Controlled Intervention Trial Research Articles

Patients living alone with dementia: course of health‐related quality of life over time and the impact of collaborative care in Germany

AbstractBackgroundLittle is known about the progression of patient‐reported outcomes in community‐dwelling people living alone with cognitive impairment (PLACI) and the efficacy and cost‐effectiveness of collaborative care models, initiating evidence‐based care and support for this vulnerable subgroup. Thus, this study aims to demonstrate the longitudinal course of patient‐reported outcomes and assess the efficacy and cost‐effectiveness of collaborative care in PLACI compared to those not living alone.MethodDelpHi‐MV (Dementia: Life‐ and person‐centred help in Mecklenburg‐Western Pomerania) is a German general practitioner‐based, randomized controlled intervention trial. The present analyses are based on longitudinal (24 months) data of 352 patients (≥70 years, community‐dwelling). Patient‐reported outcomes were assessed using the SF‐12, dividing patients' health‐related quality of life (HRQoL) into mental and physical parts. Descriptive statistics were used to demonstrate HRQoL longitudinally. The efficacy and cost‐effectiveness of the collaborative care model were assessed by multivariate regression models and by cost‐effectiveness‐acceptability curves, separately for PLACI vs those living not alone.ResultN = 178 (51%) patients were living alone and more likely female (73% vs 49%) and older (81 years vs 79 years) than those living not alone. Considering PLACI only, mental and physical HRQoL decreased over time (‐2.4 and ‐2.2) without collaborative care and increased (+1.4 and +2.5) with collaborative care. Multivariate models confirmed the significant positive impact of collaborative care on mental HRQoL (b = +3.1, p = 0.032) over time. The probability of cost‐effectiveness was 96% at a willingness‐to‐pay of 40,000€ /QALY for PLACI, much higher than in those living not alone (26%).ConclusionHRQoL would decrease over time in PLACI. Collaborative care could improve patients' everyday lives, especially mental health. Thus, when such models are implemented, health policy could gain the highest cost savings and effects on HRQoL in PLACI.

The need for standardised outcomes in pharmacist interventions in chronic kidney disease: a systematic review of randomised controlled trials

Abstract Introduction People living with chronic kidney disease (CKD) have a high prevalence of polypharmacy. Polypharmacy presents a significant burden and the risk of inappropriate prescribing in people with CKD is a cause for concern due to age-related changes associated with pharmacodynamics (e.g., increased sensitivity towards adverse drug events) and pharmacokinetics (e.g., reduced renal excretion)1. Strategies for the successful management of CKD include controlling cardiovascular risk factors, lifestyle modifications, and treating comorbidities. There is an ever-increasing role of pharmacists in managing CKD, from medication reviews to optimising risk factors2. However, currently, there is a lack of quality data on the impact of pharmacists in CKD management; this is partly due to the wide range of variable outcomes used in studies and a lack of standardised outcome reporting. Aim We aimed to explore the range of outcomes and measures used in pharmacist-led research in CKD that could be recommended for standardised use. Methods A systematic review of randomised controlled trials (RCTs) of interventions in a CKD population with significant pharmacist input was conducted. Searches were conducted in the following databases: MEDLINE, Scopus, and Web of Science. Databases were searched until January 2022; searches were re-run in February 2023. Data was extracted pertaining to clinical (e.g., mortality), economic (e.g., healthcare-associated costs), and humanistic (e.g., quality of life (QoL)) outcomes. Ethical approval was not required because this review is based exclusively on published literature. Results 38 reports of 32 RCTs were identified, with sample sizes of RCTs ranging from 24 to 32,917 participants. Most studies were conducted in the United States (16/32), whilst one was conducted in the United Kingdom. Of these, 12/32 (37.5%) were exclusively conducted in people on dialysis, six in kidney transplant recipients, 13 in those with non-dialysis dependent CKD, and one study in a mixed cohort. The interventions delivered by pharmacists were heterogenous and included medicine reconciliation, patient counselling, and dose adjustment. A wide range of outcomes were reported including blood pressure, CKD progression, and QoL. The most frequently reported outcome was blood pressure, which was used as an endpoint in 12/32 (37.5%) studies. There was significant heterogeneity in the measures and methods used for reported outcomes. For example, in 11/32 studies (34.4%) where medication adherence was assessed, five separate outcome measures were used: variations of the Morisky Medication Scale (6/11), pharmacy refill records (2/11), Basel Assessment of Adherence to Immunosuppressive Medication Scale (1/11), a comparison of the quantity of medications prescribed with those present in containers (1/11), and the endstage renal disease adherence questionnaire (1/11). Discussion/Conclusion Nephrology is well adept in the use of standardised core outcome sets (COS) (e.g., the Standardised Outcomes in Nephrology initiative)3, yet such COS may not be appropriate to more specialist interventions where different or more relevant outcomes may be needed. The plethora of outcome measures identified in our review suggests a better standardisation of reporting is needed to facilitate consolidation of pharmacy research in the area and further support for the role of the pharmacist in CKD management.

DAPagliflozin for the attenuation of albuminuria in Patients with hEaRt failure and type 2 diabetes (DAPPER study): a multicentre, randomised, open-label, parallel-group, standard treatment-controlled trial

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the urinary albumin-to-creatinine ratio (UACR) in patients with elevated levels of albuminuria in the presence or absence of heart failure (HF) or type 2 diabetes mellitus (T2D). However, these effects have not yet been reported in the presence of both HF and T2D. This lack of evidence prompted us to conduct a clinical trial on the effects of dapagliflozin on UACR in patients with HF and T2D. DAPPER is a multicentre, randomised, open-labeled, parallel-group, standard treatment-controlled trial that enrolled patients at 18 medical facilities in Japan. Eligible participants with both HF and T2D and aged between 20 and 85 years were randomly assigned to a dapagliflozin or control (anti-diabetic drugs other than SGLT 2 inhibitors) group with a 1:1 allocation. The primary outcome was changes in UACR from baseline after a two-year observation, and secondary endpoints were cardiovascular (CV) events and parameters related to HF. This trial was registered with the UMIN-CTR registry, UMIN000025102 and the Japan Registry of Clinical Trials, jRCTs051180135. Between 12 May 2017 and 31 March 2020, 294 patients were randomly assigned to the dapagliflozin group (n=146) or control group (n=148). The mean age of patients was 72.1 years and 29% were female. The mean glycated hemoglobin value was 6.9%, mean NT-proBNP was 429.1pg/mL, mean estimated GFR was 65.7mL/min/1.73m2, and median UACR was 25.0 (8.8-74.6) mg/g Cr in the dapagliflozin group and 25.6 (8.2-95.0) mg/g Cr in the control group. Of the 146 patients in the dapagliflozin group, 122 completed the study, and 107 (87.7%) were taking 5mg of dapagliflozin daily at the end of the observation period. The primary outcome did not significantly differ between the dapagliflozin and control groups. Among the secondary endpoints, the mean decrease in left ventricular end-diastolic dimensions as one of the echocardiographic parameters was larger in the dapagliflozin group than in the control group. The composite endpoint, defined as CV death or hospitalisation for CV events, hospitalisation for HF events, hospitalisation for all causes, and an additional change in prescriptions for heart failure in a two-year observation, was less frequent in the dapagliflozin group than in the control group. Although dapagliflozin at a dose of 5mg daily did not reduce urinary albumin excretion in patients with HF and T2D from that in the controls, our findings suggest that dapagliflozin decreased CV events and suppressed left ventricular remodeling. AstraZeneca KK, Ono Pharmaceutical Co., Ltd.

Solutions to Enhance Health with Alternative Treatments (SEHAT) protocol: a double-blinded randomised controlled trial for gut microbiota-targeted treatment of severe acute malnutrition using rice bran in ready-to-use therapeutic foods in Indonesia

IntroductionCurrent formulations of ready-to-use therapeutic foods (RUTFs) to treat severe acute malnutrition (SAM) in children focus on nutrient density and quantity. Less attention is given to foods targeting gut microbiota...

Cancer-Associated Venous Thromboembolism-Diagnostic and Therapeutic Considerations: An Update Based on the Revised AWMF S2k Guideline.

Patients with cancer are prone to develop venous thromboembolism (VTE) with negative impact on quality of life, morbidity, and mortality. Treatment of established VTE is often complex in patients with cancer. Treatment of cancer-associated VTE (CAT) basically comprises initial and maintenance treatment, for 3 to 6 months, secondary preventions, and treatment in special situations. Therapeutic anticoagulation is the treatment of choice in CAT. In addition to the efficacy and safety of low-molecular-weight heparin (LMWH) that had been recommended for decades, direct oral anti-factor Xa inhibitors, a subgroup of direct oral anticoagulants (DOACs), demonstrated their advantages along with the accompanying concerns in several randomized controlled treatment trials of CAT. The latest guidelines, such as the German AWMF-S2k Guideline "Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism," agree with each other on most aspects with respect to the treatment of CAT. Encompassing recent clinical studies, and meta-analyses, as well as the focus on some special management aspects of CAT, the objective of this review is to present a current overview and recommendations for the treatment of CAT.

Effect of wearing peripheral focus-out glasses on emmetropization in Chinese children aged 6–8 years: study protocol for a 2-year randomized controlled intervention trial

BackgroundMyopia is one of the most common eye diseases causing visual impairment and blindness, and the high prevalence in adolescents remains a major public health concern. Based on clinical studies using optical defocus to regulate ocular growth and refractive changes through visual feedback, we hypothesize that early wearing of peripheral myopic defocusing spectacles in children with high risk of myopia may slow the process of emmetropization and even prevent the onset of myopia by inducing more peripheral myopic defocus. The aim of this study is to investigate whether the wearing of peripheral focus-out glasses can be effective in delaying emmetropization in non-myopic children aged 6–8 years.MethodsThe study is a 2-year randomized controlled trial. A total of 160 subjects will be randomized into the experimental group or the control group. The experimental group will be fitted with direct emmetropia with focus-out glasses (DEFOG) to guide the emmetropization process. The control group will not receive any treatment and will serve as a blank control group. The primary aim is to determine whether non-myopic children wearing DEFOG lenses are superior to those who do not receive any intervention on the progression of cycloplegic objective refraction over 2 years.DiscussionThis is the first randomized controlled trial aiming at myopic prevention by non-invasive intervention in non-myopic children. This study aims to initially investigate whether wearing peripheral focus-out glasses can effectively delay the process of emmetropization in children aged 6–8 years with high risk of myopia, which might give potential clues for further exploration on early prevention of myopia.Trial registrationClinicalTrials.gov NCT05689567. Registered on 10 January 2023.

Identifying behaviour change techniques in 287 randomized controlled trials of audit and feedback interventions targeting practice change among healthcare professionals

BackgroundAudit and feedback (A&F) is among the most widely used implementation strategies, providing healthcare professionals with summaries of their practice performance to prompt behaviour change and optimize care. Wide variability in effectiveness of A&F has spurred efforts to explore why some A&F interventions are more effective than others. Unpacking the variability of the content of A&F interventions in terms of their component behaviours change techniques (BCTs) may help advance our understanding of how A&F works best. This study aimed to systematically specify BCTs in A&F interventions targeting healthcare professional practice change.MethodsWe conducted a directed content analysis of intervention descriptions in 287 randomized trials included in an ongoing Cochrane systematic review update of A&F interventions (searched up to June 2020). Three trained researchers identified and categorized BCTs in all trial arms (treatment & control/comparator) using the 93-item BCT Taxonomy version 1. The original BCT definitions and examples in the taxonomy were adapted to include A&F-specific decision rules and examples. Two additional BCTs (‘Education (unspecified)’ and ‘Feedback (unspecified)’) were added, such that 95 BCTs were considered for coding.ResultsIn total, 47/95 BCTs (49%) were identified across 360 treatment arms at least once (median = 5.0, IQR = 2.3, range = 1-29). The most common BCTs were ‘Feedback on behaviour’ (present 89% of the time; e.g. feedback on drug prescribing), ‘Instruction on how to perform the behaviour’ (71%; e.g. issuing a clinical guideline), ‘Social comparison’ (52%; e.g. feedback on performance of peers), ‘Credible source’ (41%; e.g. endorsements from respected professional body), and ‘Education (unspecified)’ (31%; e.g. giving a lecture to staff). A total of 130/287 (45%) control/comparator arms contained at least one BCT (median = 2.0, IQR = 3.0, range = 0–15 per arm), of which the most common were identical to those identified in treatment arms.ConclusionsA&F interventions to improve healthcare professional practice include a moderate range of BCTs, focusing predominantly on providing behavioural feedback, sharing guidelines, peer comparison data, education, and leveraging credible sources. We encourage the use of our A&F-specific list of BCTs to improve knowledge of what is being delivered in A&F interventions. Our study provides a basis for exploring which BCTs are associated with intervention effectiveness.Trial registrationsN/A.

Cognitive behavioral therapy for managing obesity in patients with chronic kidney disease: Study protocol for a randomized controlled trial

Obesity is one of the main risk factors for progression of chronic kidney disease (CKD). Weight loss interventions have limited efficacy in patients with pre-dialysis CKD. Our objective is to test the efficacy of a cognitive behavioral therapy program for obesity management in patients with CKD. We will conduct a randomized controlled intervention trial to evaluate the effects of cognitive behavioral therapy for obesity on weight loss, change in proteinuria, weight maintenance, quality of life, depression symptoms, and anxiety symptoms in patients with CKD. The duration of the intervention will be 16 weeks. The primary study outcomes will be body mass index (BMI) and proteinuria. CKD patients will be randomized into two groups: an intervention group with cognitive behavioral therapy, sessions with a dietitian and a kinesiologist, and a control group with sessions with a dietitian and a kinesiologist, without cognitive behavioral therapy. Study outcomes will be assessed at baseline, immediately after the 16-week intervention, 3 months after the end of the intervention, and 12 months after the end of the intervention. This study will be the first to evaluate the efficacy of cognitive behavioral therapy for obesity in patients with CKD. We expect that our results will contribute to new ways of non-pharmacological treatment of CKD. Clinical trial registrationClinicalTrials.Gov, NCT05927337.

Placebo analgesia in physical and psychological interventions: Systematic review and meta-analysis of three-armed trials.

The magnitude of placebo effects from physical and psychological 'sham' is unknown but could impact efficacy trials and treatment understanding. To quantify placebo effects, this systematic review of three-armed randomised controlled trials (RCTs) of physical and psychological interventions for pain compared outcomes in 'sham' control intervention and non-exposure arms. RCTs with treatment, 'sham' control intervention, and non-exposure groups were included, enrolling adults with any pain. A protocol was pre-registered (PROSPERO: CRD42023413324), and twelve databases searched from 2008 to July 2023. Trial methods and blinding were analysed descriptively and risk of bias assessed. Meta-analysis of pain measures at short-, medium- and long-term was performed with random-effects models of standardised mean differences (SMD).Studies were sub-grouped according to control intervention type. Seventeen RCTs were included. The average short-term placebo effect was small (0.21 SMD, 0.1-0.33 95% CI, p = 0.0002, 1440 participants). It showed no heterogeneity (Tau2 = 0.1, I2 = 11%, p = 0.3), preventing meta-regression analyses of effect modifiers. However, sub-group analyses revealed larger placebo effects in manual control interventions compared to disabled devices and miscellaneous control interventions. Overall, placebo analgesia accounted for 39% of treatments' short-term effectiveness. No placebo effects were found at medium-term (7 RCTs, 381 participants) or long-term follow-up (3 RCTs, 173 participants). The observed placebo analgesia has mechanistic and methodological implications, though its clinical importance may be limited. Control intervention design affects placebo effects, highlighting the importance of considering methodology in RCT interpretation. Review limitations include a small number of long-term studies and sample heterogeneity. This systematic review directly quantifies placebo effects from physical and psychological 'sham' control interventions and compares them to treatments' overall effectiveness. By doing so, the review enhances our understanding of placebo effects, their relative contribution in clinical trials, and their susceptibly to trial design. It poses further questions regarding the influence of blinding, participant expectations, and features of the therapeutic context. Overall, the insights provided by this review carry methodological significance and are important for the interpretation and synthesis of efficacy trials in this field.

Comparative effectiveness of multiple different treatment regimens for nonalcoholic fatty liver disease with type 2 diabetes mellitus: a systematic review and Bayesian network meta-analysis of randomised controlled trials

BackgroundNonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are closely related and mutually contribute to the disease’s development. There are many treatment options available to patients. We provide a comprehensive overview of the evidence on the treatment effects of several potential interventions for NAFLD with T2DM.MethodsThis systematic review and network meta-analysis included searches of PubMed, Embase, Cochrane Library, and Web of Science from inception to June 30, 2023, for randomised controlled trials of treatment of NAFLD with T2DM. We performed Bayesian network meta-analyses to summarise effect estimates of comparisons between interventions. We applied the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) frameworks to rate all comparative outcomes’ certainty in effect estimates, categorise interventions, and present the findings. This study was registered with PROSPERO, CRD42022342373.ResultsFour thousand three hundred and sixty-nine records were retrieved from the database and other methods, of which 24 records were eligible for studies enrolling 1589 participants. Eight clinical indicators and 14 interventions were finally in focus. Referring to the lower surface under the cumulative ranking curves (SUCRA) and the league matrix table, exenatide and liraglutide, which are also glucagon-like peptide-1 receptor agonists (GLP-1RAs), showed excellent potential to reduce liver fat content, control glycemia, reduce body weight, and improve liver function and insulin resistance. Exenatide was more effective in reducing glycated haemoglobin (HbA1c) (mean difference (MD) 0.32, 95%CI 0.12 to 0.52), lowering BMI (MD 0.81, 95%CI 0.18 to 1.45), and lowering alanine transaminase (ALT) (MD 10.96, 95%CI 5.27 to 16.66) compared to liraglutide. However, this evidence was assessed as low certainty. Omega-3 was the only intervention that did not have a tendency to lower HbA1c, with standard-treatment (STA-TRE) as reference (MD − 0.17, 95%CI − 0.42 to 0.07). Glimepiride is the only intervention that causes an increase in ALT levels, with standard-treatment (STA-TRE) as reference (MD − 11.72, 95%CI − 17.82 to − 5.57). Based on the available evidence, the treatment effects of pioglitazone, dapagliflozin, and liraglutide have a high degree of confidence.ConclusionsThe high confidence mandates the confident application of these findings as guides for clinical practice. Dapagliflozin and pioglitazone are used for glycaemic control in patients with NAFLD combined with T2DM, and liraglutide is used for weight loss therapy in patients with abdominal obesity. The available evidence does not demonstrate the credibility of the effectiveness of other interventions in reducing liver fat content, visceral fat area, ALT, and insulin resistance. Future studies should focus on the clinical application of GLP-1Ras and the long-term prognosis of patients.

A brief mind-body intervention to reduce pain and anxiety during prostate needle biopsy: a clinically integrated randomized controlled trial with 2-staged consent

ObjectivesMany patients experience pain, anxiety, and discomfort with prostate biopsy, which may discourage enrollment in active surveillance programs or follow-up biopsy. Guided meditation can significantly reduce pain and anxiety during percutaneous biopsy. We sought to evaluate the effectiveness of a brief mind-body intervention on patient-reported outcomes after prostate biopsy. Methods and materialsWe performed a clinically-integrated randomized controlled trial of a brief mind-body intervention during biopsy compared to usual care at a single tertiary care center from 2018 to 2022. All patients offered transrectal ultrasound-guided prostate biopsy in the clinic with local anesthesia were eligible for enrollment. This clinically integrated trial was conducted simultaneously with a randomized controlled trial of 1-stage and 2-stage consent. The primary outcome was patient-reported pain, anxiety, discomfort, and tolerability on a visual-analog scale (0–10). A 15% improvement was prespecified as clinically relevant. We compared the proportion of men in each arm reporting a severe score (7–10) on any of the 4 scales using Fisher's exact test and then compared means for each scale separately using ANCOVA with randomization stratum (first vs. prior biopsy) as a covariate. ResultsOf 263 eligible patients, 238 enrolled (119 per arm). One hundred seventy-two (72%) enrolled with 2-stage consent. A total of 37/94 (39%) and 38/102 (37%) patients randomized to usual care and intervention, respectively, reported severe scores in any of the 4 domains, a difference of 2.1% (95% confidence interval [CI] -13, 17%, P = 0.8). There was no evidence of a difference in mean postbiopsy anxiety (P = 0.3), discomfort (P = 0.09), pain (P = 0.4) or tolerability scores (P = 0.2). ConclusionsA clinically meaningful benefit for this brief mind-body intervention during prostate biopsy is unlikely. Robust patient enrollment is feasible using 2-stage consent.

Treatment effect of respiratory therapy with intermittent hypoxic-hyperoxic training (IHHT) on functional capacity in patients with post COVID19 conditions: a controlled treatment trial

Abstract Introduction COVID-19 can cause long-term lung and systemic damage that will lead to increasing numbers of patients disabled by reduced functional capacity. Intermittent hypoxia-hyperoxia training (IHHT) is a respiratory therapeutic concept which has been suggested to improve exercise performance via controlled hypoxic conditioning. The purpose of the present study is to investigate the therapeutic effect of IHHT on the recovery process during inpatient rehabilitation in post-COVID conditions. Methods A prospective, single-center, randomized controlled trial was conducted in 145 (37 men) patients with post COVID19 conditions aged 27-84 years, who were admitted to a hospitalized rehabilitation program (duration 27±5 days). Patients were 1:1 allocated to the standard rehabilitation program or IHHT on top of standard rehabilitation. The patients in IHHT group attended regular (alternate days) treatments of hypoxia-hyperoxia breathing sessions (10–12% O2 hypoxia breathing followed by 30-35% O2 hyperoxia breathing in 6-8 cycles for a total of 45 min). The primary endpoint of the trial was improvement in walking distance in a six-minute walk test (6MWT) between groups. Further endpoints of functional testing included stair climbing test (SCT), patient global assessment, fatigue assessment scale (FAS) and Quality of life (QoL) assessed by EQ5-D analog scale. Subjective perceived health was assessed by Median Corona Recovery Score (MCRS). Results The IHHT group demonstrated in comparison to controls a significant improved primary endpoint (6MWT difference, IHHT group vs controls: 91.7 vs. 32.5m, P<0.001), improved stair climbing (SCT -1.9 vs. -0.5 sek, P<0.001), improved QoL (EQ5-D analog scale change 31.3 vs. 2.9, P<0.001), improved fatigue (FAS -8.9 vs. 3.6, P<0.001) and improved perceived health (MCRS -10.3 vs. -2, P<0.001, all IHHT group vs. controls). The IHHT group exhibited a significant increase in hemoglobin content and a significant decrease in CRP compared to baseline (P<0.001), whereas these changes were not observed in the control group. Conclusion Respiratory treatment by IHHT in patients with post COVID conditions resulted in improved functional capacity in multiple of functional tests and in improved QoL and perceived health.

SuRxgWell: study protocol for a randomized controlled trial of telemedicine-based digital cognitive behavioral intervention for high anxiety and depression among patients undergoing elective hip and knee arthroplasty surgery

BackgroundMood disorders (anxiety, depression), sleep disorders, and catastrophizing lead to increased post-operative pain perception, increase in postoperative opioid consumption, decreased engagement with physical activity, and increased resource utilization in surgical patients. Psychosocial disorders significantly affect postoperative outcome. Unfortunately, studies focused on perioperative psychological assessment and treatment are scarce. We propose to test whether digital cognitive behavioral intervention (dCBI) can help surgical patients. dCBI such as RxWell™ is a proven treatment for mood disorders in medical patients such as reducing depression in patients with inflammatory bowel disease. We hypothesize that RxWell™ will also be effective in surgical patients. This study aims to test whether RxWell™ can improve preoperative mood disorders and subsequently reduce postoperative pain and opioid requirement in patients scheduled for primary total hip and knee arthroplasty (THA, TKA). We named the trial as the SuRxgWell trial.MethodsThis is a randomized, controlled trial that will enroll primary and unilateral THA or TKA patients with anxiety and/or depression symptoms before surgery to receive the SuRxgWell dCBI program and investigate its impact on postoperative outcomes including postoperative pain, anxiety, depression, sleep disorder, and catastrophizing. After signing an informed consent, subjects will be screened using the PROMIS questionnaires, and subjects with a T-score of ≥ 60 on the short Patient-Reported Outcomes Measurement Information System (PROMIS) 4a Anxiety and/or short PROMIS 4a Depression questionnaires will be randomized to either usual care (control group) or the cognitive behavioral intervention, RxWell™, plus usual care (intervention group). The control group will receive information on how to locate tools to address anxiety and depression, whereas the intervention group will have access to SuRxgWell 1 month prior to surgery and up to 3 months after surgery. The allocation will be 3:1 (intervention to control). Investigators will be blinded, but research coordinators approaching patients and research subjects will not.The primary outcome will be day of surgery anxiety or depression symptoms measured with the PROMIS Short Form v1.0 -Anxiety 4a/Depression and Generalized Anxiety Disorder Measure (GAD-7) and Patient Health Questionnaire (PHQ-8). Secondary end points include measuring other health-related quality of life outcomes including sleep disturbance, fatigue, ability to participate in social roles, pain interference, cognitive function, pain catastrophizing, and physical function. Other secondary outcomes include collecting data about preoperative and postoperative pain scores, and pain medication usage, and orthopedic functional recovery at baseline, day of surgery, and 1, 2, and 3 months after the surgery with the Pain Catastrophizing Scale, the Knee injury and Osteoarthritis Outcome Score (KOOS), and Hip injury and Osteoarthritis Outcome Score (HOOS). In addition, subjects will be asked to complete a GAD-7 and PHQ-8 questionnaires bi-weekly (via the RxWell™ app for the interventional group or REDCAP for the control group). Data about postsurgical complications, and resource utilization will also be recorded. We will also receive monthly reports measuring the usage and engagement of RxWell use for each participant randomized to that arm. The primary hypotheses will be assessed with intention-to-treat estimates, and differences in primary outcome will be tested using independent two sample t-tests. This trial is registered to the ClinicalTrials.gov database (NCT05658796) and supported by the DAPM, UPMC Health Plan, and the NIH.DiscussionOur trial will evaluate the feasibility of digital cognitive behavioral intervention as a perioperative tool to improve anxiety and depression before and after major orthopedic surgery in comparison to education. If digital cognitive behavioral intervention proves to be effective, this might have important clinical implications, reducing the incidence of chronic postsurgical pain and improving outcomes.

Novel approach to depression in ischemic heart disease: attenuation of autonomic dysfunction lowers depression scores

Abstract Introduction Depression in ischemic heart disease (IHD) is associated with increased mortality, and autonomic nervous system dysfunction (ANSD) may link the two conditions. Regulatory functions of the autonomic nervous system with respect to IHD risk factors include heart rate, blood pressure, serum cholesterol, and glycated hemoglobin. While painful sensitivity to pressure (Pressure-Pain Sensitivity, PPS) at the sternum rises with increased depression in IHD, reduction of elevated PPS reflects lower depression scores, lower ANSD, and lower mortality rates in IHD. Beta-adrenoreceptor blockade (BB) inhibits the anti-depressive effect associated with reduced PPS measures as well as the efferent sympathetic autonomic activity. Purpose We tested the hypothesis that lowering of elevated PPS measures is associated with restored autonomic regulation of depression, measured as the association between baseline depression scores and subsequent lowering of the depression score. We determined whether autonomic regulation in depression is associated with non-pharmacological reduction of elevated PPS measures. Methods In a randomized controlled intervention trial of IHD that included 213 individuals with elevated PPS, 20% of participants had elevated Major Depression Inventory scores (MDIS). We compared subjects with previously defined minimum reduction of at least 15 PPS units (PPS reverters) with subjects without this effect (PPS non-reverters), as well as non-users with users of BB. We recorded linear regressions of depression score changes as the dependent variable versus baseline depression scores as the independent variable. We compared active and control treatments by dividing participants into three pre-study defined groups of no depression (MDIS < 15), incipient depression (15 < MDIS < 20), and manifest depression (MDIS > 20). Results For reverters (N=72) compared to non-reverters (N=93), the mean anti-depressive effect increased in favor of reverters by a rate of 0.3 MDI units (95% CI 0.10–0.5, P=0.004) per unit increase in baseline MDIS. Comparing BB non-users (N=97) with BB users (N=67), the rate in favor of BB non-users was 0.4 units (95% CI 0.2-0.6, P=0.0002). In combination, comparing reverting non-users of BB (N=27) to non-reverting BB users (N=52), the rate in favor of the former group was 0.7 MDI (95% CI 0.4-0.9, P<0.00001). For reverting BB non-users, Cohen’s effect size reached 1.5. For the comparison of active and control groups for the three levels of MDIS, the trend was significant at P=0.04. Conclusions In patients with IHD, depression is associated with disruption of specific sympathetic beta-adrenergic regulatory functions of the autonomic nervous system. The findings imply that lowering of elevated PPS measures is associated with enhanced autonomic regulation of depression scores, and with marked clinical effect in individuals with elevated depression scores, but with no effect in BB users.

Abstract 17390: The Impact of The Covid-19 Pandemic on Perceived Stress in Rural Caregivers Participating in a Cardiovascular Risk Reduction Intervention

Introduction: Interventions to reduce cardiovascular disease (CVD) risk factors are key for improving the health and well-being of rural caregivers who are often referred to as invisible patients. The Rural Intervention for Caregivers’ Heart Health (RICHH), a CVD risk reduction intervention (2017-2022) included a stress management module. The COVID-19 pandemic (2020-2021) had an unknown impact on this intervention on perceived stress. The aim of this study was to determine whether the COVID-19 pandemic moderated the effects of RICHH on perceived stress for rural caregivers. Methods: This was a randomized controlled trial of a CVD risk reduction intervention that promoted self-care. Caregivers were randomized to usual care or the RICHH intervention. Data were collected at baseline, 4 and 12 months. Participants were grouped into two groups by COVID-19 timing: 1) the pre-pandemic group (n=145) completed the study before the pandemic; and 2) the pandemic group (n=114) completed the study during the pandemic. A piecewise linear mixed-effect model was used to evaluate the impact of the intervention and COVID-19 timing on perceived stress (Cohen’s Perceived Stress Scale). Results: The effect of the intervention on perceived stress in 259 participants (mean age = 55 ± 13 years, 78% female, 95% white, and 73 % married) was significant in the pandemic group (β= -.59, SE = .14, P < .001) but not in the pre-pandemic group (β = -.10, SE = .13, P = .45 [Figure1). The differences in perceived stress changes between the pre-COVID and during-COVID groups was significant, indicating a moderating effect of COVID (β = -.50, SE = .19, P = .009). Conclusion: The RICHH intervention helped to mitigate stress during the COVID-19 pandemic among those in the intervention group at the 4 months, however this effect was not sustained at 12 months. It remains unclear if the reduction in perceived stress during the pandemic was due to participation in the intervention or weekly contact with an interventionist.

Efficacy of pharmacological and non-pharmacological therapy on pain intensity and disability of older people with chronic nonspecific low back pain: a protocol for a network meta-analysis

BackgroundThe purpose of this network meta-analysis (NMA) is to investigate the efficacy of pharmacological and non-pharmacological therapy on pain intensity and disability of older people with chronic nonspecific low back pain, providing comprehensive evidence for an informed decision-making.MethodsWe will perform a systematic search to identify randomized controlled trials of pharmacological and non-pharmacological interventions for older people with chronic nonspecific low back pain. MEDLINE, Cochrane Library, Embase, AMED, PsycINFO, and PEDro will be searched without language or date restrictions. Our primary outcomes are pain intensity and disability. Risk of bias will be assessed for all studies using the revised Cochrane risk-of-bias (RoB) tool 2.0. For each pairwise comparison between the different interventions, estimated mean differences and their 95% confidence intervals will be presented. Standard pairwise meta-analyses will be performed using random effects models in STATA version 16. The competing interventions will be ranked using the surface under the cumulative ranking curve (SUCRA) for the outcomes of interest at short and long terms. The confidence in the results from NMA will be assessed using the Confidence in Network Meta‐Analysis (CINeMA) framework.DiscussionThis NMA compares efficacy of interventions for nonspecific chronic low back pain in older people. It will provide reliable evidence for patients, clinicians, stakeholders, and researchers in this field where competing therapies, many of extraordinarily little value, are commonly used in clinical practice.Systematic review registrationPROSPERO CRD42022312565

Abstract 17418: Daily Intake of Fruits and Vegetables Moderates the Effect of a Nutrition Intervention on Symptom Burden in Patients With Heart Failure

Introduction: Patients with heart failure (HF) often remain symptomatic after optimization of medical treatment. Complementary interventions may reduce symptom burden. We conducted a 6-month randomized controlled trial of a nutrition intervention (NIHFT) to reduce fluid overload, oxidative stress, and inflammation, which are major pathologic pathways underlying HF symptoms.Aims: 1) To examine the effects of NIHFT on HF symptom burden (i.e., shortness of breath, edema, and fatigue); and 2) to determine if intake of fruits and vegetables, primary sources of antioxidants and anti-inflammatories, moderated the effect of the NIHFT on HF symptom burden. Methods: Patients with HF (n=116) with complete baseline data were included (61% male, 63±12 years old, 64% NYHA III/IV). Intervention group received 1) individualized educational intervention for sodium reduction that included promoting fruit and vegetable intake, 2) daily low sodium tomato or vegetable juice, and 3) omega-3 supplementation (1050 mg EPA, 150 mg DHA/capsule/day) for 6 months. Symptom burden was measured by the Memorial Symptom Assessment Scale-HF at baseline and 3 and 6-month. Daily intake of fruits and vegetables at baseline was dichotomized (≤1 vs ≥2 servings/day). A linear mixed-effect model was used. Results: There was no direct effect of the NIHFT on symptom burden. However, baseline intake of fruits and vegetables moderated the effect of the intervention on overall symptom burden scores (beta estimate= -4.67, SE=1.89, P=0.015). Reduction in symptom burden was greater among patients with lower baseline fruit and vegetable intake compared to those with higher intake. Among the subscales (i.e., frequency, severity, and distress) of overall symptom burden, frequency (beta estimate= -1.63, SE=0.66, P=0.014) and severity (beta estimate= -1.81, SE=0.61, P=0.004) were significantly moderated by the intake of fruits and vegetables. Conclusions: The findings indicate that the nutrition intervention was more effective in reducing symptom burden for patients with lower baseline intake of fruits and vegetables. This suggests that increased fruit and vegetable intake may further reduce HF symptom burden in patients on optimal medication therapy.

Examining oncologist involvement in a nurse-led primary palliative care intervention.

264 Background: Patients with advanced cancer are recommended to receive palliative care (PC) early, but a limited PC specialty workforce limits feasibility. Primary PC, administered by providers outside the PC specialty, has been proposed as a way to increase access to PC. However, prior studies of primary PC have not demonstrated benefit, possibly due to lack of collaboration within the care team. We examine oncologist involvement in the largest primary PC study to date, where primary PC was delivered by oncology nurses. Methods: CONNECT (NCT02712229) was a cluster-randomized controlled trial of a primary PC intervention conducted at 17 community oncology clinics in Western Pennsylvania from 2016-2020. Selected clinic nurses (N=23) were trained to deliver up to 3 monthly primary PC visits, formulating a care plan after each visit. Nurses were asked to update the patient’s oncologist after each visit and to document this communication. We use descriptive statistics to examine level of oncologist involvement in these primary PC visits, based on nurse documentation. Results: Of 336 patients randomized to receive the primary PC intervention, 266 completed at least one study visit, and 233 (87.6%) had at least one visit where the nurse reported updating the oncologist afterwards. Of 674 total study visits, nurses reported updating the oncologist in 553 (82.0%) of them, most commonly in person (77.0%), followed by email (13.4%) and phone (9.6%). For in person or phone exchanges, mean length of interaction was 8.3 (SD 5.7) minutes, with a median of 5.0 minutes. For visits where communication occurred between the nurse and oncologist, the nurse reported presenting their specific care plan only 29.5% of the time (163/553 visits). In 96.9% (158/163) of cases, the oncologist was reported as receptive to the presented care plan, with no further details given in the 5 instances where the oncologist was reported as not receptive. When the oncologist was receptive to the care plan, it was reported that no changes were made by the oncologist in 94.3% (149/158) of cases. In the handful of cases where changes were made, changes involved ordering additional tests (3), changes to non-oncologic medications or therapeutics (2), involving other providers (1), changing oncologic treatment (1), and modifying the patient’s visit schedule (1). Conclusions: In a large trial of oncology nurse-led primary PC, oncologist involvement in care plans was not robust. More extensive team collaboration may be required in future primary PC interventions to increase the efficacy of primary PC. Clinical trial information: NCT02712229 .

Deficiencies in reporting inclusion/exclusion criteria and characteristics of patients in randomized controlled trials of therapeutic interventions in pressure injuries: a systematic methodological review.

Wound care is a complex procedure and the related research may include many variables. Deficiencies in the sample inclusion and exclusion criteria may limit the generalizability of randomized controlled trials (RCTs) for wound patients in the real world. This study aimed to evaluate deficiencies in reporting the inclusion and exclusion criteria and the characteristics of patients in RCTs of pressure injuries (PI) therapeutic interventions. We conducted a systematic methodological review in which 40 full text RCTs of PI treatment interventions published in English, from 2008 to 2020, were identified. Data on the general characteristics of the included RCTs and data about inclusion/exclusion criteria and characteristics of patients were collected. The inclusion/exclusion criteria were categorized into five domains (definition of disease, precision, safety, ethical/legal and administrative). Study duration (in weeks) was 8.0 (quartile 1: 2.0; quartile 3: 48.0); only 5.0% of the trials mentioned race, skin colour or ethnicity, and 37.5% reported the duration of the wound. Only 9 (22.5%) studies reported the drugs that the included patients were using and 10 (25.0%) RCTs reported adverse events. The presence of the five domains was observed only in 12.5% of RCTs and only 12 (30.0%) had the precision domain. Much more research is required in systematic assessments of the external validity of trials because there is substantial disparity between the information that is provided by RCTs and the information that is required by clinicians. We concluded that there are deficiencies in reporting of data related to inclusion/exclusion criteria and characteristics of patients of RCTs assessing PI therapeutic interventions.

The Development and Validation of the Elementary Activity Interest Measure

Educators are often trying to foster Science, Technology, Engineering, and Math (STEM) engagement by facilitating interest in STEM content, but research suggests that STEM interest generally declines through the primary and secondary grades. To counter this trend, STEM interventions have begun to focus on younger students. To support this work, we developed the Elementary Activity Interest Measure (EAIM) to allow for teachers and researchers to more easily measure interest in younger populations. Embedded within a large, randomized control trial intervention designed to increase learning about STEM content, our data from both a pilot study (16 classrooms comprised of 194 students) and the RCT (all fourth-grade classrooms in a large, urban school district comprised of 1712 students) indicate that the proposed use of the EAIM scores are supported by the collected evidence of reliability and validity. Further, EAIM scores correlate both with performance in science (Polikoff et al., 2018) as well as positive and negative emotions. Utilizing graphics and targeted specifically for elementary aged students, the EAIM is designed to measure interest in large-scale studies and is easily modifiable for teachers/practitioners to check if their interventions are producing the desired results.