The quantitatively minor phospholipid phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] fulfils many cellular functions in the plasma membrane (PM), whereas its major synthetic precursor, phosphatidylinositol 4-phosphate (PI4P), has no assigned PM roles apart from PI(4,5)P2 synthesis. We used a combination of pharmacological and chemical genetic approaches to probe the function of PM PI4P, which was not required for the synthesis or functions of PI(4,5)P2. However, depletion of both lipids was required to prevent PM targeting of proteins that interact with acidic lipids, or activation of the transient receptor potential vanilloid 1 cation channel. Therefore, PI4P contributes to the pool of polyanionic lipids that define plasma membrane identity, and to some functions previously attributed specifically to PI(4,5)P2 that may be fulfilled by a more general polyanionic lipid requirement.

ObjectivesTo describe the rates for consulting a general practitioner (GP) for sequelae after acute covid-19 in patients admitted to hospital with covid-19 and those managed in the community, and to determine how the rates change over time for patients in the community and after vaccination for covid-19.DesignPopulation based study.Setting1392 general practices in England contributing to the Clinical Practice Research Datalink Aurum database.Participants456 002 patients with a diagnosis of covid-19 between 1 August 2020 and 14 February 2021 (44.7% men; median age 61 years), admitted to hospital within two weeks of diagnosis or managed in the community, and followed-up for a maximum of 9.2 months. A negative control group included individuals without covid-19 (n=38 511) and patients with influenza before the pandemic (n=21 803).Main outcome measuresComparison of rates for consulting a GP for new symptoms, diseases, prescriptions, and healthcare use in individuals admitted to hospital and those managed in the community, separately, before and after covid-19 infection, using Cox regression and negative binomial regression for healthcare use. The analysis was repeated for the negative control and influenza cohorts. In individuals in the community, outcomes were also described over time after a diagnosis of covid-19, and compared before and after vaccination for individuals who were symptomatic after covid-19 infection, using negative binomial regression.ResultsRelative to the negative control and influenza cohorts, patients in the community (n=437 943) had significantly higher GP consultation rates for multiple sequelae, and the most common were loss of smell or taste, or both (adjusted hazard ratio 5.28, 95% confidence interval 3.89 to 7.17, P<0.001); venous thromboembolism (3.35, 2.87 to 3.91, P<0.001); lung fibrosis (2.41, 1.37 to 4.25, P=0.002), and muscle pain (1.89, 1.63 to 2.20, P<0.001); and also for healthcare use after a diagnosis of covid-19 compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients in the community were joint pain (2.5%), anxiety (1.2%), and prescriptions for non-steroidal anti-inflammatory drugs (1.2%). Patients admitted to hospital (n=18 059) also had significantly higher GP consultation rates for multiple sequelae, most commonly for venous thromboembolism (16.21, 11.28 to 23.31, P<0.001), nausea (4.64, 2.24 to 9.21, P<0.001), prescriptions for paracetamol (3.68, 2.86 to 4.74, P<0.001), renal failure (3.42, 2.67 to 4.38, P<0.001), and healthcare use after a covid-19 diagnosis compared with 12 months before infection. For absolute proportions, the most common outcomes ≥4 weeks after a covid-19 diagnosis in patients admitted to hospital were venous thromboembolism (3.5%), joint pain (2.7%), and breathlessness (2.8%). In patients in the community, anxiety and depression, abdominal pain, diarrhoea, general pain, nausea, chest tightness, and tinnitus persisted throughout follow-up. GP consultation rates were reduced for all symptoms, prescriptions, and healthcare use, except for neuropathic pain, cognitive impairment, strong opiates, and paracetamol use in patients in the community after the first vaccination dose for covid-19 relative to before vaccination. GP consultation rates were also reduced for ischaemic heart disease, asthma, and gastro-oesophageal disease.ConclusionsGP consultation rates for sequelae after acute covid-19 infection differed between patients with covid-19 who were admitted to hospital and those managed in the community. For individuals in the community, rates of some sequelae decreased over time but those for others, such as anxiety and depression, persisted. Rates of some outcomes decreased after vaccination in this group.

Interstitial lung disease (ILD) is a collective term representing a diverse group of pulmonary fibrotic and inflammatory conditions. Due to the diversity of ILD conditions, paucity of guidance and updates to diagnostic criteria over time, it has been challenging to precisely determine ILD incidence and prevalence. This systematic review provides a synthesis of published data at a global level and highlights gaps in the current knowledge base. Medline and Embase databases were searched systematically for studies reporting incidence and prevalence of various ILDs. Randomised controlled trials, case reports and conference abstracts were excluded. 80 studies were included, the most described subgroup was autoimmune-related ILD, and the most studied conditions were rheumatoid arthritis (RA)-associated ILD, systemic sclerosis associated (SSc) ILD and idiopathic pulmonary fibrosis (IPF). The prevalence of IPF was mostly established using healthcare datasets, whereas the prevalence of autoimmune ILD tended to be reported in smaller autoimmune cohorts. The prevalence of IPF ranged from 7 to 1650 per 100 000 persons. Prevalence of SSc ILD and RA ILD ranged from 26.1% to 88.1% and 0.6% to 63.7%, respectively. Significant heterogeneity was observed in the reported incidence of various ILD subtypes. This review demonstrates the challenges in establishing trends over time across regions and highlights a need to standardise ILD diagnostic criteria.PROSPERO registration number: CRD42020203035.

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Background Cardiovascular disease is prevalent in idiopathic pulmonary fibrosis (IPF), yet the extent of left-sided heart failure (HF) burden, whether this has changed with time and whether HF impacts mortality risk in these patients are unknown. The aims of this study were therefore to determine the temporal trends in incidence and prevalence of left-sided HF in patients with IPF in England and compare these to published estimates in the general population and those with comparable chronic respiratory conditions such as chronic obstructive pulmonary disease (COPD), as well as determine the risk of all-cause and cause-specific mortality in patients with comorbid left-sided HF and IPF at population-level using electronic healthcare data. Methods Clinical Practice Research Datalink (CPRD) Aurum primary-care data linked to mortality and secondary-care data was used to identify IPF patients in England. Left-sided HF prevalence and incidence rates were calculated for each calendar year between 2010 and 2019, stratified by age and sex. Risk of all-cause, cardiovascular and IPF-specific mortality was calculated using multivariate Cox regression. Results From 40,577patients with an IPF code in CPRD Aurum, 25, 341 IPF patients met inclusion criteria. Left-sided HF prevalence decreased from 33.4% (95% CI 32.2–34.6) in 2010 to 20.9% (20.0–21.7) in 2019. Left-sided HF incidence rate per 100 person-years (95% CI) remained stable between 2010 and 2017 but decreased from 4.3 (3.9–4.8) in 2017 to 3.4 (3.0–3.9) in 2019. Throughout follow-up, prevalence and incidence were higher in men and with increasing age. Comorbid HF was associated with poorer survival (adjusted HR (95%CI) 1.08 (1.03–1.14) for all-cause mortality; 1.32 (1.09–1.59) for cardiovascular mortality). Conclusion Left-sided HF burden in IPF patients in England remains high, with incidence almost 4 times higher than in COPD, a comparable lung disease with similar cardiovascular risk factors. Comorbid left-sided HF is also a poor prognostic marker. More substantial reduction in left-sided HF prevalence than incidence suggests persistently high IPF mortality. Given rising IPF incidence in the UK, this calls for better management of comorbidities such as left-sided HF to help optimise IPF survival.

Objective To compare post-COVID-19 sequelae between hospitalised and non-hospitalised individuals Design Population-based cohort study Setting 1,383 general practices in England contributing to Clinical Practice Research Database Aurum Participants 46,687 COVID-19 cases diagnosed between 1st August to 17th October 2020 (45.4% male; mean age 40), either hospitalised within two weeks of diagnosis or non-hospitalised, and followed-up for a maximum of three months. Main outcome measures Event rates of new symptoms, diseases, prescriptions and healthcare utilisation in hospitalised and non-hospitalised individuals, with between-group comparison using Cox regression. Outcomes compared at 6 and 12 months prior to index date, equating to first UK wave and pre-pandemic. Non-hospitalised group outcomes stratified by age and sex. Results 45,272 of 46,687 people were non-hospitalised; 1,415 hospitalised. Hospitalised patients had higher rates of 13/26 symptoms and 11/19 diseases post-COVID-19 than the community group, received more prescriptions and utilised more healthcare. The largest differences were noted for rates per 100,000 person-weeks [95%CI] of breathlessness: 536 [432 to 663] v. 85 [77 to 93]; joint pain: 295 [221 to 392] v. 168 [158 to 179]; diabetes: 303 [225 to 416] v. 36 [32 to 42], hypertension: 244 [178 to 344] v. 47 [41 to 53]. Although low, rates of chest tightness, tinnitus and lung fibrosis were higher in the community group. 4.2% (1882/45,272) of the community group had a post-acute burden, most frequently reporting anxiety, breathlessness, chest pain and fatigue. In those non-hospitalised, age and sex differences existed in outcome rates. Healthcare utilisation in the community group increased 28.5% post-COVID-19 relative to pre-pandemic. Conclusions Post-COVID-19 sequelae differ between hospitalised and non-hospitalised individuals, with age and sex-specific differences in those non-hospitalised. Most COVID-19 cases managed in the community do not report ongoing issues to healthcare professionals. Post-COVID-19 follow-up and management strategies need to be tailored to specific groups.