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al guidance deserve further investigation as predictors of cancer. Non-verbal cues that trigger gut feelings appear to be reliant on continuity of care and clinical experience; they tend to remain poorly recorded and are, therefore, inaccessible to researchers.

Pain management in acute otitis media (AOM) is often suboptimal, potentially leading to unnecessary discomfort, GP reconsultation, and antibiotic prescribing.

To assess the effectiveness of a GP-targeted educational intervention to improve pain management in children with AOM.

Pragmatic, cluster randomised controlled trial (RCT). GPs in 37 practices (intervention

= 19; control

= 18) across the Netherlands recruited 224 children with GP-confirmed AOM and ear pain (intervention

= 94; control

= 130) between February 2015 and May 2018.

GPs in practices allocated to the intervention group were trained (online and face-to-face) to discuss pain management with parents using an information leaflet, and prompted to prescribe weight-appropriate dosed paracetamol. Ibuprofen was additionally prescribed if pain control was still insufficient. GPs in the control group provided usual care.

Mean ear pain scores over the first 3 days were similar between groups (4.66 versus 4.36; adjusted mean difference = -0.05; 95% confidence intervals [CI] = -0.93 to 0.83), whereas analgesic use, in particular ibuprofen, was higher in the intervention group. The total number of antibiotic prescriptions during the 28-day follow-up was similar (mean rate 0.43 versus 0.47; adjusted rate ratio [aRR] 0.97; 95% CI = 0.68 to 1.38). Parents of children in the intervention group were more likely to reconsult for AOM-related complaints (mean rate 0.70 versus 0.41; aRR 1.73; 95% CI = 1.14 to 2.62).

An intervention aimed at improving pain management for AOM increases analgesic use, particularly ibuprofen, but does not provide symptomatic benefit. Atuzabrutinib GPs are advised to carefully weigh the potential benefits of ibuprofen against its possible harms.

An intervention aimed at improving pain management for AOM increases analgesic use, particularly ibuprofen, but does not provide symptomatic benefit. GPs are advised to carefully weigh the potential benefits of ibuprofen against its possible harms.

Sinusoidal dilatation and congestion (SDC) in liver biopsy may be obstructive (due to venous outflow impairment) or non-obstructive in nature. The significance of this finding in the post-liver transplant setting remains unexplored.

We herein retrospectively analysed all post-transplant liver biopsies showing SDC and examined histopathological features in detail. Association with transaminitis and concurrent graft rejection was assessed.

A total of 30 post-transplant liver biopsies from 27 patients showed SDC with atrophy of hepatocyte cords (SDC; incidence 7.4%). All patients had transaminitis. Most patients (n=22; 81.5%) were asymptomatic with deranged liver function tests (LFTs) detected during routine follow-up, raising clinical suspicion of graft rejection. SDC was non-obstructive in 19 (70.4%) and obstructive (due to sinusoidal obstruction syndrome (SOS)) in 8 (29.6%) cases. The incidence of SOS was 2%. SDC was mild, moderate and severe in 18 (66.7%), 7 (25.9%) and 2 (7.4%) cases, respectively. Perivenular and centrilobular sinusoidal fibrosis was seen in the obstructive SDC group (n=3, 11.1%). Concurrent graft rejection was present in 7 (25.9%) cases, of which acute cellular rejection comprised 5 (18.5%), and late acute rejection accounted for 2 cases (7.4%). Serum tacrolimus levels ranged from normal (n=14) to below and above normal (n=5 each). Modulation of immunosuppressive therapy led to normalisation of LFTs in one patient.

Obstructive and non-obstructive SDC in post-liver transplant patients presenting with transaminitis mimics graft rejection clinically and may represent a form of drug-induced liver injury. Liver biopsy plays a crucial role in the diagnosis.

Obstructive and non-obstructive SDC in post-liver transplant patients presenting with transaminitis mimics graft rejection clinically and may represent a form of drug-induced liver injury. Liver biopsy plays a crucial role in the diagnosis.

Primary mediastinal large B-cell lymphoma (PMBL) diagnosis can be challenging on needle biopsies. Robust techniques are needed to ensure diagnosis of this lymphoma which is highly sensitive to recently developed therapy protocols.

In this study, we sought to determine precise PMBL phenotype, compared with diffuse large B-cell lymphoma not otherwise specified, by combining immunohistochemistry with anti-MAL antibody and RNA in situ hybridisation (RNAscope) with specific MAL probes.

The overall MAL positivity level reached 93% (14/15) of cases of PMBL. Among the 15 cases enrolled in the study, 11 were undoubtedly positive for MAL immunostaining whereas 13 were positive by RNA in situ hybridisation. Interestingly, one case that was negative by in situ hybridisation turned out to be positive by immunohistochemistry.

Taken together, our results demonstrate that in situ detection of both

transcripts and protein are complementary and increase the sensitivity and specificity of PMBL diagnosis.

Taken together, our results demonstrate that in situ detection of both MAL transcripts and protein are complementary and increase the sensitivity and specificity of PMBL diagnosis.

Epilepsy mortality rates are rising. It is unknown whether rates are rising due to an increase in epilepsy prevalence, changes in epilepsy causes of death, increase in the lethality or epilepsy or failures of treatment. To address these questions, we compare epilepsy mortality rates in the USA with all-cause and all-neurological mortality for the years 1999 to 2017.

To determine changes in US epilepsy mortality rates versus all-cause mortality, and to evaluate changes in the leading causes of death in people with epilepsy.

Retrospective population-based multiple cause-of-death study.

Change in age-adjusted epilepsy mortality rates compared with mortality rates for all-cause and all-neurological mortality.

Changes in the leading causes of death in epilepsy.

From 1999 to 2017, epilepsy mortality rates in the USA increased 98.8%, from 5.83 per million in 1999 to 11.59 per million (95% CI 88.2%-110.0%), while all-cause mortality declined 16.4% from 8756.34 per million to 7319.17 per million (95% CI 16.

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