Implementation Science to Achieve Equity in Heart Failure Care: A Scientific Statement From the American Heart Association.

Guideline-directed medical therapies and guideline-directed nonpharmacological therapies improve quality of life and survival in patients with heart failure (HF), but eligible patients, particularly women and individuals from underrepresented racial and ethnic groups, are often not treated with these therapies. Implementation science uses evidence-based theories and frameworks to identify strategies that facilitate uptake of evidence to improve health. In this scientific statement, we provide an overview of implementation trials in HF, assess their use of conceptual frameworks and health equity principles, and provide pragmatic guidance for equity in HF. Overall, behavioral nudges, multidisciplinary care, and digital health strategies increased uptake of therapies in HF effectively but did not include equity goals. Few HF studies focused on achieving equity in HF by engaging stakeholders, quantifying barriers and facilitators to HF therapies, developing strategies for equity informed by theory or frameworks, evaluating implementation measures for equity, and titrating strategies for equity. Among these HF equity studies, feasibility was established in using various educational strategies to promote organizational change and equitable care. A couple include ongoing randomized controlled pragmatic trials for HF equity. There is great need for additional HF implementation trials designed to promote delivery of equitable guideline-directed therapy.

Estimation of DAPT Study Treatment Effects in Contemporary Clinical Practice: Findings From the EXTEND-DAPT Study.

BACKGROUND: Differences in patient characteristics, changes in treatment algorithms, and advances in medical technology could each influence the applicability of older randomized trial results to contemporary clinical practice. The DAPT Study (Dual Antiplatelet Therapy) found that longer-duration DAPT decreased ischemic events at the expense of greater bleeding, but subsequent evolution in stent technology and clinical practice may attenuate the benefit of prolonged DAPT in a contemporary population. We evaluated whether the DAPT Study population is different from a contemporary population of US patients receiving percutaneous coronary intervention and estimated the treatment effect of extended-duration antiplatelet therapy after percutaneous coronary intervention in this more contemporary cohort. METHODS: We compared the characteristics of drug-eluting stent-treated patients randomly assigned in the DAPT Study to a sample of more contemporary drug-eluting stent-treated patients in the National Cardiovascular Data Registry CathPCI Registry from July 2016 to June 2017. After linking trial and registry data, we used inverse-odds of trial participation weighting to account for patient and procedural characteristics and estimated a contemporary real-world treatment effect of 30 versus 12 months of DAPT after coronary stent procedures. RESULTS: The US drug-eluting stent-treated trial cohort included 8864 DAPT Study patients, and the registry cohort included 568 540 patients. Compared with the trial population, registry patients had more comorbidities and were more likely to present with myocardial infarction and receive 2nd-generation drug-eluting stents. After reweighting trial results to represent the registry population, there was no longer a significant effect of prolonged DAPT on reducing stent thrombosis (reweighted treatment effect: -0.40 [95% CI, -0.99% to 0.15%]), major adverse cardiac and cerebrovascular events (reweighted treatment effect, -0.52 [95% CI, -2.62% to 1.03%]), or myocardial infarction (reweighted treatment effect, -0.97% [95% CI, -2.75% to 0.18%]), but the increase in bleeding with prolonged DAPT persisted (reweighted treatment effect, 2.42% [95% CI, 0.79% to 3.91%]). CONCLUSIONS: The differences between the patients and devices used in contemporary clinical practice compared with the DAPT Study were associated with the attenuation of benefits and greater harms attributable to prolonged DAPT duration. These findings limit the applicability of the average treatment effects from the DAPT Study in modern clinical practice.

Effects of aripiprazole long-acting injectable antipsychotic on hospitalization in recent-onset schizophrenia.

OBJECTIVE: Recent-onset schizophrenia (ROS) represents a critical period that can greatly influence the clinical course of schizophrenia. The use of long-acting injectable antipsychotics (LAIs) in this period is increasingly being considered as a first-line treatment option. Aripiprazole LAI (ALAI) is the newest of all LAI's available on the market, with limited data on its effects on hospitalization rates after first episode of schizophrenia. It was our goal to evaluate whether ALAI has an effect on hospitalization rates, number of bed days and clinical improvement in patients with ROS. METHODS: This mirror-image study included 138 inpatients suffering from schizophrenia. We collected sociodemographic data on all individuals, number of hospitalization days, hospitalization rates as well as Clinical Global Impression Scale-severity of illness (CGI-S) and Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS) scores at the initiation of ALAI and at the end of a 1 year follow up. RESULTS: Mean number of hospitalizations and hospitalization days in the year after starting ALAI significantly decreased compared to the year before (p = 0.005 and p < 0.001). Mean scores on both CGI and CRDPSS also significantly decreased after initiating ALAI (p < 0.001). CONCLUSION: Results suggest that ALAI is an important therapeutic option in patients with ROS. It leads to reduced usage of hospital services, potentially reducing the socio-economic healthcare burden.

Symptom, alexithymia and self-image outcomes of Mentalisation-based treatment for borderline personality disorder: a naturalistic study.

BACKGROUND: Mentalisation-based treatment (MBT) in borderline personality disorder (BPD) has a growing evidence base, but there is a lack of effectiveness and moderator studies. The present study examined the effectiveness of MBT in a naturalistic setting and explored psychiatric and psychological moderators of outcome. METHOD: Borderline and general psychiatric symptoms, suicidality, self-harm, alexithymia and self-image were measured in a group of BPD patients (n = 75) receiving MBT; assessments were made at baseline, and subsequently after 6, 12 and 18 months (when treatment ended). Borderline symptoms were the primary outcome variable. RESULTS: Borderline symptoms improved significantly (d = 0.79, p < .001), as did general psychiatric symptoms, suicidality, self-harm, self-rated alexithymia and self-image. BPD severity or psychological moderators had no effect on outcome. Younger patients improved more on self-harm, although this could be explained by the fact that older patients had considerably lower baseline self-harm. CONCLUSIONS: MBT seems to be an effective treatment in a naturalistic setting for BPD patients. This study is one of the first studies of MBT showing that outcomes related to mentalisation, self-image and self-rated alexithymia improved. Initial symptom severity did not influence results indicating that MBT treatment is well adapted to patients with severe BPD symptoms. TRIAL REGISTRATION: The study was retrospectively registered 25 September 2017 in the ClinicalTrials.gov PRS registry, no. NCT03295838 .

A naturalistic study of high-dose unilateral ECT among severely depressed inpatients: how does it work in the clinical practice?

BACKGROUND: Naturalistic studies can be useful tools to understand how an intervention works in the real clinical practice. This study aims to investigate the outcomes in a naturalistically treated depressed inpatients cohort, who were referred, or not, to unilateral ECT. METHODS: Depressed adults according to MINI admitted in a psychiatric unit were divided in unilateral ECT treated and non-ECT treated. Main outcomes were: depression improvement in Hamilton Rating Scale for Depression (HDRS-17) scores; response (HDRS-17 improvement ≥50 %); remission (HDRS-17 score ≤7); length of hospitalization. RESULTS: Forty-three patients were included in unilateral ECT group and 104 in non-ECT group. No differences of psychotic symptoms, melancholic features or past maniac episode were found between groups. Unilateral ECT group had a mean HDRS-17 score higher than non-ECT group at admission (ECT: 25.05 ± 1.03; non-ECT: 21.61 ± 0.69; p = 0.001), but no significant difference was found at discharge (ECT: 7.70 ± 0.81; non-ECT: 7.40 ± 0.51; p = 0.75). Unilateral ECT group had a larger HDRS-17 score reduction during treatment (ECT: 18.24 ± 1.18; non-ECT:14.20 ± 0.76; p = 0.004). There were no significant differences in response and remission rates between groups. Unilateral ECT group had longer mean duration of hospitalization in days (ECT: 35.48 ± 2.48; non-ECT: 24.57 ± 1.50; p < 0.001), but there were no difference in mean time of treatment (ECT group:27.66 ± 1.95; non-ECT: 24.57 ± 1.50; p = 0.25). CONCLUSIONS: Unilateral high-dose ECT is still a useful treatment option, in the real world clinical practice, to reduce the intensity of depressive symptoms in highly depressed inpatients.

Assessing disease control in inflammatory bowel disease: a real world cross-sectional study in the UK (PODCAST-IBD).

OBJECTIVE: Proportion Of suboptimal Disease Control And Strategy of Treatment in IBD (PODCAST-IBD) was an international real-world study which aimed to quantify disease control in IBD using STRIDE-II recommendations. DESIGN/METHOD: Cross-sectional assessment of IBD patients attending routine clinic appointments in four UK centers October 2022 to January 2023. Clinician-reported outcomes, patient-reported outcomes and retrospective data from medical chart review were used to assess IBD control against red flags aligned to STRIDE-II. RESULTS: Data were available from 198 UK patients. IBD was suboptimally controlled in 52.4% (54/103) of patients with Crohn's disease (CD) and 45.3% (43/95) with ulcerative colitis (UC). Impaired quality of life (QOL), defined as Short inflammatory bowel disease questionnaire (SIBDQ) score <50, was the main contributor to suboptimal disease control. Suboptimal disease control has a detrimental impact on fatigue and disability with significantly lower mean Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) score in suboptimally controlled disease (CD: 81.5 vs 125, UC: 87.4 vs 122.8) and IBD Disk. Suboptimal disease control results in higher health care resource use (HCRU) (CD: £4,746 vs £1,924; UC: £2,428 vs £1,121) and higher rates of work productivity loss (CD: 41.7% vs 11.9%, UC: 38.0% vs 22.6%). CONCLUSION: IBD was suboptimally controlled in around one-half of patients. Impaired QOL was the most common contributor (64%, 62/97) to suboptimal control. Suboptimal control had a considerable economic impact; HCRU more than doubled and productivity fell. Physicians could consider regular QOL assessments to prompt timely disease monitoring to enable identification of early active disease and appropriate treatment.

Inflammatory bowel disease (IBD), which encompasses Crohn's disease (CD) and ulcerative colitis (UC), is a life-long, painful and debilitating disease. Symptoms include abdominal pain, diarrhea and extreme tiredness (fatigue) and may also affect the eyes, joints and skin. People with IBD have periods of time where their symptoms are not controlled (known as relapse), with minimal symptoms (known as remission) at other times. This paper reports on people from the UK who participated in the wider international PODCAST-IBD study. The PODCAST-IBD study used information from people with IBD, their doctors and their medical notes to assess how well IBD was controlled and the impact of suboptimal disease control on their lives and use of healthcare. Overall, IBD was suboptimally controlled in around one-half of the people with IBD: 52.4% (54/103) of those with CD and 45.3% (43/95) with UC. Reduced quality of life (QOL) was the most common contributor to suboptimal control with almost two-thirds of people reporting impaired QOL. Suboptimal control of IBD impacts on people's everyday life ­ resulting in fatigue and disability, reducing QOL and making it difficult to work. Suboptimal control of IBD also has a considerable economic impact since it results in increased healthcare use. It might be helpful for doctors to consider regular QOL assessments to help to identify those people whose IBD is not well controlled to ensure that they receive appropriate treatment to control disease and improve their lives.

Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis: the EASI-SWITCH RCT.

Background: Neutropenic sepsis is a common complication of systemic anticancer treatment. There is variation in practice in timing of switch to oral antibiotics after commencement of empirical intravenous antibiotic therapy. Objectives: To establish the clinical and cost effectiveness of early switch to oral antibiotics in patients with neutropenic sepsis at low risk of infective complications. Design: A randomised, multicentre, open-label, allocation concealed, non-inferiority trial to establish the clinical and cost effectiveness of early oral switch in comparison to standard care. Setting: Nineteen UK oncology centres. Participants: Patients aged 16 years and over receiving systemic anticancer therapy with fever (≥ 38°C), or symptoms and signs of sepsis, and neutropenia (≤ 1.0 × 109/l) within 24 hours of randomisation, with a Multinational Association for Supportive Care in Cancer score of ≥ 21 and receiving intravenous piperacillin/tazobactam or meropenem for < 24 hours were eligible. Patients with acute leukaemia or stem cell transplant were excluded. Intervention: Early switch to oral ciprofloxacin (750 mg twice daily) and co-amoxiclav (625 mg three times daily) within 12-24 hours of starting intravenous antibiotics to complete 5 days treatment in total. Control was standard care, that is, continuation of intravenous antibiotics for at least 48 hours with ongoing treatment at physician discretion. Main outcome measures: Treatment failure, a composite measure assessed at day 14 based on the following criteria: fever persistence or recurrence within 72 hours of starting intravenous antibiotics; escalation from protocolised antibiotics; critical care support or death. Results: The study was closed early due to under-recruitment with 129 patients recruited; hence, a definitive conclusion regarding non-inferiority cannot be made. Sixty-five patients were randomised to the early switch arm and 64 to the standard care arm with subsequent intention-to-treat and per-protocol analyses including 125 (intervention n = 61 and control n = 64) and 113 (intervention n = 53 and control n = 60) patients, respectively. In the intention-to-treat population the treatment failure rates were 14.1% in the control group and 24.6% in the intervention group, difference = 10.5% (95% confidence interval 0.11 to 0.22). In the per-protocol population the treatment failure rates were 13.3% and 17.7% in control and intervention groups, respectively; difference = 3.7% (95% confidence interval 0.04 to 0.148). Treatment failure predominantly consisted of persistence or recurrence of fever and/or physician-directed escalation from protocolised antibiotics with no critical care admissions or deaths. The median length of stay was shorter in the intervention group and adverse events reported were similar in both groups. Patients, particularly those with care-giving responsibilities, expressed a preference for early switch. However, differences in health-related quality of life and health resource use were small and not statistically significant. Conclusions: Non-inferiority for early oral switch could not be proven due to trial under-recruitment. The findings suggest this may be an acceptable treatment strategy for some patients who can adhere to such a treatment regimen and would prefer a potentially reduced duration of hospitalisation while accepting increased risk of treatment failure resulting in re-admission. Further research should explore tools for patient stratification for low-risk de-escalation or ambulatory pathways including use of biomarkers and/or point-of-care rapid microbiological testing as an adjunct to clinical decision-making tools. This could include application to shorter-duration antimicrobial therapy in line with other antimicrobial stewardship studies. Trial registration: This trial is registered as ISRCTN84288963. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/140/05) and is published in full in Health Technology Assessment; Vol. 28, No. 14. See the NIHR Funding and Awards website for further award information.

Neutropenic sepsis, or infection with a low white blood cell count, can occur following cancer treatment. Usually patients receive treatment with intravenous antibiotics (antibiotics delivered into a vein) for two or more days. Patients at low risk of complications from their infection may be able to have a shorter period of intravenous antibiotics benefitting both patients and the NHS. The trial compared whether changing from intravenous to oral antibiotics (antibiotics taken by mouth as tablets or liquid) 12­24 hours after starting antibiotic treatment ('early switch') is as effective as usual care. Patients could take part if they had started intravenous antibiotics for low-risk neutropenic sepsis. Patients were randomly allocated to 'early switch' or to usual care. The main outcome measured was treatment failure. Treatment failure happened if fever persisted or recurred despite antibiotics, if patients needed to change antibiotics, if they needed to be re-admitted to hospital or needed to be admitted to intensive care within 14 days or died. We had originally intended that 628 patients would take part, but after review of the design of the study the number needed to take part was revised to 230. We were not able to complete the trial as planned as unfortunately only 129 patients took part. As the trial was smaller than expected we were not able to draw conclusions as to whether 'early switch' is no less effective than usual care. Our findings suggest that 'early switch' might result in a shorter time in hospital initially; however, treatment failure was more likely to occur, meaning some patients had to return to hospital for further antibiotics. There were no differences in side effects and no serious complications from treatment or treatment failure (such as intensive care admission or death) among the 65 patients in the 'early switch' group. Patients were satisfied with 'early switch'. Early switch may be a treatment option for some patients with low-risk neutropenic sepsis who would prefer a shorter duration of hospital admission but accept a risk of needing hospital re-admission.

Behavior of total alkaline phosphatase after radium-233 therapy in metastatic castration-resistant prostate cancer: a single-center, real-world retrospective study.

Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.

Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.

Patient-Tailored Interventions to Improve Specialty Medication Adherence: Results from a Prospective Randomized Controlled Trial.

BACKGROUND: Specialty medication nonadherence results in poor clinical outcomes and increased costs. This study evaluated the impact of patient-tailored interventions on specialty medication adherence. METHODS: A pragmatic, randomized controlled trial was conducted at a single-center health-system specialty pharmacy from May 2019 to August 2021. Participants included recently nonadherent patients prescribed self-administered specialty medications from multiple specialty clinics. Eligible patients were stratified by historical clinic rates of nonadherence and randomized 1:1 to usual care or intervention arms. Intervention patients received patient-tailored interventions and 8 months of follow-up. A Wilcoxon test was used to analyze the difference in 6-, 8-, and 12-month post-enrollment adherence, calculated using proportion of days covered, between the intervention and usual care arms. RESULTS: Four hundred and thirty eight patients were randomized. Baseline characteristics were similar between groups: mostly women (68%), white (82%), with a median age of 54 years (interquartile range, 40, 64). The most common reasons for nonadherence in the intervention arm were memory (37%) and unreachability (28%). There was a significant difference in median proportion of days covered between patients in the usual care and intervention arms at 8-months (0.88 vs 0.94, P < .001), 6-months (0.90 vs 0.95, P = .003), and 12-months post-enrollment (0.87 vs 0.93, P < .001). CONCLUSIONS: Patient-tailored interventions resulted in significant specialty medication adherence improvement compared with standard of care. Specialty pharmacies should consider targeting nonadherent patients for adherence interventions.

Evaluating fitness-for-use of electronic health records in pragmatic clinical trials: reported practices and recommendations.

OBJECTIVE: To empirically explore how pragmatic clinical trials (PCTs) that used real-world data (RWD) assessed study-specific fitness-for-use. METHODS: We conducted interviews and surveys with PCT teams who used electronic health record (EHR) data to ascertain endpoints. The survey cataloged key concerns about RWD, activities used to assess data fitness-for-use, and related barriers encountered by study teams. Patterns and commonalities across trials were used to develop recommendations for study-specific fitness-for-use assessments. RESULTS: Of 15 invited trial teams, 7 interviews were conducted. Of 31 invited trials, 15 responded to the survey. Most respondents had prior experience using RWD (93%). Major concerns about EHR data were data reliability, missingness or incompleteness of EHR elements, variation in data quality across study sites, and presence of implausible or incorrect values. Although many PCTs conducted fitness-for-use activities (eg, data quality assessments, 11/14, 79%), less than a quarter did so before choosing a data source. Fitness-for-use activities, findings, and resulting study design changes were not often publically documented. Overall costs and personnel costs were barriers to fitness-for-use assessments. DISCUSSION: These results support three recommendations for PCTs that use EHR data for endpoint ascertainment. Trials should detail the rationale and plan for study-specific fitness-for-use activities, conduct study-specific fitness-for-use assessments early in the prestudy phase to inform study design changes before the trial begins, and share results of fitness-for-use assessments and description of relevant challenges and facilitators. CONCLUSION: These recommendations can help researchers and end-users of real-world evidence improve characterization of RWD reliability and relevance in the PCT-specific context.

Arrhythmias Other Than Atrial Fibrillation in Those With an Irregular Pulse Detected With a Smartwatch: Findings From the Apple Heart Study.

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Applying patient-reported outcome methodology to capture patient-reported health data: Report from an NIH Collaboratory roundtable.

Patient-reported health data provide information for pragmatic clinical trials that may not be readily available from electronic health records or administrative claims data. In this report, we present key considerations for collecting patient-reported health information in pragmatic clinical trials, which are informed by best practices from patient-reported outcome research. We focus on question design and administration via electronic data collection platforms with respect to 3 types of patient-reported health data: medication use, utilization of health care services, and comorbid conditions. We summarize key scientific literature on the accuracy of these patient-reported data compared with electronic health record data. We discuss question design in detail, specifically defining the concept to be measured, patient understanding of the concept, recall periods of the question, and patient willingness to report. In addition, we discuss approaches for question administration and data collection platforms, which are key aspects of successful patient-reported data collection.

Design and analytic considerations for using patient-reported health data in pragmatic clinical trials: report from an NIH Collaboratory roundtable.

Pragmatic clinical trials often entail the use of electronic health record (EHR) and claims data, but bias and quality issues associated with these data can limit their fitness for research purposes particularly for study end points. Patient-reported health (PRH) data can be used to confirm or supplement EHR and claims data in pragmatic trials, but these data can bring their own biases. Moreover, PRH data can complicate analyses if they are discordant with other sources. Using experience in the design and conduct of multi-site pragmatic trials, we itemize the strengths and limitations of PRH data and identify situational criteria for determining when PRH data are appropriate or ideal to fill gaps in the evidence collected from EHRs. To provide guidance for the scientific rationale and appropriate use of patient-reported data in pragmatic clinical trials, we describe approaches for ascertaining and classifying study end points and addressing issues of incomplete data, data alignment, and concordance. We conclude by identifying areas that require more research.

Measuring Effects of Nondrug Interventions on Behaviors: Music & Memory Pilot Study.

BACKGROUND/OBJECTIVES: Most people with Alzheimer disease and related dementias will experience agitated and/or aggressive behaviors during the later stages of the disease. These behaviors cause significant stress for people living with dementia and their caregivers, including nursing home (NH) staff. Addressing these behaviors without the use of chemical restraints is a growing focus of policy makers and professional organizations. Unfortunately, evidence for nonpharmacological strategies for addressing dementia-related behaviors is lacking. DESIGN: Six-month, preintervention-postintervention pilot study. SETTING: US NHs (n = 4). PARTICIPANTS: Residents with advanced dementia (n = 45). INTERVENTION: Music & Memory, an individualized music program in which the music a resident preferred when she/he was young is delivered at early signs of agitation, using a personal music player. MEASUREMENTS: Dementia-related behaviors for the same residents were measured three ways: (1) observationally using the Agitation Behavior Mapping Instrument (ABMI); (2) staff report using the Cohen-Mansfield Agitation Inventory (CMAI); and (3) administratively using the Minimum Data Set-Aggressive Behavior Scale (MDS-ABS). RESULTS: ABMI score was 4.1 (SD = 3.0) preintervention while not listening to the music, 4.4 (SD = 2.3) postintervention while not listening to the music, and 1.6 (SD = 1.5) postintervention while listening to music (P < .01). CMAI score was 61.2 (SD = 16.3) preintervention and 51.2 (SD = 16.1) postintervention (P < .01). MDS-ABS score was 0.8 (SD = 1.6) preintervention and 0.7 (SD = 1.4) postintervention (P = .59). CONCLUSION: Direct observations were most likely to capture behavioral responses, followed by staff interviews. Nursing-home based, pragmatic trials that rely solely on available administrative data may fail to detect effects of nonpharmaceutical interventions on behaviors. Findings are relevant to evaluations of nonpharmaceutical strategies for addressing behaviors in NHs, and will inform a large, National Institute on Aging-funded pragmatic trial beginning spring 2019. J Am Geriatr Soc 67:2134-2138, 2019.

Comparison of Intravenous Ibuprofen with Intravenous Ketorolac in Renal Colic Pain Management; A Clinical Trial.

BACKGROUND: Choosing a proper medication for pain management of patients with acute renal colic has been a challenge for physicians treating these patients. OBJECTIVES: The present study was performed with the aim of comparing intravenous (IV) ibuprofen and IV ketorolac in pain management of these patients. METHODS: In the present double-blind clinical trial study, patients suspected with renal colic presented to the emergency department were randomly divided into 2 groups receiving IV ibuprofen or IV ketorolac and were compared regarding effectiveness (pain reduction 15, 30, and 60 minutes after injection), treatment success, and possible side effects. RESULTS: In total, 240 patients suspected with renal colic with the mean age of 27.38 ± 12.32 years were randomly divided into 2 groups of 120 individuals treated with IV ketorolac or ibuprofen (66.4% male). The two groups were in a similar condition regarding age (P = 0.56), sex (P = 0.78) history of kidney stone (P = 0.40), vital signs (P > 0.05), stone size (P = 0.73), stone location (P = 0.13), and pain severity on admission (P = 0.32). 15, 30, and 60 minutes after drug injection, pain severity in the ketorolac group was significantly higher than the group receiving ibuprofen (P < 0.0001 for all comparisons), yet these differences were not clinically significant. Fifteen minutes after the injection, the rate of treatment success was significantly higher in the group receiving IV ibuprofen (P < 0.0001). After 60 minutes, the number of completely relieved cases reached 37 (30.8%) patients in the ketorolac group and 83 (69.1%) patients in the ibuprofen group. No significant difference was seen in side effects between the two groups (P = 0.35). CONCLUSIONS: The findings of the present study show that ibuprofen is a more rapid acting drug compared to ketorolac in controlling pain caused by renal colic. In addition, its rate of complete relief from pain was twice as much as that of ketorolac. Since the side effects observed for ibuprofen in the present study were very mild, it is suggested to use this drug in treatment and pain control of renal colic patients.

Discussions on real-world acupuncture treatments for chronic low-back pain in older adults.

Chronic low-back pain (CLBP) is one of the most common pain conditions. Current clinical guidelines for low-back pain recommend acupuncture for CLBP. However, there are very few high-quality acupuncture studies on CLBP in older adults. Clinical acupuncture experts in the American Traditional Chinese Medicine Association (ATCMA) were interested in the recent grant on CLBP research announced by the National Center for Complementary and Integrative Health. The ATCMA experts held an online discussion on the subject of real-world acupuncture treatments for CLBP in older adults. Seven participants, each with more than 20 years of acupuncture practice, discussed their own unique clinical experience while another participant talked about the potential mechanism of acupuncture in pain management. As a result of the discussion, a picture of a similar treatment strategy emerged across the participants for CLBP in older adults. This discussion shows that acupuncture may have complicated mechanisms in pain management, yet it is effective for the treatment of chronic pain involving maladaptive neuroplasticity; therefore, it should be effective for CLBP in older adults.

Behavior of total alkaline phosphatase after radium-233 therapy in metastatic castration-resistant prostate cancer: a single-center, real-world retrospective study / Estudo retrospectivo de vida-real, em centro único, para avaliação do comportamento da fosfatase alcalina total após terapia com rádio-223 no câncer de próstata resistente a castração

Abstract Objective: To describe the behavior of total alkaline phosphatase (tALP) in patients with metastatic castration-resistant prostate cancer receiving radium-223 therapy, in a real-world scenario, and to describe overall survival (OS) among such patients. Materials and Methods: This was a retrospective study involving 97 patients treated between February 2017 and September 2020. Patients were stratified by the baseline tALP (normal/elevated). A tALP response was defined as a ≥ 30% reduction from baseline at week 12. For patients with elevated baseline tALP, we also evaluated treatment response as a ≥ 10% reduction in tALP after the first cycle of treatment. We defined OS as the time from the first treatment cycle to the date of death. Results: There was a significant reduction in the median tALP after each cycle of treatment (p < 0.05 for all). Data for tALP at week 12 were available for 71 of the 97 patients. Of those 71 patients, 26 (36.6%) responded. Elevated baseline tALP was observed in 47 patients, of whom 19 (40.4%) showed a response. Longer OS was observed in the patients with normal baseline tALP, in those with elevated baseline tALP that showed a response to treatment (≥ 10% reduction), and in those who received 5-6 cycles of therapy. Conclusion: The tALP may be used to predict which patients will benefit from treatment with a greater number of cycles of radium-223 therapy and will have longer OS.

Resumo Objetivo: Descrever o comportamento da fosfatase alcalina total (tALP) em pacientes com carcinoma de próstata metastático resistente a castração, submetidos a terapia com rádio-223 em um cenário do mundo real, e a sobrevida global (SG) desses pacientes. Materiais e Métodos: Estudo retrospectivo envolvento 97 pacientes, no período de fevereiro/2017 a setembro/2020. Os pacientes foram estratificados de acordo com a tALP basal (normal/elevada). A resposta à tALP foi definida como uma redução em relação à linha de base de ≥ 30% na semana-12. Para pacientes com tALP basal elevada, também foi avaliada a resposta ao tratamento como uma redução de ≥ 10% de tALP após o primeiro ciclo. A SG foi definida como o tempo entre o primeiro ciclo e a data do óbito. Resultados: A redução da tALP média após cada ciclo foi significativa (p < 0,05). A tALP na semana 12 estava disponível para 71 dos 97 pacientes. Desses 71 pacientes, 26 (36,6%) responderam. Dezenove (40,4%) dos 47 pacientes com tALP elevada apresentaram resposta. Foi observada uma SG mais longa nos pacientes com tALP basal normal, nos pacientes com tALP basal elevada que apresentaram resposta ao tratamento (redução de ≥ 10%) e nos pacientes que receberam 5-6 ciclos. Conclusão: A tALP pode ser usada para prever parte dos pacientes que se beneficiarão do tratamento com um maior número de ciclos e uma SG mais longa.

Streamlining cardiovascular clinical trials to improve efficiency and generalisability.

Controlled trials provide the most valid determination of the efficacy and safety of an intervention, but large cardiovascular clinical trials have become extremely costly and complex, making it difficult to study many important clinical questions. A critical question, and the main objective of this review, is how trials might be simplified while maintaining randomisation to preserve scientific integrity and unbiased efficacy assessments. Experience with alternative approaches is accumulating, specifically with registry-based randomised controlled trials that make use of data already collected. This approach addresses bias concerns while still capitalising on the benefits and efficiencies of a registry. Several completed or ongoing trials illustrate the feasibility of using registry-based controlled trials to answer important questions relevant to daily clinical practice. Randomised trials within healthcare organisation databases may also represent streamlined solutions for some types of investigations, although data quality (endpoint assessment) is likely to be a greater concern in those settings. These approaches are not without challenges, and issues pertaining to informed consent, blinding, data quality and regulatory standards remain to be fully explored. Collaboration among stakeholders is necessary to achieve standards for data management and analysis, to validate large data sources for use in randomised trials, and to re-evaluate ethical standards to encourage research while also ensuring that patients are protected. The rapidly evolving efforts to streamline cardiovascular clinical trials have the potential to lead to major advances in promoting better care and outcomes for patients with cardiovascular disease.

Electronic health records to facilitate clinical research.

Electronic health records (EHRs) provide opportunities to enhance patient care, embed performance measures in clinical practice, and facilitate clinical research. Concerns have been raised about the increasing recruitment challenges in trials, burdensome and obtrusive data collection, and uncertain generalizability of the results. Leveraging electronic health records to counterbalance these trends is an area of intense interest. The initial applications of electronic health records, as the primary data source is envisioned for observational studies, embedded pragmatic or post-marketing registry-based randomized studies, or comparative effectiveness studies. Advancing this approach to randomized clinical trials, electronic health records may potentially be used to assess study feasibility, to facilitate patient recruitment, and streamline data collection at baseline and follow-up. Ensuring data security and privacy, overcoming the challenges associated with linking diverse systems and maintaining infrastructure for repeat use of high quality data, are some of the challenges associated with using electronic health records in clinical research. Collaboration between academia, industry, regulatory bodies, policy makers, patients, and electronic health record vendors is critical for the greater use of electronic health records in clinical research. This manuscript identifies the key steps required to advance the role of electronic health records in cardiovascular clinical research.

Insulin Initiation in Insulin-Naïve Korean Type 2 Diabetic Patients Inadequately Controlled on Oral Antidiabetic Drugs in Real-World Practice: The Modality of Insulin Treatment Evaluation Study.

BACKGROUND: The Modality of Insulin Treatment Evaluation (MOTIV) study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with oral hypoglycemic agents (OHAs). METHODS: This multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0%) who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice. RESULTS: A total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%). Basal insulin plus one OHA was the most frequently (51.0%) used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c <7%. Body weight increased from 65.2 kg to 65.5 kg, which was not significant. Meanwhile, there was significant increase in the mean daily insulin dose from 16.9 IU at baseline to 24.5 IU at month 6 (P<0.001). Overall, 17.6% of patients experienced at least one hypoglycemic event. CONCLUSION: In a real-world setting, the initiation of basal insulin is an effective and well-tolerated treatment option in Korean patients with T2DM who are failing to meet targets with OHA therapy.