Gas Uptake and Thermodynamics in Porous Liquids Elucidated by 129Xe NMR.

We exploited 129Xe NMR to investigate xenon gas uptake and dynamics in a porous liquid formed by dissolving porous organic cages in a cavity-excluded solvent. Quantitative 129Xe NMR shows that when the amount of xenon added to the sample is lower than the amount of cages present (subsaturation), the porous liquid absorbs almost all xenon atoms from the gas phase, with 30% of the cages occupied with a Xe atom. A simple two-site exchange model enables an estimate of the chemical shift of 129Xe in the cages, which is in good agreement with the value provided by first-principles modeling. T2 relaxation times allow the determination of the exchange rate of Xe between the solvent and cage sites as well as the activation energies of the exchange. The 129Xe NMR analysis also enables determination of the free energy of confinement, and it shows that Xe binding is predominantly enthalpy-driven.

Association of primary care visit length with outpatient utilization, continuity, and care processes.

BACKGROUND: Little is known about how variation in the scheduled length of primary care visits can impact patients' patterns of health care utilization. OBJECTIVE: To evaluate how the scheduled length of in-person visits with primary care physicians (PCPs) was associated with PCP and patient characteristics, outpatient utilization, and preventive care receipt. METHODS: This retrospective cohort study examined data from a large American academic health system. PCP visit length template was defined as either 15- and 30-min scheduled appointments (i.e. 15/30), or 20- and 40-min scheduled appointments (i.e. 20/40). RESULTS: Of 222 included PCPs, 85 (38.3%) used the 15/30 template and 137 (61.7%) used the 20/40 template. The 15/30 group had higher proportions of male (49.4%, vs. 35.8% in the 20/40 group) and family medicine (37.6% vs. 21.2%) physicians. In adjusted patient-level analysis (N = 238,806), having a 15/30 PCP was associated with 9% more primary care visits (incidence rate ratio [IRR], 1.09; 95% confidence interval [CI], 1.03-1.14), and 8% fewer specialty care visits (IRR, 0.92; 95% CI, 0.86-0.98). PCP visit length template was not associated with significant differences in obstetrics/gynaecology visits, continuity of care, or preventive care receipt. In interaction analyses, having a 15/30 PCP was associated with additional primary care visits among non-Hispanic White patients (IRR, 1.10; 95% CI, 1.04-1.16) but not among non-Hispanic Black patients. CONCLUSION: PCPs' choices about the scheduled length of in-person visits may impact their patients' specialty care use, and have varying impacts across different racial/ethnic groups.

Discrimination of GLUTs by Fructose Isomers Enables Simultaneous Screening of GLUT5 and GLUT2 Activity in Live Cells.

Facilitative carbohydrate transporters (GLUTs, SLC2 gene family) are transmembrane proteins transporting hexoses and other sugars based on cellular metabolic demands. While a direct link between GLUTs and metabolic disorders has framed them as important biological and medicinal targets, targeting disease-relevant GLUTs remains challenging. In this study, we aimed to identify substrate-GLUT interactions that would discriminate between major fructose transporters. We examined the uptake distribution for conformational and configurational isomers of fructose using the corresponding conformationally locked fluorescently labeled mimetics as probes for assessing GLUT preferences in real time. Through comparative analysis of the uptake of the probes in the yeast-based single GLUT expression systems and the multi-GLUT mammalian cell environment, we established the ability of fructose transporters to discriminate between fructose conformers and epimers. We demonstrated that recreating the conformational and configurational mixture of fructose with molecular probes allows for the specific probe distribution, with fructofuranose mimetic being taken up preferentially through GLUT5 and ß-d-fructopyranose mimetic passing through GLUT2. The uptake of α-d-fructopyranose mimetic was found to be independent of GLUT5 or GLUT2. The results of this study provide a new approach to analyzing GLUT5 and GLUT2 activity in live cells, and the findings can be used as a proof-of-concept for multi-GLUT activity screening in live cells. The research also provides new knowledge on substrate-GLUT interactions and new tools for monitoring alterations in GLUT activities.

Broadly neutralizing antibodies target the coronavirus fusion peptide.

The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach to identify six monoclonal antibodies that bind to spike proteins from all seven human-infecting coronaviruses. All six antibodies target the conserved fusion peptide region adjacent to the S2' cleavage site. COV44-62 and COV44-79 broadly neutralize alpha- and betacoronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2 and BA.4/5, albeit with lower potency than receptor binding domain-specific antibodies. In crystal structures of COV44-62 and COV44-79 antigen-binding fragments with the SARS-CoV-2 fusion peptide, the fusion peptide epitope adopts a helical structure and includes the arginine residue at the S2' cleavage site. COV44-79 limited disease caused by SARS-CoV-2 in a Syrian hamster model. These findings highlight the fusion peptide as a candidate epitope for next-generation coronavirus vaccine development.

Postsurgical Latent Pain Sensitization Is Driven by Descending Serotonergic Facilitation and Masked by µ-Opioid Receptor Constitutive Activity in the Rostral Ventromedial Medulla.

Following tissue injury, latent sensitization (LS) of nociceptive signaling can persist indefinitely, kept in remission by compensatory µ-opioid receptor constitutive activity (MORCA) in the dorsal horn of the spinal cord. To demonstrate LS, we conducted plantar incision in mice and then waited 3-4 weeks for hypersensitivity to resolve. At this time (remission), systemic administration of the opioid receptor antagonist/inverse agonist naltrexone reinstated mechanical and heat hypersensitivity. We first tested the hypothesis that LS extends to serotonergic neurons in the rostral ventral medulla (RVM) that convey pronociceptive input to the spinal cord. We report that in male and female mice, hypersensitivity was accompanied by increased Fos expression in serotonergic neurons of the RVM, abolished on chemogenetic inhibition of RVM 5-HT neurons, and blocked by intrathecal injection of the 5-HT3R antagonist ondansetron; the 5-HT2AR antagonist MDL-11 939 had no effect. Second, to test for MORCA, we microinjected the MOR inverse agonist d-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) and/or neutral opioid receptor antagonist 6ß-naltrexol. Intra-RVM CTAP produced mechanical hypersensitivity at both hindpaws; 6ß-naltrexol had no effect by itself, but blocked CTAP-induced hypersensitivity. This indicates that MORCA, rather than an opioid ligand-dependent mechanism, maintains LS in remission. We conclude that incision establishes LS in descending RVM 5-HT neurons that drives pronociceptive 5-HT3R signaling in the dorsal horn, and this LS is tonically opposed by MORCA in the RVM. The 5-HT3 receptor is a promising therapeutic target for the development of drugs to prevent the transition from acute to chronic postsurgical pain.SIGNIFICANCE STATEMENT Surgery leads to latent pain sensitization and a compensatory state of endogenous pain control that is maintained long after tissue healing. Here, we show that either chemogenetic inhibition of serotonergic neuron activity in the RVM or pharmacological inhibition of 5-HT3 receptor signaling at the spinal cord blocks behavioral signs of postsurgical latent sensitization. We conclude that MORCA in the RVM opposes descending serotonergic facilitation of LS and that the 5-HT3 receptor is a promising therapeutic target for the development of drugs to prevent the transition from acute to chronic postsurgical pain.

Incidence rates and predictors of microvascular and macrovascular complications in patients with type 2 diabetes: Results from the longitudinal global discover study.

BACKGROUND: Micro- and macrovascular complications are a major cause of morbidity and mortality in people with type 2 diabetes (T2D). We sought to understand the global incidence rates and predictors of these complications. METHODS: We examined the incidence of vascular complications over 3 years of follow-up in the DISCOVER study-a global, observational study of people with T2D initiating second-line glucose-lowering therapy. Hierarchical Cox proportional hazards regression models examined factors associated with development of micro- and macrovascular complications during follow-up. RESULTS: Among 11,357 people with T2D from 33 countries (mean age 56.9 ± 11.7 years, T2D duration 5.7 ± 5.1 years, HbA1c 8.4 ± 1.7%), 19.0% had a microvascular complication at enrolment (most commonly neuropathy), and 13.2% had a macrovascular complication (most commonly coronary disease). Over 3 years of follow-up, 16.0% developed an incident microvascular complication, and 6.6% had an incident macrovascular complication. At the end of 3 years of follow-up, 31.5% of patients had at least one microvascular complication, and 16.6% had at least one macrovascular complication. Higher HbA1c and smoking were associated with greater risk of both incident micro- and macrovascular complications. Known macrovascular complications at baseline was the strongest predictor for development of new microvascular complications (HR 1.40, 95% CI 1.21 -1.61) and new macrovascular complications (HR 3.39, 95% CI 2.84 -4.06). CONCLUSIONS: In this global study, both the prevalence and 3-year incidence of vascular complications were high in patients with relatively short T2D duration, highlighting the need for early risk-factor modification.

Prevalence and progression of chronic kidney disease among patients with type 2 diabetes: Insights from the DISCOVER study.

We report the prevalence and change in severity of chronic kidney disease (CKD) in DISCOVER, a global, 3-year, prospective, observational study of patients with type 2 diabetes (T2D) initiating second-line glucose-lowering therapy. CKD stages were defined according to estimated glomerular filtration rate (eGFR). Overall, 7843 patients from 35 countries had a baseline serum creatinine measurement. Of these (56.7% male; mean age: 58.1 years; mean eGFR: 87.5 mL/min/1.73 m2 ), baseline prevalence estimates for stage 0-1, 2, 3 and 4-5 CKD were 51.4%, 37.7%, 9.4% and 1.4%, respectively. A total of 5819 patients (74.2%) also had at least one follow-up serum creatinine measurement (median time between measurements: 2.9 years, interquartile range: 1.9-3.0 years). Mean eGFR decreased slightly to 85.7 mL/min/1.73 m2 over follow-up. CKD progression (increase of ≥1 stage) occurred in 15.7% of patients, and regression (decrease of ≥1 stage) in 12.0%. In summary, a substantial proportion of patients with T2D developed CKD or had CKD progression after the initiation of second-line therapy. Renal function should be regularly monitored in these patients, to ensure early CKD diagnosis and treatment.

Inherent Ethyl Acetate Selectivity in a Trianglimine Molecular Solid.

Ethyl acetate is an important chemical raw material and solvent. It is also a key volatile organic compound in the brewing industry and a marker for lung cancer. Materials that are highly selective toward ethyl acetate are needed for its separation and detection. Here, we report a trianglimine macrocycle (TAMC) that selectively adsorbs ethyl acetate by forming a solvate. Crystal structure prediction showed this to be the lowest energy solvate structure available. This solvate leaves a metastable, "templated" cavity after solvent removal. Adsorption and breakthrough experiments confirmed that TAMC has adequate adsorption kinetics to separate ethyl acetate from azeotropic mixtures with ethanol, which is a challenging and energy-intensive industrial separation.

Forehead location and large segmental pattern of facial port-wine stains predict risk of Sturge-Weber syndrome.

BACKGROUND: Children with forehead port-wine stains (PWSs) are at risk of Sturge-Weber syndrome (SWS). However, most will not develop neurologic manifestations. OBJECTIVE: To identify children at greatest risk of SWS. METHOD: In this retrospective cohort study of children with a forehead PWS, PWSs were classified as "large segmental" (half or more of a contiguous area of the hemiforehead or median pattern) or "trace/small segmental" (less than half of the hemiforehead). The outcome measure was a diagnosis of SWS. RESULTS: Ninety-six children had a forehead PWS. Fifty-one had a large segmental PWS, and 45 had a trace/small segmental PWS. All 21 children with SWS had large segmental forehead PWSs. Large segmental forehead PWSs had a higher specificity (0.71 vs 0.27, P < .0001) and a higher positive predictive value (0.41 vs 0.22, P < .0001) for SWS than any forehead involvement by a PWS. LIMITATIONS: Retrospective study at a referral center. CONCLUSION: Children with large segmental forehead PWSs are at highest risk of SWS.

Examining the relationship between impulsivity-related personality traits and e-cigarette use in adults.

AIMS: The present study aimed to investigate the relationship between impulsivity-related personality traits based on the UPPS-P model and e-cigarette use. The study used a sample of mainly European adults and compared e-cigarette users with non-smokers, cigarette smokers and dual users (those who currently smoke cigarettes and use e-cigarettes). Additionally, the relationship between impulsivity-related traits and frequency and intensity of e-cigarette use was examined, while the main reasons for e-cigarette use were also assessed. METHODS: Participants were 720 adults (234 non-smokers, 164 smokers, 150 e-cigarette users, 172 dual users), who completed online questionnaires regarding sociodemographics, smoking/e-cigarette use behaviour, and impulsivity (UPPS-P scale). RESULTS: Impulsivity-related traits did not significantly differentiate e-cigarette users from non-smokers. E-cigarette users showed lower levels of lack of perseverance than cigarette smokers, and they exhibited lower levels of negative and positive urgency than dual users. Negative urgency also significantly differentiated smokers and non-smokers, with smokers having higher levels of the trait. No significant results were found examining the relationship between the impulsivity-related traits and e-cigarette behaviour (number of days vaping per month, number of times vaping per day, and millilitres of e-liquid used per day). The main reason given for e-cigarette use was the perception that it is less harmful than cigarettes. CONCLUSION: The present study found that trait impulsivity differentiated e-cigarette users from cigarette smokers and dual users, but did not differentiate e-cigarette users from non-smokers. Such findings are important to not only help us identify factors associated with e-cigarette use, but also to potentially inform treatment plans and decisions.

Controlling Gas Selectivity in Molecular Porous Liquids by Tuning the Cage Window Size.

Control of pore window size is the standard approach for tuning gas selectivity in porous solids. Here, we present the first example where this is translated into a molecular porous liquid formed from organic cage molecules. Reduction of the cage window size by chemical synthesis switches the selectivity from Xe-selective to CH4 -selective, which is understood using 129 Xe, 1 H, and pulsed-field gradient NMR spectroscopy.

Examining the Psychometric Properties of the CEAC (Comparing e-Cigarette and Cigarette) Questionnaire and Its Usefulness as a Predictor of e-Cigarette Use.

Background: Electronic cigarette (e-cigarette) use continues to rise, while there is conflicting evidence about the health effects of its use. As such, research is needed to better determine risks factors for e-cigarette use. Accumulating evidence suggests that attitudes toward e-cigarette use could be a potential risk factor for e-cigarette use. Objectives: This study sought to examine the psychometric properties of the Comparing E-cigarette And Cigarette questionnaire (CEAC), and to replicate a structural model of the relationship between impulsive-related personality traits and e-cigarette use mediated by positive attitudes toward e-cigarettes. Methods: Participants were 525 adults (mean age = 33.42, SD = 11.27) who completed the CEAC and UPPS-P (trait impulsivity) questionnaires online. Results: Confirmatory factor analysis of the CEAC replicated the a priori factor structure of the questionnaire reasonably well (χ2(df = 32) =172.85, CFI = 0.94, TLI = 0.91, RMSEA = 0.09 (0.08-0.11, 90% Confidence Interval, SRMR = 0.06). Structural path analysis showed that deficits in conscientiousness was significantly negatively related to e-cigarette attitudes (ß = -0.20, p = .01), while urgency (ß = 0.19, p = .018) showed a significant positive relationship to e-cigarette attitudes. E-cigarette users showed significantly more positive attitudes toward e-cigarettes than nonusers (ß = 0.59, p < .001). No significant direct effects were found between impulsivity-related traits and e-cigarette use. Conclusions: The present study suggests that impulsivity-related traits and attitudes toward e-cigarettes are likely to be important risk factors for e-cigarette use. Future prospective and experimental studies should test if the causal model described in this study predicts risk for e-cigarette use, and whether this model could therefore be used to guide strategies for reducing risk for e-cigarette use.

Impulsivity related personality traits and cigarette smoking in adults: A meta-analysis using the UPPS-P model of impulsivity and reward sensitivity.

BACKGROUND: Although there is considerable evidence of an association between impulsivity and cigarette smoking, the magnitude of this association varies across studies. Impulsivity comprises several discrete traits that may influence cigarette use in different ways. The present meta-analysis aims to examine the direction and magnitude of relationships between specific impulsivity-related traits, namely lack of premeditation, lack of perseverance, sensation seeking, negative urgency, positive urgency and reward sensitivity and both smoking status and severity of nicotine dependence in adults across studies and to delineate differences in effects across these relationships. METHODS: Ninety-seven studies were meta-analysed using random-effects models to examine the relationship between impulsivity-related traits and smoking status and severity of nicotine dependence. A number of demographic and methodological variables were also assessed as potential moderators. RESULTS: Smoking status and severity of nicotine dependence were significantly associated with all impulsivity-related traits except reward sensitivity. Lack of premeditation and positive urgency showed the largest associations with smoking status (r = 0.20, r = 0.24 respectively), while positive urgency showed the largest association with severity of nicotine dependence (r = 0.23). Study design moderated associations between lack of premeditation and lack of perseverance and smoking status, with larger effects found in cross-sectional compared to prospective studies. CONCLUSIONS: Finding suggest that impulsivity is associated with an increased likelihood of being a smoker and greater nicotine dependence. Specific impulsivity-related traits differentially relate to smoking status and severity of nicotine dependence. Understanding the complexity of impulsivity-related traits in relation to smoking can help to identify potential smokers and could inform cessation treatment.

Understanding gas capacity, guest selectivity, and diffusion in porous liquids.

Porous liquids are a new class of material that could have applications in areas such as gas separation and homogeneous catalysis. Here we use a combination of measurement techniques, molecular simulations, and control experiments to advance the quantitative understanding of these liquids. In particular, we show that the cage cavities remain unoccupied in the absence of a suitable guest, and that the liquids can adsorb large quantities of gas, with gas occupancy in the cages as high as 72% and 74% for Xe and SF6, respectively. Gases can be reversibly loaded and released by using non-chemical triggers such as sonication, suggesting potential for gas separation schemes. Diffusion NMR experiments show that gases are in dynamic equilibrium between a bound and unbound state in the cage cavities, in agreement with recent simulations for related porous liquids. Comparison with gas adsorption in porous organic cage solids suggests that porous liquids have similar gas binding affinities, and that the physical properties of the cage molecule are translated into the liquid state. By contrast, some physical properties are different: for example, solid homochiral porous cages show enantioselectivity for chiral aromatic alcohols, whereas the equivalent homochiral porous liquids do not. This can be attributed to a loss of supramolecular organisation in the isotropic porous liquid.

Helminths in organ transplantation.

With transplantation becoming an increasingly routine form of treatment for diverse populations, and with international travel becoming ever more accessible and affordable, the danger of transplantation-mediated helminth infections, exacerbated by coincident immunosuppression, must be considered. In this Review, we attempt to catalogue all clinically-relevant helminthiases that have been reported to coincide with transplantation, whether by transplantation-mediated transmission, reactivation of latent infections in an immunosuppressed context, or possible de-novo infection during the immunosuppressed peritransplant period. Helminthiasis has been reported in cases of kidney, liver, bowel, pancreas, heart, lung, and stem-cell transplant, and blood transfusion. For each helminthiasis, known risk factors, symptoms, and suggested options for screening and treatment are given. We conclude that helminths are a small but important and potentially severe source of disease after transplantation, and, with options for diagnosis and treatment, these pathogens warrant greater consideration during organ implantation. The achievement of immunological tolerance using helminth-derived products is also an exciting future prospect.

Residential neighbourhood greenspace is associated with reduced risk of incident diabetes in older people: a prospective cohort study.

BACKGROUND: Three cross sectional studies suggest that neighbourhood greenspace may protect against incident diabetes. This study uses data from a longitudinal study with a large sample size to investigate the association between greenspace and the occurrence of incident diabetes over time. METHODS: Data was from the European Prospective Investigation of Cancer Norfolk, UK, cohort, recruitment 1993-2007 (N = 23,865). Neighbourhoods were defined as 800 m circular buffers around participants' home locations, according to their home postcode (zip code). Greenspace exposure was defined as the percentage of the home neighbourhood that was woodland, grassland, arable land, mountain, heath and bog, according to the UK Land Cover Map. Cox proportional hazards regression examined the association between neighbourhood greenspace exposure and incident diabetes. The population attributable fraction assessed the proportion of diabetes cases attributable to exposure to least green neighbourhoods. Mediation analysis assessed if physical activity explained associations between greenspace and diabetes. Interaction analysis was used to test for the modifying effect of rurality and socio-economic status on the relationship between greenspace and diabetes. Models were adjusted for known and hypothesised confounders. RESULTS: The mean age of participants was 59 years at baseline and 55.1% were female. The mean follow-up time was 11.3 years. Individuals living in the greenest neighbourhood quartile had a 19% lower relative hazard of developing diabetes (HR 0.81; 95% CI 0.67, 0.99; p = 0.035; linear trend p = 0.010). The hazard ratio remained similar (HR 0.81; 95% CI 0.65, 0.99; p = 0.042) after adjusting for age, sex, BMI, whether a parent had been diagnosed with diabetes and socio-economic status at the individual and neighbourhood level. A HR of 0.97 was attributed to the pathway through physical activity in a fully adjusted model, although this was non-significant (95% CI 0.88, 1.08; p = 0.603). The incidence of diabetes in the least green neighbourhoods (with 20% greenspace on average) would fall by 10.7% (95% CI -2.1%, 25.2%; p = 0.106) if they were as green as the average neighbourhood observed across the whole cohort (59% greenspace on average). There were no significant interactions between rurality or socio-economic status and level of greenspace. CONCLUSIONS: Greener home neighbourhoods may protect against risk of diabetes in older adults, although this study does not support a mediation role for physical activity. Causal mechanisms underlying the associations require further investigation.

Oropharyngeal pH Testing Does Not Predict Response to Proton Pump Inhibitor Therapy in Patients with Laryngeal Symptoms.

OBJECTIVES: Predicting response to proton pump inhibitor (PPI) therapy in patients with laryngeal symptoms is challenging. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. In this study, we aimed to investigate the prognostic potential of oropharyngeal pH monitoring to predict responsiveness to PPI therapy in patients with laryngeal symptoms. METHODS: We conducted a physician-blinded prospective cohort study at a single academic institution between January 2013 and October 2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-h oropharyngeal pH monitoring, followed by an 8- to 12-week trial of omeprazole 40 mg daily. Prior to and following PPI therapy, patients completed various symptom questionnaires. The primary outcome was the association between PPI response and oropharyngeal pH metrics. PPI response was separated into three subgroups based on the post-treatment RSI score and % RSI response: non-response=RSI ≥13; partial response=post-treatment RSI <13 and change in RSI <50%; and complete response=post-treatment RSI <13 and change in RSI ≥50%. The primary analysis utilized a multinomial logistic regression controlling for the pre-treatment RSI score. A secondary analysis assessed the relationship between the change in RSI (post-pre) and oropharyngeal pH metrics via ordinary least square regression. RESULTS: Thirty-four patients completed the study and were included in final analysis. Symptom response to PPI therapy was as follows: 50% no response, 15% partial response, and 35% complete response. Non-responders had a higher pre-treatment RSI (P<0.01). There were no significant differences in oropharyngeal acid exposure (below pH of 4.0, 5.0, 5.5, 6.0, and RYAN scores) between responder types. The secondary analysis noted a trend between lower PPI response and a greater total percent time below pH of 5.0 (P=0.03), upright percent time below pH of 5.0 (P=0.07), and RYAN supine (corrected; P=0.03), as well as an association between PPI response and greater decreases in the Anxiety Sensitivity Inventory (P<0.01), Brief Symptom Inventory-18 (P<0.01), and Negative Affect Scale (P<0.01). CONCLUSIONS: Oropharyngeal pH testing did not predict laryngeal symptom response to PPI therapy. Contrary to hypothesis, our study signaled that the degree of oropharyngeal acid exposure is inversely related to PPI response. In addition, reduction in negative affect and psychological distress parallels PPI response.

PIM-1 mixed matrix membranes for gas separations using cost-effective hypercrosslinked nanoparticle fillers.

High-free-volume glassy polymers, such as polymers of intrinsic microporosity (PIMs) and poly(trimethylsilylpropyne), have attracted attention as membrane materials due to their high permeability. However, loss of free volume over time, or aging, limits their applicability. Introduction of a secondary filler phase can reduce this aging but either cost or instability rules out scale up for many fillers. Here, we report a cheap, acid-tolerant, nanoparticulate hypercrosslinked polymer 'sponge' as an alternative filler. On adding the filler, permeability is enhanced and aging is strongly retarded. This is accompanied by a CO2/N2 selectivity that increases over time, surpassing the Robeson upper bound.

Patient-centred care, health behaviours and cardiovascular risk factor levels in people with recently diagnosed type 2 diabetes: 5-year follow-up of the ADDITION-Plus trial cohort.

OBJECTIVE: To examine the association between the experience of patient-centred care (PCC), health behaviours and cardiovascular disease (CVD) risk factor levels among people with type 2 diabetes. DESIGN: Population-based prospective cohort study. SETTING: 34 general practices in East Anglia, UK, delivering organised diabetes care. PARTICIPANTS: 478 patients recently diagnosed with type 2 diabetes aged between 40 and 69 years enrolled in the ADDITION-Plus trial. MAIN OUTCOME MEASURES: Self-reported and objectively measured health behaviours (diet, physical activity, smoking status), CVD risk factor levels (blood pressure, lipid levels, glycated haemoglobin, body mass index, waist circumference) and modelled 10-year CVD risk. RESULTS: Better experiences of PCC early in the course of living with diabetes were not associated with meaningful differences in self-reported physical activity levels including total activity energy expenditure (ß-coefficient: 0.080 MET h/day (95% CI 0.017 to 0.143; p=0.01)), moderate-to-vigorous physical activity (ß-coefficient: 5.328 min/day (95% CI 0.796 to 9.859; p=0.01)) and reduced sedentary time (ß-coefficient: -1.633 min/day (95% CI -2.897 to -0.368; p=0.01)). PCC was not associated with clinically meaningful differences in levels of high-density lipoprotein cholesterol (ß-coefficient: 0.002 mmol/L (95% CI 0.001 to 0.004; p=0.03)), systolic blood pressure (ß-coefficient: -0.561 mm Hg (95% CI -0.653 to -0.468; p=0.01)) or diastolic blood pressure (ß-coefficient: -0.565 mm Hg (95% CI -0.654 to -0.476; p=0.01)). Over an extended follow-up of 5 years, we observed no clear evidence that PCC was associated with self-reported, clinical or biochemical outcomes, except for waist circumference (ß-coefficient: 0.085 cm (95% CI 0.015 to 0.155; p=0.02)). CONCLUSIONS: We found little evidence that experience of PCC early in the course of diabetes was associated with clinically important changes in health-related behaviours or CVD risk factors. TRIAL REGISTRATION NUMBER: ISRCTN99175498; Post-results.