Statin prescribing for people with severe mental illnesses: a staggered cohort study of 'real-world' impacts

OBJECTIVES: To estimate the 'real-world effectiveness of statins for primary prevention of cardiovascular disease (CVD) and for lipid modification in people with severe mental illnesses (SMI), including schizophrenia and bipolar disorder. DESIGN: Series of staggered cohorts. We estimated the effect of statin prescribing on CVD outcomes using a multivariable Poisson regression model or linear regression for cholesterol outcomes. SETTING: 587 general practice (GP) surgeries across the UK reporting data to The Health Improvement Network. PARTICIPANTS: All permanently registered GP patients aged 40-84 years between 2002 and 2012 who had a diagnosis of SMI. Exclusion criteria were pre-existing CVD, statin-contraindicating conditions or a statin prescription within the 24 months prior to the study start. EXPOSURE: One or more statin prescriptions during a 24-month 'baseline' period (vs no statin prescription during the same period). MAIN OUTCOME MEASURES: The primary outcome was combined first myocardial infarction and stroke. All-cause mortality and total cholesterol concentration were secondary outcomes. RESULTS: We identified 2944 statin users and 42 886 statin non-users across the staggered cohorts. Statin prescribing was not associated with significant reduction in CVD events (incident rate ratio 0.89; 95% CI 0.68 to 1.15) or all-cause mortality (0.89; 95% CI 0.78 to 1.02). Statin prescribing was, however, associated with statistically significant reductions in total cholesterol of 1.2 mmol/L (95% CI 1.1 to 1.3) for up to 2 years after adjusting for differences in baseline characteristics. On average, total cholesterol decreased from 6.3 to 4.6 in statin users and 5.4 to 5.3 mmol/L in non-users. CONCLUSIONS: We found that statin prescribing to people with SMI in UK primary care was effective for lipid modification but not CVD events. The latter finding may reflect insufficient power to detect a smaller effect size than that observed in randomised controlled trials of statins in people without SMI

Time trends in access to smoking cessation support for people with depression or severe mental illness: a cohort study in English primary care

OBJECTIVES: To investigate delivery of smoking cessation interventions, recorded quit attempts and successful quitting rates within primary care in smokers with depression or severe mental illness (SMI) compared with those without. DESIGN: Longitudinal cohort study using primary healthcare records. SETTING: English primary care. PARTICIPANTS: 882 849 patients registered with participating practices recorded as current smokers during 2007-2014, including three groups: (1) 13 078 with SMI, (2) 55 630 with no SMI but recent depression and (3) 814 141 with no SMI nor recent depression. OUTCOMES: Recorded advice to quit smoking, referrals to smoking cessation services, prescriptions for smoking cessation medication, recorded quit attempts and changes of smoking status. RESULTS: The majority (>70%) of smokers had recorded smoking cessation advice. This was consistently higher in those with SMI than the other cohorts of patients, although the gap greatly reduced in more recent years. Increases in smoking cessation advice over time were not accompanied by increases in recorded attempts to quit or changes of smoking status. Overall nicotine replacement therapy prescribing by general practitioners (GPs) was higher in those with SMI (10.1%) and depression (8.7%) than those without (5.9%), but a downward time trend was observed in all groups. Bupropion and varenicline prescribing was very low and lower for those with SMI. Few smokers (<5%) had referrals to stop smoking services, though this increased over time, but no significant differences were observed between those with and without mental health problems. CONCLUSIONS: There was no evidence of consistent inequalities in access to GP-delivered smoking cessation interventions for people with mental health conditions. Smoking cessation advice was widely reported as taking place in all groups. In order to address the widening gap in smoking prevalence in those with poor mental health compared with those without, the emphasis should be on addressing the quality of advice and support given

Sociodemographic inequalities in the management of depression in adults aged 55 and over:An analysis of English primary care data

We do not know how primary care treatment of depression varies by age across both psychotropic medication and psychological therapies. Cohort study including 19 710 people aged 55+ with GP recorded depression diagnoses and 26 276 people with recorded depression symptoms during the period 2009–2013, from 373 General Practices in The Health Improvement Network (THIN) database in England. Main outcomes were initiation of treatment with anti-depressants, anxiolytics, hypnotics, anti-psychotic drugs, referrals to psychological therapies within 6 months of onset. Treatment rates with antidepressants are high for those recorded with new depression diagnoses (87.1%) or symptoms of depression (58.7%). Treatment in those with depression diagnoses varies little by age. In those with depressive symptoms there was a J-shaped pattern with reduced antidepressant treatment in those in their 60s and 70s followed by increased treatment in the oldest age groups (85+ years), compared with those aged 55–59 years. Other psychotropic drug prescribing (hypnotics/anxiolytics, antipsychotics) all increase with increasing age. Recorded referrals for psychological therapies were low, and decreased steadily with increasing age, such that women aged 75–79 years with depression diagnoses had around six times lower odds of referral (OR 0.17, 95% CI 0.1–0.29) than those aged 55–59 years, and men aged 80–84 years had around seven times lower (OR 0.14, 95% CI 0.05–0.36). The oldest age groups with new depression diagnoses and symptoms have fewer recorded referrals to psychological therapies, and higher psychotropic drug treatment rates in primary care. This suggests potential inequalities in access to psychological therapies

Protein surface functionalisation as a general strategy for facilitating biomimetic mineralisation of ZIF-8

The durability of enzymes in harsh conditions can be enhanced by encapsulation within metal-organic frameworks (MOFs) via a process called biomimetic mineralisation. Herein we show that the surface charge and chemistry of a protein determines its ability to seed MOF growth. We demonstrate that chemical modification of amino acids on the protein surface is an effective method for systematically controlling biomimetic mineralisation by zeolitic imidazolate framework-8 (ZIF-8). Reaction of surface lysine residues with succinic (or acetic) anhydride facilitates biomimetic mineralisation by increasing the surface negative charge, whereas reaction of surface carboxylate moieties with ethylenediamine affords a more positively charged protein and hinders the process. Moreover, computational studies confirm that the surface electrostatic potential of a protein is a good indicator of its ability to induce biomimetic mineralisation. This study highlights the important role played by protein surface chemistry in encapsulation and outlines a general method for facilitating the biomimetic mineralisation of proteins

Prevalence of frailty in rural community-dwelling older adults in Kegalle district of Sri Lanka: a population-based cross-sectional study

OBJECTIVE: Our main objective was to describe the prevalence and associated sociodemographic factors of frailty and pre-frailty in rural community-dwelling older adults in Kegalle district of Sri Lanka. DESIGN: Community-based cross-sectional study. SETTING: The study was conducted in rural areas of Kegalle district in Sri Lanka. PARTICIPANTS: A total of 746 community-dwelling older adults aged ≥60 years were included in the study. RESULTS: The prevalence of frailty and pre-frailty in rural Kegalle district was 15.2% (95% CI 12.3% to 18.6%) and 48.5% (95% CI 43.8% to 53.2%), respectively. We found a strong association between age and both frailty and pre-frailty. There were strong associations between longest-held occupation and frailty and education level and pre-frailty. CONCLUSIONS: The prevalence of frailty in this rural Sri Lankan older population was high compared with high-income and upper middle-income countries. The profile of health and social care services in Sri Lanka needs to address frailty and its consequences

High‑Throughput Electron Diffraction Reveals a Hidden Novel Metal–Organic Framework for Electrocatalysis

AbstractMetal‐organic frameworks (MOFs) are known for their versatile combination of inorganic building units and organic linkers, which offers immense opportunities in a wide range of applications. However, many MOFs are typically synthesized as multiphasic polycrystalline powders, which are challenging for studies by X‐ray diffraction. Therefore, developing new structural characterization techniques is highly desired in order to accelerate discoveries of new materials. Here, we report a high‐throughput approach for structural analysis of MOF nano‐ and sub‐microcrystals by three‐dimensional electron diffraction (3DED). A new zeolitic‐imidazolate framework (ZIF), denoted ZIF‐EC1, was first discovered in a trace amount during the study of a known ZIF‐CO3‐1 material by 3DED. The structures of both ZIFs were solved and refined using 3DED data. ZIF‐EC1 has a dense 3D framework structure, which is built by linking mono‐ and bi‐nuclear Zn clusters and 2‐methylimidazolates (mIm−). With a composition of Zn3(mIm)5(OH), ZIF‐EC1 exhibits high N and Zn densities. We show that the N‐doped carbon material derived from ZIF‐EC1 is a promising electrocatalyst for oxygen reduction reaction (ORR). The discovery of this new MOF and its conversion to an efficient electrocatalyst highlights the power of 3DED in developing new materials and their applications

BMI upon discharge from hospital and its relationship with survival: an observational study utilising linked patient records

OBJECTIVE: Current advice for patients being discharged from hospital suggests a body mass index of 18.5 to 24 kgm(-2), although this aspirational target may often not be achieved. We examined the relationship between body mass index on discharge from hospital and subsequent mortality over a maximum follow-up of 3.8 years. DESIGN: We conducted a survival analysis using linked hospital records data with national hospital episode statistics and national death certification data. PARTICIPANTS & SETTING: The analysis included adult patients who were admitted to University Hospitals Birmingham NHS Foundation Trust for a period of over 24 h during 2011, excluding day cases and regular day case attenders. MAIN OUTCOME MEASURES: The relationship between body mass index and mortality at medium term was estimated separately in both men and women, after accounting for case-mix. RESULTS: For both males and females, the relationship between body mass index at discharge and the loge hazard of death was strongly non-linear (p = 0.0002 for females and p < 0.0001 for males) and predictive (both p < 0.0001). In all models, the optimal body mass index range associated with best survival was 25 to 35 kgm(-2), with a sharp increase in risk for lower body mass index. CONCLUSIONS: There was little evidence to support current aspirational body mass index targets in the discharge population. Hospitals should ensure adequate nutrition especially among those with a reduced body mass index

Effect of pulse-current-based protocols on the lithium dendrite formation and evolution in all-solid-state batteries

Understanding the cause of lithium dendrites formation and propagation is essential for developing practical all-solid-state batteries. Li dendrites are associated with mechanical stress accumulation and can cause cell failure at current densities below the threshold suggested by industry research (i.e., >5 mA/cm2). Here, we apply a MHz-pulse-current protocol to circumvent low-current cell failure for developing all-solid-state Li metal cells operating up to a current density of 6.5 mA/cm2. Additionally, we propose a mechanistic analysis of the experimental results to prove that lithium activity near solid-state electrolyte defect tips is critical for reliable cell cycling. It is demonstrated that when lithium is geometrically constrained and local current plating rates exceed the exchange current density, the electrolyte region close to the defect releases the accumulated elastic energy favouring fracturing. As the build-up of this critical activity requires a certain period, applying current pulses of shorter duration can thus improve the cycling performance of all-solid-solid-state lithium batteries.publishedVersio