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References
PMC10398902
1. Introduction
Obesity, obesity, cardiovascular diseases, cancer, eating disorders, weight gain, overweight, eating disorder, deaths, diabetes
OBESITY, OBESITY, CEREBROVASCULAR DISEASES, CARDIOVASCULAR DISEASES, CANCER, PATHOLOGY, DIABETES
Obesity and overweight cause 3.4 million deaths annually, primarily due to cardiovascular diseases, cerebrovascular diseases, diabetes, and cancer [It would be ideal if such prevention programs also reduced eating disorder onset because eating pathology predicts weight gain [Several prevention programs have been designed to reduce future onset of both obesity and eating disorders (e.g., [As prior research has shown a dissonance-based eating disorder prevention program successfully prevents eating disorder onset [In the present trial, two factors which were hypothesized to improve Adding food response inhibition and attention training to A 2-factorial design was used to test whether implementing single- versus mixed-sex A report on the acute effects from this trial confirmed that
PMC9960991
2. Methods
PMC9960991
2.1. Participants and Procedures
At baseline, participants (
PMC9960991
2.4. Data Analyses
overweight, overweight/obesity or eating disorders
OBESE
To examine continuous outcome change by single-sex versus mixed-sex group and food response and attention training versus sham training, we fitted generalized additive models (GAM). GAMs were used because outcome change was nonlinear. These analyses were intent-to-treat and included all participants randomized to the conditions. Because participants in the four conditions differed on baseline percent body fat (FTo test whether the onset of overweight/obesity or eating disorders differed by condition, Cox proportional hazard models were fitted. Participants were classified as underweight, healthy, overweight, or obese used the criteria in Gallagher et al. [
PMC9960991
3. Results
eating disorder
Participants with versus without complete data did not differ on any of the outcomes at baseline. For percent body fat, the model with the three-way interaction between group-type, response training, and time, fitted better than simpler models. Results for the percent body fat GAM are shown in Complier analysis revealed that, averaging across conditions, participants who attended five or more Onset of overweight/obesity and of any eating disorder over follow-up did not differ across conditions (
PMC9960991
Author Contributions
Conceptualization, E.S. and P.R.; methodology, E.S. and P.R.; software, C.D.; validation, C.D.; formal analysis, C.D.; investigation, E.S., P.R., H.S. and M.L.B.; resources, E.S. and P.R.; data curation, C.D.; writing—original draft preparation, E.S., P.R. and C.D.; writing—review and editing, E.S., P.R., H.S. and M.L.B.; visualization, C.D.; supervision, P.R., H.S. and M.L.B.; project administration, E.S. and P.R.; funding acquisition, E.S., P.R., H.S., C.D. and M.L.B. All authors have read and agreed to the published version of the manuscript.
PMC9960991
Institutional Review Board Statement
The Oregon Research Institute Institutional Review Board approved this study.
PMC9960991
Informed Consent Statement
Informed written consent was provided by all participants before data were collected.
PMC9960991
Data Availability Statement
Data can be requested from the first author.
PMC9960991
Conflicts of Interest
The authors declare no conflict of interest.
PMC9960991
References
Eating Disorder
Participant flow through the study.All panels present change in percent body fat over the 2-year follow-up in each of the four conditions. Model Predicted Change in Percent Body Fat by Condition.Descriptive Summary for Study Variables by Condition.Akaike Information Criteria (AIC) for Candidate Models by Outcome.Note. T:G:RT refers to the three-way interaction of time, group, and response training; T:G to the interaction of time and group; and T:RT to the interaction of time and response training. ΔAIC refers to the difference in the current model’s AIC and the model with the smallest AIC. The bold-faced model refers to the selected model based on AIC.Coefficient Estimates for the Body Fat Model.Onset of any Eating Disorder or Overweight/Obesity during the Study by Condition.
PMC9960991
Background
DJD, MEB, HMES
SCHISTOSOMIASIS
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PH, MEB, DJD and JB are patent holders for a multivalent anthelminthic vaccine including schistosomiasis. GAD is an employee of the Sponsor, NIAID. RLA, RC-O, CGF, FT, MR, SG, JKK, JSL, MFG, GL, LH, WAK, SP, HMES: None.Recombinant
PMC10089325
Methods
A randomized, observer-blind, controlled, Phase 1b clinical trial was conducted in 60 healthy adults living in a region of Brazil with ongoing
PMC10089325
Conclusions
Vaccination of adults with
PMC10089325
Author summary
Infection
INFECTION
Infection caused by
PMC10089325
Data Availability
All relevant clinical data are within the manuscript and its
PMC10089325
Methods
PMC10089325
Ethics statement
The study was approved by the ethics committees of the Federal University of Minas Gerais, the George Washington University, Baylor College of Medicine, and the Brazilian Ministry of Health. Written informed consent was obtained from volunteers who successfully completed a questionnaire assessing comprehension of study procedures and risks before the initiation of study procedures. The trial has been registered at
PMC10089325
Study vaccines
The The comparator was the Euvax B (LG Life Sciences, South Korea) recombinant hepatitis B vaccine containing 20 μg hepatitis B surface antigen and 0.5 mg aluminum per dose. Euvax B was supplied in multi-dose vials each containing enough vaccine to deliver ten-1.0 ml doses.
PMC10089325
Study site and population
intestinal helminths, Infection
INFECTION
This Phase 1b, randomized, observer-blind (within cohort), controlled, dose-escalation clinical trial was conducted in Americaninhas, Minas Gerais, Brazil, by a research team based at the Instituto René Rachou, part of the Fundação Oswaldo Cruz of the federal Brazilian Ministry of Health. Previous studies conducted in Americaninhas and the surrounding area have demonstrated ongoing Sixty healthy male and non-pregnant, non-breastfeeding female adults aged 18 to 50 years, inclusive, were recruited. Exclusion criteria included positivity for IgE antibodies to Infection with the intestinal helminths
PMC10089325
Clinical procedures
Participants were progressively enrolled into 3 cohorts. In each cohort of 20, participants were randomly assigned to receive Within each cohort, an initial 5 participants (2
PMC10089325
Blinding
Participants, investigators, personnel performing study-related assessments following vaccine administration, and laboratory personnel performing antibody assays were blinded to study product assignment. Randomization was performed using an internet-based randomization system (Advantage eClinical, The Emmes Company, Rockville, MD). The randomization scheme was provided to unblinded study personnel (
PMC10089325
Clinical assessments
myalgia, fever, fatigue, toxicity, erythema, pain, dizziness, nausea,, headache, tenderness, chills, arthralgia
ADVERSE EVENTS, ERYTHEMA, INJECTION SITE SWELLING, REACTOGENICITY, EVENTS
Reactogenicity was measured from the time of each study vaccination (study days 1, 57, 113) through 7 days after each study vaccination by the occurrence of solicited injection site and systemic reactogenicity events. Solicited symptoms included erythema, induration/swelling, pain, and tenderness as injection site reactions; and fever, chills, myalgia, arthralgia, nausea, vomiting, headache, dizziness, malaise, and fatigue as systemic reactions.Unsolicited adverse events (AEs) were recorded from the time of each vaccination through 28 days after each study product administration. New-onset chronic medical conditions (NOCMCs), including AEs of special interest (AESI), and serious AEs (SAEs) were recorded from the time of the first study vaccination (day 1) through the final study visit. Active surveillance for AESIs of autoimmune (Participants were observed in the study clinic for at least 60 minutes after vaccination to assess immediate reactogenicity. They were subsequently assessed at 1, 3, 7, 14, and 28 days after each vaccination, and then at regular intervals until 12 months after the third injection. AEs were assigned severity of mild (easily tolerated), moderate (interfered with activities of daily living), or severe (prevented activities of daily living); causality in relation to study product was determined based on investigator judgement. Injection site swelling and erythema were assessed as small (25 to 50 mm in diameter), medium (51 to 100 mm), or large (>100 mm); whereas oral temperature was graded as mild (38.0°C to 38.4°C), moderate (38.5°C to 38.9°C), or severe (≥39.0°C).Clinical laboratory evaluations were performed on the day of vaccination and 7 days later to measure alanine aminotransferase (ALT), creatinine, and complete blood count (CBC) including hemoglobin (Hgb), platelets, and white blood cells (WBC). Abnormal safety laboratory test results were assessed as mild, moderate, or severe according to standardized toxicity tables [
PMC10089325
Laboratory methods
Immunoglobulin E (IgE) antibodies specific to Cat. No.: 250203. Lot Number:2012283). In brief, 96-well plates were prepared with either 1 μg/mL recombinant Immunoglobulin G (IgG) antibodies specific to IgG subclass antibodies specific to All antibody data from the ELISAs have been uploaded to the Dryad Digital Repository (unique digital object identifier: 10.5061/dryad.612jm647c) [
PMC10089325
Statistical methods
EVENTS, EVENT, EVENT
Safety data were summarized for the safety population consisting of all enrolled participants who received at least one dose of study product (Any medical condition that was present at the time that the participant was screened was considered baseline and not reported as an AE, unless it worsened in severity or increased in frequency during the study. When calculating the incidence of AEs (The proportion of participants reporting at least 1 solicited AE was summarized by event, vaccine group, and maximum severity, along with the 95% Wilson score confidence interval (CI) for the proportion. Event rates were compared between each vaccine group and the pooled comparator vaccine group using Fisher’s Exact Test. The proportion of participants reporting at least 1 unsolicited AE was summarized by vaccine group for each vaccination and across all vaccinations. Clinical laboratory events were summarized by severity, time point, and vaccine group.
PMC10089325
Immunogenicity analysis
The immunology results described are restricted to the per-protocol immunogenicity population, which did not include all values from the 4 participants who did not receive all 3 doses of study product, as described below. For these participants, specimens collected after the missed vaccine dose were excluded from the immunogenicity analyses. All comparisons between IgG and 3 IgG subclass (IgG1, IgG3, and IgG4) antibodies to the The RFor each individual and post-vaccination time point, the ratio of the post-vaccination antibody level to the baseline level was calculated (A post-hoc Cochran Armitage test of trend was performed to investigate a possible dose-response relationship in the proportion of total IgG seroresponders among participants receiving No imputation methods were planned for missing values.
PMC10089325
Results
PMC10089325
Participant flow and baseline data
A total of 127 adults were screened and 60 were enrolled in the study (
PMC10089325
CONSORT diagram: participant flow.
All 60 enrolled participants received at least 1 dose of study vaccine, while 56 (93%) received all 3 planned doses (Demographic and baseline characteristics are summarized in
PMC10089325
Demographic and baseline characteristics of study participants by vaccine group.
Note: N = Number of participants in the Safety Population; SD = standard deviation.
PMC10089325
Safety results
deaths
None of the study participants in the safety population discontinued the study due to an AE, and no AESIs, NOCMCs, or deaths occurred during the clinical trial. One participant who received 30 μg
PMC10089325
Solicited AEs
EVENT
Out of 60 participants in the study, 45 (75%) experienced at least 1 solicited symptom, with 41 (68%) and 25 (42%) having at least 1 solicited injection site or systemic event, respectively (
PMC10089325
Number and percentage of participants experiencing solicited injection site events after any dose of vaccine by event, maximum severity, and vaccine group.
PMC10089325
Number and percentage of participants experiencing solicited systemic events after any dose of vaccine by event, maximum severity, and vaccine group.
EVENTS
No severe solicited AEs were observed in any study participant. In the combined group of participants who received any dose of A significantly greater percentage of participants experienced solicited events in the pooled group who received any dose of
PMC10089325
Unsolicited AEs
pruritus
Forty-eight participants experienced 96 non-serious unsolicited AEs, most of which were mild in severity. Three out of 60 participants (5%) experienced at least 1 unsolicited AE of mild or moderate severity that was assessed as being related to study vaccine by the study investigators. These 3 participants experienced 7 (5 mild, 2 moderate) vaccine-related unsolicited AEs. Of these, 1 (moderate pruritus at the injection site) occurred after the third injection in a participant who received 100μg In the pooled group of participants who received 1 of the 3 dose concentrations of
PMC10089325
Clinical laboratory AEs
Overall, 10 participants experienced 13 mild or moderate clinical laboratory abnormalities following vaccination (
PMC10089325
Immunogenicity
PMC10089325
ELISA quality control statistics
The R
PMC10089325
Total IgG responses
Several participants across all vaccine groups had detectable, albeit low, levels of total IgG and IgG subclass antibodies to
PMC10089325
Geometric mean anti-
B hepatitis B
Per-protocol immunogenicity population. Vaccinations were administered on study days 1, 57, and 113. Error bars represent 95% confidence intervals. Euvax B hepatitis B recipients were pooled across cohorts.Only 1 comparator vaccine recipient developed a significant rise in anti-There were significantly more (86%) antigen-specific IgG responders in the 100 μg with AP 10–701 group than in the comparator vaccine (8%) group (
PMC10089325
Fold change from baseline in anti-
B hepatitis B
Per-protocol immunogenicity population. Vaccinations were administered on study days 1, 57, and 113. Error bars represent 95% confidence intervals. Euvax B hepatitis B recipients were pooled across cohorts.When assessed by ANCOVA, there were no significant differences in adjusted mean log IgG antibody responses at study day 127 between those who were vaccinated with
PMC10089325
Supporting information
PMC10089325
Summary statistics for the duration (days) of solicited adverse events, by vaccine group.
(DOCX)Click here for additional data file.(DOCX)Click here for additional data file.
PMC10089325
Listing of clinical laboratory adverse events experienced by study participants.
(DOCX)Click here for additional data file.We thank the study participants for their cooperation throughout the trial; the study team in Brazil, especially Cássia Senra, Simone Pinto, Stella Sobrinho, Ana Raquel Godoy, Fernanda Gambogi, and Roberta Rodrigues; Christiane Correa Rodrigues Cimini for being the independent safety monitor; and, Arthur Clinton White, Jr., Thomas Richie, and Kirsten Lyke for serving as members of the independent study Safety Monitoring Committee.
PMC10089325
Background/aims:
The stepped-wedge design has been extensively studied in the setting of the cluster randomized trial, but less so for the individually randomized trial. This article derives the optimal allocation of individuals to treatment sequences. The focus is on designs where all individuals start in the control condition and at the beginning of each time period some of them cross over to the intervention, so that at the end of the trial all of them receive the intervention.
PMC10262341
Methods:
DECAY
The statistical model that takes into account the nesting of repeated measurements within subjects is presented. It is also shown how possible attrition is taken into account. The effect of the intervention is assumed to be sustained so that it does not change after the treatment switch. An exponential decay correlation structure is assumed, implying that the correlation between any two time point decreases with the time lag. Matrix algebra is used to derive the relation between the allocation of units to treatment sequences and the variance of the treatment effect estimator. The optimal allocation is the one that results in smallest variance.
PMC10262341
Results:
Results are presented for three to six treatment sequences. It is shown that the optimal allocation highly depends on the correlation parameter
PMC10262341
Conclusion:
This article provides the methodology for designing individually randomized stepped-wedge designs, taking into account the possibility of attrition. As such it helps researchers to plan their trial in an efficient way. To use the methodology, prior estimates of the degree of attrition and intraclass correlation coefficient are needed. It is advocated that researchers clearly report the estimates of these quantities to help facilitate planning future trials.
PMC10262341
Introduction
Since the study by Hussey and Hughes,Graphical representation of a stepped-wedge design with five sequences.The implementation of a stepped-wedge design has seen an increasing use in cluster randomized trials.Stepped-wedge designs are often implemented such that an equal number of clusters or individuals is assigned to each treatment sequence (i.e. a uniform allocation). However, for cluster randomized trials, it has already been shown that this is not necessarily the best choice.This contribution is organized as follows. In the ‘Methods’ section, the statistical model that relates outcome to time period and treatment condition is introduced and it is shown how the treatment effect and its variance are estimated in studies without and with attrition. The variance of the treatment effect estimate is used as optimality criterion and this section also shows how constrained optimization is used to numerically derive the optimal allocation to treatment sequences. The ‘Results’ section presents optimal allocations for three to six sequences along with the efficiency of the uniform allocation relative to the optimal allocation. The optimal allocations may not always be feasible from a practical point of view and the ‘Methods’ section deals with optimal allocations where the proportions of individuals allocated to each sequence are bounded by an upper and lower limit. Conclusion and discussion are given in the last section.
PMC10262341
Methods
PMC10262341
Statistical model
All individuals start in the control condition, and in each time period a number of individuals crosses over the intervention. The number of time periods Here, The model can be written in matrix–vector notation. The model for individual where is the vector of length is the is the vector of length is the vector of length is the Given an estimate with corresponding variance–covariance matrix The treatment effect estimate The stepped-wedge design is a multi-period design, and it is very likely individuals drop out during the course of the study. The last observation of individual The proportion individuals allocated to sequence In practical settings, the lower and upper bounds 0 and 1 for A simple equation for the relation between the allocation
PMC10262341
Relative efficiency
Once the optimal allocation has been derived, it can be compared to the uniform allocation. The relative efficiency quantifies the loss of efficiency of using the uniform allocation
PMC10262341
Results
PMC10262341
References
PMC10262341
Purpose
Communicated by Michael I Lindinger.Sodium bicarbonate (SB) supplementation can improve exercise performance, but few studies consider how effective it is in female athletes. The aim of the study was to establish the effect of individually timed pre-exercise SB ingestion on 2 km rowing time trial (TT) performance in female athletes.
PMC10191925
Methods
SD, ®
Eleven female CrossFit® athletes (mean ± SD age, 29 y ± 4 y, body mass, 64.5 kg ± 7.1 kg, height, 1.7 m ± 0.09 m, peak oxygen uptake [VO
PMC10191925
Results
The ingestion of SB improved rowing performance (514.3 ± 44.6 s) compared to the PLA (529.9 ± 45.4 s) and FAM trials (522.2 ± 43.1 s) (
PMC10191925
Conclusions
Ingesting a 0.3 g·kg
PMC10191925
Keywords
PMC10191925
Introduction
alkalosis, metabolic alkalosis, ®, fatigue
METABOLIC ALKALOSIS, ALKALOSIS
During high-intensity exercise, fatigue refers to the abrupt deterioration of exercise performance, a gradual increase in perceived exertion which inevitably leads to an inability to maintain the intended magnitude of intensity (Ament and Verkerke et al. 2009). Performance of high-intensity exercise, which demands a large contribution from anaerobic metabolic pathways is associated with a decrease in muscle and blood pH (Hollidge-Hovart et al. In an attempt to delay the deleterious effects of fatigue on sport and exercise performance, nutritional strategies have previously been utilised. During single bouts of high-intensity exercise of ~ 1 to 10 min in duration (Gough et al. Although the extant research highlights the efficacy of SB as an effective buffering agent, a recent umbrella review of meta-analyses (Grgic et al. 2017) determined that > 77% of participants in the existing research literature were male. It is, therefore, reasonable to suggest that the generalizability of such literature is skewed, with one meta-analyses declaring it impossible to determine a precise estimate of the pooled effect size for performance (Saunders et al. This study, therefore, investigated the effect of SB ingestion on female performance in CrossFit® athletes using a time-to-peak ingestion protocol. It was hypothesised that an acute loading ingestion protocol of SB would induce metabolic alkalosis and improve 2 km time trial (TT) performance when performed at individual time-to-peak alkalosis.
PMC10191925
Methods
SD
Eleven female CrossFit athletes took part in this study (mean ± SD age, 29 y ± 4 y, body mass, 64.5 kg ± 7.1 kg, height, 1.7 m ± 0.09 m, peak oxygen uptake [VODuring visit one, participants completed a maximal cardiopulmonary exercise test to determine VOTo determine VOGiven the large inter-individual variability in time-to-peak blood [HCO3On arrival at the laboratory, participants were required to remain seated for 20 min before a pre-ingestion (baseline) capillary blood sample was obtained. Under double-blind, placebo-controlled, randomised crossover conditions, participants were required to ingest either 0.3 g·kg
PMC10191925
Statistical analysis
stroke
STROKE, BLOOD
Normality testing was completed using a Shapiro–Wilk test on all variables to determine the appropriate statistical test. Performance measures, time to completion, stroke rate and power output and GI symptoms were then subsequently analysed using a one-way analysis of variance (ANOVA) for repeated measures. Blood metabolites ([HCO
PMC10191925
Results
blood [HCONo gastrointestinal symptoms
The peak [HCOIndividual time to peak and mean (± SD) metabolite responses to 0.3 g·kgTime to Peak(min)Mean ± SD 2 km TT performance time (During the time trials, the ingestion of SB resulted in significantly altered blood [HCOMean ± SD blood [HCONo gastrointestinal symptoms were observed either prior to ingestion in any of the trials, or at any point throughout the FAM trials. Some GI symptoms were reported in both the PLA and the SB trials, but the frequency of the symptom reports (Table Individual GI symptom scores immediately pre-exercise. Recorded symptoms are displayed in bold, and scores are displayed in parentheses
PMC10191925
Discussion
alkalosis
TTP, ALKALOSIS
The present study is the first to investigate the effects of SB ingestion on exercise performance in trained female CrossFit athletes. Furthermore, this study also used the contemporary approach of determining the individualised time to peak alkalosis to optimise the pre-exercise ingestion time whilst also delivering the SB dose using a GI symptom-limiting technique. The key finding was that every participant performed their fastest 2 km rowing TT representing a mean improvement of 2.24% compared to the PLA. The enhanced performance observed following SB ingestion is likely attributable to increases in extracellular buffering capacity, since pre-exercise blood [HCOExisting literature on the effects of SB on high-intensity exercise protocols have yielded equivocal results with some reporting a positive effect amongst female athletes (Delextrat et al. Furthermore, using a delivery method such as enteric-coated SB to limit the potential GI symptom severity (Hilton et al. In the present study the individual the TTP ranged from 75 to 150 min, which is consistent with enteric-coated SB delivery (Hilton et al. Given that the level of alkalosis appears to be dose-dependent, the magnitude of alkalosis, or more specifically, the concentration of [HCOFew studies have utilised a female only participant population when investigating SB ingestion and high-intensity exercise performance. This may be due to evidence suggesting that anaerobic exercise performance may be impacted by menstrual cycle phase; with poorer performances being documented typically in the early follicular phase (Materson
PMC10191925
Conclusion
alkalosis, ®
ALKALOSIS
This is the first study to investigate the effects of enteric-coated SB ingestion on 2 km TT performance in trained female CrossFit® athletes. The main finding is that optimising the timing of the start of exercise to coincide with peak alkalosis, improves TT performance by ~ 2.24% in female athletes. The ingestion of a 0.3 g·kg
PMC10191925
Author contributions
RM and LM conceived and designed research. RM and SAS conducted experiments and undertook the data analysis with BS. RM, LM, NH, AS wrote the manuscript. All authors read and approved the manuscript.
PMC10191925
Funding
No funding was received for planning or conducting this work.
PMC10191925
Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
PMC10191925
Declarations
PMC10191925
Conflict of interest
All authors declare that they have no competing Interest and have no financial or non-financial interests.
PMC10191925
References
PMC10191925
Background
Postoperative rehabilitation after primary total hip arthroplasty (p-THA) differs between the Netherlands and Germany. Aim is to compare clinical effectiveness and to get a first impression of cost effectiveness of Dutch versus German usual care after p-THA.
PMC10294515
Methods
A transnational prospective controlled observational trial. Clinical effectiveness was assessed with self-reported questionnaires and functional tests. Measurements were taken preoperatively and 4 weeks, 12 weeks, and 6 months postoperatively. For cost effectiveness, long-term economic aspects were assessed from a societal perspective.
PMC10294515
Results
124 working-age patients finished the measurements. German usual care leads to a significantly larger proportion (65.6% versus 47.5%) of satisfied patients 12 weeks postoperatively and significantly better self-reported function and Five Times Sit-to-Stand Test (FTSST) results. German usual care is generally 45% more expensive than Dutch usual care, and 20% more expensive for working-age patients. A scenario analysis assumed that German patients work the same number of hours as the Dutch, and that productivity costs are the same. This analysis revealed German care is still more expensive but the difference decreased to 8%.
PMC10294515
Conclusions
German rehabilitation is clinically advantageous yet more expensive, although comparisons are less straightforward as the socioeconomic context differs between the two countries.
PMC10294515
Trial registration
The study is registered in the German Registry of Clinical Trials (DRKS00011345, 18/11/2016).
PMC10294515
Supplementary Information
The online version contains supplementary material available at 10.1186/s12891-023-06654-w.
PMC10294515
Keywords
PMC10294515
Background
Osteoarthritis, OA
OSTEOARTHRITIS, JOINT DISORDER
Osteoarthritis (OA) is an age-related chronic progressive joint disorder [THA-related procedures and recovery differ significantly between Germany and the Netherlands. In the Netherlands, as in many other Western countries, there is an increasing tendency to perform p-THA following a fast-track approach. This allows people to leave the hospital within a few days of surgery. A disadvantage is that Dutch patients are minimally supported in their rehabilitation process during hospital admission and after discharge. Postoperative physiotherapy is essentially not covered by Dutch basic health insurance [By contrast, in Germany, most patients stay hospitalized for approximately 8–10 days following p-THA [Due to the expected increase in the number of hip OA patients in both Germany and the Netherlands, the question arises as to which country’s postoperative p-THA approach is more effective in terms of functional outcome, patient satisfaction, and cost effectiveness. As patients with OA are among the main users of the healthcare system, the expected increase in p-THA will result in a higher socioeconomic burden of OA, especially among employable patients [
PMC10294515
Methods
PMC10294515
Study design
Trauma
The study was conducted as a transnational prospective controlled observational trial analyzing the clinical and cost effectiveness of the Dutch versus the German rehabilitation approach following p-THA. It is a mutual project of the orthopedic departments of University Medical Center Groningen (UMCG) in the Netherlands and University Hospital for Orthopedics and Trauma Surgery Pius-Hospital, Medical Campus University of Oldenburg in Germany. Participating hospitals in the Netherlands were Ommelander Ziekenhuis Groningen (OZG) and Medical Center Leeuwarden (MCL), a large teaching hospital and a general hospital, respectively. German patients had surgery at Pius Hospital in Oldenburg and were inpatients at the rehabilitation center Reha-Zentrum am Meer in Bad Zwischenahn. All study-related measures were performed in accordance with the ethical principles formulated by the Declaration of Helsinki in its current version. In conformity, the study protocol was reviewed and ethical approval was provided by both the institutional review boards of both University Medical Center Groningen (METc2015/483) and Hannover Medical School (no. 2874–2015). Details of the study design are provided elsewhere [
PMC10294515
Study population
The following criteria were set up to determine patient eligibility. Inclusion criteria were employable patients aged 18–65, clinical evidence of hip OA according to Altman et al. [
PMC10294515
Outcome measures
Preoperative demographic data, preoperative diagnosis, height, weight, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, and perioperative/postoperative complications were recorded from electronic patient files. Measurements were taken preoperatively (T
PMC10294515
Primary outcome measure
Primary outcome was the patient acceptable symptom state (PASS), an instrument to measure a patient’s response to a treatment or intervention [
PMC10294515
Secondary outcome measures
disability, pain
To measure health-related quality of life, the Short Form 36 (SF-36) and the EuroQol 5 Dimensions 3 Level Questionnaire (EQ-5D-3L) were used. SF-36 is a widely used generic health status questionnaire, consisting of 36 questions organized into eight multi-item scales: physical functioning, role limitations due to physical problems, bodily pain, general mental health, social functioning, role limitations due to emotional problems, vitality, and general health perceptions. Each raw scale score is transformed into a linear 0–100 scale. A higher score represents less disability. The German- and Dutch-language versions are proven practical, reliable, and valid among general and chronically diseased populations [To assess functional status objectively, the Timed Up & Go Test (TUG) and the Five Times Sit-to-Stand Test (FTSST) were conducted. The TUG is considered a practical and reliable test to assess physical mobility [
PMC10294515
Cost effectiveness
hip complaints, Productivity loss calculations, pain
The economic evaluation was conducted in collaboration with the Patient Centered Health Technology Assessment Unit of UMCG. The aim was to obtain a first impression of the direct and indirect costs of postoperative care incurred in each of the two countries, since no pertinent data were previously available in the literature.Direct costs post-treatment resulted from expenditures within the scope of care at the hospital, postoperative medical rehabilitation, other care providers (general practitioner, orthopedic technician, social worker), transportation, assistance at home, and other additional costs for the patients (over-the-counter medication, therapeutic services, remodeling measures). Indirect costs resulted from lost productivity due to incapacity for work.Information on resource consumption was collected via a patient self-reported questionnaire, which is a generally accepted concept. Using this instrument, questions were asked about frequency and duration of medical visits and rehabilitation, use of therapeutic services, household chores, extra expenses incurred due to the hip complaints (e.g., for pain medication), time to return to work, extent of employment, need for professional retraining.The monetary values on the Dutch side were obtained from the Dutch cost manual [Productivity loss calculations followed the human capital approach, where missed working hours were multiplied by the respective hourly productivity costs over a time horizon of six months. Basis for the calculation of lost working time (in hours) was the number of working hours per week reported by each patient in the aforementioned questionnaire and the time of their return to work.An overview of cost types, units and price per unit incurred in each country can be found in Additional file
PMC10294515
Sample size
PASS
The sample size calculation was based on the PASS. The PASS is a novel approach to measure patients’ response to a treatment or intervention, and is an easy method to establish whether a patient has achieved therapeutic success [
PMC10294515
Statistical analyses
POSTOPERATIVE COMPLICATIONS
Collected data were analyzed using SPSS software (V.23; IBM, Armonk, NY, USA). Main characteristics of both groups as well as intraoperative and postoperative complications were analyzed descriptively.
PMC10294515
Primary Outcome Data Analysis
To distinguish patients who benefited from their p-THA and subsequent medical rehabilitation or follow-up (responders) from those who did not (non-responders), a receiver operating characteristic (ROC) curve was calculated as recommended in literature [
PMC10294515
Secondary Outcome Data analysis
SECONDARY
Because data were collected at four timepoints, a multilevel analysis was performed to compare the secondary outcome measures. This made it possible to compare differences in both within-country and between-countries data at the different timepoints [
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Cost Analysis
The respective mean values of all costs were calculated. Additionally, based on bootstrapping (5000 replications) the corresponding 95% CI were calculated. In a scenario analysis the correspondence between amount of work (in weekly hours) and productivity costs (per hour) in both countries was simulated in order to better compare the determined costs between the two countries. Information on resource use was collected via the aforementioned patient self-reported cost questionnaire.
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Results
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Discussion
Primary aim of this study was to compare clinical effectiveness between the common medical rehabilitation approach after p-THA in Germany and the common approach in the Netherlands for working-age patients against the background of the prognosis that the majority of p-THA patients will be from the working-age population [Looking at clinical effectiveness, data collected in the present study confirm the hypothesis that the German procedure results in a significantly higher proportion of patients (65.6% of German vs. 47.5% of Dutch participants) who are satisfied 12 weeks after p-THA and who have benefited from surgery and subsequent follow-up treatment. At 6 months postoperatively, German patients were still more satisfied than Dutch patients (69.4% vs. 58.1%). Overall, German patients are twice as likely to benefit from surgery and related medical rehabilitation measures and thus achieve greater satisfaction.The German cohort scored significantly better on self-reported function. Some of these differences were clinically relevant, especially on the subdomains of the SF-36, namely Füssenich et al. also compared the usual p-THA treatment in the Netherlands to the German approach [In terms of cost analyses, the present study should and can only provide a first impression. Cost comparisons are challenging because of the substantial between-country differences in socioeconomic context and essential structures of the healthcare system. On one side of the border, for example, there are certain specialists, medical professionals and/or therapeutic approaches that do not exist in the other country (e.g., outpatient specialists, land-based and/or water-based medical rehabilitation). For this reason, all information on resource use was collected via a patient self-reported questionnaire, which was partly adapted to the respective system. Where precise monetary evaluation rates could not be determined on the German side, data from the OECD were tapped, with the OECD health expenditure of both countries used as a share of GDP in each case to reflect country-specific prices of healthcare facilities. A more accurate impression could only be obtained if all costs were available without restriction in both countries.The German approach appears considerably more expensive than the Dutch, given the much more intensive multimodal and interdisciplinary medical p-THA rehabilitation in Germany. The German approach is also more expensive given the higher productivity losses due to work absenteeism. This can be explained by a higher amount of regular weekly working hours and higher wage costs in Germany. Overall, considering this study’s total population, medical rehabilitation costs in connection with p-THA are almost twice as high in Germany (45%) as in the Netherlands. However, when comparing only patients who are actively employed a more balanced picture emerges where the costs in Germany are only about 20% higher than in the Netherlands.As mentioned, the average weekly working hours of German patients are higher than those of Dutch patients, as is the hourly wage in Germany (Additional file For clinical practice, the present study’s results suggest that it must be questioned whether it wouldn’t be useful for the Netherlands to adopt the German approach to medical rehabilitation after p-THA, or at least aspects of it. In the 1970s, when the first p-THAs were implanted, most patients were already of advanced retirement age and had a lower activity level [The present study must be evaluated, given its limitations. Among these is that the concept of common p-THA follow-up in the Netherlands is difficult to define, as implementation of physiotherapeutic measures can vary widely from patient to patient. Both the Dutch Orthopaedic Association and the Royal Dutch Physiotherapy Association recommend continuous physiotherapy follow-up after p-THA and hospital discharge to correct remaining dysfunctions; increase muscle strength, mobility, and stability; harmonize gait; and minimize limitations in activities of daily living [Another limitation could be that on the German side only those patients were included who agreed at study enrollment to have their rehabilitation treatment in the cooperating rehabilitation center, which represents a possible selection bias. However, it should be noted that the evidence-based rehabilitation standards defined for p-THA by the DRV apply equally to all rehabilitation facilities and implementation is standardized. In this respect, it can be assumed that the effects would not have been substantial even if such a bias had existed.Another limitation is that no comparison between German and Dutch patients was possible regarding payment of wage replacement benefits, since only a minority of German patients could provide information on receipt of such benefits and Dutch patients were not asked about their income during their absence from work. The cost comparison is limited by the fact that early rehabilitation services at the hospital were not specifically considered in the present cost analysis. German patients stay longer at the hospital postoperatively and thus also receive physiotherapeutic services longer in the sense of early rehabilitation compared to the Dutch.Future studies should follow p-THA patients from both countries and systems over a longer period to evaluate the long-term effects of the respective follow-up treatments on functional capacity, activities, and participation. This should include an examination of the influence of cultural differences on rehabilitation outcomes. Since the economic comparison of the medical rehabilitation approaches in the current study can only give a first impression, it would also be important to conduct studies that shed further light on the economic aspect. Such studies should include larger cohorts and follow them over a longer period.
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Conclusions
This study identified that a more intense aftercare following p-THA as performed in Germany is clinically advantageous. From a cost-effectiveness perspective comparisons are less straightforward, as the socioeconomic context differs between the two countries. The results nonetheless give food for thought as to whether the German approach, or at least aspects of it, could be beneficial for the expanding group of employable patients in the Netherlands.
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Acknowledgements
We would like to thank the students who assisted with the measurements, R.E. Stewart and I.H.F. Reininga for their statistical help, and Dr. F. Diederich for the health economic advice.
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Authors’ contributions
There are no conflicts of interest. AH is a coordinating manager in social medicine at one of the third-party funders (DRV Oldenburg-Bremen), but this did not affect the results of the present study.GHS Conceptualization, Methodology, Investigation, Resources, Writing - Original Draft, Writing - Review & Editing, Supervision, Project administration, Funding acquisition; MS Conceptualization, Methodology, Writing - Original Draft, Writing - Review & Editing, Supervision, Project administration, Funding acquisition; AW Formal analysis, Investigation, Resources, Writing - Original Draft, Visualization, Project administration; SKB Conceptualization, Methodology, Funding acquisition; DL Conceptualization, Methodology, Funding acquisition; GD Conceptualization, Methodology; JSD Resources; BD Resources; KMV Formal analysis; GECS Resources; AH Funding acquisition. All authors read and approved the final manuscript.
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Funding
This study was partly funded by the intramural research fund
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Availability of data and materials
Available upon request from the corresponding author (Martin Stevens).
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Declarations
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