Clinical Outcomes In People Research Articles

Measuring the impact of CFTR modulation on sweat chloride in cystic fibrosis: Rationale and design of the CHEC-SC study

BackgroundThe Characterizing CFTR Modulated Changes in Sweat Chloride and their Association with Clinical Outcomes (CHEC-SC) study is a large epidemiologic study designed to determine the relationship between sweat chloride response and clinical outcomes in people with cystic fibrosis (CF) on commercially approved CFTR modulators. A challenge to study feasibility was capturing sweat chloride measurements before modulator initiation. We tested the hypothesis that historic sweat chloride approximated contemporary pre-modulator values to estimate CFTR modulator-induced changes, allowing a single-visit study design. MethodsGOAL and PROSPECT were multi-center prospective studies of individuals initiating ivacaftor or lumacaftor-ivacaftor. At enrollment, pre-modulator sweat chloride was measured and historic results recorded. Post-modulator sweat chloride was measured at 1, 3 and 6 months. For this analysis, differences between historic and pre-modulator sweat chloride were estimated. CFTR modulator-induced sweat chloride mean changes were compared using historic and pre-modulator sweat chloride. ResultsPaired historic and pre-modulator sweat chloride (n=406 participants) revealed a non-significant mean change of -1.0 mmol/L (95% CI: -2.71, 0.66) over an average of 17.2 years. Calculating sweat response to ivacaftor or lumacaftor-ivacaftor using historic or pre-modulator values resulted in similar estimates of modulator response. Based on these results, the CHEC-SC study was designed with a single, post-modulator sweat chloride measurement. ConclusionsHistoric sweat chloride values provide a reliable estimate of pre-modulator sweat chloride for people starting on modulator therapy. The CHEC-SC study anticipates capturing approximately 5,000 sweat chloride values, providing an unprecedented understanding of sweat chloride across the CF population in the era of CFTR modulators.

Entering the era of highly effective modulator therapies.

Since the discovery of the gene responsible for cystic fibrosis (CF) in 1989, hopes have been pinned on a future with novel therapies tackling the basis of the disease rather than its symptoms. These have become a reality over the last decade with the development through to the clinic of CF transmembrane conductance regulator (CFTR) modulators. These are oral drugs which improve CFTR protein function through either increasing the time the channel pore is open (potentiators) or facilitating its trafficking through the cell to its location on the cell membrane (correctors). The first potentiator, ivacaftor, is now licensed and available clinically in many parts of the world. It is highly effective with impressive clinical impact in the lungs and gastrointestinal tract; longer-term data from patient registries show fewer exacerbations, a slower rate of lung function loss and reduced need for transplantation in patients receiving ivacaftor. However, as a single drug, it is suitable for only a small minority of patients. The commonest CFTR mutation, F508del, requires both correction and potentiation for clinical efficacy. Two dual-agent drugs (lumacaftor/ivacaftor and tezacaftor/ivacaftor) have progressed through to licensing, although their short term impact is more modest than that of ivacaftor; this is likely due to only partial correction of protein misfolding and trafficking. Most recently, triple compounds have been developed: two different corrector molecules (elexacaftor and tezacaftor) which, by addressing different regions in the misfolded F508del protein, more effectively improve trafficking. In addition to large improvements in clinical outcomes in people with two copies of F508del, the combination is sufficiently effective that it works in patients with only one copy of F508del and a second, nonmodulator responsive mutation. For the first time, we thus have a drug suitable for around 85% of people with CF. Even more gains are likely to be possible when these drugs can be used in younger children, although more sensitive outcome measures are needed for this age group. Special consideration is needed for people with very rare mutations; those with nonmodulatable mutation combinations will likely require gene or messenger RNA-based therapeutic approaches, many of which are being explored. Although this progress is hugely to be celebrated, we still have more work to do. The international collaboration between trials networks, pharma, patient organizations, registries, and people with CF is something we are all rightly proud of, but innovative trial design and implementation will be needed if we are to continue to build on this progress and further develop drugs for people with CF.

Impact of body composition on clinical outcomes in people with gastric cancer undergoing radical gastrectomy after neoadjuvant treatment

ObjectivesThe influence of body composition on clinical outcomes in individuals with gastric cancer (GC) undergoing radical gastrectomy after neoadjuvant treatment (NT) remains unclear. The purpose of this retrospective study was to investigate the association between body composition before NT or after NT and clinical outcomes in individuals with GC receiving multimodal treatments. MethodsThis retrospective study included individuals with GC who received NT followed by radical gastrectomy between January 2016 and December 2018. Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured by cross-sectional areas at the level of third lumbar vertebra based on single-slice computed tomography scan prior to NT and prior to the surgical operation. Sarcopenia, high VAT, and high SAT were defined using cutoff points of skeletal muscle index, visceral fat area, and subcutaneous fat area. Univariate and multivariate analyses were performed to evaluate risk factors of NT-related adverse events, postoperative complications and predictors of long-term survival. ResultsA total of 110 individuals with GC were enrolled in this study. Sarcopenia was present in 62.7% of them before NT and in 56.4% after NT. Sarcopenia before NT was associated with more NT-related adverse events (odds ratio, 2.901; 95% confidence interval [CI], 1.205–6.983; P = 0.018). High VAT after NT (≥106 cm2) was associated with an increasing incidence of postoperative complications (odds ratio, 4.261; 95% CI, 1.332–13.632; P = 0.015). No body-composition parameter was relevant to tumor pathologic response to NT. As for long-term survival, poor overall survival was associated with both low VAT before NT (<120 cm2; hazard ratio [HR], 2.542; 95% CI, 1.111–5.817; P = 0.027) and low SAT after NT (<99.5 cm2; HR, 2.743; 95% CI, 1.248–6.027; P = 0.012). Similarly, shorter disease-free survival was associated with low VAT before NT (<120 cm2; HR, 2.502; 95% CI, 1.222–5.124; P = 0.012) and low VAT after NT (<106 cm2; HR, 2.505; 95% CI, 1.172–5.358; P = 0.018). ConclusionsBody composition measured by computed tomography could predict NT-related adverse events, postoperative complications, and long-term survival in multimodal treatments for GC. More meaningfully, adipose-tissue status has significant prognostic value for individuals with advanced GC.

The Intersection Between HIV and COVID-19: Findings From the WHO Global Clinical Platform

Background: Evidence on the association between HIV infection and the risk of poor clinical outcomes in people with COVID-19 remains inconclusive. The World Health Organization (WHO) has established a Global Clinical Platform aimed to assess clinical features and risk factors for severe/fatal COVID-19 among individuals hospitalized with suspected or confirmed SARS-CoV-2 infection.Methods: Between January 2020-June 2021 anonymized individual-level clinical data from 338,566 patients hospitalized in 38 countries were reported to the WHO Clinical Platform using a standardized set of variables including demographics, vital signs, underlying conditions, laboratory values, therapeutics and medical care received, and clinical outcomes. Descriptive and regression analyses whether HIV status was a risk factor for severity at admission and in-hospital mortality among people hospitalized for COVID-19.Findings: Of 197,479 patients reporting HIV status, 8.6% (16,955) were living with HIV (PLHIV), and 94.6% (16,283) were from Africa. Among those, 37.1% were male, mean age was 45.5 years, 38.3% were admitted with severe or critical illness and 24.7% died in-hospital. Among 10,166 individuals with information about antiretroviral therapy (ART) status, 91.5% were on ART. When compared to those without HIV, PLHIV had 15% increased odds of severe/critical presentation (aOR=1.15, 95%CI 1.10–1.20) and 38% more likely to die in-hospital (aHR=1.38, 95%CI 1.34-1.41). Among PLHIV, being male, age 45-75 years, having chronic cardiac disease or hypertension increased the odds of severe/critical COVID-19; male sex, age>18 years, having diabetes, hypertension, malignancy, TB, or chronic kidney disease increased the risk of in-hospital mortality.Interpretation: In this sample of hospitalized people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was a significant independent risk factor for both severe/critical COVID-19 at admission and in-hospital mortality. These findings have informed the WHO COVID-19 Clinical Management Guidelines and SAGE recommendations around COVID-19 vaccination prioritization among vulnerable groups.Funding Information: None.Declaration of Interests: R.H. received funding from the Wellcome Trust, CIHR UKRI/MRC and ICODA. None of the other authors have any conflicts of interest to disclose.Ethics Approval Statement: The analysis plan25 was submitted to the WHO Ethical Review Committee which granted a waiver from ethical review clearance as this was passive, anonymized clinical surveillance. Ethical clearance was obtained, where necessary, by relevant institutional or national bodies.

P054 Clinical outcomes in people with cystic fibrosis treated with lumacaftor/ivacaftor in routine clinical practice in Sweden

P054 Clinical outcomes in people with cystic fibrosis treated with lumacaftor/ivacaftor in routine clinical practice in Sweden

Impact of adiposity on clinical outcomes in people living with a Fontan circulation

BackgroundTo assess the association between body composition and the risk of adverse outcomes in Fontan patients. MethodsParticipants from the Australian and New Zealand Fontan Registry with dual-energy X-ray absorptiometry scans were included. Appendicular lean mass (ALM), appendicular lean mass index (ALM divided by height squared; ALMI) and total body fat mass percentage (%BF) were calculated. ALMI and %BF z-scores were derived using age- and sex-matched reference ranges. The primary outcome was Fontan failure (death, transplantation, New York Heart Association functional class III/IV, protein-losing enteropathy, and plastic bronchitis) or moderate-or-severe ventricular dysfunction. Results144 patients were included. Mean %BF was 29% (SD 10) with 50% having increased adiposity. Mean ALMI z-score was −1.4 (SD 1.1); one third of patients had skeletal muscle deficiency (ALMI z-score < −1 and −2) and another third had Fontan-associated myopaenia (ALMI z-score < −2). Age and %BF were associated with the risk of the endpoint in univariable regression (age: HR 1.09 per year, 95% CI 1.02–1.17, p = 0.01; %BF: HR 1.08, 95% CI 1.01–1.17, p = 0.03). On multivariable regression, every 1% increase in %BF was associated with a 10% increased risk of reaching the clinical endpoint (HR 1.10, 95% CI 1.01–1.19; p = 0.03). ALM was not associated with the endpoint (HR 1.02 per kg, 95% CI 0.88–1.20, p = 0.77). ConclusionsIncreased adiposity is associated with higher risk for adverse outcomes. Prospective studies to assess lifestyle interventions to optimise body composition should be prioritised.

Respiratory muscle training for cystic fibrosis.

Cystic fibrosis is the most common autosomal recessive disease in white populations, and causes respiratory dysfunction in the majority of individuals. Numerous types of respiratory muscle training to improve respiratory function and health-related quality of life in people with cystic fibrosis have been reported in the literature. Hence a systematic review of the literature is needed to establish the effectiveness of respiratory muscle training (either inspiratory or expiratory muscle training) on clinical outcomes in cystic fibrosis. This is an update of a previously published review. To determine the effectiveness of respiratory muscle training on clinical outcomes in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials register comprising of references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of most recent search: 11 June 2020. A hand search of the Journal of Cystic Fibrosis and Pediatric Pulmonology was performed, along with an electronic search of online trial databases. Date of most recent search: 05 October2020. Randomised controlled studies comparing respiratory muscle training with a control group in people with cystic fibrosis. Review authors independently selected articles for inclusion, evaluated the methodological quality of the studies, and extracted data. Additional information was sought from trial authors where necessary. The quality of the evidence was assessed using the GRADE system. Authors identified 20studies, of which 10studies with 238participants met the review's inclusion criteria. There was wide variation in the methodological and written quality of the included studies. Four of the 10 included studies were published as abstracts only and lacked concise details, thus limiting the information available. Eight studies were parallel studies and two of a cross-over design. Respiratory muscle training interventions varied dramatically, with frequency, intensity and duration ranging from thrice weekly to twice daily, 20% to 80% of maximal effort, and 10 to 30 minutes, respectively. Participant numbers ranged from 11 to 39 participants in the included studies; five studies were in adults only, one in children only and four in a combination of children and adults. No differences between treatment and control were reported in the primary outcome of pulmonary function (forced expiratory volume in one second and forced vital capacity) or postural stability (very low-quality evidence). Although no change was reported in exercise capacity as assessed by the maximum rate of oxygen use and distance completed in a six minute walk test, a 10% improvement in exercise duration was found when working at 60% of maximal effort in one study (n = 20) (very low-quality evidence). In a further study (n = 18), when working at 80% of maximal effort, health-related quality of life improved in the mastery and emotion domains (very low-quality evidence). With regards to the review's secondary outcomes, one study (n = 11) found a change in intramural pressure, functional residual capacity and maximal inspiratory pressure following training (very low-quality evidence). Another study (n=36) reported improvements in maximal inspiratory pressure following training (P < 0.001) (very low-quality evidence). A further study (n = 22) reported that respiratory muscle endurance was longer in the training group (P < 0.01). No studies reported significant differences on any other secondary outcomes. Meta-analyses could not be performed due to a lack of consistency and insufficient detail in reported outcome measures. There is insufficient evidence to suggest whether this intervention is beneficial or not. Healthcare practitioners should consider the use of respiratory muscle training on a case-by-case basis. Further research of reputable methodological quality is needed to determine the effectiveness of respiratory muscle training in people with cystic fibrosis. Researchers should consider the following clinical outcomes in future studies; respiratory muscle function, pulmonary function, exercise capacity, hospital admissions, and health-related quality of life. Sensory-perceptual changes, such as respiratory effort sensation (e.g. rating of perceived breathlessness) and peripheral effort sensation (e.g. rating of perceived exertion) may also help to elucidate mechanisms underpinning the effectiveness of respiratory muscle training.

Clinical Outcomes in People with Difficult-to-Control Asthma Using Electronic Monitoring to Support Medication Adherence

Nonadherence in difficult-to-control asthma can be identified using 7-day FeNO suppression testing where patients take additional fluticasone via Diskus with an Inhaler Compliance Assessment (INCA) acoustic monitoring device attached, and self-measure FeNO at home. However, this is inconvenient for patients attending a tertiary center and limited by FeNO meter availability. It is not known if this approach alters clinical outcomes. To examine patient acceptability and the effectiveness of replacing usual combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy with a fluticasone/salmeterol Diskus 500+INCA for 28 days as the initial intervention, compared with the 7-day FeNO suppression test, and to explore clinical outcomes after INCA monitoring. A service evaluation of FeNO suppression testing was undertaken in clinical practice. Twenty-one of 23 subjects offered replacement of their usual ICS/LABA with fluticasone/salmeterol+INCA as the initial intervention accepted and completed 28 days of monitoring. Fourteen (66.6%) patients reduced their FeNO by >42% (FeNO suppressors), accompanied by improvements in forced expiratory volume in 1 second, Asthma Control Questionnaire, and blood eosinophils, similar to the 7-day test (n= 74). Twenty-two of 62 (35.5%) FeNO suppressors progressed to biological therapy, compared with 24 of 33 (72.7%) nonsuppressors (P= .0006). FeNO suppressors taking maintenance prednisolone (n= 13) who did not receive biological therapy reduced the median baseline dose from 10 to 3 mg, with further reductions limited by adrenal suppression. Replacing existing inhaled therapy with fluticasone/salmeterol+INCA for 28 days is acceptable to the majority of people with difficult-to-control asthma and identifies prior medication nonadherence. INCA monitoring coupled with clinical support potentially improves patient adherence and asthma control, preventing unnecessary progression to biological therapy.

Relationship between jumping to conclusions and clinical outcomes in people at clinical high-risk for psychosis

Psychosis is associated with a reasoning bias, which manifests as a tendency to 'jump to conclusions'. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes. In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A 'beads' task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point. There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ. In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.

Correlates of stigma for patients with cancer: a systematic review and meta-analysis.

The systematic review and meta-analysis was performed to summarize the available evidence and identify the correlates of cancer stigma. PubMed, EMBASE, Web of Science, the Cochrane Library, and PsycINFO were electronically searched to identify eligible studies about correlates of stigma for patients with cancer. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of included studies. A meta-analysis was performed using the statistical program R. Thirty-one studies involving a total of 7114 patients were included in the systematic review and meta-analysis. The results of the meta-analysis showed that cancer stigma shared positive associations with male gender, symptoms, depression, anxiety, body image loss, self-blame, social constraint, intrusive thoughts, and ambivalence over emotional expression, and negative associations with income, NK cell subsets, QOL, self-esteem, self-efficacy, cancer screening attendance, doctor's empathy, and medical satisfaction. The results of the descriptive analysis indicated that cancer stigma was positively associated with self-perception of aging, anger, internal attributions, stressful life events, self-perceived burden, and sleep dysfunction, while negatively associated with patient-provider communication and sleep quality. Healthcare staff should pay attention to the identified correlates of cancer stigma. The results of our research can inform the design of interventions to reduce stigma and to improve clinical outcomes in people with cancer.

Identification and prevalence of frailty in diabetes mellitus and association with clinical outcomes: a systematic review protocol

IntroductionDiabetes mellitus is common and growing in prevalence, and an increasing proportion of people with diabetes are living to older age. Frailty is, therefore, becoming an important concept in diabetes....

Do working practices of cancer nurse specialists improve clinical outcomes? Retrospective cohort analysis from the English National Lung Cancer Audit

BackgroundCancer nurse specialists are advanced practitioners who offer continuity of care and expert support for people diagnosed with specific cancers. Health Education England's Cancer Workforce Plan prioritises expansion of cancer nurse specialist numbers by 2021 as part of the Cancer Taskforce Strategy for England. ObjectiveTo assess whether working practices of advanced practice specialist nurses are associated with clinical outcomes for people with lung cancer. MethodsAdults with non-small cell lung cancer followed from 30 days post-diagnosis in English secondary care were obtained from the English National Lung Cancer Audit, 2007 to 2011. A national survey of lung cancer nurse specialists provided information on self-reported working practices. Mortality and unplanned admissions from 30 days to 12 months post diagnosis were respectively analysed using Cox and Poisson regression. Outcomes were assessed according to patients’ receipt of initial assessments by a lung cancer nurse specialist and according to trust-level reported working practices. Regression models were adjusted for individual sociodemographic and clinical characteristics, error adjusted for intracorrelations within regional cancer networks, and presented separately according to patients’ treatment pathways (surgery, chemotherapy, radiotherapy, or no anti-cancer therapy). ResultsData for 108,115 people with lung cancer were analysed and associations with mortality and unplanned admissions were infrequent. Among people receiving only radiotherapy, however, the hazard for death was 17% lower among those who received an assessment by a lung cancer nurse specialist, compared with no assessment (hazard ratio = 0.83, 95% confidence interval 0.73–0.94; p = 0.003). The hazard was also lower among those receiving surgery (hazard ratio = 0.91, 0.84–0.99; p = 0.028). Among those receiving radiotherapy, nurse specialists’ reported confidence within multidisciplinary team settings was associated with a lower risk of death (hazard ratio = 0.88, 0.78–1.00; p = 0.049) and a lower rate of unplanned cancer-related admissions (incidence rate ratio = 0.83, 0.73–0.95; p = 0.007). Lung cancer nurse specialist assessments before/at diagnosis, were associated with a 5% lower rate of unplanned admissions, compared to when assessments occurred after diagnosis. ConclusionThe contribution of nurse specialist working practices was occasionally associated with better outcomes for people with lung cancer. These were not limited to a single treatment pathway, but do indicate discrete relationships within pathways. Our study provides initial measures of overall lung cancer nurse specialist working practices at trusts, however, more detailed studies with longitudinal measurement of lung cancer nurse specialist-patient interaction are needed to better ascertain impacts on long-term patient outcomes. The findings highlight opportunities for potential improvement in effectiveness of service and care management.

Coronavirus disease 2019 (COVID-19) outcomes in HIV/AIDS patients: a systematic review.

ObjectivesThe aim of the study was to systematically review current studies reporting on clinical outcomes in people living with HIV (PLHIV) infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2).MethodsWe conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta‐analysis (PRISMA) guidelines. A comprehensive literature search was conducted in Global Health, SCOPUS, Medline and EMBASE using pertinent key words and Medical Subject Headings (MeSH) terms relating to coronavirus disease 2019 (COVID‐19) and HIV. A narrative synthesis was undertaken. Articles are summarized in relevant sections.ResultsTwo hundred and eighty‐five articles were identified after duplicates had been removed. After screening, eight studies were analysed, totalling 70 HIV‐infected patients (57 without AIDS and 13 with AIDS). Three themes were identified: (1) controlled HIV infection does not appear to result in poorer COVID‐19 outcomes, (2) more data are needed to determine COVID‐19 outcomes in patients with AIDS and (3) HIV‐infected patients presenting with COVID‐19 symptoms should be investigated for superinfections.ConclusionsOur findings suggest that PLHIV with well‐controlled disease are not at risk of poorer COVID‐19 disease outcomes than the general population. It is not clear whether those with poorly controlled HIV disease and AIDS have poorer outcomes. Superimposed bacterial pneumonia may be a risk factor for more severe COVID‐19 but further research is urgently needed to elucidate whether PLHIV are more at risk than the general population.

COVID-19 and fat embolism: a hypothesis to explain the severe clinical outcome in people with obesity.

As the number of confirmed cases of COVID-19 surges past 4.7 million globally and deaths surpass 315,000, clinicians and pathologists are untiringly working to comprehend the damage produced by the coronavirus through the body. They are understanding that, yet the lungs are massively deranged, COVID-19 infection can outspread to many organs including the blood vessels and heart, gut, brain, and kidneys [1]. A systemic therapeutic approach is necessary; we thus analyzed a global interpretation of multi-organ symptoms and signs to propose a new pathogenetic hypothesis, with potential drug therapy implications, in COVID-19 people with obesity. Recent studies point to obesity as a critical risk factor for being hospitalized with COVID-19 [2,3,4]. Indeed, a high prevalence of obesity has been observed in COVID-19 patients requiring invasive mechanical ventilation [5], a robust proxy of SARS-CoV2 severity. In patients under the age of 60, those with obesity were at almost double risk of being admitted to critical care when compared with normal-weight patients [6].

69-OR: Freestyle Libre System Use Is Associated with Reduction in Inpatient and Outpatient Emergency Acute Diabetes Events and All-Cause Hospitalizations in Patients with Type 2 Diabetes

Continuous glucose monitors (CGMs) improve glycemic control compared with self-monitoring of blood glucose. We aim to describe clinical outcomes in people with type 2 diabetes (T2D) who received FreeStyle Libre® system. IBM MarketScan™ Commercial Claims and Medicare Supplemental databases were used in this retrospective, observational analysis. MarketScan contains insurance billing claims for inpatient, outpatient, and pharmacy expenses. Cohort requirements included: de novo FreeStyle Libre system purchase in 2017 Q4-2018 Q2, diagnosis of T2D, ≥18 years old, fast- or short-acting insulin, and ≥6-months pre-CGM observation time. Primary outcome was acute diabetes events (ADE): hospitalization with hyper-/hypoglycemia as the primary diagnosis or outpatient emergency associated with a code of hyper-/hypoglycemia. Secondary outcome was all-cause hospitalizations. Andersen-Gill Cox regression compared event rates 6-months pre-/post-CGM. The cohort (n=1,244, age 53.6±9.7 years, 53.8% male) experienced a reduction in ADE from 0.158 to 0.077 events/patient-year (HR: 0.49 [0.34 0.69]; P:&amp;lt;0.001). Hospitalizations also reduced from 0.345 to 0.247 events/patient-year (HR: 0.72 [0.58 0.88]; P:0.002). After FreeStyle Libre system purchase, T2D patients had lower rates of ADE and all-cause hospitalizations. Disclosure R.M. Bergenstal: Consultant; Self; Ascensia Diabetes Care, Johnson &amp; Johnson. Other Relationship; Self; Abbott, Dexcom, Inc., Hygieia, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Onduo, Roche Diabetes Care, Sanofi, UnitedHealth Group. M.S.D. Kerr: Employee; Self; Abbott. G.J. Roberts: Employee; Self; Abbott. D. Souto: Employee; Self; Abbott. Y. Nabutovsky: Employee; Self; Abbott. I.B. Hirsch: Consultant; Self; Abbott, Bigfoot Biomedical, Roche Diabetes Care. Research Support; Self; Medtronic, Omnipod.

OP0155-HPR EFFECT OF THE DR. BART APPLICATION ON HEALTHCARE USE AND CLINICAL OUTCOMES IN PEOPLE WITH OSTEOARTHRITIS OF THE KNEE AND / OR HIP IN THE NETHERLANDS; A RANDOMIZED CONTROLLED TRIAL

Background:Self-management is of paramount importance in non-surgical treatment of knee and/or hip osteoarthritis(OA). Modern technologies offer the possibility to support self-management 24/7. We developed an e-self-management application (dr. Bart app) for people with knee and/or hip OA. A central element of the dr. Bart app is that the app proposes a selection of 72 preformulated goals to induce health behaviors based on the ‘tiny habits method’1Objectives:To evaluate the short-term effects of the use of the dr. Bart app, compared to usual care, on the number of secondary health care consultations and clinical outcomes in people with knee/hip OA in the Netherlands.Methods:A randomized controlled design involving participants ≥50 years with self-reported knee and/or hip OA, randomly allocated to the dr. Bart app or usual care. Participants were recruited from the community through advertisements in local newspapers and social media campaigns. In Figure 1 the theoretical framework of the dr. Bart app is presented. Participants received online questionnaires at baseline and after 3 and 6 months of follow-up. The primary outcome was the number of consultations in secondary health care due to OA in the knee/hip in the past six months. Secondary outcome measures were self-management behavior, pain, symptoms, functional limitations, physical activity, quality of life, and illness perceptions. Data were analyzed using negative binomial regression or linear mixed models, as appropriate, corrected for baseline, main OA-location (knee or hip), and interaction between treatment group and time.Figure 1.Theoretical framework of the dr. Bart app.Results:In total 427 eligible participants were allocated to either the dr. Bart group (n=214) or usual care (n=213). Mean age of the participants was 62.1 (SD 7.3) years, with the majority being female (72%) and having symptoms predominantly in their knee(s) (73%). Response rates for the follow-up questionnaires were 75.4% and 69.3% at 3 and 6 months, respectively. With respect to the number of consultations in secondary health care we found a non-significant incidence rate ratio (1.20 (95% CI: 0.67; 2.19)) between the dr. Bart app group and the usual care group. We found a positive overall treatment effect of the dr. Bart app on symptoms (2.6 (95% CI: 0.4; 4.9)), pain (3.5 (95% CI: 0.9; 6.0)) and, activities of daily living (2.9 (95% CI: 0.2; 5.6)), see Table 1. We found non-significant differences between groups for self-management behavior, physical activity, health-related quality of life and illness perceptions.Table 1.Overall treatment effect and treatment effects at 3 and 6 months of the dr. Bart app.MeasuresTreatment effects of dr. Bart appΔ3 months§ ∞(95 % CI)Δ6 months§ ∞(95 % CI)Δ overall§(95 % CI)Number of consultations in secondary health care †1.05 (0.55; 2.02)1.32 (0.89; 2.87)1.20 (0.67; 2.16)KOOS/HOOS- Symptoms1.5 (-1.2;4.1)2.6 (-0.4; 5.6)2.6 (0.4; 4.9)*- Pain3.1 (0.2; 5.9)*0.9 (-2.0; 3.8)3.5 (0.9; 6.0)*- Activities of daily living2.5 (-0.7; 5.7)0.9(-2.6; 4.4)2.9 (0.2; 5.6)*- Functioning in sport and recreation-1.7 (-6.4; 2.9)7.7 (2.7; 12.7)*1.9 (-2.0; 5.9)* Indicates p-value &lt; 0.05† Reported as incidence rate ratio§Adjusted for baseline value, treatment group and main OA-location (knee/hip)∞Adjusted for time, and interaction between treatment group and timeAbbreviations: KOOS; Knee Injury and Osteoarthritis Outcome Score; HOOS; Hip Disability and Osteoarthritis Outcome Score.Conclusion:The dr. Bart app did not reduce the number of secondary health care consultations compared to usual care. However, we found positive effects attributable to the dr. Bart app on pain, symptoms, activities of daily living and functioning in sport and recreation in people with knee/hip OA, suggesting that the dr. Bart app has potential to positively influence health in people with knee/hip OA.

Rural chronic disease research patterns in the United Kingdom, United States, Canada, Australia and New Zealand: a systematic integrative review

BackgroundPeople living in rural and remote communities commonly experience significant health disadvantages. Geographical barriers and reduced specialist and generalist services impact access to care when compared with metropolitan context. Innovative models of care have been developed for people living with chronic diseases in rural areas with the goal of overcoming these inequities. The aim of this paper was to describe the characteristics and outcomes of studies investigating innovative models of care for people living with chronic disease in rural areas of developed countries where a metropolitan comparator was included.MethodsAn integrative systematic review was undertaken. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was used to understand the empirical and theoretical data on clinical outcomes for people living with chronic disease in rural compared with metropolitan contexts and their models of care in Australia, New Zealand, United States, Canada and the United Kingdom.ResultsLiterature searching revealed 620 articles published in English between 1st January 2000 and 31st March 2019. One hundred sixty were included in the review including 68 from the United States, 59 from Australia and New Zealand (5), 21 from Canada and 11 from the United Kingdom and Ireland. 53% (84) focused on cardiovascular disease; 27% (43) diabetes mellitus; 8% (12) chronic obstructive pulmonary disease; and 13% (27) chronic kidney disease. Mortality was only reported in 10% (16) of studies and only 18% (29) reported data on Indigenous populations.ConclusionsThis integrated review reveals that the published literature on common chronic health issues pertaining to rural and remote populations is largely descriptive. Only a small number of publications focus on mortality and comparative health outcomes from health care models in both urban and non-urban populations. Innovative service models and telehealth are together well represented in the published literature but data on health outcomes is relatively sparse. There is significant scope for further directly comparative studies detailing the effect of service delivery models on the health outcomes of urban and rural populations. We believe that such data would further knowledge in this field and help to break the deadly synergy between increased rurality and poorer outcomes for people with chronic disease.

Perturbations in myocardial energy metabolism in the ischemic heart

As an organ that must continuously pump oxygenated blood throughout the body, the heart has an enormous metabolic demand, which is primarily met via oxidative metabolism of fatty acids and carbohydrates. Because of its high metabolic demand, during times of reduced oxygen supply such as ischemia, the heart becomes highly susceptible to injury, and if flow is not re-established, myocardial tissue is lost and can result in death (myocardial infarction). Of interest, both myocardial ischemia and reperfusion are associated with a number of perturbations in energy metabolism that contribute to the pathology of ischemic heart disease. This includes marked elevations in glycolysis to counteract the reduction in oxidative metabolism, whereas fatty acids predominate as the primary fuel source for residual oxidative metabolism. During the early stages of cardiac recovery after successful reperfusion of the ischemic heart, fatty acid oxidation rates also rapidly recover at the expense of low glucose oxidation rates. These metabolic perturbations increase myocardial acidosis due to glycolysis being uncoupled from glucose oxidation, which impairs cardiac efficiency. As such, therapeutic approaches to stimulate glucose oxidation or inhibit fatty acid oxidation have the potential to correct dysregulated myocardial energy metabolism during ischemia and reperfusion, which improves cardiac efficiency and may lead to improved clinical outcomes in people with ischemic heart disease. L

Effect of the dr. Bart application on healthcare use and clinical outcomes in people with osteoarthritis of the knee and/or hip in the Netherlands; a randomized controlled trial

To evaluate the short-term effects of use of the dr. Bart app, compared to usual care, on the number of secondary health care consultations and clinical outcomes in people with knee/hip OA in the Netherlands. A randomized controlled design involving participants ≥50 years with self-reported knee and/or hip OA recruited from the community. The number of secondary health care consultations (primary outcome) and secondary outcomes were assessed at baseline, 3 and 6 months via online questionnaires. Data were analyzed using longitudinal mixed models, corrected for baseline values. Due to the design of this study, blinding of participants and researchers was not possible. In total, 427 eligible participants were allocated to either the dr. Bart group (n=214) or usual care (n=213). We found no difference between groups in the number of secondary (i.e., orthopaedic surgeon, rheumatologist, or physician assistant) health care consultations (incidence rate ratio (IRR) 1.20 (95% CI: 0.67; 2.19)). We found positive treatment effects of the dr. Bart app on symptoms (2.6 (95% CI: 0.4; 4.9)), pain (3.5 (95% CI: 0.9; 6.0)), and activities of daily living (2.9 (95% CI: 0.2; 5.6)) on a 0-100 scale, higher score indicating less complaints, but not in any other secondary outcome. The dr. Bart app did not change the number of secondary health care consultations compared to usual care. However, we found small positive effects (not clinically relevant) on pain, symptoms, and activities of daily living in people with knee/hip OA. Dutch Trial Register (Trial Number NTR6693/NL6505) (https://www.trialregister.nl/trial/6505).

Prevalence and incidence of clinical outcomes in patients presenting to secondary mental health care with mood instability and sleep disturbance.

Mood instability and sleep disturbance are common symptoms in people with mental illness. Both features are clinically important and associated with poorer illness trajectories. We compared clinical outcomes in people presenting to secondary mental health care with mood instability and/or sleep disturbance with outcomes in people without either mood instability or sleep disturbance. Data were from electronic health records of 31,391 patients ages 16-65 years presenting to secondary mental health services between 2008 and 2016. Mood instability and sleep disturbance were identified using natural language processing. Prevalence of mood instability and sleep disturbance were estimated at baseline. Incidence rate ratios were estimates for clinical outcomes including psychiatric diagnoses, prescribed medication, and hospitalization within 2-years of presentation in persons with mood instability and/or sleep disturbance compared to individuals without either symptom. Mood instability was present in 9.58%, and sleep disturbance in 26.26% of patients within 1-month of presenting to secondary mental health services. Compared with individuals without either symptom, those with mood instability and sleep disturbance showed significantly increased incidence of prescription of any psychotropic medication (incidence rate ratios [IRR] = 7.04, 95% confidence intervals [CI] 6.53-7.59), and hospitalization (IRR = 5.32, 95% CI 5.32, 4.67-6.07) within 2-years of presentation. Incidence rates of most clinical outcomes were considerably increased among persons with both mood instability and sleep disturbance, relative to persons with only one symptom. Mood instability and sleep disturbance are present in a wide range of mental disorders, beyond those in which they are conventionally considered to be symptoms. They are associated with poor outcomes, particularly when they occur together. The poor prognosis associated with mood instability and sleep disorder may be, in part, because they are often treated as secondary symptoms. Mood instability and sleep disturbance need better recognition as clinical targets for treatment in their own right.