Recommendations for defining preventable HIV-related mortality for public health monitoring in the era of Getting to Zero: an expert consensus.

Getting to Zero is a commonly cited strategic aim to reduce mortality due to both HIV and avoidable deaths among people with HIV. However, no clear definitions are attached to these aims with regard to what constitutes HIV-related or preventable mortality, and their ambition is limited. This Position Paper presents consensus recommendations to define preventable HIV-related mortality for a pragmatic approach to public health monitoring by use of national HIV surveillance data. These recommendations were informed by a comprehensive literature review and agreed by 42 international experts, including clinicians, public health professionals, researchers, commissioners, and community representatives. By applying the recommendations to 2019 national HIV surveillance data from the UK, we show that 30% of deaths among people with HIV were HIV-related or possibly HIV-related, and at least 63% of these deaths were preventable or potentially preventable. The application of these recommendations by health authorities will ensure consistent monitoring of HIV elimination targets and allow for the identification of inequalities and areas for intervention.

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study.

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

International multicenter study comparing demographics, therapy and outcomes in bleeding from Mallory Weiss tears and peptic ulcers.

Background and study aims Mallory Weiss tears (MWTs) are relatively uncommon causes of upper gastrointestinal bleeding (UGIB), and patients are generally considered at low risk of poor outcome, although data are limited. There is uncertainty about use of endoscopic therapy. We aimed to describe and compare an international cohort of patients presenting with UGIB secondary to MWT and peptic ulcer bleeding (PUB). Patients and methods From an international dataset of patients undergoing endoscopy for acute UGIB at seven hospitals, we assessed patients with MWT bleeding, including the endoscopic stigmata and endoscopic therapy applied. We compared baseline parameters, rebleeding rate, and 30-day mortality between patients with MWT and PUB. Results A total of 3648 patients presented with UGIB, 125 of whom (3.4 %) had bleeding from a MWT. Those patients were younger (61 vs 69 years, P  < 0.0001) and more likely to be men (66 % vs 53 %, P  = 0.006) compared to the patients PUB. The most common endoscopic stigmata seen in MWTs were oozing blood (26 %) or clean base (26 %). Of the patients with MWT, 53 (42 %) received endoscopic therapy. Forty-eight of them (90 %) had epinephrine injections and 25 (48 %) had through-the-scope clips. The rebleeding rate was lower in MWT patients compared with PUB patients (4.9 % vs 12 %, P  = 0.016), but mortality was similar (5.7 vs 7.0 %, P  = 0.71). Conclusions Although patients presenting with MWT were younger, with a lower rebleeding rate, their mortality was similar to that of patients with PUB. Endoscopic therapy was applied to 42 % MWT patients, with epinephrine injection as the most common modality.

Linear Discriminant Analysis for Investigating Differences in Upper Body Movement Symmetry in Horses before/after Diagnostic Analgesia in Relation to Expert Judgement.

Diagnostic analgesia and lunging are parts of the equine lameness examination, aiding veterinarians in localizing the anatomical region(s) causing pain-related movement deficits. Expectation bias of visual assessment and complex movement asymmetry changes in lame horses on the lunge highlight the need to investigate data-driven approaches for optimally integrating quantitative gait data into veterinary decision-making to remove bias. A retrospective analysis was conducted with inertial sensor movement symmetry data before/after diagnostic analgesia relative to subjective judgement of efficacy of diagnostic analgesia in 53 horses. Horses were trotted on the straight and on the lunge. Linear discriminant analysis (LDA) applied to ten movement asymmetry features quantified the accuracy of classifying negative, partial and complete responses to diagnostic analgesia and investigated the influence of movement direction and surface type on the quality of the data-driven separation between diagnostic analgesia categories. The contribution of movement asymmetry features to decision-making was also studied. Leave-one-out classification accuracy varied considerably (38.3-57.4% for forelimb and 36.1-56.1% for hindlimb diagnostic analgesia). The highest inter-category distances (best separation) were found with the blocked limb on the inside of the circle, on hard ground for forelimb diagnostic analgesia and on soft ground for hindlimb diagnostic analgesia. These exercises deserve special attention when consulting quantitative gait data in lame horses. Head and pelvic upward movement and withers minimum differences were the features with the highest weighting within the first canonical LDA function across exercises and forelimb and hindlimb diagnostic analgesia. This highlights that movement changes after diagnostic analgesia affect the whole upper body. Classification accuracies based on quantitative movement asymmetry changes indicate considerable overlap between subjective diagnostic analgesia categories.

The use and feasibility of a CBT intervention.

BACKGROUND: Mental illness is common and disruptive in adolescents. However, only a small proportion receives treatment. Low intensity preventative interventions may reduce symptoms and increase access to treatment, but few are targeted at young people. A Cognitive Behaviour Therapy (CBT) based guided self-help programme has been adapted for use in secondary schools; it covers 7 distinct topics, each with an accompanying booklet and lesson plan. This study investigates its use and feasibility in this context and examines pupil and teacher attitudes. METHOD: Approximately 280 second year school pupils received two lessons on a single life-skills area. Attitudes toward each booklet and class were evaluated by questionnaire and results summarised using descriptive statistics. Qualitative data were gathered from teacher and pupil focus groups. RESULTS: 56.3% of pupils agreed the lesson was very interesting and 64.5% felt they learned something new and worthwhile. A minority felt motivated by the lesson (43.1%) or would recommend it to a friend (48.4%). The majority of pupils agreed they had developed life-skills; however these were not specific to the topic covered by their class. Content analysis of the focus groups identified four central themes - Acceptability, Guidance, Target Population and Changes - which largely reflected the quantitative results. CONCLUSION: Overall, the lessons and booklets were well received by pupils and teachers: the design and language were popular and it functioned well as a group activity with pupils happy to discuss the majority of issues. The intervention has the potential to be popular, affordable and effective approach to school-based mental health interventions.