Usual Clinical Care Research Articles

A preliminary study on the effects of the Peer-Led Self-Management (PLSM) program on self-efficacy, self-management, and physiological measures in older adults with diabetes: A block randomized controlled trial

This study explored the effects and feasibility of the peer-led self-management (PLSM) program for older adults with diabetes. Twenty-eight participants from 10 communities in southern Taiwan were randomly allocated to experimental and control groups. Those in the experimental group were enrolled in a 4-week PLSM program; those in the control group received a self-management manual and continued their usual clinical care. Improvement in outcomes (self-efficacy, self-management, physiological measures) over time in both groups were evaluated. After PLSM intervention, self-efficacy and self-management had improved; body weight and body mass index measures of the experimental group at post-test 1 and post-test 2 were significantly lower than those of the control group (p < .001); HbA1c, total cholesterol, and triglycerides at post-test 2 were also significantly better (p < .001; p = .03; p = .02). We discuss preliminary benefits and feasibility of the PLSM program.

Evaluating the Effectiveness of Diabetes Shared Medical Appointments (SMAs) as Implemented in Five Veterans Affairs Health Systems: a Multi-site Cluster Randomized Pragmatic Trial

ObjectiveTo examine whether diabetes shared medical appointments (SMAs) implemented as part of usual clinical practice in diverse health systems are more effective than usual care in improving and sustaining A1c improvements.Research Design and MethodsA multi-site cluster randomized pragmatic trial examining implementation in clinical practice of diabetes SMAs in five Veterans Affairs (VA) health systems was conducted from 2016 to 2020 among 1537 adults with type 2 diabetes and elevated A1cs. Eligible patients were randomly assigned to either: (1) invitation to participate in a series of SMAs totaling 8–9 h; or (2) continuation of usual care. Relative change in A1c (primary outcome) and in systolic blood pressure, insulin starts, statin starts, and anti-hypertensive medication classes (secondary outcomes) were measured as part of usual clinical care at baseline, at 6 months and at 12 months (~7 months after conclusion of the final SMA in four of five sites). We examined outcomes in three samples of SMA participants: all those scheduled for a SMA, those attending at least one SMA, and those attending at least half of SMAs.ResultsBaseline mean A1c was 9.0%. Participants scheduled for an SMA achieved A1c reductions 0.35% points greater than the control group between baseline and 6-months follow up (p = .001). Those who attended at least one SMA achieved reductions 0.42 % points greater (p < .001), and those who attended at least half of scheduled SMAs achieved reductions 0.53 % points greater (p < .001) than the control group. At 12-month follow-up, the three SMA analysis samples achieved reductions from baseline ranging from 0.16 % points (p = 0.12) to 0.29 % points (p = .06) greater than the control group.ConclusionsDiabetes SMAs as implemented in real-life diverse clinical practices improve glycemic control more than usual care immediately after the SMAs, but relative gains are not maintained. Our findings suggest the need for further study of whether a longer term SMA model or other follow-up strategies would sustain relative clinical improvements associated with this intervention.Trial RegistrationClinicalTrials.gov ID NCT02132676

Patients’ appraisals about a multicomponent intervention for fibromyalgia syndrome in primary care: a focus group study

ABSTRACT Purpose To assess fibromyalgia patients’ experiences and appraisals about a multidisciplinary intervention programme, in Catalonia’s primary care, regarding its format and contents, benefits, and health impact in the short and long term. Method Qualitative interpretative research design through hermeneutic phenomenology perspective. Two focus groups discussions were conducted in February and July 2020. The purposive heterogeneous sample included 19 fibromyalgia patients who attended a multicomponent programme. In addition, thematic analysis on the verbatims was performed. Results Findings were organized into five main domains with an explanatory theme each. Overall, the informants valued the programme as a positive experience due to its holistic approach, health benefits, suffering relief, group effect, and fibromyalgia legitimacy promotion. Detected improvable aspects focused on extending the timeframe, including family members as beneficiaries, deepening the thematic contents, and getting regular access to this healthcare service. Furthermore, the intervention was considered feasible to be incorporated into usual clinical care. Conclusion the programme fulfilled users’ expectations about results and procedure and showed promise as a treatment strategy to reinforce the usual practice. Our findings suggest a broad perspective on fibromyalgia patients’ suffering, which urges us to adjust the intervention programme to their real health needs.

Hospitalization risk in pediatric patients with bipolar disorder treated with lurasidone vs. other oral atypical antipsychotics: a real-world retrospective claims database study

Background Real-world evidence on atypical antipsychotic (AAP) use in pediatric bipolar disorder is limited. Objective To assess the risk of all-cause and psychiatric hospitalization among pediatric patients with bipolar disorder when treated with lurasidone versus other atypical antipsychotics (AAPs). Methods This retrospective cohort study used commercial claims data (January 1, 2011 to June 30, 2017) to identify pediatric patients (age ≤17 years) with bipolar disorder treated with oral atypical antipsychotics (N = 16,201). The date of the first claim for an AAP defined the index date, with pre- and post-index periods of 180 days. Each month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, or risperidone, no/minimal treatment, or other. The risk of all-cause and psychiatric hospitalizations (defined by a psychiatric diagnosis on the facility claim) was analyzed based on treatment in the current month, time-varying covariates (prior treatment-month classification, hospitalization in the prior month, emergency room visit in the prior month), and fixed covariates (age, gender, pervasive development disorder/mental retardation, disruptive behavior/conduct disorder, attention deficit hyperactivity disorder, depression, anxiety, adjustment disorder, obesity, diabetes, antidepressants, anxiolytics, other co-medication) using a marginal structural model. Results Treatment with aripiprazole (OR = 1.60, 95% CI: 1.08–2.36) and olanzapine (OR = 1.68, CI: 1.03–2.71) was associated with significantly higher odds of all-cause hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.03, CI: 0.69–1.54) or risperidone (OR = 1.02, CI: 0.68–1.53) was not. Similarly, treatment with aripiprazole (OR = 1.61, 95% CI: 1.08–2.38) and olanzapine (OR = 1.73, CI: 1.06–2.80) was associated with significantly higher odds of psychiatric hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.02, CI: 0.68–1.54) or risperidone (OR = 1.01, CI: 0.67–1.51) was not. Conclusion In usual clinical care, pediatric patients with bipolar disorder treated with lurasidone had a significantly lower risk of all-cause and psychiatric hospitalizations when compared to aripiprazole and olanzapine, but not quetiapine or risperidone.

A Remote Nutritional Intervention to Change the Dietary Habits of Patients Undergoing Ablation of Atrial Fibrillation: Randomized Controlled Trial.

BackgroundThe Prevention With Mediterranean Diet (PREDIMED) trial supported the effectiveness of a nutritional intervention conducted by a dietitian to prevent cardiovascular disease. However, the effect of a remote intervention to follow the Mediterranean diet has been less explored.ObjectiveThis study aims to assess the effectiveness of a remotely provided Mediterranean diet–based nutritional intervention in obtaining favorable dietary changes in the context of a secondary prevention trial of atrial fibrillation (AF).MethodsThe PREvention of recurrent arrhythmias with Mediterranean diet (PREDIMAR) study is a 2-year multicenter, randomized, controlled, single-blinded trial to assess the effect of the Mediterranean diet enriched with extra virgin olive oil (EVOO) on the prevention of atrial tachyarrhythmia recurrence after catheter ablation. Participants in sinus rhythm after ablation were randomly assigned to an intervention group (Mediterranean diet enriched with EVOO) or a control group (usual clinical care). The remote nutritional intervention included phone contacts (1 per 3 months) and web-based interventions with provision of dietary recommendations, and participants had access to a web page, a mobile app, and printed resources. The information is divided into 6 areas: Recommended foods, Menus, News and Online resources, Practical tips, Mediterranean diet classroom, and Your personal experience. At baseline and at 1-year and 2-year follow-up, the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire and a semiquantitative food frequency questionnaire were collected by a dietitian by phone.ResultsA total of 720 subjects were randomized (365 to the intervention group, 355 to the control group). Up to September 2020, 560 subjects completed the first year (560/574, retention rate 95.6%) and 304 completed the second year (304/322, retention rate 94.4%) of the intervention. After 24 months of follow-up, increased adherence to the Mediterranean diet was observed in both groups, but the improvement was significantly higher in the intervention group than in the control group (net between-group difference: 1.8 points in the MEDAS questionnaire (95% CI 1.4-2.2; P<.001). Compared with the control group, the Mediterranean diet intervention group showed a significant increase in the consumption of fruits (P<.001), olive oil (P<.001), whole grain cereals (P=.002), pulses (P<.001), nuts (P<.001), white fish (P<.001), fatty fish (P<.001), and white meat (P=.007), and a significant reduction in refined cereals (P<.001), red and processed meat (P<.001), and sweets (P<.001) at 2 years of intervention. In terms of nutrients, the intervention group significantly increased their intake of omega-3 (P<.001) and fiber (P<.001), and they decreased their intake of carbohydrates (P=.02) and saturated fatty acids (P<.001) compared with the control group.ConclusionsThe remote nutritional intervention using a website and phone calls seems to be effective in increasing adherence to the Mediterranean diet pattern among AF patients treated with catheter ablation.Trial RegistrationClinicalTrials.gov NCT03053843; https://www.clinicaltrials.gov/ct2/show/NCT03053843

Open-label, single-centre, cluster-randomised controlled trial to Evaluate the Potential Impact of Computerisedantimicrobial stewardship (EPIC) on the antimicrobial use after cardiovascular surgeries: EPIC trial study original protocol

IntroductionInappropriate antimicrobial use increases the prevalence of antimicrobial-resistant bacteria. Surgeons are reluctant to implement recommendations of guidelines in clinical practice. Antimicrobial stewardship (AMS) is effective in antimicrobial management, but it...

A study protocol for the development of a multivariable model predicting 6- and 12-month mortality for people with dementia living in residential aged care facilities (RACFs) in Australia

BackgroundFor residential aged care facility (RACF) residents with dementia, lack of prognostic guidance presents a significant challenge for end of life care planning. In an attempt to address this issue, models have been developed to assess mortality risk for people with advanced dementia, predominantly using long-term care minimum data set (MDS) information from the USA. A limitation of these models is that the information contained within the MDS used for model development was not collected for the purpose of identifying prognostic factors. The models developed using MDS data have had relatively modest ability to discriminate mortality risk and are difficult to apply outside the MDS setting. This study will aim to develop a model to estimate 6- and 12-month mortality risk for people with dementia from prognostic indicators recorded during usual clinical care provided in RACFs in Australia.MethodsA secondary analysis will be conducted for a cohort of people with dementia from RACFs participating in a cluster-randomized trial of a palliative care education intervention (IMPETUS-D). Ten prognostic indicator variables were identified based on a literature review of clinical features associated with increased mortality for people with dementia living in RACFs. Variables will be extracted from RACF files at baseline and mortality measured at 6 and 12 months after baseline data collection. A multivariable logistic regression model will be developed for 6- and 12-month mortality outcome measures using backwards elimination with a fractional polynomial approach for continuous variables. Internal validation will be undertaken using bootstrapping methods. Discrimination of the model for 6- and 12-month mortality will be presented as receiver operating curves with c statistics. Calibration curves will be presented comparing observed and predicted event rates for each decile of risk as well as flexible calibration curves derived using loess-based functions.DiscussionThe model developed in this study aims to improve clinical assessment of mortality risk for people with dementia living in RACFs in Australia. Further external validation in different populations will be required before the model could be developed into a tool to assist with clinical decision-making in the future.

A phase 2a randomised, double-blind, placebo-controlled, parallel-group, add-on clinical trial of ebselen (SPI-1005) as a novel treatment for mania or hypomania

RationaleLithium is an effective prophylactic and anti-manic treatment in bipolar disorder; however, its use is declining through perceived poor tolerance and toxicity. Lithium inhibits inositol monophosphatase (IMPase), a probable key therapeutic mechanism. The anti-inflammatory drug, ebselen, also inhibits IMPase and appears well-tolerated and safe.ObjectivesTo assess the efficacy of adjunctive ebselen in mania using the Young Mania Rating Scale (YMRS) (primary outcome) and the Altman Self-Rating Mania (ASRM) Scale and Clinical Global Impression-Severity Scale (CGI-S) among the secondary outcomes.MethodsRandomised, double-blind, placebo-controlled, parallel-group trial conducted between October 2017 and June 2019, at Oxford Health NHS Foundation Trust. Pharmacy-controlled randomisation was computer-generated, with full allocation concealment. In/outpatients (n = 68) aged 18–70, experiencing mania or hypomania, were assigned to 3 weeks ebselen (600 mg bd) (n = 33) or placebo (n = 35). Participants received usual clinical care and psychotropic medication.ResultsEbselen was numerically, but not statistically, superior to placebo in lowering scores on the YMRS (adjusted mean difference and 95% confidence interval, − 1.71 (− 5.34 to 1.91), p = 0.35) and ASRM (− 1.36 (− 3.75 to 1.17), p = 0.29). However, scores on the CGI-S were significantly lower at week 3 in ebselen-treated participants (adjusted mean difference, − 0.58 (− 1.14 to − 0.03), p = 0.04). A post hoc analysis excluding patients taking concomitant valproate treatment magnified the difference between ebselen and placebo on the YMRS. Adverse events were comparable between groups, and mild.ConclusionsEbselen merits further investigation where concomitant psychotropic medication is better controlled and participants taking valproate are excluded. If effective, ebselen’s superior tolerance and safety could make it a useful alternative to lithium.Trial registrationTrial Registry: www.clinicaltrials.gov, Identifier: NCT03013400.

RCT of Harti Hauora Tamariki: a holistic family-centred programme for child health and equity

Abstract Background In Aotearoa New Zealand (NZ), paediatric admissions (&amp; readmissions) with diseases of poverty are common &amp; this preventable burden is more severe for Māori (Indigenous) tamariki (children) &amp; their whānau (families). In response, the Harti Hauora Tamariki (HHT) programme was developed. This is family-centred multilevel programme that consists of: culturally safe engagement for whānau; comprehensive high-quality wellbeing screening; standardised evidence-based protocols for addressing identified need(s); &amp; navigation for and with whānau into services &amp; support. Methods In 2019, over 980 children (0-4 years) admitted to the acute paediatric ward at Waikato Hospital in Aotearoa NZ were randomised (with their whānau) to intervention (HHT) or usual clinical care. Measures of effectiveness include the level of unmet need identified; the impact of HHT on meeting those needs &amp; achieving improved outcomes for tamariki; qualitative assessment of how HHT led to the outcomes; &amp; whānau satisfaction with hospital care. The primary quantitative endpoint is relative readmission risk. Results Qualitative case studies demonstrate the importance of engagement with staff and services, and that the HHT programme can create a high trust environment where whānau feel safe to reveal their needs. Needs are common. Many needs identified that impact whānau wellbeing (such as food insecurity and lack or resources including carseats) are not recognised through standard hospital care. Quantitative primary and secondary outcome analyses are underway. Conclusions Enhanced health promotion and prevention measures are required to achieve health equity for children in Aotearoa NZ, and the whole of health system (including secondary hospital care) has the responsibility and ability to manage such measures. The HHT programme is whānau-centred, adaptable, evidence-based, and able to address the broader determinants of common paediatric illness as well as support wellbeing and whānau ora. Key messages A family-centred holistic screening programme, with culturally safe engagement, improves inpatient care and enhances the determinants of health. Indigenous leadership and commitment to Indigenous wellbeing and health equity facilitates effective evolution and programme improvement, within the framework of a randomised controlled trial.

Effect of Clinician Training in the Modular Approach to Therapy for Children vs Usual Care on Clinical Outcomes and Use of Empirically Supported Treatments

The Modular Approach to Therapy for Children (MATCH) was developed to address the comorbidities common among clinically referred youth, with beneficial outcomes shown in 2 US randomized clinical trials, where it outperformed both usual clinical care and single disorder-specific treatments. To determine whether MATCH training of clinicians would result in more use of empirically supported treatment (EST) and better clinical outcomes than usual care (UC) in the publicly funded, multidisciplinary context of New Zealand. This multisite, single-blind, computer-randomized clinical effectiveness trial compared MATCH with UC in child and adolescent mental health services in 5 regions of New Zealand. Recruitment occurred from March 2014 to July 2015, and a 3-month follow-up assessment was completed by May 2016. Clinicians at participating child and adolescent mental health services were randomized (1:1) to undertake training in MATCH or to deliver UC, and young people with anxiety, depression, trauma-related symptoms, or disruptive behavior seeking treatment at child and adolescent mental health services were randomized (1:1) to receive MATCH or UC. Participants and research assistants were blind to allocation. Data analysis was performed from April 2016 to July 2017. MATCH comprises EST components for flexible management of common mental health problems. UC includes case management and psychological therapies. Both can include pharmacotherapy. There were 3 primary outcomes: trajectory of change of clinical severity, as measured by weekly ratings on the Brief Problem Monitor (BPM); fidelity to EST content, as measured by audio recordings of therapy sessions coded using the Therapy Integrity in Evidence Based Interventions: Observational Coding System; and efficiency of service delivery, as measured by duration of therapy (days) and clinician time (minutes). The study included 65 clinicians (mean age, 38.7 years; range, 23.0-64.0 years; 54 female [83%]; MATCH, 32 clinicians; UC, 33 clinicians) and 206 young people (mean age, 11.2 years; range 7.0-14.0 years; 122 female [61%]; MATCH, 102 patients; UC, 104 patients). For the BPM total ratings for parents, there was a mean (SE) slope of -1.04 (0.14) (1-year change, -6.12) in the MATCH group vs -1.04 (0.10) (1-year change, -6.17) in the UC group (effect size, 0.00; 95% CI, -0.27 to 0.28; P = .96). For the BPM total for youths, the mean (SE) slope was -0.74 (0.15) (1-year change, -4.35) in the MATCH group vs -0.73 (0.10) (1-year change, -4.32) in the UC group (effect size, -0.02; 95% CI, -0.30 to 0.26; P = .97). Primary analyses (intention-to-treat) showed no difference in clinical outcomes or efficiency despite significantly higher fidelity to EST content in the MATCH group (58 coded sessions; mean [SD], 80.0% [20.0%]) than the UC group (51 coded sessions; mean [SD], 57.0% [32.0%]; F(1,108) = 23.0; P < .001). With regard to efficiency of service delivery, there were no differences in total face-to-face clinician time between the MATCH group (mean [SD], 806 [527] minutes) and the UC group (mean [SD], 677 [539] minutes) or the overall duration of therapy between the MATCH group (mean [SD], 167 [107 days]) and the UC group (mean [SD], 159 [107] days). MATCH significantly increased adherence to EST practices but did not improve outcomes or efficiency. The nonsuperiority of MATCH may be attributable to high levels of EST use in UC in New Zealand. Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614000297628.

The Effect of Cognitive Training in a Day Care Center in Patients with Early Alzheimer's Disease Dementia: A Retrospective Study.

ObjectiveThis study aimed to evaluate the effect of cognitive training programs on the progression of dementia in patients with early stage Alzheimer’s disease dementia (ADD) at the day care center. MethodsFrom January 2015 to December 2018, a total of 119 patients with early ADD were evaluated. All subjects were classified into two groups according to participate in cognitive training program in addition to usual standard clinical care. Changes in scores for minimental status examination-dementia screening (MMSE-DS) and clinical dementia rating-sum of boxes (CDR-SOB) during the 12 months were compared between two groups. Multivariable logistic regression analyses were performed. ResultsAs compared to case-subjects (n=43), the MMSE-DS and CDR-SOB scores were significantly worse at 12 months in the control-subjects (n=76). A statistically significant difference between the two groups was observed due to changes in MMSE-DS (p=0.012) and CDR-SOB (p<0.001) scores. Multivariable logistic regression analysis showed that the cognitive training program (odds ratio and 95% confidence interval: 0.225, 0.070–0.725) was independently associated with less progression of ADD. ConclusionThe cognitive training program was associated with benefits in maintaining cognitive function for patients with early-stage ADD that were receiving medical treatment.

Effectiveness of the Ready to Reduce Risk (3R) complex intervention for the primary prevention of cardiovascular disease: a pragmatic randomised controlled trial

BackgroundCardiovascular disease is responsible for 31% of all global deaths. Primary prevention strategies are needed to improve longer-term adherence to statins and healthy lifestyle behaviours to reduce risk in people at risk of cardiovascular disease.MethodsPragmatic randomised controlled trial recruited between May 2016 and March 2017 from primary care practices, England. Participants (n = 212) prescribed statins for primary prevention of cardiovascular disease with total cholesterol level ≥ 5 mmol/l were randomised: 105 to the intervention group and 107 to the control group, stratified by age and sex. The 3R intervention involved two facilitated, structured group education sessions focusing on medication adherence to statins, lifestyle behaviours and cardiovascular risk, with 44 weeks of medication reminders and motivational text messages and two supportive, coaching phone calls (at approximately 2 weeks and 6 months). The control group continued with usual clinical care. Both groups received a basic information leaflet. The primary outcome was medication adherence to statins objectively measured by a biochemical urine test. Self-reported adherence and practice prescription data provided additional measures. Secondary outcomes included cholesterol profile, blood pressure, anthropometric data, cardiovascular risk score, and self-reported lifestyle behaviours and psychological measures (health/medication beliefs, quality of life, health status). All outcomes were assessed at 12 months.ResultsBaseline adherence to statins was 47% (control) and 62% (intervention). No significant difference between the groups found for medication adherence to statins using either the urine test (OR 1.02, 95% CI 0.34 to 3.06, P = 0.968) or other measures. This may have been due to the higher than expected adherence levels at baseline. The adjusted mean difference between the groups (in favour of the intervention group) for diastolic blood pressure (− 4.28 mmHg (95% CI − 0.98 to − 1.58, P = 0.002)) and waist circumference (− 2.55 cm (95% CI − 4.55 to − 0.55, P = 0.012)). The intervention group also showed greater perceived control of treatment and more coherent understanding of the condition.ConclusionsThe 3R programme successfully led to longer-term improvements in important clinical lifestyle indicators but no improvement in medication adherence, raising questions about the suitability of such a broad, multiple risk factor approach for improving medication adherence for primary prevention of CVD.Trial registrationInternational Standard Randomized Controlled Trial Number (ISRCTN16863160), March 11, 2006.

Mobile Health Apps in Pediatric Obesity Treatment: Process Outcomes From a Feasibility Study of a Multicomponent Intervention

BackgroundMulticomponent family interventions underline current best practice in childhood obesity treatment. Mobile health (mHealth) adjuncts that address eating and physical activity behaviors have shown promise in clinical studies.ObjectiveThis study aimed to describe process methods for applying an mHealth intervention to reduce the rate of eating and monitor physical activity among children with obesity.MethodsThe study protocol was designed to incorporate 2 mHealth apps as an adjunct to usual care treatment for obesity. Children and adolescents (aged 9-16 years) with obesity (BMI ≥98th centile) were recruited in person from a weight management service at a tertiary health care center in the Republic of Ireland. Eligible participants and their parents received information leaflets, and informed consent and assent were signed. Participants completed 2 weeks of baseline testing, including behavioral and quality of life questionnaires, anthropometry, rate of eating by Mandolean, and physical activity level using a smart watch and the myBigO smartphone app. Thereafter, participants were randomized to the (1) intervention (usual clinical care+Mandolean training to reduce the rate of eating) or (2) control (usual clinical care) groups. Gender and age group (9.0-12.9 years and 13.0-16.9 years) stratifications were applied. At the end of a 4-week treatment period, participants repeated the 2-week testing period. Process evaluation measures included recruitment, study retention, fidelity parameters, acceptability, and user satisfaction.ResultsA total of 20 participants were enrolled in the study. A web-based randomization system assigned 8 participants to the intervention group and 12 participants to the control group. Attrition rates were higher among the participants in the intervention group (5/8, 63%) than those in the control group (3/12, 25%). Intervention participants undertook a median of 1.0 training meal using Mandolean (25th centile 0, 75th centile 9.3), which represented 19.2% of planned intervention exposure. Only 50% (9/18) of participants with smart watches logged physical activity data. Significant differences in psychosocial profile were observed at baseline between the groups. The Child Behavior Checklist (CBCL) mean total score was 71.7 (SD 3.1) in the intervention group vs 57.6 (SD 6.6) in the control group, t-test P<.001, and also different among those who completed the planned protocol compared with those who withdrew early (CBCL mean total score 59.0, SD 9.3, vs 67.9, SD 5.6, respectively; t-test P=.04).ConclusionsA high early attrition rate was a key barrier to full study implementation. Perceived task burden in combination with behavioral issues may have contributed to attrition. Low exposure to the experimental intervention was explained by poor acceptability of Mandolean as a home-based tool for treatment. Self-monitoring using myBigO and the smartwatch was acceptable among this cohort. Further technical and usability studies are needed to improve adherence in our patient group in the tertiary setting.

Duration of Targeted Therapy in Patients With Advanced Non–small-cell Lung Cancer Identified by Circulating Tumor DNA Analysis

BackgroundOutcomes of therapy targeting molecular driver alterations detected in advanced non–small-cell lung (NSCLC) using circulating tumor DNA (ctDNA) have not been widely reported in patients who are targeted therapy-naive. Patients and MethodsWe performed a multicenter retrospective review of patients with unresectable stage IIIB to IV NSCLC who received matched therapy after a targetable driver alteration was identified using a commercial ctDNA assay through usual clinical care. Eligible patients must not have received targeted therapy prior to ctDNA testing (prior chemotherapy or immunotherapy was permitted). Kaplan-Meier analysis was used to estimate the median duration of targeted therapy. Patients still on targeted therapy were censored at last follow-up. ResultsSeventy-six patients met inclusion criteria. The median age of diagnosis of NSCLC was 64.5 years (range, 31-87 years), 67% were female, 74% were never-smokers, and 97% had adenocarcinoma histology. Twenty-one (28%) patients received systemic treatment prior to targeted therapy, including chemotherapy (n = 17), immunotherapy (n = 5), and/or a biologic (n = 4). Thirty-three (43%) patients remain on targeted therapy at the time of data analysis. The median time on targeted therapy was similar to what has been reported for tissue-detected oncogenic driver mutations in the targeted therapy-naive setting. ConclusionsPatients with ctDNA-detected drivers had durable time on targeted therapy. These treatment outcomes data compliment previous studies that have shown enhanced targetable biomarker discovery rates and high tissue concordance of ctDNA testing when incorporated at initial diagnosis of NSCLC. Identification of NSCLC driver mutations using well-validated ctDNA assays can be used for clinical decision-making and targeted therapy assignment.

Pharmacogenetics of hypoglycemia associated with sulfonylurea therapy in usual clinical care.

Hypoglycemia is a common complication among type 2 diabetes mellitus (T2DM) patients receiving sulfonylurea therapy. The aim of this study was to determine if genetic contributions to sulfonylurea pharmacokinetics or pharmacodynamics substantially affect the risk of hypoglycemia in these patients. In a retrospective case-control study in European American patients with T2DM, we examined the potential association between CYP2C9 reduced function variants and sulfonylurea-related hypoglycemia. We also explored the relationship between sulfonylurea-related hypoglycemia and several candidate genetic variants previously reported to alter the response to sulfonylureas. We detected no evidence of association between CYP2C9 reduced function alleles or any of the candidate genetic variants and sulfonylurea-related hypoglycemia. In conclusion, we identified no clinically significant predictors of hypoglycemia among genes associated with sulfonylurea pharmacokinetics or pharmacodynamics.

Fertility Preservation in Cancer Patients During the Coronavirus (COVID-19) Pandemic

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also identified as Corona virus disease 19 (COVID-19), has recently produced a dramatic and widespread sanitary emergency. However, despite the necessity to assist a substantial number of affected patients, it is also essential to, at the same time, guarantee the usual clinical care, particularly to cancer patients, including fertility preservation (FP) strategies before the beginning of the anti-cancer treatments. The FP techniques for adult female patients include oocyte and embryo cryopreservation, which require both adequate ovarian reserve (OR) and controlled ovarian stimulation (COS) to promote multiple follicular growth. However, ovarian tissue cryopreservation is an additional FP practice suitable when an anti-cancer treatment is urgently required, whereas, for male patients, sperm cryopreservation is a simple and well-adopted procedure. Here, we focus on the current conditions in terms of agreements and rules of FP procedures during this COVID-19 pandemic to achieve and provide useful recommendations for the adoption of these techniques in patients with cancer.

O4.5. LONG TERM EFFECTS OF EARLY INTERVENTION SERVICES FOR FIRST EPISODE PSYCHOSIS: OUTCOMES OVER FIVE YEARS FROM THE RECOVERY AFTER A 1ST EPISODE OF SCHIZOPHRENIA-EARLY TREATMENT PROGRAM (RAISE-ETP)

BackgroundEarly intervention services (EIS) for first episode psychosis (FEP) are now implemented worldwide and these integrated and team-based treatment programs improve FEP outcomes while patients are participating. EIS service and treatment models provide care for limited periods followed by return to standard services. Cross sectional follow-up studies conducted after EIS participation ends have not been able to find advantages compared with standard care. The RAISE-ETP study was the first US-based, multi-center randomized clinical trial to compare an EIS, labeled NAVIGATE, to usual clinical care. Those who received NAVIGATE experienced significant improvement in symptoms and functioning compared to those who received usual care during the initial two-year treatment period. We now report clinical outcomes covering five years, a time frame that includes care after EIS participation ended.MethodsRAISE-ETP was a cluster randomized clinical trial conducted at 34 US sites; 17 sites provided NAVIGATE to 223 participants and 17 sites provided usual clinical care to 181 participants. NAVIGATE was available until the last randomized subject had the opportunity for two years of services. Participants were assessed every six months for up to 60 months by masked, centralized assessors utilizing live two-way video and with the Heinrichs-Carpenter Quality of Life Scale (QLS) and the Positive and Negative Syndrome Scale (PANSS).ResultsParticipants had a mean age of 23 years and the majority were male; (78% in NAVIGATE and 66% in usual care). The mean opportunity for NAVIGATE treatment was 33.8 (SD=5.1) months; the longest 44.4 months. Compared with usual care, NAVIGATE over 5 years was associated with a 13.14 unit QLS (p<0.001) and 7.73 unit PANSS (p<0.002) better improvement and 2.5 fewer inpatient days (p=0.02). NAVIGATE opportunity length did not affect QLS outcome; duration of untreated psychosis did not moderate differential QLS outcome.DiscussionRAISE-ETP provides compelling evidence of a substantial long-term benefit for FEP treatment with the NAVIGATE EIS compared with standard care.

P88 Intensive management in moderate established rheumatoid arthritis: the titrate trial

Abstract Background Intensive management (IM) using treat-to-target principles has been shown to be effective in many trials of early rheumatoid arthritis (RA) in patients with high disease activity levels. There is no trial evidence that this approach benefits patients with moderately active RA - a dominant group in clinics. We tested the hypothesis that IM increases remission rates in established moderate RA patients (DAS28-ESR 3.2-5.1) receiving stable conventional synthetic disease modifying drugs (csDMARDs) compared to standard care (SC). IM comprised of: (a)monthly clinical assessments; (b)treat-to-target titrated medication including biologics; (c)psycho-social support delivered by trained nurses and other practitioners in motivational interviewing techniques. Methods A multicentre individually randomised trial compared IM (using combination DMARDs, depot steroid, biologics in non-responders, alongside supportive care using motivational interviewing techniques from trained nurses) to standard care (SC) patients receiving their usual clinical care. The primary outcome was 12-months remission by DAS28-ESR. Secondary outcomes: alternative remission assessments, disability via the health assessment questionnaire (HAQ), pain, fatigue, erosive progression and harm. Multivariable logistic and linear regression compared treatment approaches under intention-to-treat with multiple imputation for missing data. Cost, quality-adjusted life years (QALYs) from the EQ-5D-5L instrument mapped to EQ5D-3L, and incremental cost-effectiveness ratios (ICERs) were calculated, for within trial period. Results 459 patients were screened and 335 randomised (168 IM; 167 SC); 303(90%) gave 12-month outcome measures. 139(83%) IM patients attended sessions. At 12 months IM significantly increased DAS28-ESR remissions compared to SC (32% vs 18%, p = 0.004) and other remission assessments. IM increased DAS28-ESR low disease activity (48% vs 32%, p = 0.005). Clinically important reductions in HAQ were seen in patients who achieved remission following IM (mean change at 12-months -0.40; 95% confidence intervals -0.57,-0.22), as well as improvements in both fatigue and pain. There was a minimal increase in erosive damage over 12 months in both groups. Serious adverse events (IM = 15 vs SC = 11) and other adverse events (114 IM,151 SC) were similar between groups. The base case ICER was £43,972 (€51,474) with a probability of being cost effective at £30,000/€35,000 of 0.17. The ICER fell to £29,363 (€24,384) after including patients’ personal costs and lost working time with a probability IM is cost-effective of 0.5 at UK willing to pay thresholds. This estimate was based on the historic prices of biologics and the probability is higher when current drug acquisition costs are applied. Conclusion IM by trained nurses in motivational interviewing techniques is clinically effective in moderate established RA, achieving more remission without increasing harm. It also gave clinically important improvement in pain and fatigue. There is a strong case to adopt this approach in routine practice as increasing remission rates may improve long-term outcomes, reduce future biologic prescribing and thereby improve long term cost-effectiveness. Disclosures E. Nikiphorou None.

GERiatric Screening in the treatment of elderly patients with Ovarian Carcinoma (GERSOC): study protocol for a pragmatic, cluster randomised controlled trial

BackgroundApproximately 40% of the newly diagnosed patients with advanced ovarian cancer are aged 70 years or older. Standard treatment for advanced disease consists of cytoreductive surgery and combination chemotherapy. In older patients, standard treatment is often withheld or prematurely stopped due to suspected frailty. It remains challenging to distinguish fit elderly patients who can endure standard therapy from frail patients who may benefit from an adapted treatment strategy. As a comprehensive geriatric assessment (CGA) can contribute to the identification of frail patients and improve tailored therapy in this population, screening tests were developed to select those who may benefit from a CGA. However, the use of these geriatric screening tests has rarely been compared with usual clinical care. The GERSOC-trial will evaluate whether geriatric screening in elderly patients with advanced-stage ovarian cancer improves treatment completion and quality of life.MethodsThis pragmatic, cluster randomised controlled trial will be conducted at a minimum of 20 hospitals in the Netherlands. Hospitals are randomly assigned to geriatric screening care (in which a geriatric screening comprised of the G8 questionnaire and the Timed Up and Go test is performed), or care as usual (in which current usual care is continued). A total of 320 patients aged ≥ 70 years with primary, advanced-stage ovarian carcinoma will be included. Patients considered fit on geriatric screening will receive standard treatment; patients who are considered unfit will be referred to a geriatrician for analysis and treatment advice. The primary outcome is the percentage difference in completed standard and adapted therapies between the two study arms. Secondary outcomes include quality of life, cost-effectiveness and survival.DiscussionThis trial aims to gather evidence for the use of geriatric screening in treatment decision-making in elderly patients with advanced ovarian cancer. If proven feasible, beneficial and cost-effective, geriatric screening may be implemented in routine clinical practice.Trial registrationNetherlands Trial Registry, ID: NL6745. Registered on 2 August 2017.

Randomized trial results of alerting primary clinicians to severe weight loss among older adults in the Low Indexes of Metabolism Intervention Trial part A

To test whether alerting clinicians to severe weight loss in older patients leads to higher dietitian visit rates, to higher body mass index (BMI) levels and, mainly, to lower annual death risk. The randomized controlled trial included patients aged ≥75 years, with BMI ≤23 kg/m2 that decreased ≥2 kg/m2 during the previous 2 years. All participants received usual care. Additionally, an email alert was sent only to clinicians of participants assigned to the email alert group. The follow-up period was 12 months. Among 706 participants (mean age 83 ± 6 years; mean baseline BMI 20.5 kg/m2 ), the BMI record was updated in 541 (77%) participants, and 123 participants died. Dietitian visits were reported for 22 patients (6%) in the email group (n = 362) and 14 patients (4%) in the control group (n = 344; OR 1.5, 95% CI 0.8-2.9; P = 0.24). Measured BMI were raised by a mean of 0.69 (95% CI 0.43-0.95) kg/m2 versus 0.79 (95% CI 0.48-1.1) kg/m2 (P = 0.63). A total of 77 patients (21%) died in the intervention group versus 47 (14%) in the control group (P = 0.008; number needed to harm = 13; 95% CI 7-43). In this trial, alerting clinical staff to severe weight loss in patients aged ≥75 years was not associated with higher visit rates to a dietitian or change in BMI, but was associated with a significantly higher death rate than usual clinical care. Geriatr Gerontol Int 2020; 20: 329-335.