The Long-Term Impacts of an Integrated Care Programme on Hospital Utilisation among Older Adults in the South of England: A Synthetic Control Study

Introduction: Reducing hospital use is often viewed as a possible positive consequence of introducing integrated care (IC). We investigated the impact of an IC programme in North East Hampshire and Farnham (NEHF), in southern England, on hospital utilisation among older adults over a 55 months period. Method: We used a Generalised Synthetic Control design to investigate the effect of implementing IC in NEHF between 2015 and 2020. For a range of hospital use outcomes, we estimated the trajectory that each would have followed in the absence of IC and compared it with the actual trajectory to estimate the potential impact of IC. Results: Three years into the programme, emergency admission rates started reducing in NEHF relative to its synthetic control, particularly those resulting in overnight hospital stays. By year 5 of the study overall emergency admission rates were 9.8% lower (95% confidence interval: –17.2% to –0.6%). We found no sustained difference in rates of emergency department (ED) visits, and average length of hospital stay was significantly higher from year 2. Conclusion: An IC programme in NEHF led to lower than estimated emergency admission rates; however, the interpretation of the impact of IC on admissions is complicated as lower rates did not appear until three years into the programme and the reliability of the synthetic control weakens over a long time horizon. There was no sustained change in ED visit rates

Relationship Between Image Quality and Bias in 3D Echocardiographic Measures: Data From the SABRE (Southall and Brent Revisited) Study

Background: Image‐quality (IQ) compromises left ventricle assessment by 3‐dimensional echocardiography (3DE). Sicker/frailer patients often have suboptimal IQ, and therefore observed associations may be biased by IQ. We investigated its effect in an observational study of older people and when IQ was modified experimentally in healthy volunteers. / Methods and Results: 3DE feasibility by IQ was assessed in 1294 individuals who attended the second wave of the Southall and Brent Revisited study and was compared with 2‐dimensional (2D)‐echocardiography feasibility in 147 individuals. Upon successful analysis, means of ejection fraction (3D‐EF) and global longitudinal strain (3D‐GLS) (plus 2D‐EF) were compared in individuals with poor versus good IQ. In 2 studies of healthy participants, 3DE‐IQ was impaired by (1) intentionally poor echocardiographic technique, and (2) use of a sheet of ultrasound‐attenuating material (neoprene rubber; 2–4 mm). The feasibility was 41% (529/1294) for 3DE versus 61% (89/147) for 2D‐EF, P<0.0001. Among acceptable images (n=529), good IQ by the 2015 American Society of Echocardiography/European Association of Cardiovascular Imaging criteria was 33.6% (178/529) and 71.3% (377/529) for 3D‐EF and 3D‐GLS, respectively. Individuals with poor IQ had lower 3D‐EF and 3D‐GLS (absolute) than those with good IQ (3D‐EF: 52.8±6.0% versus 55.7±5.7%, Mean‐Δ −2.9 [−3.9, 1.8]; 3D‐GLS: 18.6±3.2% versus 19.2±2.9%, Mean‐Δ −0.6 [−1.1, 0.0]). In 2 experimental models of poor IQ (n=36 for both), mean differences were (−2.6 to −3.2) for 3D‐EF and (−1.2 to −2.0) for 3D‐GLS. Similar findings were found for other 3DE left ventricle volumes and strain parameters. / Conclusions: 3DE parameters have low feasibility and values are systematically lower in individuals with poor IQ. Although 3D‐EF and 3D‐GLS have potential advantages over conventional echocardiography, further technical improvements are required to improve the utility of 3DE in clinical practice

Tacrolimus for the treatment of fistulas in patients with crohn’s disease: a randomized, placebo-controlled trial

AbstractBackground & Aims:This study determined the effectiveness of tacrolimus for the treatment of Crohn's disease fistulas.Methods:The study was a randomized, double-blind, placebo-controlled, multicenter clinical trial. Forty-eight patients with Crohn's disease and draining perianal or enterocutaneous fistulas were randomized to treatment with oral tacrolimus 0.2 mg · kg−1 · day−1 or placebo for 10 weeks. The primary outcome measure was fistula improvement as defined by closure of ≥50% of particular fistulas that were draining at baseline and maintenance of that closure for at least 4 weeks. A secondary outcome measure was fistula remission as defined by closure of all fistulas and maintenance of that closure for at least 4 weeks.Results:Forty-three percent of tacrolimus-treated patients had fistula improvement compared with 8% of placebo-treated patients (P = 0.004). Ten percent of tacrolimus-treated patients had fistula remission compared with 8% of placebo-treated patients (P = 0.86). Adverse events significantly associated with tacrolimus, including headache, increased serum creatinine level, insomnia, leg cramps, paresthesias, and tremor, were managed with dose reduction.Conclusions:Oral tacrolimus 0.2 mg · kg−1 · day−1 is effective for fistula improvement, but not fistula remission, in patients with perianal Crohn's disease. Adverse events associated with tacrolimus can be managed by dose reduction. Lower doses of tacrolimus should be evaluated

Community Management of Endemic Scabies in Remote Aboriginal Communities of Northern Australia: Low Treatment Uptake and High Ongoing Acquisition

Like many impoverished areas around the world, Aboriginal communities in Australia experience an unacceptably high burden of scabies, skin infections, and secondary complications. Young children are most at risk. Our study investigated scabies in a remote setting with very high rates of skin disease, a high level of household overcrowding, and limited infrastructure for sanitation and preventive health measures. We assessed uptake of scabies treatment and scabies acquisition following provision of treatment by a community-based skin program. In a household where scabies was present, we found that treatment with topical permethrin cream of all close contacts can significantly reduce a susceptible individual's risk of infection. Our findings also demonstrate the challenges of achieving a high level of treatment participation, with limited permethrin use observed among household contacts. This suggests an urgent need for a more practical treatment option. International efforts to reduce childhood morbidity and mortality have demonstrated the efficacy of numerous child health interventions but have also highlighted the deficits in their delivery and implementation. Experiences like this, where the effectiveness of a coordinated local program delivering an efficacious intervention is hampered by poor treatment uptake and ongoing transmission, are an important and timely message for researchers, program managers, and policy-makers

How many human proteoforms are there?

Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA- and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype

Lifetime risk of being diagnosed with, or dying from, prostate cancer by major ethnic group in England 2008-2010

Background In the UK, a man’s lifetime risk of being diagnosed with prostate cancer is 1 in 8. We calculated both the lifetime risk of being diagnosed with and dying from prostate cancer by major ethnic group. Methods Public Health England provided prostate cancer incidence and mortality data for England (2008–2010) by major ethnic group. Ethnicity and mortality data were incomplete, requiring various assumptions and adjustments before lifetime risk was calculated using DevCan (percent, range). Results The lifetime risk of being diagnosed with prostate cancer is approximately 1 in 8 (13.3 %, 13.2–15.0 %) for White men, 1 in 4 (29.3 %, 23.5–37.2 %) for Black men, and 1 in 13 (7.9 %, 6.3–10.5 %) for Asian men, whereas that of dying from prostate cancer is approximately 1 in 24 (4.2 %, 4.2–4.7 %) for White men, 1 in 12 (8.7 %, 7.6–10.6 %) for Black men, and 1 in 44 (2.3 %, 1.9–3.0 %) for Asian men. Conclusions In England, Black men are at twice the risk of being diagnosed with, and dying from, prostate cancer compared to White men. This is an important message to communicate to Black men. White, Black, and Asian men with a prostate cancer diagnosis are all as likely to die from the disease, independent of their ethnicity. Nonetheless, proportionally more Black men are dying from prostate cancer in England

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone