGS: During the first COVID-19 lockdown, the majority of PLWO reported deterioration of their mental health and health-related behaviours such as diet, physical activity (PA) and sleep. With 55% reporting an unhealthier diet, 61% reduced PA and 80% worsening of their sleep. Higher depression and lower wellbeing scores were found to associate with the greatest adverse impact upon health-related behaviours. PLWO who were attending WMS prior to the first lockdown reported a greater deterioration of their diet, with nearly 50% reporting worsening of their diet and PA worsening compared to PLWO who were not attending WMS. Most participants took two or more risk mitigating actions (73%). PLWO attending WMS reported reduced access (44%) with insufficient information (49%) from their clinical service providers. The majority of participants reported no change in perceived weight stigma. INTERPRETATION: This study shows the detrimental impact of the first COVID-19 lockdown on PLWO in relation to health-related behaviours, mental health and access to WMS. Our findings show that PLWO with poor mental health and those attending WMS were most adversely impacted and highlights the need for greater mental health support and continued provision of support from WMS for PLWO during future lockdowns. FUNDING: This research was funded through National Institute for Health Research University College London Hospitals Biomedical Research Centre funding

Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode and drug naive schizophrenic patients

BACKGROUND: Recent magnetic resonance spectroscopy (MRS) studies report that glutamine is altered in the brains of schizophrenic patients. There were also conflicting findings on glutamate in cerebrospinal fluid (CSF) of schizophrenic patients, and absent for glutamine. This study aims to clarify the question of glutamine and glutamate in CSF of first episode and drug naive schizophrenic patients. METHOD: Levels of glutamine and glutamate in CSF of 25 first episode and drug-naive male schizophrenic patients and 17 age-matched male healthy controls were measured by a high performance liquid chromatography. RESULTS: The ratio (126.1 (median), 117.7 ± 27.4 (mean ± S.D.)) of glutamine to glutamate in the CSF of patients was significantly (z = -3.29, p = 0.001) higher than that (81.01 (median), 89.1 ± 22.5 (mean ± S.D.)) of normal controls although each level of glutamine and glutamate in patients was not different from that of normal controls. CONCLUSION: Our data suggests that a disfunction in glutamate-glutamine cycle in the brain may play a role in the pathophysiology of schizophrenia

The implications of defining obesity as a disease: a report from the Association for the Study of Obesity 2021 annual conference

Unlike various countries and organisations, including the World Health Organisation and the European Parliament, the United Kingdom does not formally recognise obesity as a disease. This report presents the discussion on the potential impact of defining obesity as a disease on the patient, the healthcare system, the economy, and the wider society. A group of speakers from a wide range of disciplines came together to debate the topic bringing their knowledge and expertise from backgrounds in medicine, psychology, economics, and politics as well as the experience of people living with obesity. The aim of their debate was not to decide whether obesity should be classified as a disease but rather to explore what the implications of doing so would be, what the gaps in the available data are, as well as to provide up-to-date information on the topic from experts in the field. There were four topics where speakers presented their viewpoints, each one including a question-and-answer section for debate. The first one focused on the impact that the recognition of obesity could have on people living with obesity regarding the change in their behaviour, either positive and empowering or more stigmatising. During the second one, the impact of defining obesity as a disease on the National Health Service and the wider economy was discussed. The primary outcome was the need for more robust data as the one available does not represent the actual cost of obesity. The third topic was related to the policy implications regarding treatment provision, focusing on the public's power to influence policy. Finally, the last issue discussed, included the implications of public health actions, highlighting the importance of the government's actions and private stakeholders. The speakers agreed that no matter where they stand on this debate, the goal is common: to provide a healthcare system that supports and protects the patients, strategies that protect the economy and broader society, and policies that reduce stigma and promote health equity. Many questions are left to be answered regarding how these goals can be achieved. However, this discussion has set a good foundation providing evidence that can be used by the public, clinicians, and policymakers to make that happen

Evolving health information technology and the timely availability of visit diagnoses from ambulatory visits: A natural experiment in an integrated delivery system

<p>Abstract</p> <p>Background</p> <p>Health information technology (HIT) may improve health care quality and outcomes, in part by making information available in a timelier manner. However, there are few studies documenting the changes in timely availability of data with the use of a sophisticated electronic medical record (EMR), nor a description of how the timely availability of data might differ with different types of EMRs. We hypothesized that timely availability of data would improve with use of increasingly sophisticated forms of HIT.</p> <p>Methods</p> <p>We used an historical observation design (2004–2006) using electronic data from office visits in an integrated delivery system with three types of HIT: Basic, Intermediate, and Advanced. We calculated the monthly percentage of visits using the various types of HIT for entry of visit diagnoses into the delivery system's electronic database, and the time between the visit and the availability of the visit diagnoses in the database.</p> <p>Results</p> <p>In January 2004, when only Basic HIT was available, 10% of office visits had diagnoses entered on the same day as the visit and 90% within a week; 85% of office visits used paper forms for recording visit diagnoses, 16% used Basic at that time. By December 2006, 95% of all office visits had diagnoses available on the same day as the visit, when 98% of office visits used some form of HIT for entry of visit diagnoses (Advanced HIT for 67% of visits).</p> <p>Conclusion</p> <p>Use of HIT systems is associated with dramatic increases in the timely availability of diagnostic information, though the effects may vary by sophistication of HIT system. Timely clinical data are critical for real-time population surveillance, and valuable for routine clinical care.</p

Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders

Guanidino compounds (GCs), such as creatine, phosphocreatine, guanidinoacetic acid, creatinine, methylguanidine, guanidinosuccinic acid, γ-guanidinobutyric acid, β-guanidinopropionic acid, guanidinoethane sulfonic acid and α-guanidinoglutaric acid, are present in the mammalian brain. Although creatine and phosphocreatine play important roles in energy homeostasis in the brain, accumulation of GCs may induce epileptic discharges and convulsions. This review focuses on how physiologically important and/or neurotoxic GCs are distributed in the brain under physiological and pathological conditions. Transporters for GCs at the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB) have emerged as substantial contributors to GCs distribution in the brain. Creatine transporter (CRT/solute carrier (SLC) 6A8) expressed at the BBB regulates creatine concentration in the brain, and represents a major pathway for supply of creatine from the circulating blood to the brain. CRT may be a key factor facilitating blood-to-brain guanidinoacetate transport in patients deficient in S-adenosylmethionine:guanidinoacetate N-methyltransferase, the creatine biosynthetic enzyme, resulting in cerebral accumulation of guanidinoacetate. CRT, taurine transporter (TauT/SLC6A6) and organic cation transporter (OCT3/SLC22A3) expressed at the BCSFB are involved in guanidinoacetic acid or creatinine efflux transport from CSF. Interestingly, BBB efflux transport of GCs, including guanidinoacetate and creatinine, is negligible, though the BBB has a variety of efflux transport systems for synthetic precursors of GCs, such as amino acids and neurotransmitters. Instead, the BCSFB functions as a major cerebral clearance system for GCs. In conclusion, transport of GCs at the BBB and BCSFB appears to be the key determinant of the cerebral levels of GCs, and changes in the transport characteristics may cause the abnormal distribution of GCs in the brain seen in patients with certain neurological disorders

L-lysine as adjunctive treatment in patients with schizophrenia: a single-blinded, randomized, cross-over pilot study

<p>Abstract</p> <p>Background</p> <p>Accumulating evidence suggests that the brain's nitric oxide (NO) signalling system may be involved in the pathophysiology of schizophrenia and could thus constitute a novel treatment target. The study was designed to investigate the benefit of L-lysine, an amino acid that interferes with NO production, as an add-on treatment for schizophrenia.</p> <p>Methods</p> <p>L-lysine, 6 g/day, was administered to 10 patients with schizophrenia as an adjunctive to their conventional antipsychotic medication. The study was designed as a single-blinded, cross-over study where patients were randomly assigned to initial treatment with either L-lysine or placebo and screened at baseline, after four weeks when treatment was crossed over, and after eight weeks.</p> <p>Results</p> <p>L-lysine treatment caused a significant increase in blood concentration of L-lysine and was well tolerated. A significant decrease in positive symptom severity, measured by the Positive And Negative Syndrome Scale (PANSS), was detected. A certain decrease in score was also observed during placebo treatment and the effects on PANSS could not unequivocally be assigned to the L-lysine treatment. Furthermore, performance on the Wisconsin Card Sorting Test was significantly improved compared to baseline, an effect probably biased by training. Subjective reports from three of the patients indicated decreased symptom severity and enhanced cognitive functioning.</p> <p>Conclusions</p> <p>Four-week L-lysine treatment of 6 g/day caused a significant increase in blood concentration of L-lysine that was well tolerated. Patients showed a significant decrease in positive symptoms as assessed by PANSS in addition to self-reported symptom improvement by three patients. The NO-signalling pathway is an interesting, potentially new treatment target for schizophrenia; however, the effects of L-lysine need further evaluation to decide the amino acid's potentially beneficial effects on symptom severity in schizophrenia.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT00996242">NCT00996242</a></p

Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

Efficient processing of information by the central nervous system (CNS) represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB), which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF) from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF) barrier (BCSFB), which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs) that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC) transport proteins at those two barriers and underlines differences in their expression between the two barriers. Also, many blood-borne molecules and xenobiotics can diffuse into brain ISF and then into neuronal membranes due to their physicochemical properties. Entry of these compounds could be detrimental for neural transmission and signalling. Thus, BBB and BCSFB express transport proteins that actively restrict entry of lipophilic and amphipathic substances from blood and/or remove those molecules from the brain extracellular fluids. The third part of this review concentrates on the molecular biology of ATP-binding cassette (ABC)-transporters and those SLC transporters that are involved in efflux transport of xenobiotics, their expression at the BBB and BCSFB and differences in expression in the two major blood-brain interfaces. In addition, transport and diffusion of ions by the BBB and CP epithelium are involved in the formation of fluid, the ISF and CSF, respectively, so the last part of this review discusses molecular biology of ion transporters/exchangers and ion channels in the brain endothelial and CP epithelial cells

Epigenomic profiling of preterm infants reveals DNA methylation differences at sites associated with neural function

DNA methylation (DNAm) plays a determining role in neural cell fate and provides a molecular link between early-life stress and neuropsychiatric disease. Preterm birth is a profound environmental stressor that is closely associated with alterations in connectivity of neural systems and long-term neuropsychiatric impairment. The aims of this study were to examine the relationship between preterm birth and DNAm, and to investigate factors that contribute to variance in DNAm. DNA was collected from preterm infants (birth<33 weeks gestation) and healthy controls (birth>37 weeks), and a genome-wide analysis of DNAm was performed; diffusion magnetic resonance imaging (dMRI) data were acquired from the preterm group. The major fasciculi were segmented, and fractional anisotropy, mean diffusivity and tract shape were calculated. Principal components (PC) analysis was used to investigate the contribution of MRI features and clinical variables to variance in DNAm. Differential methylation was found within 25 gene bodies and 58 promoters of protein-coding genes in preterm infants compared with controls; 10 of these have neural functions. Differences detected in the array were validated with pyrosequencing. Ninety-five percent of the variance in DNAm in preterm infants was explained by 23 PCs; corticospinal tract shape associated with 6th PC, and gender and early nutritional exposure associated with the 7th PC. Preterm birth is associated with alterations in the methylome at sites that influence neural development and function. Differential methylation analysis has identified several promising candidate genes for understanding the genetic/epigenetic basis of preterm brain injury

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013