have any demonstrable effect on patient experience.

Colorectal cancer (CRC) diagnostics are challenging in primary care and reliable diagnostic aids are desired. Qualitative faecal immunochemical tests (FITs) have been used for suspected CRC in Sweden since the mid-2000s, but evidence regarding their effectiveness is scarce. Anaemia and thrombocytosis are both associated with CRC.

To evaluate the usefulness of qualitative FITs requested for symptomatic patients in primary care, alone and combined with findings of anaemia and thrombocytosis, in the diagnosis of CRC.

A population-based cohort study using electronic health records and data from the Swedish Cancer Register, covering five Swedish regions.

Patients aged ≥18 years in the five regions who had provided FITs requested by primary care practitioners from 1 January 2015 to 31 December 2015 were identified. FIT and blood-count data were registered and all CRC diagnoses made within 2 years were retrieved. Diagnostic measurements were calculated.

In total, 15 789 patients provided FITs (four different brands); of these patients, 304 were later diagnosed with CRC. Haemoglobin levels were available for 13 863 patients, and platelet counts for 10 973 patients. Calculated for the different FIT brands only, the sensitivities for CRC were 81.6%-100%; specificities 65.7%-79.5%; positive predictive values 4.7%-8.1%; and negative predictive values 99.5%-100%. Erastin manufacturer Calculated for the finding of either a positive FIT or anaemia, the sensitivities increased to 88.9-100%. Adding thrombocytosis did not further increase the diagnostic performance.

Qualitative FITs requested in primary care seem to be useful as rule-in tests for referral when CRC is suspected. A negative FIT and no anaemia indicate a low risk of CRC.

Qualitative FITs requested in primary care seem to be useful as rule-in tests for referral when CRC is suspected. A negative FIT and no anaemia indicate a low risk of CRC.

High-quality, personalised palliative care should be available to all, but timely recognition of end of life may be a barrier to end-of-life care for older people.

To investigate the timing of end-of-life recognition, palliative registration, and the recording of end-of-life preferences in primary care for people aged ≥75 years.

Retrospective cohort study using national primary care record data, covering 34% of GP practices in England.

ResearchOne data from electronic healthcare records (EHRs) of people aged ≥75 years who died in England between 1 January 2015 and 1 January 2016 were examined. Clinical codes relating to end-of-life recognition, palliative registration, and end-of-life preferences were extracted, and the number of months that elapsed between the code being entered and death taking place were calculated. The timing for each outcome and proportion of relevant EHRs were reported.

Death was recorded for a total of 13 149 people in ResearchOne data during the 1-year study window. Of those years. The findings suggest that older people’s deaths may not be anticipated by health professionals, compromising equitable access to palliative care.

Electronic health records (EHRs) are increasingly used for research; however, multicomponent outcome measures such as daily functioning cannot yet be readily extracted.

To evaluate whether an electronic frailty index based on routine primary care data can be used as a measure for daily functioning in research with community-dwelling older persons (aged ≥75 years).

Cohort study among participants of the Integrated Systemic Care for Older People (ISCOPE) trial (11 476 eligible; 7285 in observational cohort; 3141 in trial; over-representation of frail people).

At baseline (T0) and after 12 months (T12), daily functioning was measured with the Groningen Activities Restriction Scale (GARS, range 18-72). Electronic frailty index scores (range 0-1) at T0 and T12 were computed from the EHRs. The electronic frailty index (electronic Frailty Index – Utrecht) was tested for responsiveness and compared with the GARS as a gold standard for daily functioning.

In total, 1390 participants with complete EHR and follow-up data were selected (31.4% male; median age = 81 years, interquartile range = 78-85). The electronic frailty index increased with age, was higher for females, and lower for participants living with a partner. It was responsive after an acute major medical event; however, the correlation between the electronic frailty index and GARS at T0 and over time was limited.

Because the electronic frailty index does not reflect daily functioning, further research on new methods to measure daily functioning with routine care data (for example, other proxies) is needed before EHRs can be a useful data source for research with older persons.

Because the electronic frailty index does not reflect daily functioning, further research on new methods to measure daily functioning with routine care data (for example, other proxies) is needed before EHRs can be a useful data source for research with older persons.Besides cytoplasmic lipase-dependent adipocyte fat mobilization, the metabolic role of lysosomal acid lipase (LAL), highly expressed in adipocytes, is unclear. We show that the isolated adipocyte fraction, but not the total undigested adipose tissue (ATs), from obese patients has decreased LAL expression compared with that from nonobese people. Lentiviral-mediated LAL knockdown in the 3T3L1 mouse cell line to mimic the obese adipocytes condition did not affect lysosome density or autophagic flux, but it did increase triglyceride storage and disrupt endoplasmic reticulum cholesterol, as indicated by activated SREBP. Conversely, mice with adipose-specific LAL overexpression (Adpn-rtTA x TetO-hLAL) gained less weight and body fat than did control mice fed a high-fat diet, resulting in ameliorated glucose tolerance. Blood cholesterol level in the former was lower than that of control mice, although triglyceridemia in the two groups of mice was similar. The adipose-specific LAL-overexpressing mouse phenotype depends on the housing temperature and develops only under mild hypothermic stress (e.g., room temperature) but not at thermoneutrality (30°C), demonstrating the prominent contribution of brown AT (BAT) thermogenesis. LAL overexpression increased levels of BAT free cholesterol, decreased SREBP targets, and induced the expression of genes involved in initial steps of mitochondrial steroidogenesis, suggesting conversion of lysosome-derived cholesterol to pregnenolone. In conclusion, our study demonstrates that adipose LAL drives tissue-cholesterol homeostasis and affects BAT metabolism, suggesting beneficial LAL activation in anti-obesity approaches aimed at reactivating thermogenic energy expenditure.