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PMC10390614
Introduction
postoperative pain, LFCN block, pain, fractures, femoral head necrosis, THA
DISEASES, COMPLICATIONS, DEEP VEIN THROMBOSIS
Total hip arthroplasty (THA) is a widely used method for treating hip fractures, femoral head necrosis, and other diseases. Early postoperative lower limb functional exercise and ambulation after THA are important for relieving pain and reducing the risk of complications such as deep vein thrombosis [At present, there are no randomized controlled trials studying the efficacy of PENG block combined with LFCN block. This study aims to assess the efficacy of PENG block performed with LFCN block in controlling postoperative pain and promoting motor function recovery and to compare its effectiveness with S-FICB. We hope that the results of this study will provide a clinical reference for the improvement of perioperative pain management and rehabilitation programs in THA.
PMC10390614
Materials and methods
PMC10390614
Recruitment and randomization
This study was registered in the Chinese Clinical Trial Registry (ChiCTR2100051521) and secured by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University on 6/16/2021. After signing the informed consent, a total of 92 patients undergoing elective one- sided THA were enrolled over a period of 9 months (11/10/2021 to 8/25/2022) (Fig. CONSORT diagram. PENG, pericapsular nerve group block; S-FICB, supra-inguinal fascia iliaca blockAll the subjects were randomly allocated to either the PENG + LFCN group or the S-FICB group in a 1:1 ratio using the random allocation scheme provided by RESEARCH-RANDOMIZE (
PMC10390614
Ultrasound-guided block procedures
anterior inferior iliac spine, fascia iliaca block, pain, femoral cutaneous nerve, transverse abdominus muscle
LOCAL INFILTRATION, INFILTRATED
Peripheral vein access was established after the patients entered operating room, and non-invasive blood pressure (NIBP), heart rate (HR), and peripheral capillary oxygen saturation (SpOPENG + LFCN block: The low-frequency curvilinear probe (3–5 MHz) of ultrasound (GE Logiq e, GE Healthcare, USA) was placed in a transverse plane over the anterior inferior iliac spine (AIIS) and aligned with the pubic ramus by rotating the probe counterclockwise to obtain a hyperechoic bright line, which is the iliopubic eminence (IPE). In this view, the iliopsoas muscle and psoas tendon, the femoral artery, and pectineus muscle were observed. Using the in-plane injection technique, a 22G, 80 mm insulated block needle was inserted in a lateral-to-medial direction, and the tip was placed between the psoas tendon anteriorly and the pubic ramus posteriorly. After no blood was drawn back, the LA (20 ml, 0.33% ropivacaine) was injected to get an image of the psoas tendon uplifted (Fig. Images of ultrasound-guided pericapsular nerve group (PENG) block. The figure on the left shows the ultrasonic anatomy of PENG block; the needle tip was positioned between the psoas tendon and the pubic ramus using an in-plane approach. The figure on the right shows the local anesthetic spread following injection. Asterisk, target for local anesthetic injection; arrow, needle pathway; area circled by dashed line, local anesthetic spread; AIIS, anterior inferior iliac spine; IPE, iliopubic eminence; PT, psoas tendon; FA, femoral arteryImages of ultrasound-guided lateral femoral cutaneous nerve (LFCN) block. The needle tip was positioned in the tunnel formed by the fascia between the sartorius and the tensor fascia lata. Dashed arrow, needle pathway; large arrows, LFCN; TFL, tensor fascia lata; RF rectus femoris; Sa, sartoriusS-FICB: A high-frequency linear probe (6–12 MHz) of ultrasound (GE Logiq e, GE Healthcare, USA) was used. The probe was placed adjacent to the inguinal ligament with its long axis parallel to the ligament. After the femoral artery and the femoral nerve was observed, the probe was moved laterally to identify the sartorius muscle and placed it at the center of the screen. Then the probe was moved cephalically to the anterior superior iliac spine (ASIS) until the image of the sartorius muscle disappeared, and the medial side of ASIS was identified as the iliacus muscle. Next, by rotating the medial end of the ultrasound probe toward the umbilicus, the ASIS, iliac bone, and abdominal muscles were observed on the screen. Using the in-plane technique, a 22G, 80 mm insulated block needle was inserted in a lateral-to-medial direction. When the needle tip penetrated below the fascia iliacus, the LA (30 ml, 0.33% ropivacaine) was injected following negative aspiration to obtain an image showing the LA spread between the iliacus muscle and the fascia iliacus (Fig. Images of ultrasound-guided supra-inguinal fascia iliaca block (S-FICB). The needle tip was located under the fascia iliacus between the transversal abdominus muscle and iliac muscle. Dashed arrow, needle pathway. IO internal oblique muscle, TA transverse abdominus muscle, IM iliacus muscle, ASIS anterior superior iliac spinePain scores with a straight leg raise of the affected limb to 15 degrees were assessed by the same blinded investigator before and 30 min after block performance. Subsequently, this investigator assessed the block of LFCN by testing for loss of pain sensation on the lateral thigh. Successful block performance was defined as a reduction in pain score compared to before the intervention and loss of pain sensation on the lateral thigh. Case of unsuccessful block performance were not included in the statistical analysis. If the nerve block was unsuccessful, the investigator who previously assessed the effects of the block would ask the surgeon to perform local infiltration analgesia (LIA) at the end of the surgical procedure, which involved injecting 20 ml 0.33% ropivacaine around the joint capsule and 10 ml 0.33% ropivacaine infiltrated around the wound.
PMC10390614
Anesthesia and postoperative analgesia
nerve block, pain
Following the nerve block, patients received general anesthesia administered by an anesthesiologist who was blinded to the allocation result. All the patients were treated with 10 mg of intravenous dexamethasone before surgery. For anesthesia induction, propofol (2.0–2.5 mg/kg), sufentanil (0.4–0.5 μg/kg), and vecuronium (0.1 mg/kg) were administered. Surgical interventions were performed by four teams of orthopedic surgeons using posterolateral approaches.During the operation, propofol (2–5 mg/kg/h), remifentanil (0.1–0.5 μg/kg/min), and sevoflurane (1–2% concentration) were used for anesthesia maintenance at the discretion of the anesthesiologist. The bispectral index (BIS) was maintained between 40 and 60, and the fluctuation ranges of invasive systolic blood pressure (ISBP) and heart rate (HR) were kept within 20% of the preoperative level.All the patients received 2 mg intravenous tropisetron at the end of the surgery, and patient-controlled intravenous analgesia (PCIA) was initiated before patients were sent to post-anesthesia care unit (PACU). The PCIA combination of drugs consisted of 800 mg of tramadol, 100 mg of flurbiprofen axetil, and 54 ml of normal saline, and with a total volume of 80 ml. The PCIA system was set to deliver 5 ml for the first dose, a background infusion rate of 1 ml/h, a patient-controlled dose of 2 ml, and a lockout time of 15 min. In addition to PCIA, the patients were treated with intravenous parecoxib sodium (40 mg per 24 h) for background pain control in the general ward during 48 h. Tramadol was administered orally for rescue analgesia when the pain score (VAS) ≥ 5, and the specific dose was evaluated by the ward surgeon.
PMC10390614
The primary outcome
Our primary outcome was “time to first walk”, defined as the duration between the end of surgery and the first time the patient was able to walk with the assistance of a walking aid under the guidance of a rehabilitation physician.
PMC10390614
The secondary outcomes
nerve block-related, paresthesia, postoperative nausea and vomiting, dislocation, pain, hip flexion, PONV
FLICKERING, PARESTHESIA, CONTRACTION, SECONDARY, COMPLICATIONS
The secondary outcomes postoperatively included intraoperative remifentanil consumption, the degree of hip flexion on the operative side at 6 h, 24 h, and 48 h, lower limb muscle strength of the operative side at 6 h, 24 h, and 48 h, static and dynamic pain scores at 6 h, 24 h, and 48 h, the number of rescue analgesia, postoperative nausea and vomiting (PONV) at 48 h, and the rate of nerve block-related complications. The incidences of vascular puncture, paresthesia, and LA toxicity were also recorded by a supervisor during the block. Since the postoperative 12 h in this study were generally late at night, we only collected the outcomes at 6 h, 24 h, and 48 h to avoid disturbing the patients’ rest.The hip flexion degree of the operative side was measured using angle gauge in supine position (to avoid hip dislocation due to hip flexion beyond 90°).The lower limb muscle strength of the operative side was assessed using a manual muscle test (MMT) in supine position. The strength of quadriceps muscle group, iliopsoas muscle, sartorius muscle could be evaluated, mainly to evaluate the quadriceps muscle strength: Grade 0, no contraction; Grade 1, flickering contraction (no active knee extension and leg lift, only slight quadriceps contraction); Grade 2, full range of motion (ROM) with eliminated gravity (hip flexion, knee extension with eliminated gravity); Grade 3, full ROM with against gravity (leg lift and knee extension with against gravity but no resistance); Grade 4, full ROM with against gravity with minimal resistance (leg lift and knee extension with against gravity and minimal resistance); Grade 5: full ROM with against gravity with maximal resistance (leg lift and knee extension with against gravity and maximal resistance).Static and dynamic pain scores was recorded at 6 h, 24 h, and 48 h (0, no pain; 10, worst imaginable pain).
PMC10390614
Sample size calculation
We used PASS 16.0 software to calculate the sample size. Based on our preliminary study, we estimated that the first postoperative walking time of the S-FICB group would be 27.6 ± 12.3 h and the PENG + LFCN group would be 18.5 ± 12.3 h value. Under these assumptions, with
PMC10390614
Statistical analysis
We performed statistical analysis using IBM SPSS Statistics 20.0 software. Continuous variables with normal distribution were expressed as mean (SD) or percentage (%), and we used median (range) to express continuous variables that presented skewed distribution. Student’s
PMC10390614
Acknowledgements
We thank Xiaohong Wang, Daiyu Chen, and Qian Yang for their help with writing the manuscript and their expertise.
PMC10390614
Author contributions
All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by KH, CZ, and WD. The first draft of the manuscript was written by LL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
PMC10390614
Funding
No funds, grants, or other support was received.
PMC10390614
Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
PMC10390614
Declarations
PMC10390614
Conflict of interest
No conflicts of interest.
PMC10390614
References
PMC10390614
Abstract
PMC10320042
Introduction
Effective PrEP use is critical for impact, but data are limited on common patterns of continuation and coverage among persons using PrEP in real‐world settings.
PMC10320042
Methods
REGRESSION
Data are from the Partners Scale‐Up Project, a programmatic stepped‐wedge cluster‐randomized trial to integrate PrEP delivery in 25 Kenyan public health facilities conducted between February 2017 and December 2021. We evaluated PrEP continuation using visit attendance and pharmacy refill records, and computed medication possession ratio to define coverage during the first year of use. Latent class mixture models were used to identify and characterize membership to different PrEP continuation patterns. Multinomial logistic regression was used to examine the association between group trajectories and demographic and behaviour characteristics.
PMC10320042
Results
Overall, 4898 persons initiated PrEP, 54% (2640) were female, mean age was 33 years (standard deviation 11) and 84% (4092) had partners living with HIV. PrEP continuation was 57%, 44%, and 34% at 1, 3, and 6 months, respectively. Four unique trajectories of PrEP coverage were identified: (1) one‐fourth (1154) exhibited consistent high coverage throughout the year with 93%, 94%, 96%, and 67% continuing PrEP at months 1, 3, 6, and 12, respectively; (2) 13% (682) showed high coverage trajectory throughout 6 months but coverage rapidly declined thereafter (94%, 93%, 63%, and 10% continued at months 1, 3, 6, and 12, respectively); (3) 18.9% (918) exhibited moderate coverage trajectory with 91% of clients refilling PrEP at month 1 but nearly all dropped‐off thereafter (37%, 5%, and 4% continued at months 3, 6, and 12, respectively); and (4) 43.8% (2144) exhibited immediate discontinuation trajectory, in which nearly all did not have any subsequent PrEP refill. Overall, being female, older age, having partners living with HIV or of unknown HIV status were statistically associated with better PrEP continuation trajectories compared to the immediate discontinuation trajectory (
PMC10320042
Conclusions
two‐fifths
In this analysis of a real‐world PrEP implementation programme in Kenya, we found four distinct patterns of PrEP continuation, with one‐third of users exhibiting consistent high continuation throughout 12 months and two‐fifths with immediate discontinuation patterns. These data may help guide tailored interventions to support PrEP continuation in this setting.
PMC10320042
INTRODUCTION
MAY
Oral pre‐exposure prophylaxis is a highly effective HIV prevention strategy for men and women when taken with its effectiveness highly dependent on adherence [Access to oral PrEP in real‐world settings is gradually scaling up in many African settings, including in Kenya which officially launched PrEP implementation in May 2017 [
PMC10320042
METHODS
PMC10320042
Setting and population
Data are from the Partners Scale‐Up Project (ClinicalTrials.gov: NCT03052010) which has previously been reported [
PMC10320042
Procedures for PrEP initiation
The primary objective of the project was to sustainably catalyse scale‐up of PrEP delivery and to study the process of integrating PrEP services within existing public health structures. Thus, all direct PrEP delivery services, including PrEP demand creation, HIV risk assessment, PrEP eligibility determination, HIV testing, counselling, prescribing, dispensing and client follow‐up activities were fully performed by existing Ministry of Health (MOH) healthcare providers, without additional financial support beyond training and technical assistance. Healthcare providers typically included clinical officers, nurses, HIV counsellors and pharmacy technicians already stationed at the implementing clinics. PrEP eligibility was determined according to the Kenya MOH PrEP guidelines [
PMC10320042
Procedures for follow‐up of clients on PrEP
Clients who initiated PrEP were followed according to the Kenya national PrEP guidelines [
PMC10320042
Data collection
For this programmatic project, all clinical and programme data were documented by the facility staff on MOH tools that include PrEP registers and the clinical encounter form which is the standard MOH form for documenting individual‐level clinical records for clients on PrEP, and pharmacy logs for tracking drug prescriptions and dispensing. Over the study duration, PrEP client records, including demographics, HIV behaviour risk assessment and PrEP eligibility, PrEP prescription, dispensing, visit attendance and refills were abstracted off the standard MOH tools typically on a weekly basis by trained project‐dedicated staff into a central database using the SurveyCTO platform. For data quality assurance, we conducted several rounds of data cleaning exercise termed “data reconciliation” which involved project‐dedicated staff triangulating all MOH data sources to ascertain the correctness and completeness of data records. Given the programmatic nature of the data collection, the records reconciliation process focused on ensuring completeness of selected key variables that included: visit attendance, PrEP prescription and dispensing dates, number of PrEP pills/bottles dispensed, HIV test results, de‐identified unique client code, and all baseline demographics and HIV risk behaviours. Discrepancies in data on these records were resolved by confirmation from the facility healthcare providers.The Partners Scale‐Up Project was reviewed and approved by the University of Washington Human Subjects Division, Seattle (STUDY00002183) and the Scientific and Ethics Review Unit of the Kenya Medical Research Institute (SERU/CCR/0048/3328, SERU/CMR/0040/3338) enabling abstraction and analysis of de‐identified and delinked programmatic data. Thus, individual consent was not required for programmatic procedures [
PMC10320042
Analysis
SECONDARY
The present analysis was restricted to the individuals’ first year of PrEP use. We conducted secondary data analysis of the parent Partners Scale‐Up Project to identify trajectories of PrEP continuation and coverage and factors associated with assignment to the different PrEP continuation trajectories. The primary outcomes were PrEP continuation and PrEP medication possession ratio (MPR) as a measure of coverage. Continuation was defined as documented visit attendance and or PrEP dispensing from pharmacy records. Refill visits completed in the period between 14 days before the expected visit date to 15 days before the next expected visit date were classified as attended. The MPR, referred to as coverage hereafter, was estimated for fixed 30‐day monthly (aligned with 30 pills per bottle), quarterly and annual periods to help account for cycling on and off PrEP. Coverage as measured by the medication possession was computed as the ratio of the total number of pills dispensed at last visit divided by the number of days in each computed period since PrEP dispensing (i.e. monthly, quarterly or annual). Coverage greater than 1 (i.e., indicating the client came back for a PrEP refill before the expected date with pills ran out) was truncated to 1, for each computed period. If a client did not have PrEP in possession, they were considered not covered during that period. For example, if a client was prescribed 30 PrEP tablets but returned for refill after 90 days (3 months), they would be considered fully covered in the first month but not covered in the second and third months and their 3‐month coverage during that period will be computed as 30 out of 90 days (or ∼33%). Dropout and non‐visit attendance were primary study outcomes and thus not treated as missing data. Although it is not possible to fully ascertain or test the true data‐generating process on the PrEP discontinuation outcome [We fit latent class mixture models (LCMMs) to identify distinct patterns of coverage in this study population [
PMC10320042
RESULTS
Overall, a total of 4898 individuals initiated PrEP in the Partners Scale‐Up project between February 2017 and June 2020; 2640 (54%) were female, mean age was 33 years (standard deviation 11), the majority were married and monogamous (75%), and 4092 (84%) reported to have a partner known to live with HIV (Table Baseline demographic and behaviour characteristics by group trajectory
PMC10320042
Baseline demographic and behaviour characteristics by trajectory
Overall, among the 4898 persons who initiated PrEP, we identified four unique patterns of PrEP coverage during the first year of PrEP use classified as: (1) consistent high coverage, (2) high coverage, (3) moderate coverage, and (4) immediate discontinuation. The consistent high coverage group comprised 23.6% (1154) of the sample and demonstrated high levels of coverage throughout the 12‐month period. Clients in this group trajectory attended a median of 5 (IQR 4–7) follow‐up visits. The high coverage trajectory comprised 13.9% (682) of the sample and exhibited high coverage that persisted through the first month 6 followed by a rapid decline thereafter. Clients in this trajectory attended a median of 3 (IQR 2–4) follow‐up visits. The moderate coverage trajectory comprised 18.7% (918) of the sample and showed high coverage for only month 3 with coverage rapidly declining thereafter. Clients in this moderate trajectory attended a median of 2 (IQR 1–2) follow‐up visits. The immediate discontinuation group comprised 43.7% (2144) of the sample and exhibited immediate drop‐off in PrEP coverage with 0 (IQR 0–0) median number of visits attended after initiation, indicating that these were clients who initiated PrEP but never came back for a refill.The general characteristics of clients assigned to each group trajectory using the maximum probability assignment rule are presented in Table 
PMC10320042
Patterns of coverage and continuation on PrEP by identified group trajectory
The graphic and quantitative representation of the four distinct trajectories of PrEP coverage are shown in Table Quantitative summary of quarterly PrEP coverage and continuation by group trajectoryViolin scatter plot of coverage (MPR) over 12 months, by group trajectory. *Presents the distribution of the PrEP coverage over the 12‐month period since initiation for each individual in the sample by class trajectory.Profile of PrEP coverage from the latent class mixture model.Individuals in the high coverage trajectory also exhibited high mean quarterly PrEP coverage that was above 90% in the first 6 months of PrEP use but rapidly declined thereafter (Table 
PMC10320042
Correlates of assignment to the respective trajectory class membership
REGRESSION
Results from the multinomial logistic regression model are presented in Figure Forest plot of relative risk ratios and 95% confidence intervals of being assigned to each trajectory relative to the “immediate discontinuation” group trajectory for various baseline demographic and behaviour characteristics.
PMC10320042
DISCUSSION
prevention‐effectiveness, HIV serodifferent couples
In this evaluation of a large programmatic PrEP project in Kenyan public health HIV care clinics, we found moderate continuation on PrEP with a high drop‐off for most clients within 6 months post‐initiation that was characterized by four unique PrEP continuation patterns. More than a third of the individuals exhibited high continuation and coverage patterns on PrEP throughout the first year of use and about two fifth never returned for PrEP refill after initiation.For HIV prevention as opposed to treatment, effective PrEP use is not lifelong but means aligning PrEP use with periods of elevated HIV risk objectively or perceived (i.e. prevention‐effectiveness adherence) [We found that differentiation of coverage and continuation patterns between the four trajectories emerged within 1 month post‐PrEP initiation consistent with patterns of persistence observed for daily medication in other prevention fields [We previously demonstrated that for HIV serodifferent couples [This work has several limitations. First, latent class analysis is an exploratory data‐driven evaluation for which, the emergent number of classes depends on the sample size and study time. In this analysis, the large study population permitted more than sufficient power to identify clinically meaningful trajectories. Second, the final class selection and naming of trajectories is based on the researcher judgement which may not be replicable [
PMC10320042
CONCLUSIONS
In this analysis from a large real‐world PrEP implementation programme in Kenyan facilities, we found evidence of distinct patterns of persistence and continuation on PrEP, with more than one‐third of the study population exhibiting patterns of consistent high PrEP continuation throughout the first 12 months of use. These findings may be useful in tailoring targeted interventions to support continuation and effective PrEP use in this setting.
PMC10320042
COMPETING INTERESTS
JMB is an employee of Gilead Sciences. KKM has received an Investigator Sponsored Research Grant from Gilead Sciences not related to this work awarded to the University of Washington. All other authors declare no competing interests.
PMC10320042
FUNDING
R01MH123267
The study was supported by the National Institute of Mental Health of the US National Institutes of Health (grants R01MH095507, R00MH118134, R01MH123267 and R01AI155086) and the Bill & Melinda Gates Foundation (grant OPP10556051). The project funders had no role in the study design or writing of the report.
PMC10320042
AUTHORS’ CONTRIBUTIONS
Study conceptualization and funding acquisition: KKM and JMB. Data collection tool development: KKM, EMI, JM, and SP. Data collection: KKM, EMI, BN, KN, EB, NM, JO, JM, and SP. Project administration: KKM, EMI, JMB, EB, NM, JO, and JM. Data analysis: TS and AP. Writing—original draft: AP and KKM. Writing—review and editing: All authors. All authors participated in the critical review and have read and approved the final manuscript.
PMC10320042
Supporting information
Supplemental file 1: PrEP Rapid Assessment Screening Tool.Click here for additional data file.Supplemental file 2: Goodness of fit values for the different number of groups in the model.Click here for additional data file.Figure S1Click here for additional data file.
PMC10320042
ACKNOWLEDGEMENTS
We thank the men and women who participated in this project and the staff at implementing facilities and all the project staff for their motivation and dedication.
PMC10320042
DATA AVAILABILITY STATEMENT
Public sharing of individual participant data was not included in the informed consent form of the project and cannot be posted in a supplemental file or a public repository because of legal and ethical restrictions. De‐identified data underlying this project can be made available to interested researchers upon reasonable request by contacting the International Clinical Research Center at the University of Washington (icrc@uw.edu).
PMC10320042
REFERENCES
PMC10320042
Background
Chronic pain, pain
CHRONIC PAIN
Chronic pain conditions involve numerous physical and psychological challenges, and while psychosocial self-management interventions can be of benefit for people living with chronic pain, such in-person treatment is not always accessible. Digital self-management approaches could improve this disparity, potentially bolstering outreach and providing easy, relatively low-cost access to pain self-management interventions.
PMC10492177
Objective
pain
CHRONIC PAIN
This randomized controlled trial aimed to evaluate the short-term efficacy of EPIO (ie, inspired by the Greek goddess for the soothing of pain, Epione), a digital self-management intervention, for people living with chronic pain.
PMC10492177
Methods
Patients (N=266) were randomly assigned to either the EPIO intervention (n=132) or a care-as-usual control group (n=134). Outcome measures included
PMC10492177
Results
pain
The participants were primarily female (210/259, 81.1%), with a median age of 49 (range 22-78) years and a variety of pain conditions. Analyses (n=229) after 3 months revealed no statistically significant changes for the primary outcome of pain interference (
PMC10492177
Conclusions
depression, pain
CHRONIC PAIN
Evidence-informed, user-centered digital pain self-management interventions such as EPIO may have the potential to effectively support self-management and improve psychological functioning in the form of reduced symptoms of depression and improved capacity to regulate thoughts, feelings, and behavior for people living with chronic pain.
PMC10492177
Trial Registration
ClinicalTrials.gov NCT03705104; https://clinicaltrials.gov/ct2/show/NCT03705104
PMC10492177
Introduction
PMC10492177
Background
chronic pain, Chronic pain, pain
CHRONIC PAIN
Chronic pain conditions are common and can be disabling and distressing [Psychological treatment approaches such as cognitive behavioral therapy (CBT) [Digital solutions may have the potential to improve outreach and provide easy and relatively low-cost access to pain self-management interventions [In response to the identified limitations in existing digital pain self-management interventions, we designed, developed, and feasibility pilot-tested EPIO (ie, inspired by the Greek goddess for the soothing of pain, Epione), a digital pain self-management intervention aimed at supporting patients living with chronic pain [In line with recommendations from the Medical Research Council (MRC) framework for the evaluation of complex interventions [
PMC10492177
Objectives
depression, fatigue, anxiety, pain
SECONDARY
This study aimed to examine short-term (ie, 3 months) efficacy findings from an RCT testing the digital pain self-management intervention program EPIO. It was hypothesized that participants receiving EPIO, compared with participants in a care-as-usual control group, would experience significant improvements in primary (ie, pain interference) and secondary (ie, depression, anxiety, self-regulatory fatigue, HRQoL, pain catastrophizing, and pain acceptance) outcomes after 3 months of access to the EPIO program. System use, usefulness, and ease of use were examined on an exploratory basis.
PMC10492177
Methods
PMC10492177
Study Design
pain
A 2-armed RCT was used with participants randomly assigned to (1) the digital pain self-management intervention program EPIO or (2) a care-as-usual control group.
PMC10492177
Participants and Recruitment
pain, psychosis, psychological illness, migraine, chronic pain, cancer-related pain
MIGRAINE, CHRONIC PAIN
Participants were people living with chronic pain, recruited from November 2019 to February 2021 through a major medical institution (Oslo University Hospital, Norway), collaborating with local health care services and primary care practices, social media channels, and patient organizations’ web pages. The eligibility criteria were as follows: (1) living with chronic pain in general (ie, across pain classification and etiology); (2) pain duration ≥3 months (ie, self-reported); (3) age ≥18 years; (4) access to a smartphone or tablet; (5) ability to understand oral and written Norwegian; and (6) ability to attend an in-person introduction session either at a nearby health care facility or by using a secure video link (ie, due to pandemic restrictions as of spring 2020). The exclusion criteria included cancer-related pain, migraine, and untreated severe psychological illness (eg, psychosis), all of which were self-reported.
PMC10492177
Study Procedure
chronic pain
CHRONIC PAIN
Patients living with chronic pain were verbally informed about the EPIO study by collaborating partners or through flyers at various health care sites. If interested, the patient’s contact information was forwarded to the project team, who then provided additional information about study participation to those interested. Patients could also contact the study staff directly through a study phone number or website. Study information was also published on social media (eg, Facebook), and these posts were frequently republished by individuals or patient organizations.All participants provided written informed consent before completing the baseline outcome measures through a secure research server at the Services for Sensitive Data (The intervention group participated in a face-to-face introduction session where they received (1) an introduction to the EPIO intervention program, (2) help to download the EPIO app from the Apple App Store or Google Play Store, and (3) guidance on how to use the program. The introduction session was initially planned to be an in-person session but was also provided digitally (ie, videoconference) as of spring 2020 due to the ongoing COVID-19 pandemic.The study period was 3 months after the introduction session. The intervention group received follow-up phone calls from the members of the project team at approximately 3 and 7 weeks with standard questions about status (eg, to see how the use of the EPIO program was going and whether they had any use-related questions). The project team could also be contacted through the project study phone for questions or technical assistance. System use was logged, and outcome measures were completed through the secure research server. Participants completing at least 6 (67%) of the total 9 EPIO modules during the study period were defined as program completers for study purposes [
PMC10492177
The EPIO Intervention Program
chronic pain
CHRONIC PAIN, MUSCLE RELAXATION
The app-based EPIO program consists of 9 CBT-based modules with aspects of ACT, each combining educational information (eg, thought challenges, coping strategies, values, and activity pacing) with practical and related exercises (eg, diaphragmatic breathing, progressive muscle relaxation, visualization, and mindfulness) for people living with chronic pain [Example screenshots of the EPIO intervention program.
PMC10492177
Care-As-Usual Control Group
Participants in the care-as-usual control group completed the study outcome measures at baseline and at 3 months, without any additional follow-up from the research team. The project team did not seek to monitor or control any type of additional care potentially sought by participants in the care-as-usual control group during the study period. If interested, participants in the control group received access to the EPIO program after the completion of the study (ie, 12 months).
PMC10492177
Data Collection and Outcome Measures
TSD
All questionnaires and outcome measures were completed by the participants (ie, self-report) using the secure TSD server. Participants completed a study-specific sociodemographic and disease-related questionnaire at baseline, and outcome measures were collected at baseline (ie, before randomization) and at 3 months (ie, follow-up) after the introduction session.
PMC10492177
Psychosocial Outcome Measures
PMC10492177
System Use, Usefulness, and Ease of Use
TSD
Details related to use and program progress (ie, system use) were collected automatically, stored on a secure research server (ie, TSD), and later extracted in accordance with informed consent and existing safety and privacy regulations. At the 3-month follow-up, participants completed a 6-item study-specific questionnaire related to usefulness and ease of use based on the research team’s previous experience [
PMC10492177
Power Analysis and Sample Estimates
eHealth interventions for comparable samples have shown a Cohen
PMC10492177
Statistical Analyses
depression, fatigue, anxiety, pain
REGRESSION
Baseline characteristics, usefulness, ease of use, and user patterns were summarized with means and SDs for normally distributed variables and medians and ranges for variables with skewed distributions. The type of distribution was assessed using the visual inspection of histograms and q-q plots and by comparing means and medians. Categorical data were presented as counts and percentages. Change scores, defined as a difference between scores at baseline and at 3 months, were calculated for pain interference, anxiety, depression, self-regulatory fatigue, HRQoL, pain catastrophizing, and pain acceptance and used as dependent variables in linear regression models. As statistically significant differences were observed between the intervention and care-as-usual control groups for age and years living with pain, these variables were included in the intention-to-treat analysis as possible confounders. We included only individuals with data on both assessment points; thus, there were no missing data and no imputation of missing values was necessary. Model fit was tested using visual inspection of the residual plots of histograms, and the model fit was satisfactory for all the presented variables (ie, change scores).
PMC10492177
Ethics Approval, Informed Consent, and Participation
TSD
The study was registered in ClinicalTrials.gov (NCT03705104) and approved by the Regional Committee for Medical and Health Research Ethics (REK 2018/8911) and the Hospital Privacy Protection Committee (ie, institutional review board equivalent; PVO 2017/6697). The study method and results were reported following the CONSORT-EHEALTH (Consolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online Telehealth) checklist of information to include when reporting an RCT (All potential participants received information about the nature of the study and details about study participation before deciding whether to participate. All study participants provided written informed consent. The signed consent forms were stored separately from any study data under lock and key in a separate departmental cabinet. Data from questionnaires and outcome measures were collected through the secure TSD platform throughout the study, and all personally identifiable information was deidentified from the TSD database before exporting the study data to a local secure server for further analysis. The participants did not receive compensation for participation in the study.
PMC10492177
Results
PMC10492177
Group Differences
SECONDARY
Primary and secondary outcomes, assessing between-group differences in changes from baseline to the 3-month follow-up, are reported in
PMC10492177
System Use, Usefulness, and Ease of Use
In total, 63 of 125 (50.4%) participants in the intervention group completed at least 6 of the 9 modules within the 3-month study period and were considered completers. There were no significant differences in sociodemographic variables or outcome measures (ie, MD in change) between program completers and noncompleters (all
PMC10492177
Discussion
PMC10492177
Principal Findings
chronic pain, fatigue, anxiety, pain
CHRONIC PAIN, SECONDARY
In this RCT, people with chronic pain having access to the digital pain self-management intervention EPIO, compared with care-as-usual controls, did not report statistically significantly different changes in the primary outcome of pain interference on function after 3 months nor in the secondary outcomes of anxiety, HRQoL, pain catastrophizing, or pain acceptance. However, participants in the intervention group reported a significant decrease in symptoms of With The numerous physical and psychosocial challenges associated with living with chronic pain may naturally contribute to symptoms of Participants receiving EPIO, compared with participants in the care-as-usual control group, also reported a statistically significant decrease in Considering the possibility that self-regulatory fatigue may be a At the 3-month follow-up, half of the participants had completed at least 6 out of 9 modules, slightly below the completion rate in the EPIO feasibility pilot study (62%) [There are several professional challenges in the transfer of traditional in-person service models to digital self-management interventions. In-person treatment entails several evident values, such as the therapist-patient relationship, but little is known about the type and frequency of human interaction that may be preferred or that may provide optimal effect. Reviews have indicated that professionally guided digital self-management interventions may be more effective than self-guided interventions [Finally, participants in this study described the EPIO program as useful (95/109, 87.2%) and easy to use (101/109, 92.7%), with easily understandable exercises (106/109, 97.2%) and excellent system usability (92.5 of 100). These findings are in line with those from the EPIO feasibility pilot study [
PMC10492177
Study Limitations, Strengths, and Future Directions
chronic pain, pain
CHRONIC PAIN
This study had several limitations. First, participants were recruited through social media and by collaborating with project partners, which may suggest that the study population consisted of highly motivated individuals. Therefore, it is not clear whether people with chronic pain would, in general, be interested in or benefit from a digital self-management intervention such as EPIO. However, therapeutic interventions are likely mainly effective if the participants are indeed interested in participating, which may support the notion that interested participants may be more likely to benefit from such self-management programs.Second, most participants in this study were female, were White, had higher education, and had lived with chronic pain for many years. Randomization in this study was computerized and stratified by sex to ensure even sex group distribution, but future studies should seek to identify ways to include more balanced proportions of participants (eg, sex, ethnicity, education, and years with pain) in self-management interventions [Third, the EPIO intervention was developed aiming to target chronic pain Fourth, the intervention group was compared with a care-as-usual control group, in which the participants did not receive the EPIO intervention program or any other care from the project team. However, as there was no way of controlling or assessing whether participants in the control group sought any other type of care (eg, self-management courses or mindfulness interventions) during the study period, there is a potential risk that this unknown factor could have impacted the study results. Given this challenge with rather pragmatic RCTs, inquiring about the potential additional external care received by members of the care-as-usual control group might have provided further details about this unknown factor.Fifth, the study did not include a numerical primary outcome measure cut-off score for study inclusion, and it is possible that such a cut-off score (eg, only including participants providing a score above mild pain interference, such as >3 or >5) could have affected the primary outcome results of this study. However, with pain and the interference of pain being an individual and subjective experience, the rationale for excluding people living with chronic pain based on subjective scoring must be thoroughly considered before implementation.Sixth, although the statistical power for the between-group effects was adequate, future studies may consider testing potential moderating effects, for example, related to baseline medical comorbidities, in larger study samples. Finally, this study explored short-term (ie, 3 months) findings from an RCT testing the EPIO intervention program. Future research should examine these long-term findings and follow-up. Qualitative explorations may also, in line with recommendations from the MRC [The fact that the EPIO intervention program was designed and developed based on existing recommendations for digital interventions, including a solid theoretical foundation and development in close collaboration with end users and other stakeholders (eg, health care professionals), is a clear study strength. The simple blended care delivery model used in the study may also guide how such digital interventions could be delivered and implemented in the future, and future research should also aim to test and compare various delivery approaches (eg, blended care delivery vs digital self-management only). This type of research could add value to the understanding of what may constitute the optimal digital intervention and its delivery for those living with chronic pain and also identify the population groups, stages, or types of condition that may benefit from digital pain self-management.
PMC10492177
Conclusions
chronic pain, depressive symptoms, fatigue, pain
CHRONIC PAIN, RECRUITMENT
Digital pain self-management interventions, such as EPIO, delivered in a simple blended care model, may have the potential to support self-management and improve coping and psychological functioning for people living with chronic pain. Despite not showing a statistically significant impact on the primary outcome of pain interference on function after 3 months in this RCT, participants with chronic pain conditions having access to the EPIO intervention showed a statistically significant decrease in depressive symptoms and self-regulatory fatigue (ie, increased capacity to regulate thoughts, feelings, and behavior), compared with those in the care-as-usual control group. Therefore, long-term efficacy testing is warranted and in progress.The authors would like to thank the patients who participated in this study. Without them, there would be no such research. The authors would also like to thank all collaborating partners and participating health care providers for enabling recruitment and supporting this project. Finally, the authors would like to thank the research project team members, including the content development group and the design and software team at the Department of Digital Health Research at Oslo University Hospital, for their exceptional efforts throughout the project.Conflicts of Interest: LSN is an unpaid board member of dHealth AS, a company eventually aiming to commercialize the EPIO program. All other authors declare no other conflicts of interest.CONSORT-eHEALTH (Consolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online Telehealth) checklist (V 1.6.1).Estimates at both time points and between-group differences in the change from baseline to the 3-month follow-up.
PMC10492177
Abbreviations
Depression, Anxiety, Pain
acceptance and commitment therapyBrief Pain Inventorycognitive behavioral therapyConsolidated Standards of Reporting Trials of Electronic and Mobile Health Applications and Online TelehealthChronic Pain Acceptance QuestionnaireHospital Anxiety and Depression Scalehealth-related quality of lifemean differenceMedical Research CouncilPain Catastrophizing ScaleSF-36 Short Form Health Surveyrandomized controlled trialSystem Usability ScaleTjenester for Sensitive Data (Services for Sensitive Data)
PMC10492177
Data Availability
Data sets from this study are, due to the nature of patient-sensitive information, not available for public sharing through public archives or repositories. However, deidentified data from this study will be made available in accordance with institutional standards upon contacting the corresponding author.
PMC10492177
Aims
The CHA
PMC10465382
Materials and methods
atrial fibrillation
ATRIAL FIBRILLATION
This is an observational analysis of 1127 atrial fibrillation patients previously enrolled in the MISOAC-AF trial. After a median 2.6-year follow-up period, baseline and follow-up CHA
PMC10465382
Results
The mean baseline, follow-up, and Delta CHA
PMC10465382
Conclusion
atrial fibrillation
ATRIAL FIBRILLATION
In atrial fibrillation patients, changes in CHA
PMC10465382
Trial registration
This is an observational, post-hoc analysis of the MISOAC-AF randomized controlled trial, registered on ClinicalTrials.gov (identifier: NCT02941978; registered: October 21, 2016).
PMC10465382
Supplementary Information
The online version contains supplementary material available at 10.1007/s00380-023-02278-1.
PMC10465382
Keywords
Open access funding provided by HEAL-Link Greece.
PMC10465382
Introduction
stroke, cardiac arrhythmias, arrhythmia, AF
CARDIAC ARRHYTHMIAS, ATRIAL FIBRILLATION (AF), ARRHYTHMIA, STROKE, DISEASE
Atrial fibrillation (AF) dominates the field of cardiac arrhythmias by being the most common arrhythmia globally, with a rapidly increasing occurrence and an extensive disease burden [As the majority of AF patients are among the elderly population, they present with an inconstant variety of stroke risk-contributing comorbidities [In this study we aimed to assess the connection between the accumulation of new-onset comorbidities, depicted as changes in CHA
PMC10465382
Materials and methods
PMC10465382
Study population
non-valvular Atrial Fibrillation
This study constitutes a post-hoc, observational analysis of the MISOAC-AF trial (Motivational Interviewing to Support Oral Anti Coagulation adherence in patients with non-valvular Atrial Fibrillation, ClinicalTrials.gov identifier: NCT02941978), a prospective randomized controlled trial, conducted in the cardiology ward of a tertiary hospital. The detailed study design and its results have been published previously [The baseline population of the present study consisted, in its entirety, of adult patients with non-valvular AF who were enrolled in MISOAC-AF. The participants were originally recruited between December 2015 and June 2018. Study approval was obtained by the Ethics Committee of the Aristotle University of Thessaloniki (Reference 173/30.11.2015). The study was in accordance with the principles of the declaration of Helsinki [
PMC10465382
Data collection
All associated data, such as demographic and baseline clinical characteristics, personal information, medication history and baseline CHA
PMC10465382
Data processing and statistical analysis
stroke
STROKE, EVENTS, ISCHEMIC STROKE
The investigated outcome was the incidence of ischemic stroke. The electronic records were used in conjunction with the details provided during the follow-up interviews, to determine stroke events and the onset of any new comorbidities. All the above data were used to calculate the participants’ follow-up CHAFollowing the calculation of the Delta CHA
PMC10465382
Results
PMC10465382
Impact of the Delta CHA
The Kaplan–Meier curve for the stroke-free probability, for different Delta CHAKaplan – Meier analysis survival curves for separate groups of Delta CHA
PMC10465382
Predictive validity of the Delta CHA
The ROC curve for the baseline, follow-up, and Delta CHAReceiver operating characteristics (ROC) curve for the Baseline, Follow-up, and Delta CHA
PMC10465382
Discussion
stroke, CHF
CHF, STROKE
This observational study indicates the dynamic state of stroke risk in patients with AF, as assessed through the CHAThe predictive value of Delta CHAThe Delta CHAA more recent study appraised the association of Delta CHAEvidently, the previous studies enforced strict enrollment criteria to their participants. With the exception of the study by Yoon et al. [Interestingly, despite the known association of the sustained types of AF with a higher incidence of CHF [Based on the results of our study, future research should assess the effectiveness of an increased vigilance management strategy for patients with higher-than-baseline follow-up CHA
PMC10465382
Limitations of the study
The observational nature of the study may involve limitations. The relatively small study sample may be a potential liability compared to previously performed research. However, the less restrictive enrollment criteria allowed a more adequate representation of real conditions. The determination of only two CHA
PMC10465382
Conclusions
stroke
STROKE
The stroke risk in AF patients is non-static, as demonstrated by the changes in their CHA
PMC10465382
Acknowledgements
None.
PMC10465382
Author contributions
AS and ID conceived the study. AS, ASP, AK, and DVM were responsible for patient enrollment and follow-up. ET, EG, OK, and AB were involved in data acquisition. ET, AS, and ASP performed the statistical analyses. AT and GG had the overall study supervision. ET and AT wrote the original draft of the manuscript. All authors reviewed and edited the original draft and approved the final version of the manuscript.
PMC10465382
Funding
Open access funding provided by HEAL-Link Greece. No financial support was received for the present or the original (MISOAC-AF) study or publication of this article.
PMC10465382
Data availability
Anonymized data can be made available upon reasonable request to the corresponding author.
PMC10465382
Declarations
PMC10465382
Conflict of interest
The authors declare that they have no conflict of interest.
PMC10465382
Ethical approval
Study approval was obtained by the Ethics Committee of the Aristotle University of Thessaloniki (Reference 173/30.11.2015). The study was performed in line with the principles of the Declaration of Helsinki.
PMC10465382
Consent to participate
Written informed consent was obtained from the patients prior to their participation to this study.
PMC10465382
References
PMC10465382
Background
chronic whiplash-associated disorders, WADs
Neck-specific exercises (NSE) supervised by a physiotherapist twice a week for 12 weeks have shown good results in chronic whiplash-associated disorders (WADs), but the effect of exercise delivered via the internet is unknown.
PMC10337460