title
stringlengths 1
1.19k
| keywords
stringlengths 0
668
| concept
stringlengths 0
909
| paragraph
stringlengths 0
61.8k
| PMID
stringlengths 10
11
|
|---|---|---|---|---|
Questionnaires | Patients in the RobExReha-Patients group received training with the RobExReha device. A session consisted of the donning and setup of the device, subsequent gaming therapy, termination of the session and doffing of the device. Amount and mode of robotic support as well as the length of the gaming sessions were adjusted by the therapist according to the patient’s needs. Figure
User Interface of the RobExReha system for the therapist. In this screen, the therapy session could be planned and adapted: Separate gaming sessions could be added and adjusted in length (german description: “Dauer”), as well as the rest length between the sessions (“Pausezeit zwischen den Spielen”). Additionally, the requirements in terms of range of motion (“Beweglichkeit”) and the support by the robot (“Kraft”) could be adjusted via this interface by the therapist. Under the “Calc-Mode” the paradigm of robotic support (adaptive/non-adaptive) could be chosen;The therapists administered the RobExReha device in at least five sessions to a patient before answering the questionnaire. They were responsible for donning, doffing, and configuring the training session as well as supervising the patient.The patients in the Reference Group received rehabilitation training with the commercially available ArmeoPower or ArmeoSpring (Hocoma AG, Switzerland) as part of their inpatient schedule. Six patients in the Reference Group trained with the ArmeoPower device and five with the ArmeoSpring device, with a mean of 15 (± 25, min: 4, max: 90) completed therapy sessions. They received no further intervention regarding this study. This data acquisition was done during the developmental stage of the RobExReha device and thus before the data acquisition of the RobExReha device.
Overview over the standardized questionnaires used for the usability evaluationQUEST: Quebec User Evaluation of Satisfaction with assistive technology, pAR: presence in augmented reality questionnaire, SUS: System Usability Scale, UEQ-short: short version of the User Experience Questionnaire | PMC10422755 |
||
Statistical methods | ± | Both patient groups filled out the Quebec User Evaluation of Satisfaction with assistive Technology (QUEST) [As the RobExReha-Patients group used the HoloLens for the gaming environment, they additionally filled out the “presence in augmented reality” (pAR) questionnaire (adapted from [The therapists completed a questionnaire consisting of the same adapted device subscale of the QUEST as the patients, the system usability scale (SUS) [The results were evaluated descriptively and the results of QUEST and RTLX from the RobExReha-Patients and the Reference Group were compared using Mann-Whitney U-test. Due to the exploratory character of the study, no correction for multiple comparisons was done. Analyses were done in Matlab (The MathWorks Inc., US) and SPSS (IBM, US). The alpha level was set to 0.05 for all analyses. Data is presented as either the mean (± standard deviation) or the median (min-max). | PMC10422755 |
|
Results | PMC10422755 |
|||
Safety | temporary shoulder pain, shoulder pain | ADVERSE EVENTS, ADVERSE EVENT | No serious adverse events occurred and none of the patients mentioned feeling unsafe at any time. However, one study-related non-serious adverse event was registered: temporary shoulder pain, which vanished within an hour after the therapeutic intervention. This patient had an unstable sitting posture in the wheelchair, which likely contributed to the shoulder pain.Three of 54 therapy sessions had to be terminated earlier due to technical problems and four due to patient reasons (lack of attention, discomfort in the wheelchair or onset of shoulder pain). | PMC10422755 |
Usability | PMC10422755 |
|||
Feasibility and technical aspects | spasticity | Concerning the robotic set up, the positioning of the LBR arm on the cart (Fig. For three patients, the arm weighing process did not function as intended. As a result, the default weight of 0.01 kg was shown by the robot and the weight needed to be estimated and corrected manually. These patients suffered pronounced spasticity in the elbow flexors. | PMC10422755 |
|
Video protocol – donning and doffing times | pain | Starting and preparing the RobExReha system included the activation of the system and HoloLens, the connection of the HoloLens to the robot, donning the elbow brace onto the patient’s arm and connecting it to the robot flange, weighing of the arm as well as preparation and donning of the HoloLens. This collectively took a median of 293 s (range 173–452 s). The two most time-consuming steps of the starting procedure were donning the HoloLens, which took a median of 49 s (10–151 s), and donning of the elbow brace, which took a median of 47 s (40–100 s).Termination and doffing of the RobExReha system included a pain assessment, disconnecting the brace from the robot and doffing of the brace and HoloLens. In total, this took a median of 67.5 s (29–114 s). Doffing the HoloLens took a median of 17.5 s (13–37 s). Disconnecting the brace from the robot was perceived as easy, which was reflected by the median disconnection time of 12 s (6–28 s). | PMC10422755 |
|
Questionnaires | PMC10422755 |
|||
Discussion | orthosis |
Results of the Quebec User Evaluation of Satisfaction with assistive technology (QUEST) patients’ questionnaire: Scores can range from 1 (not satisfied at all) to 5 (highly satisfied). Asterisks indicate significant differences. Circles indicate outliersThe results of the QUEST (see Fig. The RobExReha-Patients found the arm orthosis, grip module and HoloLens AR-glasses to have limitations: Four patients mentioned that the orthosis (especially the part for the upper arm) could be more comfortable. Four patients found the grip module to be uncomfortable or not be adaptable enough (in length and/or in wrist motion). Two patients mentioned the HoloLens being uncomfortable or heavy.The results of the RTLX questionnaire are displayed in Fig.
Results of the -Raw Task Load Index (RTLX) subscale scores displayed as boxplotsThe results from the pAR questionnaire are shown in Fig.
Results of the presence in Augmented Reality (pAR) questionnaireFurther remarks from the patients regarding the visualization of the game through the HoloLens concerned the limited field of view. This led to difficulty in understanding the game (two patients) and the process of applying and adjusting the glasses, which one patient perceived as taking too much time.The therapists that administered the RobExReha system rated the usability overall slightly lower in the QUEST (mean: 3,7 ± 0.7, range: 2.8–4.6) than the patient groups. The items that were ranked lowest were “reliability and safety” (3.1 ± 0.7), “effectiveness” (3.3 ± 1.5) and “adjustability” (3.5 ± 0.7). The QUEST item ranked highest by the therapists was the “dimension” (mean: 4.8 ± 0.5). The overall mean usability as measured with the SUS was 60.5 (SD 21.8 range 25-82.5). The UEQ-short (Fig.
Results of the evaluation by the RobExReha-Therapists Group: The two aspects that the therapists liked most about the system were the integration of the Augmented Reality Gaming aspect, and the donning procedure of the robotic device. The magnetic coupling of the brace enables the therapists to don and adjust the brace in a comfortable position prior to connecting the arm to the robot, which was perceived as highly usable.The objective was to evaluate the safety, clinical feasibility and usability, and potential benefits of a novel arm rehabilitation device based on an LBR robot and a serious game in AR (RobExReha system), from both a patient’s and therapist’s perspective. Key results indicate a safe use of the device with neurologically impaired patients and an acceptable to good usability reported by patients’ and therapists’ questionnaires. The combination of augmented reality using the HoloLens with a robotic arm training has shown to work for the patients that participated in the study. Furthermore, some features were identified that need improvement, such as an increase in system stability or better adjustability of the arm orthosis. | PMC10422755 |
|
Safety and clinical feasibility | shoulder pain | CONSTRICTION, MINOR | The results suggest that the use of the RobExReha system was safe and feasible in neurological patients. None of the patients mentioned safety concerns. The occurrence of shoulder pain in one patient, however, highlights that special caution should be taken when treating patients with limited stability in the trunk and shoulder girdle with the RobexReha system.The positioning of the LBR arm in the RobexReha system needs further adjustments to meet the needs of the patients’ range of motion, as it led to movement constrictions in some cases. The implementation of the compensation alert for detecting shoulder compensation proved to be useful once the threshold was properly adjusted. We believe that the alert successfully helped the patients to re-focus on the trunk stability without therapist intervention. Such functionality is very useful for enhancing self-efficacy and reducing the supervision effort.The HoloLens was generally feasible and well-tolerated with only minor fitting issues. | PMC10422755 |
Donning and doffing | Most patients found that the device was relatively easy to put on. From a therapist’s perspective, only one therapist mentioned difficulties, specifically in the connection process of the elbow brace to the flange: sometimes the robot seemed to be in a slightly incorrect position. The large range of donning times of the HoloLens, from 10 to 151 s, reflects connection issues that were apparent in some cases. Despite this, the therapists valued the concept of the human-machine interface and perceived the donning and doffing times as acceptable. Particularly, the magnetic fixture of the elbow brace showed to be practicable in a clinical context, as it allows to don the brace in any comfortable position before attaching it to the robot. It also ensures a fast and easy disconnection from the robot. Regarding the donning and doffing times, this is supported by the results of Oliveira et al. [ | PMC10422755 |
||
Patients’ perspective | PMC10422755 |
|||
Usability questionnaires | Due to the prototype stage of the RobExReha device, we anticipated lower usability in the QUEST when compared to the Armeo Reference Group. However, this was only confirmed for the overall score and the items “reliability and safety” and “easy to use”. Yet, usability was generally rated positive by the patients in all questionnaires. Moreover, the mean QUEST score seems reasonable for a newly developed device, as it is comparable to the results from Guillén-Climent et al. who examined the usability of another novel rehabilitation device for upper extremity using robotics and serious gaming [Features largely contributing to these lower ratings were the hand module (insufficient adjustability of length and wrist positions), the upper part of the arm orthosis (discomfort) and the HoloLens (too heavy or ill-fitting). The first two issues could be addressed during further developmental iterations of the robotic interface. Concerning the AR glasses, the HoloLens 2 (Microsoft Corp., US), might offer a greater field of view and improved comfortability. Additionally, the categories “reliability” and “safety” should be assessed separately in future evaluations, as lower perceived reliability largely contributed to the low ratings of this item, and no patient mentioned feeling unsafe at any moment. | PMC10422755 |
||
Workload | The overall workload in the RTLX tended to be higher in the RobExReha group with a mean score of 41.7 compared to the Reference Group (mean: 34.1) without reaching a significant difference neither in the overall score nor domain-wise. Those are slightly lower compared to global work load scores, where video gaming had a median RTLX score of 56.5 [ | PMC10422755 |
||
3D perception | stroke, impairments in stereoscopic vision, reduced mobility of the cervical spine | STROKE, STILL | The gaming environment in AR was an important focus of this study. Specifically, concerns regarding the spatial perception of stroke patients when using the HoloLens were of interest. The feasibility of using the HoloLens in neurological patients as shown by Rohrbach et al. [Regarding the AR perception by the patients, our results are very promising: All patients perceived or learned to perceive the holograms as three-dimensional and placed in space, with limited effort. Considering eight patients had impairments in stereoscopic vision, this is a remarkable finding. Still, the visual perception was challenging for one patient with reduced mobility of the cervical spine. As the field of view of the HoloLens is limited, the implemented game required the patients to explore the space in front of them actively by moving their head. In the implemented game, the holograms were placed in space, without linking them to physical objects within the room (e.g., placing a hologram on an actual table).It can be hypothesized that the linking of the holograms onto real objects, preferably in a realistic setting (e.g., a table or shelf), could not only increase the meaningfulness of the game, but also facilitate the identification of the holograms in space. Nevertheless, as the individualized combination of different technologies guides the way to future rehabilitation [ | PMC10422755 |
Therapists’ perspective | STILL | The system was rated by the therapists in the UEQ-S as “leading edge”, “inventive”, “interesting” and “exciting”, despite some improvable features (as mentioned above) and the limitations in system stability. The overall usability as measured with the SUS was 60.5 ± 21.8 (25-82.5), which corresponds to an average of an “ok” to “good” usability [Most likely, the downgrade in usability in this study arose from system stability issues (e.g., connection problems to the HoloLens, Robot Safety Stops) that sometimes required rebooting and thus made the administration of the device rather complex and time-consuming.The RobExReha system provided a 2D-therapist view of the HoloLens view on a separate monitor. Still, most therapists remarked that they would have preferred to view the same holograms as the patient, to better support the patient. | PMC10422755 |
|
Potential optimization | cognitive and motor function, spasticity | MINOR | Although the RobExReha system was generally perceived as inventive and usable, possibilities to improve the system could be identified:
The positioning of the LBR should be adjusted to better accommodate the targeted range of motion and avoid conflicts with the axis boundaries of the LBR arm.Another solution for the weighing process for robotic calibration should be considered for the use in neurological patients, as pathological muscle tone deviations (e.g., spasticity) may be present. For example, an estimation derived from anthropometric tables combined with a feedforward model approach could resolve the problem [For future scenarios, the chosen setup with the LBR arm would allow the inclusion of a resistance mode to enlarge the applicability. As such, patients with minor impairments to those with very limited arm function could use the device. The integration of a functional hand module would further add functionality to the robot and expand the gaming scenarios.A second HoloLens for the supervising therapist would ease the support of the patient and opens possibilities of manipulating the holographic cues interactively.Further gaming scenarios adapted to different levels of cognitive and motor function would enlarge the applicability of the system (e.g., simpler, and more complex gaming scenarios to motivate patients with different abilities).The system stability should be increased to ensure good usability in clinical context. | PMC10422755 |
Limitations | left-sided impairments, stroke | STROKE | Due to the prototype stage, the RobExReha system was only available for training of the right arm, which led to limitations in patient inclusion. The Reference Group, contrarily, additionally included patients with left-sided impairments. This could lead to bias; for example, in stroke patients, as the affected hemisphere influences the symptoms. Additionally, regarding the questionnaire evaluation, only patients with good cognitive abilities were enrolled in the study, which does not reflect the wide variation of neurological patients potentially training with robotic devices.Another possible risk of bias arises as this study was not blinded and the patients, therapists and assessors were aware of which system they were evaluating. Due to shortages in personnel resources, sometimes a participant had to act as both an assessor and administering therapist, potentially leading to biased results in the questionnaires. However, given that this was a first proof-of-concept study, we consider the risk to be acceptable.Further, regarding the study design as proof-of-concept study, no conclusions on efficacy of this type of therapy can be made. | PMC10422755 |
Conclusion | We investigated a novel robotic arm therapy system in combination with an augmented reality serious game. The system demonstrated to be feasible in patients with impairments of the upper extremity from neurological causes and good cognitive function. Notably, the good acceptance and perception of the game using the HoloLens is promising.Despite the prototype stage of the RobExReha device, the system’s usability and safety was mostly rated not significantly different from an established device on the market, which is a considerable achievement. From a therapist’s perspective, the lack of reliability in terms of system instabilities largely contributed to lower usability ratings. Future developments of technology-assisted therapy devices in neurorehabilitation should thus focus on developing stable, simple, and easy-to-use systems. | PMC10422755 |
||
Acknowledgements | We would like to thank Christian Frede and his team (AmbiGate GmbH, Tübingen) for their contribution to the software of the system and Dr. Winfried Ilg (Centre for Integrative Neuroscience, Tübingen) for useful discussions and consultation. We want to thank our colleagues at BEC GmbH, Fraunhofer IPA and Schön Klinik that contributed to the development and testing of the device. Special thanks go to patients and therapists that volunteered in this study. | PMC10422755 |
||
Author’s contributions | MH, FM | AC: methodology, formal analysis, investigation, data curation, writing – original draft, visualization, project administration SR: investigation, resources, writing – original draft, MH: writing – review & editing, conceptualisation, methodology, project administration, JL: resources, writing – original draft, TA: methodology, investigation, project administration JD: conceptualization, supervision, HB: conceptualization, supervision, FM: conceptualization, methodology, project administration, funding acquisition, supervision, writing – review & editing. All authors reviewed the manuscript. | PMC10422755 |
|
Funding | The development of the RobExReha device and the clinical study were done within the scope of the “RobExReha”-project funded by the German Federal Ministry of Education and Research (BMBF) under the funding code 16SV7849. | PMC10422755 |
||
Data Availability | The dataset supporting the conclusion of this article is available on reasonable personal request. | PMC10422755 |
||
Declarations | PMC10422755 |
|||
Competing interests | This study was performed while SR was employed at BEC GmbH and JL at Fraunhofer IPA, who manufactured together with Ambigate GmbH the RobExReha system. | PMC10422755 |
||
Ethics approval and consent to participate | DER | This study conforms with the Declaration of Helsinki, all participants provided informed consent prior to enrolment. An ethical approval was obtained (Ethikkommission der Bayerischen Landesärztekammer) and the trial was registered at DRKS (DRKS00022136). | PMC10422755 |
|
Consent for publication | Not applicable. | PMC10422755 |
||
References | PMC10422755 |
|||
Background | kidney damage, autosomal dominant polycystic kidney disease, ADPKD | ADPKD, PROGRESSION, AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE | Tolvaptan slows expansion of kidney volume and kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD). Progression during childhood could be treated before irreversible kidney damage occurs, but trial data are lacking. We evaluated the safety and efficacy of tolvaptan in children/adolescents with ADPKD. | PMC10101612 |
Methods | ADPKD | ADPKD | This was the 1-year, randomized, double-blind, portion of a phase 3b, two-part trial being conducted at 20 academic pediatric nephrology centers. Key eligibility criteria were ADPKD and eGFR ≥60 ml/min per 1.73 m | PMC10101612 |
Results | Among the 91 randomized (group 1, | PMC10101612 |
||
Conclusions | ADPKD | ADPKD | Tolvaptan exhibited pharmacodynamic activity in pediatric ADPKD. Aquaretic effects were manageable, with few discontinuations. | PMC10101612 |
Clinical Trial registry name and registration number: | ADPKD | ADPKD, AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE | Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease) NCT02964273. | PMC10101612 |
Introduction | hereditary kidney disorders, ADPKD, impairment of kidney function, Autosomal dominant polycystic kidney disease | ADPKD, KIDNEY FAILURE, DISEASE PROGRESSION, AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE | Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common hereditary kidney disorders, characterized by the progressive formation and growth of cysts, leading to impairment of kidney function and eventually kidney failure.Given the phenotypic variability, uncertainty exists regarding the management of children with ADPKD or those at risk because of family history.The management of ADPKD in adults has been changed by the vasopressin V2 receptor antagonist tolvaptan. In the TEMPO 3:4 clinical trial, tolvaptan inhibited the cyst-driven increase in total kidney volume (TKV) and slowed the decline in kidney function in adults at risk of rapid disease progression, with effects on kidney function confirmed in the REPRISE trial.We conducted a phase 3, 1-year, randomized, double-blind, placebo-controlled, multicenter trial in participants with ADPKD aged 4–17 years. The trial objectives were to evaluate the pharmacodynamics, safety, and efficacy of tolvaptan in children and adolescents with ADPKD. | PMC10101612 |
Methods | PMC10101612 |
|||
Participants | Study methods have been reported.Exclusion criteria included alanine aminotransferase/aspartate aminotransferase ≥1.5 × upper limit of normal or any medical condition that could interfere with the evaluation of the trial objectives or endanger participant safety. | PMC10101612 |
||
Trial Design | This was a phase 3b, two-part trial (EudraCT number: 2016-000187-42; | PMC10101612 |
||
Treatments | Participants received tolvaptan or placebo daily in a split-dose regimen, with the first dose taken upon waking and the second 8–9 hours later ( | PMC10101612 |
||
End Points | early-stage disease | Given that treatment effects on TKV or kidney function are difficult to measure in a pediatric population with early-stage disease, pharmacodynamic parameters were considered the most appropriate coprimary end points: change from baseline in spot urine osmolality and spot urine specific gravity at week 1 in all participants. Spot urine samples were collected before the morning dose and before eating or drinking anything for breakfast from the urine void (second-morning void) taken after the first morning's void and ideally collected as a mid-stream, clean catch. The samples were analyzed as described in the | PMC10101612 |
|
Assessments | Postscreening assessment visits occurred at baseline (day 1), week 1, and monthly for 12 months. Participants aged 12–17 years underwent TKV assessment by MRI performed according to published standards at screening and month 12. | PMC10101612 |
||
Statistical Analyses | SECONDARY | A sample size of ≥60 participants aged 12–17 years was planned. It was expected that approximately 40 participants aged 4–11 years would also enroll for an anticipated total enrollment of 100 participants. As data were to be summarized descriptively, no formal power calculations to determine sample size were undertaken. All outcomes, including primary and secondary outcomes, were evaluated using observed values only (no missing data imputation). Missing data were to be mitigated by encouraging participants who withdrew from treatment to return for their remaining visits.The full analysis set, which was a modified intent-to-treat population, was used for the efficacy analyses. It consisted of all participants who were randomized to a treatment group, received ≥1 dose of the trial drug, and had both a phase A baseline and ≥1 postbaseline efficacy evaluation. The safety population consisted of all participants who received ≥1 dose of the trial drug. As the study was designed without formal efficacy testing, statistical comparisons between treatment groups (described in the | PMC10101612 |
|
Results | PMC10101612 |
|||
Baseline Characteristics | autosomal dominant polycystic kidney disease, ADPKD, anemia | ANEMIA, POLYCYSTIC KIDNEY DISEASE, NEPHROLITHIASIS, ADPKD, AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE, COLONIC DIVERTICULITIS | Demographic characteristics in the total population were similar across treatment arms (Table Baseline demographic and clinical characteristics of children and adolescents enrolled in a randomized, placebo-controlled clinical trial of tolvaptanPKD, polycystic kidney disease; ADPKD, autosomal dominant polycystic kidney disease; htTKV, height-adjusted total kidney volume.There were no participants with a medical history of nephrolithiasis, anemia, colonic diverticulitis, or vascular/cardiac abnormalities. | PMC10101612 |
Exposure to Study Medication | In all randomized participants, exposure of ≥361 days was achieved in 33 of 48 participants (69%) in the tolvaptan arm and 29 of 43 participants (67%) in the placebo arm. The average daily dose was 41 (SD 17) mg in the tolvaptan arm and 51 (SD 14) mg in the placebo arm. The most frequent modal total daily doses at month 12 were 45 mg for tolvaptan (39% participants) and 60 mg for placebo (53% participants) in group 1 and 15 mg and 22.5 mg (31% participants each) for tolvaptan and 45 mg (67% participants) for placebo in group 2 (Treatment adherence in all participants, as determined by returned study medication, was ≥90% for 46 of 48 participants (96%) in the tolvaptan arm and 40 of 43 participants (93%) in the placebo group. Plasma concentrations of the tolvaptan oxobutyric acid metabolite (DM-4103) were used to verify adherence in tolvaptan-treated participants. DM-4103 concentrations at week 1 and month 1 were consistent with reported dosing for all participants with an evaluable sample. At month 6, one of 42 participants (2%) with a pharmacokinetic sample was not adherent with reported dosing, and at month 12, five additional participants (for a total of six of 40 participants [15%]) had DM-4103 concentrations indicating limited to no dosing within the previous weeks. Of these six nonadherent participants, five participants were from group 1 and one participant was from group 2. | PMC10101612 |
||
Pharmacodynamics | nonadherence, tuberous sclerosis | SECONDARY, TUBEROUS SCLEROSIS | For the first coprimary efficacy end point (all participants), least squares (LS) mean (±SEM) reduction from baseline in spot urine osmolality (premorning dose) after 1 week of daily dosing was greater in the tolvaptan arm (−390 [28] mOsm/kg) than in the placebo arm (−90 [29] mOsm/kg; Coprimary, key secondary, and related outcomesLS, least squares; 95% CI, 95% confidence interval; MRI, magnetic resonance imaging; htTKV, height-adjusted total kidney volume.For the baseline visit, A participant with tuberous sclerosis and hence notably larger kidney volume was excluded.Participants with pharmacokinetically verified nonadherence were excluded. | PMC10101612 |
Safety and Tolerability | death, bleeding, overdose, pelvic pain, fracture, cirrhosis, fibrosis, hematuria, dizziness, kidney pain, intentional self-injury, pollakiuria, deaths | CHOLESTASIS AND JAUNDICE, BLEEDING, ADVERSE EVENTS, EVENT, CIRRHOSIS, EVENTS, HEPATIC FAILURE, FIBROSIS, HEMATURIA, NONINFECTIOUS HEPATITIS, ADVERSE EVENT, VIRAL PERICARDITIS, PETIT MAL EPILEPSY, HYPERTENSIVE CRISIS | Treatment-emergent AEs were reported for 44 of 48 participants (92%) in the tolvaptan group and 42 of 43 participants (98%) in the placebo group during phase A of the trial. The most frequent AEs are shown in Table Summary of adverse events and listing of individual treatment-emergent adverse events (by system organ class and MedDRA preferred term) occurring in ≥5% of participants in either treatment groupAE, adverse event.Defined as an AE that started after the initiation of study medication; or if the event was continuous from baseline and was serious, study medication-related, or resulted in death, discontinuation, interruption, or reduction of study medication. Multiple occurrences of treatment-emergent AEs are counted once per MedDRA preferred term.This participant discontinued trial medication but continued participating in the trial (Data on urine volume in the 24 hours after dosing were collected for a subset of tolvaptan (In the nine tolvaptan-treated participants who experienced increased creatinine, the event resolved in all patients, with no action taken regarding tolvaptan in six participants, tolvaptan interruption in two participants, and tolvaptan dose reduction in one participant. Potentially clinically significant increases in creatinine occurred in four participants in the tolvaptan group and no participant in the placebo group during phase A.For five hepatic standardized MedDRA queries (cholestasis and jaundice of hepatic origin; hepatic failure, fibrosis and cirrhosis, and other liver damage-related conditions; noninfectious hepatitis; liver-related investigations, signs, and symptoms; and liver-related coagulation and bleeding disturbances),One participant in the tolvaptan group had a serious treatment-emergent AE (viral pericarditis). Six participants in the placebo group had serious treatment-emergent AEs: one had a hand fracture and ulna fracture, one had hematuria and kidney pain, one had an intentional overdose and intentional self-injury, and one participant each had petit mal epilepsy, hypertensive crisis, and pelvic pain. None of the serious treatment-emergent AEs reported in either treatment group were assessed by the investigator as related to the study drug. There were no deaths. One participant in the tolvaptan group and two participants in the placebo group had treatment-emergent AEs that were assessed as severe (Two participants discontinued treatment because of AEs: one in the tolvaptan group (because of pollakiuria) and one in the placebo group (because of dizziness). Both events were assessed as of moderate severity and related to the study drug.Mean changes from baseline in height SD scores were similar between the tolvaptan and placebo arms across age and sex subgroups (The PedsQL Generic Core Scale and the PedsQL Multidimensional Fatigue Scale showed that quality of life was unchanged from baseline to month 12 ( | PMC10101612 |
Discussion | ADPKD, aquaretic adverse, orthostatic hypotension | ADPKD, SECONDARY, DRUG-INDUCED LIVER INJURY, EVENTS, ORTHOSTATIC HYPOTENSION | We report the first phase 3, interventional clinical trial of tolvaptan in children and adolescents with ADPKD. The current report focuses on the randomized, placebo-controlled, 1-year portion (phase A) of the study. In the absence of standardized criteria for identifying the potential for rapid progression in the pediatric ADPKD population,Changes from baseline in spot urine osmolality and specific gravity were greater in the tolvaptan group than in the placebo group, with results consistent across age groups. The observation of more dilute urine is supportive of vasopressin V2 receptor inhibition. The key secondary end point of percent change in htTKV from baseline to month 12 showed that participants aged 12–17 years at baseline experienced a lower rate of kidney volume growth with tolvaptan (2.6%) than placebo (5.8%), although the difference did not reach statistical significance. Similarly, the change in eGFR from week 1 to month 12 suggested that eGFR was preserved in the tolvaptan group relative to placebo. The exploratory statistical comparison did not show a significant effect of tolvaptan at month 12. The mean eGFR at baseline and at month 12 was >90 ml/min per 1.73 mTolvaptan was generally safe and well tolerated at the adjusted doses used in this trial. No participants experienced elevated transaminases or drug-induced liver injury. Events of increased blood creatinine and orthostatic hypotension in the tolvaptan group may have been effects of copious aquaresis with inadequate fluid replacement. Consistent with its mechanism of inhibiting the effects of antidiuretic hormone, tolvaptan was associated with aquaretic adverse effects in this population with high kidney function, increased urine volume, and an increased number of urine voids. The number of voids was highest at week 1 of treatment and declined thereafter. Despite the high mean 24-hour urine volume (>7000 ml) in the tolvaptan-treated subgroup evaluated—exceeding levels observed in adultsA limitation of this study is that it was not powered for the statistical comparison of htTKV and eGFR end points. The first study phase, as reported here, was only 12 months, further limiting conclusions regarding these end points. Given the challenges of identifying sufficient numbers of pediatric patients with ADPKD for clinical trials,The data here support the activity of tolvaptan at the vasopressin V2 receptor in children and adolescents with ADPKD, indicate the feasibility of a modified dosing strategy, and provide initial evidence of effects on TKV growth and eGFR decline that require further research. This trial provides information beyond case reporting on the use of tolvaptan in an infant ADPKD patient. | PMC10101612 |
Supplementary Material | PMC10101612 |
|||
Acknowledgments | Autosomal Dominant Polycystic Kidney Disease | AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE | The development of this manuscript was supported by Otsuka Pharmaceutical Development & Commercialization, Inc. (Rockville, MD). Editorial and writing services, including writing of a first draft, were provided by Andrew J. Horgan, PhD, of BioScience Communications, Inc. (New York, NY), activities that were also funded by Otsuka. Portions of the data presented in the manuscript were presented at the 58th ERA-EDTA Congress, held virtually June 5–8, 2021, and at the 53rd ESPN Annual Meeting, held September 16–19, 2021, in Amsterdam, The Netherlands.See related editorial, “Tolvaptan for Autosomal Dominant Polycystic Kidney Disease in Children: Why, Who, and When?,” on pages 11–13. | PMC10101612 |
Disclosures | KIDNEY DISEASES | M.A. Cadnapaphornchai reports consultancy agreements with Otsuka Pharmaceutical, honoraria from Otsuka, and an advisory or leadership role for Otsuka Tolvaptan pediatric steering committee. A. Dandurand reports employment with Cerevel Therapeutics and was an employee of Otsuka at the time of the study. A. Dandurand's spouse reports employment with Cerberus Sentinel. L.A. Greenbaum reports consultancy agreements with Advicenne, Alexion, Arrowhead Pharmaceuticals, Aurinia, Cara Therapeutics, Handok, Natera, Novartis, Otsuka, and Roche; research funding from AbbVie, Advicenne, Alexion, Apellis, Aurinia, Reata Pharmaceuticals, Roche, and Vertex; honoraria from Alexion and Otsuka; advisory or leadership role for Alexion; and DSMB payments for Akebia, Alnylam, Reata, Relypsa, Travere, and UCSD. L.M. Guay-Woodford serves a consultant for and receives honoraria from Natera, Inc. and Otsuka Pharmaceutical. M. Litwin reports consultancy agreements with Alnylam, Bayer, Otsuka, and Travere; honoraria from Alnylam, Bayer, Otsuka, and Travere; and advisory or leadership roles for Bayer and Otsuka. D. Mekahli reports consultancy for Otsuka Pharmaceuticals and Reata as a representative of the University Hospital of Leuven and the KU Leuven University; educational grants from Otsuka Pharmaceuticals and Galapagos paid to the University Hospital of Leuven—all outside the submitted work; serves on an advisory board of Galapagos, Otsuka Pharmaceuticals, Reata, and Sanofi Genzyme as a representative of the University Hospital of Leuven and KU Leuven; is a member of the European Reference Network for Rare Kidney Diseases (ERKNet); and is supported by the clinical research fund of UZ Leuven (Belgium) and the Research Foundation Flanders (FWO; G0C8920N; 1804123N). F. Schaefer reports consultancy agreements with Akebia, Alexion, Alnylam, Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Fresenius Medical Care, GSK, Otsuka, Purespring, Relypsa, and Roche; research funding from Fresenius Medical Care; honoraria from Amgen, Kyowa Kirin, Otsuka, and Roche; textbook royalties from Springer; Scientific Advisory Board activities for Alexion and Otsuka; and is a member of ERKNet. T. Seeman reports consultancy agreements with Otsuka Pharmaceutical. L. Shi, S.E. Shoaf, and K. Sikes are employees of Otsuka Pharmaceutical. | PMC10101612 |
|
Funding | This research was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. (Rockville, MD). | PMC10101612 |
||
Author Contributions | A. Dandurand, D.M. Mekahli, F. Schaefer, L. Shi, S.E. Shoaf, and K. Sikes conceptualized the study; M.A. Cadnapaphornchai, A. Dandurand, L.A. Greenbaum, L. Guay-Woodford, M. Litwin, D.M. Mekahli, F. Schaefer, T. Seeman, S.E. Shoaf, and K. Sikes were responsible for investigation; M.A. Cadnapaphornchai, A. Dandurand, L.A. Greenbaum, L. Guay-Woodford, M. Litwin, D.M. Mekahli, F. Schaefer, T. Seeman, L. Shi, S.E. Shoaf, and K. Sikes were responsible for methodology; L. Shi was responsible for formal analysis; and M.A. Cadnapaphornchai, A. Dandurand, L.A. Greenbaum, L. Guay-Woodford, M. Litwin, D.M. Mekahli, F. Schaefer, T. Seeman, L. Shi, S.E. Shoaf, and K. Sikes reviewed and edited the manuscript. | PMC10101612 |
||
Data Sharing Statement | To submit inquiries related to Otsuka clinical research, or to request access to individual participant data (IPD) associated with any Otsuka clinical trial, please visit | PMC10101612 |
||
References | PMC10101612 |
|||
Supplementary Information | In a randomised trial, we found that integrated maternal HIV and infant health services through the end of breastfeeding were significantly associated with the primary outcome of engagement in HIV care and viral suppression at 12 months postpartum, compared to the standard of care. Here, we quantitatively explore potential psychosocial modifiers and mediators of this association. Our findings suggest that the intervention was significantly more effective among women experiencing an unintended pregnancy but did not improve outcomes among women reporting risky alcohol use. Although not statistically significant, our results suggest that the intervention may also be more effective among women experiencing higher levels of poverty and HIV-related stigma. We observed no definitive mediator of the intervention effect, but women allocated to integrated services reported better relationships with their healthcare providers through 12 months postpartum. These findings point to high-risk groups that may benefit the most from integrated care, as well as groups for whom these benefits are hampered and that warrant further attention in intervention development and evaluation.The online version contains supplementary material available at 10.1007/s10461-023-04097-x. | PMC10598190 |
||
Keywords | Open access funding provided by University of Cape Town. | PMC10598190 |
||
Introduction | HIV infections | HIV INFECTIONS | Increases in the availability and uptake of antiretroviral therapy (ART), including under guidelines of universal ART for pregnant and breastfeeding women, have led to massive reductions in new paediatric HIV infections [An approach which has been posited to reduce disengagement from care is the integration of HIV care into other routine health services, although the current evidence for effectiveness is mixed [Given the promise of this model of care for postpartum women, there is a need to refine and target future implementation of this intervention. Critical to this refinement is the identification of factors that may modify intervention effects, and an exploration of mechanisms of change. A framework that may be beneficial to this is Social Action Theory (SAT). SAT delineates a model of contextual determinants as well as social interaction and individual self-regulatory processes, and the mechanisms by which these lead to health behaviours [Following the conclusion of the MCH-ART randomised controlled trial, our aim here was to quantitatively examine (i) psychosocial modifiers of the intervention effect and (ii) potential mediators of the effect. The goal of examining modifiers was to identify groups for whom the intervention was most beneficial and to whom the intervention could be targeted, as well as groups for whom the intervention was not effective and that warrant further attention in intervention development. In parallel, the goal of examining mediators was to understand how integrated services lead to improved outcomes, with a view to refining interventions by identifying the most effective components. | PMC10598190 |
Methods | This analysis draws on data from the MCH-ART trial, which evaluated integrated services during the postpartum period. The design and primary results of the trial have been previously reported [ | PMC10598190 |
||
MCH-ART Intervention | SECONDARY | Women who attended the immediate postpartum study visit and were currently breastfeeding [471 (75%) of 628 women enrolled into antenatal follow-up] were enrolled into postpartum follow-up and randomly allocated. Random allocation was to the MCH-ART intervention (integrated concurrent and co-located maternal ART and paediatric care in the MCH clinic through the end of breastfeeding) or the standard of care (control), where women were referred as soon as possible postpartum to general HIV clinics, and their infants were referred to routine child health services. Although all postpartum women may benefit from integrated HIV and MCH care, the goal of this trial was to focus on breastfeeding women, given the ongoing risk of mother-to-child transmission (MTCT). Thus, only breastfeeding women were enrolled into the trial; a secondary aim of the trial was to explore the impact of the intervention on breastfeeding practices. Women subsequently attended up to five study measurement visits separate from any routine health services, at 6 weeks and 3, 6, 9 and 12 months postpartum. This analysis includes all women with primary outcome data available at 12 months postpartum [411 (87%) of 471 women enrolled]. All participants provided written informed consent prior to study enrolment. The study was approved by the Faculty of Health Sciences Human Research Ethics Committee at the University of Cape Town, and the Institutional Review Board of Columbia University Medical Centre. | PMC10598190 |
|
Measures | Depression, HIV and HIV treatment knowledge [Depression, Viral suppression | DISORDERS | Table
Factors explored as (A) effect modifiers and (B) mediators of the intervention effect, across timepoints of assessmentAbbreviations: EPDS: Edinburgh Postnatal Depression Scale; K-10: Kessler-10 scale; AUDIT-C: Alcohol Use Disorders Identification Test – Consumption.At various antenatal and postpartum timepoints, a battery of psychosocial measures was administered. Measures were selected drawing on SAT, described above, and on factors known to be associated with adherence behaviours. We adapted previously used tools to assess HIV and HIV treatment knowledge [Depression during the past week was assessed using the Edinburgh Postnatal Depression Scale (EPDS), which has been validated for use during pregnancy [At study visits, women provided 5ml of venous blood for HIV viral load (VL) testing, conducted by the National Health Laboratory Service (NHLS) using the Abbott Molecular RealTime HIV-1 assay (Abbott Molecular, Illinois, USA). Data on health service usage was requested from the Western Cape Provincial Health Data Centre, including data pertaining to HIV care visits; pharmacy dispensing; and laboratory results. The primary outcome for the MCH-ART trial was a binary composite endpoint of retention in care and viral suppression at 12 months postpartum. Retention in care was defined as any evidence of HIV-related clinical care received between 9 and 18 months postpartum, based on routinely collected records of HIV clinical care visits, ART dispensing, and HIV-related laboratory testing. Viral suppression was defined as VL < 50 copies/ml at the 12 month postpartum study visit. Women were considered as having achieved the primary endpoint if they had both evidence of retention in care and VL < 50 copies/mL [ | PMC10598190 |
Data Analysis | Data were analysed using STATA V14.2 (Stata Corporation, College Station, Texas, USA) and R (R Foundation for Statistical Computing, Vienna, Austria). To assess modifiers of the intervention effect, we used stratified χ | PMC10598190 |
||
Results | Depression | DISORDERS | Between March 2013 and April 2014, 628 pregnant women living with HIV were enrolled into antenatal follow-up. Of these women, 471 (75%) attended the immediate postpartum study visit and reported breastfeeding, and were enrolled into the MCH-ART trial. Compared to those enrolled, women who were excluded had entered antenatal care earlier (mean: 19.3 weeks versus 20.9 weeks;
Baseline demographic characteristics and potential psychosocial modifiers of the intervention effect, by trial arm (intervention versus control)Abbreviations: SD: standard deviation; EPDS: Edinburgh Postnatal Depression Scale; K-10: Kessler-10 scale; AUDIT-C: Alcohol Use Disorders Identification Test – Consumption. All measures are from the 2 | PMC10598190 |
Modifiers of the Intervention Effect | Depression | DISORDERS | Psychosocial characteristics relevant to the analyses of effect modification are summarised in Table
Forest plot of primary outcome across subgroups of psychosocial characteristics measured prior to randomisation
Intervention effect, stratified by potential effect modifiersAbbreviations: EPDS: Edinburgh Postnatal Depression Scale; K-10: Kessler-10 scale; AUDIT-C: Alcohol Use Disorders Identification Test – Consumption.However, there was some evidence that the intervention was more effective in particular groups of women, although not all differences were statistically significant (Fig.
Proportion of women allocated to the intervention and control achieving the primary trial outcome (engagement in HIV care and viral suppression at 12 months postpartum) across subgroups of psychosocial characteristics measured prior to randomisationIn addition, the intervention effect differed significantly according to two characteristics: pregnancy intention and alcohol use. Among women reporting that their pregnancy was unintended, 76% of women in the intervention arm achieved the trial outcome, versus 49% of those in the control (RD: 0.27; 95% CI: 0.16, 0.38). In comparison, 79% and 73% of those reporting that their pregnancy was intended and allocated to the intervention and control achieved the trial outcome, respectively (RD: 0.06; 95% CI: -0.09, 0.21; p-value for interaction: 0.025). Finally, women who reported risky drinking in the 12 months prior to pregnancy recognition were significantly less likely to benefit from the intervention. In this group of women, 64% of those in the intervention arm and 60% of those in the control achieved the trial outcome (RD: 0.04; 95% CI: -0.15, 0.23), compared to 81% and 55% among those not reporting risky drinking, respectively (RD: 0.26; 95% CI: 0.16, 0.36; p-value for interaction: 0.040). | PMC10598190 |
Mediators of the Intervention Effect | No appreciable differences were observed in HIV or treatment knowledge, ART medication beliefs or adherence self-efficacy between the intervention and control group at study measurement visits after randomisation (Table
Potential postpartum mediators of the intervention effect, by trial arm (intervention versus control), and impact of potential mediators on the intervention effectAbbreviations: SD: standard deviation; 95% CI: 95% confidence interval; ART: antiretroviral therapy.
Associations between potential postpartum mediators and the primary trial outcome (engagement in HIV care and viral suppression at 12 months postpartum)Abbreviations: SD: standard deviation; ART: antiretroviral therapy. | PMC10598190 |
||
Discussion | SECONDARY | Using data from the MCH-ART study, which showed that integrated maternal and child health care during the postpartum period significantly increased retention in HIV care and viral suppression [Taken together, the intervention appeared to be most effective among women experiencing added vulnerability due to poverty, unintended pregnancy, and HIV-related stigma. We have previously demonstrated that unintended pregnancy is associated with elevated VL during the postpartum period [Our finding regarding alcohol use is of particular concern. In South Africa, alcohol use during pregnancy is a major public health problem. High levels of problematic alcohol use have been observed among women living both with and without HIV in this setting [In this secondary analysis, we observed no single definitive mediator of the intervention effect. We hypothesise that the intervention may be effective through a range of mechanisms that may operate differently within different groups of women, and should be explored in a larger trial. For example, integrated MCH services reduce the economic burden of attending separate visits and may thus be of most benefit to women experiencing higher levels of poverty [These findings should be considered in light of several limitations. They arise from a single antenatal clinic in a peri-urban area of South Africa and only women who were initiating ART during pregnancy were enrolled into the trial, thus the findings may not be generalisable to all postpartum women living with HIV. Although all postpartum women may benefit from integrated HIV and MCH care, only breastfeeding women were enrolled into the trial, thus limiting generalisability. Pregnant women were enrolled into the trial between March 2013 and April 2014 and were followed through January 2016, and changes in PMTCT and HIV care since that time may make our findings less generalisable to the current context. The psychosocial constructs explored were self-reported and are subject to recall and social desirability bias, which may be particularly relevant for behaviours such as alcohol use, although we used validated scales wherever possible. However, it is plausible that we did not observe hypothesised mediators of the intervention effect due to the challenges of measuring complex constructs, with the measures administered potentially not accurately representing the construct of interest. Although these measures were originally developed several decades ago in high-income countries, the constructs assessed and items included in these scales are still relevant and applicable to multiple settings. Although we attempted to collect patient-level data on direct and indirect costs to measure the economic burden of attending clinic visits, these data were only available for a subset of participants and it was not possible to accurately quantify costs at the individual level [ | PMC10598190 |
|
Conclusions | Despite these limitations, this analysis provides novel and important findings related to modifiers and mediators of the effectiveness of integrated care for postpartum women living with HIV. Our findings suggest that integrated services are associated with significantly better patient-provider relationships over time. Further, women who face additional vulnerabilities due to poverty and unintended pregnancy may benefit the most from integrated care, and integrated services could potentially be targeted to settings where these characteristics are particularly prevalent. Notably, the benefits of integrated care appear to be hampered by alcohol use, suggesting that women experiencing problematic alcohol use warrant further attention in intervention development and evaluation. | PMC10598190 |
||
Acknowledgements | AIDS | PEDIATRIC AIDS, AIDS, EMERGENCY | The authors would like to thank the women who participated in this study, as well as the study staff for their support of this research. This research was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the National Institute of Child Health and Human Development (NICHD), grant numbers 1R01HD074558. Additional funding comes from the Elizabeth Glaser Pediatric AIDS Foundation. Dr. Pellowski was supported by a career development grant from the National Institute of Mental Health (NIMH K01MH112443). Drs. Remien and Mellins are supported by a grant from NIMH to the HIV Center for Clinical and Behavioral Studies (P30-MH45320). | PMC10598190 |
Authors’ Contribution | LM and EJA conceived of and designed the parent study, with input from RHR and CAM. KBrittain, TP, and AZ implemented the research, data collection and data management. KBrittain and KBrown performed the data analysis. KBrittain wrote the first draft of the manuscript. All authors critically reviewed the manuscript and approved the final version. | PMC10598190 |
||
Funding | AIDS | PEDIATRIC AIDS, AIDS, EMERGENCY | Open access funding provided by the University of Cape Town. This research was supported by the President’s Emergency Plan for AIDS Relief (PEPFAR) through the National Institute of Child Health and Human Development (NICHD), grant numbers 1R01HD074558. Additional funding comes from the Elizabeth Glaser Pediatric AIDS Foundation. Drs. Remien and Mellins are supported by a grant from NIMH to the HIV Center for Clinical and Behavioral Studies (P30-MH45320). Dr. Pellowski was supported by a career development grant from the National Institute of Mental Health (NIMH K01MH112443). | PMC10598190 |
Data Availability | All relevant data are within the paper. | PMC10598190 |
||
Code Availability | N/A. | PMC10598190 |
||
Declarations | PMC10598190 |
|||
Conflict of interest | The authors have no conflicts of interest to declare. | PMC10598190 |
||
Ethics Approval | This study was performed in line with the principles of the 1964 Declaration of Helsinki and its later amendments. The study was approved by the Faculty of Health Sciences Human Research Ethics Committee at the University of Cape Town, and the Institutional Review Board of Columbia University Medical Centre. | PMC10598190 |
||
Consent to Participate | All participants provided written informed consent prior to enrolment. | PMC10598190 |
||
Consent for publication | Not applicable. | PMC10598190 |
||
References | PMC10598190 |
|||
Background | depression | Only about half the people with depression seek professional health care services. To constitute the different predictors and associating variables of health care utilisation, we model the process and aim to test our hypothesised | PMC9831378 |
|
Method | depressive symptoms | All variables are examined in an online study (baseline, three- and six-month follow-up). The sample consisted of adults with depressive symptoms (PHQ-9 sum score ≥ 8), currently not receiving mental health care treatment. To examine the prediction of variables explaining help-seeking behaviour, a path model analysis was carried out ( | PMC9831378 |
|
Results | Altogether, 1368 participants ( | PMC9831378 |
||
Conclusion | The | PMC9831378 |
||
Trial registration | German Clinical Trials Register: DRKS00023557. Registered 11 December 2020. World Health Organization, Universal Trial Number: U1111–1264-9954. Registered 16 February 2021. | PMC9831378 |
||
Supplementary Information | The online version contains supplementary material available at 10.1186/s12889-022-14937-5. | PMC9831378 |
||
Keywords | Open Access funding enabled and organized by Projekt DEAL. | PMC9831378 |
||
Methods | This study is part of a project funded by the German Research Foundation, with a published study protocol [ | PMC9831378 |
||
Sample & power analysis | depressive | Participants without current professional treatment and with at least mild depressive symptoms were included (PHQ-9 sum score ≥ 8; 48). In total, Because the path analysis is done in addition to the analyses reported in the study protocol [ | PMC9831378 |
|
Statistical analysis | REGRESSIONS | No missing scale values are detected within the relevant data. Total drop-out rate was 28.14% between baseline assessment and both follow-ups together (i.e., participation in either three- or six-month follow up). To examine potential reasons for attrition we conducted logistic regressions in which dropout is defined as not providing any follow-up data, the variable is dummy-coded as 0 = “no missing variable” and 1 = “missing value due to drop-out” [To assess the proposed influences as shown in the | PMC9831378 |
|
Results | PMC9831378 |
|||
Sample characteristics | The final sample size consisted of | PMC9831378 |
||
Discussion | The aim of this study was to test a comprehensive The For the prediction of For Regarding superordinate variables, tWe hypothesised associations between | PMC9831378 |
||
Limitations | depression, psychiatric | ATTRITION | Our analyses are based exclusively on self-reported data. New instruments yet lacking full psychometric validation were used for continuum beliefs, causal beliefs, self-efficacy measures and treatment experience. However, the new questionnaires are based on existing validated items and therefore should still be interpretable, yet not fully comparable to other studies and thus need validation. We opted for a broad operationalisation of help-seeking including general practitioners, counselling centres, or neurologists, additional to psychotherapeutic or psychiatric professionals. We aimed to reflect help-seeking with high external validity since, for example, nearly three of four people with depression are treated by general practitioners [Additionally, limitations to the representativeness of the sample are raised. On the one hand, we investigated a sample in Germany, limiting generalisability to other countries, partly due to differences regarding healthcare accessibility and statutory health insurance. Moreover, we limited our analyses to intrapersonal processes and their influencing factors. It would be important to replicate our analyses with focus on structural barriers, including factors of perceived and actual costs, availability and accessibility (e.g., transportation, hours of work, childcare requirements). Furthermore, even though we controlled for the influence of age, gender, and depression severity, there might be an influence of the socioeconomic status [The study is likely to contain a self-selection bias, as only motivated people with computer skills and access to the online panel might have been interested and able to participate. This longitudinal study assessed help-seeking behaviour over a period of up to three to six months with a drop-out from baseline to follow-ups. Attrition analyses have shown that those who drop out systematically differ from the rest of the sample in certain characteristics, further limiting representativeness. Additionally, this attrition is an indication of variables to address in further research, such as household size. So far, we limited our analyses to direct influences of the intermediary variables to provide insight on the influences of direct processes not considering combined influences nor possible reciprocal interactions between the intermediary variables. Correlational analyses revealed that they are partly negatively associated, suggesting that further analyses on the most effective combinations are needed, e.g., for drawing in-depth practical implications for creating help-seeking interventions with combined psychoeducational content. | PMC9831378 |
Conclusion | In summary, we were able to replicate findings of various influences on the help-seeking process expanding existing research of help-seeking variables and stigma through an intermediary level of subjective illness representations according to the | PMC9831378 |
||
Acknowledgements | Not applicable. | PMC9831378 |
||
Authors’ contributions | GS, LJP | The manuscript was equally developed and drafted by TM and LJP. TM and LP contributed to the design of the study and the acquisition of the data. TM and LJP analysed and interpreted the data. ST and HoM contributed to the conception of the work. ST, HoM, SiS, and GS revised the draft. GS and SiS manage the project. All authors have read and approved the final manuscript. | PMC9831378 |
|
Funding | Open Access funding enabled and organized by Projekt DEAL. The study was funded by the DFG (German Research Foundation, | PMC9831378 |
||
Availability of data and materials | The datasets generated during the current study are available from the corresponding author on reasonable request. | PMC9831378 |
||
Declarations | PMC9831378 |
|||
Ethics approval and consent to participate | The study procedure was developed in accordance with the Declaration of Helsinki and has been approved by the Ethics Commission of the University Medicine Greifswald (BB 061/18) and Leipzig (514/19-lk). Participants included in the study gave electronic informed consent following comprehensive written information about the study. | PMC9831378 |
||
Consent for publication | Not applicable. | PMC9831378 |
||
Competing interests | The authors declare that they have no competing interests. | PMC9831378 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.