Implementation of a “real-world” learning health system: Results from the evaluation of the Connected Health Cities programme

© 2020 The Authors. Learning Health Systems published by Wiley Periodicals, Inc. on behalf of the University of Michigan Background: The “learning health system” has been proposed to deliver better outcomes for patients and communities by analyzing routinely captured health information and feeding back results to clinical staff. This approach has been piloted in the Connected Health Cities (CHC) programme in four regions in the North of England. This paper presents the results of the evaluation of this program conducted between February and December 2018. Methods: Fifty nine semistructured interviews were completed with a mix of CHC programme staff and external partners who had contributed to the delivery of the CHC programme. Interviews were audio recorded and transcribed verbatim. This also included the review of project documentation including project reports and minutes of project group meetings, in addition to a short online survey that was completed by 31 members of CHC programme staff. Data were analyzed thematically. Results: Two overarching themes emerged through the thematic analysis of participant interview: (a) challenges in the implementation of learning health system pathways, and (b) benefits to the CHC approach for both staff and patients. In particular, time constraints in delivering an ambitious program of work, data quality, and accessibility, as well as the long-term sustainability of the CHC programme were noted as key challenges in implementing a LHS at scale. Conclusions: The findings from this evaluation provide valuable insight into creating learning health system at scale, including the potential benefits and likely challenges

Advances in Glucocorticoid-Induced Osteoporosis

Glucocorticoid-induced osteoporosis (GIOP) is one of the most important side effects of glucocorticoid use, as it leads to an increased risk of fractures. Recently, many published studies have focused on the cellular and molecular mechanisms of bone metabolism, the pathophysiology of GIOP, and the intervention options to prevent GIOP. In this review, recent advances in GIOP are summarized, particularly recent progress in our understanding of the mechanisms of GIOP resulting in improved insight that might result in the development of new treatment options in the near future

Building a recruitment database for asthma trials: a conceptual framework for the creation of the UK Database of Asthma Research Volunteers

Funded by Asthma UK as part of the Asthma UK Centre for Applied Research (AUK-AC-2012-01). In addition, BN, IS, CS and AS acknowledge the support of the Farr Institute, which is funded by the MRC and its consortium of funders

Osteopenia: A Diagnostic and Therapeutic Challenge

We discussed whether we are able to select a subgroup of patients with osteopenia having a high fracture risk, in which anti-osteoporotic drug treatment can be advocated. We concluded that in individuals in whom, based on clinical risk factors, a dual-energy x-ray absorptiometry (DXA) was performed in which osteopenia was diagnosed, anti-osteoporotic treatment should be prescribed in those patients with prevalent vertebral fractures, and in patients chronically using glucocorticoids, in a dosage of 7.5 mg per day or more. Although recent developments with regard to high-resolution imaging techniques (eg, peripheral quantitative computed tomography) seem to be promising, until now they do not provide substantial more reliable information than DXA in the prediction of fractures. We think that more data are urgently needed, since safe and effective drugs are available, but there is uncertainty to which patients with osteopenia these drugs should be prescribed

Can mutations in ELA2, neutrophil elastase expression or differential cell toxicity explain sulphasalazine-induced agranulocytosis?

BACKGROUND: Drug-induced agranulocytosis, a severe side effect marked by a deficit or absolute lack of granulocytic white blood cells, is a rare side-effect of the anti-inflammatory drug sulphasalazine. Mutations in the human neutrophil elastase gene (ELA2), causing increased intracellular concentration of this serine protease, inhibits neutrophil differentiation in severe congenital neutropenia (SCN). Since the clinical symptoms of agranulocytosis and SCN are similar, we hypothesized that it may origin from a common genetic variation in ELA2 or that sulphasalazine may affect human neutrophil elastase activity and protein expression. METHODS: We screened for genetic differences in ELA2 in DNA from 36 patients who had suffered from sulphasalazine-induced agranulocytosis, and compared them with 72 patients treated with sulphasalazine without blood reactions. We also performed in vitro studies of the blood cell lines HL60 and U937 after sulphasalazine exposure with respect to cell survival index, neutrophil elastase protein expression and activity. RESULTS: None of the mutations in ELA2, which previously have been reported to be associated with SCN, was found in this material. Protein expression of human neutrophil elastase in lymphoma U937 cells was not affected by treatment with concentrations equivalent to therapeutic doses. Cell survival of lymphoma U937 and promyelocytic leukemia HL-60 cells was not affected in this concentration range, but exhibited a decreased proliferative capacity with higher sulphasalazine concentrations. Interestingly the promyelocytic cells were more sensitive to sulphasalazine than the lymphoma cell line. CONCLUSION: Neutrophil elastase expression and ELA2 mutations do, however, not seem to be involved in the etilogy of sulphasalazine-induced agranulocytosis. Why sulphasalazine is more toxic to promyelocytes than to lymphocytes remains to be explained

Knowledge of actions of inhaled corticosteroids in patients who did not persist drug treatment early

Objective To evaluate, among new users of inhaled corticosteroids that did not persist treatment, knowledge of inhaled corticosteroids' actions and whether they were instructed on the use of their inhaler. Setting Fifteen community pharmacies in The Netherlands. Methods Patients were interviewed by telephone. Their general practitioners provided diagnostic information and automated dispensing records were retrieved. Main outcome measures Knowledge of patients about the actions of inhaled corticosteroids. Results 230 (80.1%) of 287 patients were willing to participate. The majority (79.1%) of 230 patients was not aware of the anti-inflammatory actions of inhaled corticosteroids. Most patients were instructed on the use of their inhaler, predominantly by their physician (53%) or pharmacy (35.2%). Conclusions Although most patients reported inhaler instruction by at least one health care provider, the majority was unaware of inhaled corticosteroids' actions. Physicians and pharmacists should reconsider the instructions they provide especially to patients who should continuously use inhaled corticosteroids

Short- and long-term glucocorticoid treatment enhances insulin signalling in human subcutaneous adipose tissue

BACKGROUND: Endogenous or exogenous glucocorticoid (GC) excess (Cushing's syndrome) is characterized by increased adiposity and insulin resistance. Although GCs cause global insulin resistance in vivo, we have previously shown that GCs are able to augment insulin action in human adipose tissue, contrasting with their action in skeletal muscle. Cushing's syndrome develops following chronic GC exposure and, in addition, is a state of hyperinsulinemia. OBJECTIVES: We have therefore compared the impact of short- (24 h) and long-term (7 days) GC administration on insulin signalling in differentiated human adipocytes in the presence of low or high concentrations of insulin. RESULTS: Both short- (24 h) and long-term (7 days) treatment of chub-s7 cells with dexamethasone (Dex) (0.5 μM) increased insulin-stimulated pTyr612IRS1 and pSer473akt/PKB, consistent with insulin sensitization. Chronic high-dose insulin treatment induced insulin resistance in chub-s7 cells. However, treatment with both high-dose insulin and Dex in combination still caused insulin sensitization. CONCLUSIONS: In this human subcutaneous adipocyte cell line, prolonged GC exposure, even in the presence of high insulin concentrations, is able to cause insulin sensitization. We suggest that this is an important mechanism driving adipogenesis and contributes to the obese phenotype of patients with Cushing's syndrome

Patients with femoral or distal forearm fracture in Germany: a prospective observational study on health care situation and outcome

BACKGROUND: Distal radius and proximal femoral fractures are typical injuries in later life, predominantly due to simple falls, but modulated by other relevant factors such as osteoporosis. Fracture incidence rates rise with age. Because of the growing proportion of elderly people in Western industrialized societies, the number of these fractures can be expected to increase further in the coming years, and with it the burden on healthcare resources. Our study therefore assessed the effects of these injuries on the health status of older people over time. The purpose of this paper is to describe the study method, clinical parameters of fracture patients during hospitalization, mortality up to one and a half years after discharge in relation to various factors such as type of fracture, and to describe changes in mobility and living situation. METHODS: Data were collected from all consecutive patients (no age limit) admitted to 423 hospitals throughout Germany with distal radius or femoral fractures (57% acute-care, femoral and forearm fractures; 43% rehabilitation, femoral fractures only) between January 2002 and September 2003. Polytrauma and coma patients were excluded. Demographic characteristics, exact fracture location, mobility and living situation, clinical and laboratory parameters were examined. Current health status was assessed in telephone interviews conducted on average 6–7 months after discharge. Where telephone contact could not be established, at least survival status (living/deceased/date of death) was determined. RESULTS: The study population consisted of 12,520 femoral fracture patients (86.8% hip fractures), average age 77.5 years, 76.5% female, and 2,031 forearm fracture patients, average age 67.6 years, 81.6% female. Women's average age was 6.6 (femoral fracture) to 10 years (forearm fracture) older than men's (p < 0.0001). Only 4.6% of femoral fracture patients experienced changes in their living situation post-discharge (53% because of the fracture event), although less than half of subjects who were able to walk without assistive devices prior to the fracture event (76.7%) could still do so at time of interview (34.9%). At time of interview, 1.5% of subjects were bed-ridden (0.2% before fracture). Forearm fracture patients reported no change in living situation at all. Of the femoral fracture patients 119 (0.95%), and of the forearm fracture patients 3 (0.15%) died during hospital stay. Post-discharge (follow-up one and a half years) 1,463 femoral fracture patients died (19.2% acute-care patients, 8.5% rehabilitation patients), but only 60 forearm fracture patients (3.0%). Ninety percent of femoral fracture deaths happened within the first year, approximately 66% within the first 6 months. More acute-care patients with a pertrochanteric fracture died within one year post-discharge (20.6%) than patients with a cervical fracture (16.1%). CONCLUSION: Mortality after proximal femoral fracture is still alarmingly high and highest after pertrochanteric fracture. Although at time of interview more than half of femoral fracture patients reported reduced mobility, most patients (96%) attempt to live at home. Since forearm fracture patients were on average 10 years younger than femoral fracture patients, forearm fractures may be a means of diagnosing an increased risk of later hip fractures