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Acknowledgements
diabetes
DIABETES
The authors of this study would like to express their sincere appreciation for all the respected participants and the Yasuj University of Medical Sciences research committee. Also, the personnel of the diabetes clinic in Yasuj are sincerely thanked for their support and cooperation.
PMC10577942
Author contributions
All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by Soraya Bagheri, Seyed Majid Ahmadi, Sajjad Reisi, and Sajad Hassanzadeh. The first draft of the manuscript was written by Seyed Majid Ahmadi, Seyed Ahmadreza Ahmadi, Isaac Moradishibany, Hosein Dolatkhah, and Sajjad Reisi, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
PMC10577942
Funding
The current investigation has been financially aided by Yasuj University of Medical Sciences (ID: 990070). This study is written based on a professional doctoral dissertation (internal medicine specialization) and has been approved by Yasuj University of Medical Sciences.
PMC10577942
Data Availability
It is possible to access the data after coordination with the corresponding author by email.
PMC10577942
Declarations
PMC10577942
Competing interests
The authors declare no competing interests.
PMC10577942
Ethics approval and consent to participate
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. The participants in the present study indicated their informed consent for participation in the research. The present article has been approved by the ethics committee of Yasuj University of Medical Sciences (IR.YUMS.REC.1400.008).
PMC10577942
Consent for publication
“Not Applicable”.
PMC10577942
Abbreviations
Diabetic Neuropathy
DIABETIC NEUROPATHY
Visual analog scaleOne-way analysis of covarianceDiabetes MellitusDiabetic Peripheral NeuropathyDiabetic NeuropathyMichigan Diabetic Neuropathy Symptom ScoreSerotonin–Norepinephrine Reuptake Inhibitors
PMC10577942
References
PMC10577942
Background
ACUTE HYPOXEMIC RESPIRATORY FAILURE
The effects of awake prone position on the breathing pattern of hypoxemic patients need to be better understood. We conducted a crossover trial to assess the physiological effects of awake prone position in patients with acute hypoxemic respiratory failure.
PMC10433569
Methods
acute hypoxemic respiratory failure
ACUTE HYPOXEMIC RESPIRATORY FAILURE
Fifteen patients with acute hypoxemic respiratory failure and PaO
PMC10433569
Results
Compared to supine position, prone position increased PaO
PMC10433569
Supplementary Information
The online version contains supplementary material available at 10.1186/s13054-023-04600-9.
PMC10433569
Keywords
PMC10433569
Background
acute hypoxemic respiratory failure
ACUTE HYPOXEMIC RESPIRATORY FAILURE, RECRUITMENT, ACUTE RESPIRATORY DISTRESS SYNDROME
In intubated patients with moderate-to-severe acute respiratory distress syndrome, prone positioning reduces intrapulmonary shunt and generates lung recruitment, optimizes ventilation/perfusion matching, lowers alveolar dead space and reduces right ventricle afterload [In recent years, prone position has been proposed in non-intubated patients with acute hypoxemic respiratory failure, with positive effects on arterial oxygenation [Despite plenty of clinical data obtained during the COVID-19 pandemic, few available studies address the physiological effects of prone position in spontaneously breathing humans with acute hypoxemic respiratory failure [We conducted a sequential, crossover trial to comprehensively evaluate the effects of awake prone positioning on gas exchange, effort-to-breathe, lung volumes and inflation pattern in adult patients with moderate-to-severe acute hypoxemic respiratory failure undergoing high-flow nasal oxygen.
PMC10433569
Methods
This sequential crossover study was conducted in the intensive care unit of a university hospital in Italy between October 2018 and June 2020. The study was funded by an unrestricted research grant by the European Society of Intensive Care Medicine (ESICM-2017 Bernhard Dräger Award). The study was approved by institutional review board (ID 1506-ethics committee Fondazione Policlinico A. Gemelli IRCCS, Rome Italy) and was conducted in accordance with the declaration of Helsinki. All enrolled patients provided written informed consent to participating in the study and data analysis. The study protocol was registered on clinicaltrials.gov (NCT03095300) on March 29, 2017.
PMC10433569
Patients
chest trauma, neutropenia
NEUTROPENIA, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, SYNDROME, ACUTE EXACERBATION OF ASTHMA, ACUTE HYPOXEMIC RESPIRATORY FAILURE, CARDIOGENIC PULMONARY EDEMA
Adult patients admitted to the intensive care unit due to acute hypoxemic respiratory failure were assessed for the enrolment. Acute hypoxemic respiratory failure was defined as an acute onset syndrome characterized by new or worsening impairment in oxygenation. Patients were considered eligible for inclusion if the following criteria were met: PaOExclusion criteria were: more than 48 h from the admission in the intensive care unit; acute exacerbation of asthma or chronic obstructive pulmonary disease; chest trauma; cardiogenic pulmonary edema; severe neutropenia (< 500 white blood cell count/mm
PMC10433569
Protocol
Patients received high-flow nasal oxygen for 1 h in the supine semirecumbent position. Gas flow was set at 60 L/min, the temperature of the humidification chamber (MR860 or ARIVO2, Fisher and Paykel healthcare) was set according to patient's comfort, FiOFor safety reasons, enteral feeding was interrupted 1 h before prone positioning and re-established after the study ended.
PMC10433569
Endpoints
LUNG
The primary objectives of this study were to assess the effects of prone position on arterial oxygenation (as defined by the PaOSecondary endpoints of the study were the effects of prone position on:Breathing pattern: respiratory rate, inspiratory effort (the negative deflection of Gas exchange: PaCORespiratory mechanics: The end-expiratory Lung inflation pattern, measured with the EIT globally and regionally in the four regions of interests (ROI: ventral, mid-ventral, mid-dorsal, dorsal-Additional file Analyzed EIT outcomes were: global and regional tidal volume, expressed in arbitrary units and calculated on a pixel-by-pixel basis; global and regional lung compliance, calculated as the ratio of tidal volume to quasi-static transpulmonary driving pressure; amount of pendelluft, expressed in terms of % of tidal volume (Additional file Respiratory mechanics and lung inflation pattern were analyzed according to a methodology described elsewhere [
PMC10433569
Sample size calculation
Given the physiological design of the study, we did not perform a formal sample size calculation. Consistently with previous investigations with similar design on the topic [
PMC10433569
Statistical analysis
EVENT
Categorical data are expressed as the event rate (%), while continuous data are expressed as the median [interquartile range]. Normality in the distribution of continuous variables was assessed with the Kolmogorov–Smirnov test.Normally distributed quantitative variables in the three study steps were compared using ANOVA for repeated measures, with Bonferroni’s correction added for paired comparisons. Ordinal and non-normally distributed quantitative variables were analyzed using the Friedman test, with post hoc Dunn's test to adjust for multiple comparisons during pairwise testing of study phases. P-values, mean differences and confidence intervals for paired comparisons are displayed, and results with two-tail Correlations between continuous variables were assessed with Pearson’s correlation, and the r and p values are reported.Statistical analysis was performed with SPSS 26.0, MATLAB R2021, and GraphPad Prism V 9.00.
PMC10433569
Gas exchange and subjective symptoms
dyspnea
ADVERSE EVENTS
None of the fifteen enrolled patients experienced any serious adverse events. Thirteen out of 15 patients showed increased blood oxygenation after 2 h of prone positioning (mean difference 45 mmHg [95% CI 23–68], PaCOThere was no change in perceived dyspnea among the three study phases, but patients exhibited less tolerability for the prone position when resupinated (
PMC10433569
Effort to breath and respiratory mechanics
Respiratory rate decreased during prone positioning (mean difference − 2 breaths per minute [95% CI − 6 to − 1], Compared to supine position, prone position increased inspiratory effort (ΔProne position was associated with changes in respiratory system resistive properties, with an increased time constant compared to both supine phases (Prone-induced changes in airway resistance were related to the change in ΔSimplified minute PTPIn prone position, end-expiratory esophageal pressure was lower (
PMC10433569
Tidal volume
Compared to supine position, prone position did not yield changes in tidal volume (all Tidal volume distribution (expressed in % of global tidal volume) in supine and prone position. Results are expressed as means (standard deviation). Prone position promoted tidal volume distribution towards dorsal, dependent lung regionsGiven the unchanged ΔPendelluft was common in our cohort (31% [14–55] of tidal volume during supine position, 55% [7–57] during prone position, 44% [13–66] after re-supination), without significant differences between treatments (
PMC10433569
End-expiratory lung impedance
Prone position increased EELI compared to supine phases before and after the intervention (mean % increase 279% [95%CI: 133 to 330], The increase in EELI occurred throughout all lung regions, but was prominent in dorsal ROIs.The increase in EELI led to a reduction in the dynamic strain during prone position, compared to both supine positions before and after pronation (mean difference − 0.22 [95% CI − 0.33 to − 0.11],
PMC10433569
Discussion
ventilator-induced lung injury, hypoxemic respiratory failure, hypoxemia, ARDS
ADVERSE EVENTS, RECRUITMENT, ADVERSE EFFECTS, ARDS, ACUTE RESPIRATORY DISTRESS SYNDROME, HYPOXEMIC RESPIRATORY FAILURE
The results of this sequential study on the physiological effects of awake prone positioning in patients with moderate-to-severe hypoxemic respiratory failure undergoing high-flow nasal oxygen can be summarized as follows:Awake prone positioning improves arterial oxygenation without serious periprocedural adverse events. However, the benefit on oxygenation is transient and, after supination, oxygenation may significantly worsen, likely reflecting patient’s deterioration.Awake prone positioning reduces respiratory rate but increases ΔAwake prone positioning increases EELI. This occurs due to recruitment of dorsal lung regions, enhanced expiratory pressure produced by higher resistance to expiratory flow and higher end-expiratory transpulmonary pressure.In prone position, the increase in EELI combined to a shift of the Prone positioning does not affect the magnitude of the pendelluft phenomenon.In intubated patients with moderate-to-severe ARDS, prone position improves oxygenation, limits ventilator-induced lung injury and decreases mortality [Over the past decade, the management of patients with hypoxemic respiratory failure has changed significantly. High-flow nasal oxygen has emerged as a means of avoiding endotracheal intubation and minimizing the adverse effects of sedation and invasive mechanical ventilation [The major SILI determinant is the intensity of ΔSeveral studies showed that awake prone position improves oxygenation, but few studies elucidated the effects of awake prone positioning on ΔOur study confirms that prone position can improve oxygenation without serious adverse events related to the procedure. This is attributable to the observed increase in EELI, caused by the positional change and, likely, to enhanced positive expiratory pressure produced by increased airway resistance to expiratory flow and higher transpulmonary end-expiratory pressure [In our cohort, prone positioning reduced respiratory rate but increased ΔIn our study, we neglected the amount of ΔIn our study, prone position reduced global and regional dynamic strain, which represents the most relevant determinant of ventilator-induced lung injury during controlled ventilation in patients with acute respiratory distress syndrome. This may contribute to the beneficial effects of prone position observed in spontaneously breathing subjects in clinical and observational studies [In our study, prone position did not affect the pendelluft phenomenon, which is one of the mechanisms of SILI [Our results have relevant clinical implications:Prone-induced improvement in oxygenation may help avoid endotracheal intubation, since hypoxemia is a relevant cause of treatment failure during noninvasive support [Prone position homogenizes lung inflation, reduces global and regional dynamic strain and respiratory rate, does not affect the amplitude of the pendelluft phenomenon, Our study has limitations. First, we assessed the effects of prone positioning after 2 h, while it has been shown that the most clinical benefit by prone positioning is observed in patients who remain prone for longer periods [
PMC10433569
Conclusions
hypoxemia
RECRUITMENT, ACUTE RESPIRATORY FAILURE
In patients undergoing high-flow nasal oxygen and exhibiting moderate-to-severe hypoxemia due to acute respiratory failure, prone position improves oxygenation by enhancing recruitment of dorsal lung regions, homogenizes ventilation distribution and reduces respiratory rate. Prone position does not affect
PMC10433569
Acknowledgements
None.
PMC10433569
Author contributions
DLG designed the study. All authors contributed to patients’ enrollment. LDC and LSM analyzed the data. DLG drafted the first version of the manuscript. AP, SMM and MA revised the manuscript. All the authors reviewed the final draft of the manuscript and agreed on submitting it to Critical Care.
PMC10433569
Funding
This study was supported by a grant by ESICM (2017 Draeger award) and by Ministero della Saluto (Ricerca corrente 2023).
PMC10433569
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10433569
Declarations
PMC10433569
Ethics approval and consent to participate
The study was approved by local Ethics Committee, and informed consent was obtained by enrolled patients according to committee recommendation.
PMC10433569
Consent for publication
Not applicable.
PMC10433569
Competing interests
DLG has received speaking fees by Gilead, Intersurgical, MSD and GE, and reports having received travel accommodation by Fisher and Paykel. MA has received personal fees by Maquet, and a research grant by Toray. DLG and MA disclose a research grant by GE.
PMC10433569
References
PMC10433569
Background:
GIRD, shoulder pain
PATHOLOGY
Maladaptation can provoke important alterations in the arthrokinematics such as an internal rotation reduction in the dominant shoulder compared with the nondominant shoulder known as glenohumeral internal rotation deficit (GIRD). Though the number of studies investigating GIRD in athletic population, there are not studies reporting the efficacy of the GIRD treatment in the nonathlete population, a kind of study required to improve our understanding of patient care with this pathology. This study aimed to describe the efficacy of the GIRD treatment in nonathlete population with shoulder pain.
PMC10519522
Methods:
GIRD, shoulder pain
An open single-arm trial with 35 patients was adopted for evaluating the efficacy of GIRD treatment in patients with shoulder pain. All patients with shoulder pain who attended the consultation, accepted, and agreed to participate in the study between October 2020 and March 2021 were included. A treatment sequence including joint manual therapy techniques and soft tissue release techniques was applied in the consultation. Then, patients were instructed to adapt the daily active biological stimulus at home. The IR before (IR
PMC10519522
Results:
painful shoulder
Treatment of the patients significantly increased the IR of the painful shoulder in all the patients (
PMC10519522
Conclusions:
painful shoulder and reduced the GIRD
The treatment administrated in this study significantly increased the internal rotation of the treated and painful shoulder and reduced the GIRD from the first consultation.
PMC10519522
Level of evidence:
Level 3.
PMC10519522
1. Introduction
Shoulder pain, GIRD, shoulder pain, pain
PATHOLOGY, RECURRENCE
Shoulder pain is a frequent disabling joint problem in the general population. The reported incidence ranges between 0.9% and 2.5%Shoulder pain is mainly related to the glenohumeral joint.Recovery from this ailment is slow and is associated with a high recurrence or persistence pain at 12-month.This study aimed to describe the efficacy of the GIRD treatment in nonathlete population with shoulder pain provoked by a soft tissue problem. Our hypothesis was that the treatment here described would be able to reduce considerably the GIRD in this kind of patients. Thus, to our knowledge, our work would be of the first studies to evaluate the treatment of GIRD in a nonathlete population, which would improve the therapeutic approach to patients with this pathology, as well as broaden the understanding of this condition for clinicians and researchers.
PMC10519522
2. Materials and Methods
PMC10519522
2.1. Study design
GIRD, NCT05108311, shoulder pain
An open single-arm trial (clinical trial registration number: NCT05108311) was adopted for evaluating the efficacy of reducing GIRD in patients with shoulder pain using an exercise routine initiated at the time of the first consultation. All patients underwent a medical examination.
PMC10519522
2.2. Ethics approval
subclavian muscle, Myofascial, scapulothoracic joints, GIRD, pectoralis muscle, sternocostoclavicular to acromioclavicular joints, Myofascial releases external rotators, adduction
MINOR
The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Clínica Universitaria de Navarra (Project 2020.095 of June 18, 2020). Informed consent was obtained from all subjects and/or their legal guardian(s) for publication of identifying information/images in an online open-access publication.The patient photographed in Figure Manual therapy protocol for GIRD treatment. Digital superficial glides on the superficial deltoid fascia (A). Anteroposterior (B) and craniocaudal (C) mobilizations of the clavicle from sternocostoclavicular to acromioclavicular joints. Myofascial release using direct manual pressure of subclavian muscle (D), pectoralis muscle (E), pectoralis minor muscle (F), and subscapularis muscle (G). Myofascial releases of external rotators with glenohumeral decoaptation facilitating triangular space, quadrangular space and triceps hiatus (H–J). Myofascial releases external rotators with glenohumeral decoaptation (K). Myofascial releases of the scapular musculature: rhomboids, trapezius (L–N), subscapularis including mobilization with a scapulothoracic joints decoaptation, and angular of the scapula (O–S). The treatment finished with a technique of supine mobilization of the posterior capsule in 90º shoulder flexion and adduction (T, U) and circumductions (V). GIRD = glenohumeral internal rotation deficit.
PMC10519522
2.3. Sample
Shoulder pain, shoulder pain
All patients with shoulder pain who attended the consultation, accepted, and agreed to participate in the study between October 1, 2020 and March 31, 2021 were included. The shoulder pain in the patients was understood as when they manifested an unpleasant sensory and emotional experience directly associated with actual or potential tissue damageAnthropometric and sociodemographic description of the sample evaluated.BMI = body mass index.Shoulder pain etiology based on the radiological findings.The percentages denote the number of patients that showed each radiological finding respect to the 35 patients included in this study.For the sample size calculation, the GRANMO calculator was used (version 7.12, Municipal Institute for Medical Research, Barcelona, Spain). The minimum sample size was calculated to be 35 patients for detecting at least a difference between IR
PMC10519522
2.4. Measurements
abduction
All participants underwent a physical examination by physiotherapist with one more than 20 years of experience (RJ-L), followed by anthropometric and sociodemographic data that is sex, age, height, weight, occupation, marital status, descent, previous surgeries, and sport habits (documented via questionnaire and by means of a structured interview). The IR of each shoulder was measured in supine position on a physiotherapy bench. The shoulder was held by the examiner at 90° abduction with 90° flexion in the elbow. Then, an assistant placed a clinical Absolute + Axis
PMC10519522
2.5. Treatment
scapular adduction, decubitus, abduction
DECUBITUS
The treatment here is applied to the patients and is based on a manual therapy aimed at increasing the IR of a painful shoulder and reducing, at the same time, the GIRD. This kind of treatment has traditionally been used to improve the range of motion in situations of mobility deficits of the shoulder joint complex, such as GIRD.Exercises to be performed by treated patients. Gold standard therapeutic subscapular exercise (A). It is important to note that a towel should be used for this exercise. The sleeper stretch: shoulder 90-degrees abduction and shoulder retropulsion with scapular adduction (B), elbow 90-degrees flexion without losing shoulder 90-degrees abduction (C), and passive internal glenohumeral rotation is performed until the point of tension, gradually gaining joint balance for 2 minutes at a time (D). It is essential that a middle position between lateral decubitus homolateral to the side be treated and prone decubitus is achieved from the pure lateral decubitus position.
PMC10519522
2.6. The minimal clinically important difference calculation
The minimal clinically important difference (MCID) was estimated from a distribution-based calculation using Cohen
PMC10519522
2.7. Statistical analysis
Data distribution was evaluated using Kolmogorov–Smirnov statistics with Lilliefors correction. Descriptive statistics are cited as means ± SD in case of normal distribution and as median and interquartile range in case of non-normal distribution for each of the variables that were calculated. A Student
PMC10519522
3. Results
painful shoulder, shoulder pain
Treatment of the patients significantly increased the IR of the painful shoulder in all the patients ((A) Internal rotation (IR) in patients with shoulder pain before (IRGIRD before and after treatment and improvement percentage are represented in Figure
PMC10519522
4. Discussion
painful shoulder and reduced the GIRD, shoulder flexion, GIRD, cross-body
POSTERIOR CAPSULAR THICKENING, STRETCHES
In this study, we aim to describe the efficacy of the GIRD treatment in nonathlete population. Although the definition of GIRD an exact value is still controversial,GIRD treatment involves targeting posterior capsular thickening and the posterior rotator cuff muscular adaptations in the form of “sleeper stretches” (arm at 90° shoulder flexion) and “cross-body stretches” (no scapular stabilization). There are two kinds of treatment for GIRD depending on who performs the treatment. One of them can be autonomously performed by the patient and the other one is assisted by the clinician. The autonomous stretches represent a huge preventiveThe treatment was effectively able to increase the IR of the painful shoulder from the first consultation. The efficacy of the treatment is supported by the MCID, as the mean IRThere are some limitations in our study. First, the number of patients treated is relatively small. Second, the ER of each shoulder was not considered. The sum of IR and ER gives rise to the total range of motion. Recently, Rose and NoonanIn conclusion, the treatment administrated in this study significantly increased the IR of the treated and painful shoulder and reduced the GIRD from the first consultation. Further studies should be addressed to corroborate the results here described through randomized clinical trials comparing different types of treatments and considering only the nonathletic population.
PMC10519522
Acknowledgments
We wish to acknowledge Dr John Jairo Aguilera-Correa for his writing assistance, and Dr Amr A. Abdelkader from the International Centre for Orthopaedics and Neurosciences (Doha, Qatar) for his help in reviewing the manuscripts for language-related aspects, and Mr. José Luis Lara-Cabrero from Clínica CEMTRO (Madrid, Spain) for his help in interpreting the treatment sequence of specialized manual therapy.
PMC10519522
Abbreviations:
shoulder pain
external rotationglenohumeral internal rotation deficitinternal rotationminimal clinically important differencestandard deviationThe authors have no funding and conflicts of interest to disclose.The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.How to cite this article: Jácome-López R, Tejada-Gallego J, Silberberg JM, García-Sanz F, García-Muro San José F. Treatment of glenohumeral internal rotation deficit in the general population with shoulder pain: An open single-arm clinical trial. Medicine 2023;102:38(e35263).
PMC10519522
References
PMC10519522
Key Points
PMC10119738
Question
Does treadmill perturbation-based balance training (PBT) reduce daily-life fall rates among community-dwelling adults 65 years or older?
PMC10119738
Findings
In this randomized clinical trial involving 140 highly functioning older adults, those who received an 4-session PBT intervention (totaling 80 minutes) experienced a statistically nonsignificant 22% reduction in daily-life fall rates over a 12-month period.
PMC10119738
Meaning
Findings of this trial suggest the need for future studies to investigate possible effects of current treadmill PBT on daily-life falls.
PMC10119738
Importance
injuries
Falls are common and the leading cause of injuries among older adults, but falls may be attenuated by the promising and time-efficient intervention called perturbation-based balance training (PBT).
PMC10119738
Objective
To evaluate the effects of a 4-session treadmill PBT intervention compared with regular treadmill walking on daily-life fall rates among community-dwelling older adults.
PMC10119738
Design, Setting, and Participants
This 12-month, assessor-blinded randomized clinical trial was conducted from March 2021 through December 2022 in Aalborg University in Denmark. Participants were community-dwelling adults 65 years or older and were able to walk without a walking aid. Participants were randomized to either PBT (intervention group) or treadmill walking (control group). Data analyses were based on the intention-to-treat principle.
PMC10119738
Interventions
Participants who were randomized to the intervention group underwent four 20-minute sessions of PBT, including 40 slip, trip, or mixed slip and trip perturbations. Participants who were randomized to the control group performed four 20-minute sessions of treadmill walking at their preferred speed. The 3 initial training sessions were completed within the first week, whereas the fourth session was performed after 6 months.
PMC10119738
Main Outcomes and Measures
fractures
Primary outcome was the daily-life fall rates that were collected from fall calendars for the 12 months after the third training session. Secondary outcomes were the proportion of participants with at least 1 fall and recurrent falls, time to first fall, fall-related fractures, fall-related injuries, fall-related health care contacts, and daily-life slip and trip falls.
PMC10119738
Results
A total of 140 highly functioning, community-dwelling older adults (mean [SD] age, 72 [5] years; 79 females [56%]), 57 (41%) of whom had a fall in the past 12 months, were included in this trial. Perturbation training had no significant effect on daily-life fall rate (incidence rate ratio [IRR]: 0.78; 95% CI, 0.48-1.27) or other fall-related metrics. However, there was a significant reduction in laboratory fall rates at the posttraining assessment (IRR, 0.20; 95% CI, 0.10-0.41), 6-month follow-up (IRR, 0.47; 95% CI, 0.26-0.86), and 12-month follow-up (IRR, 0.37; 95% CI, 0.19-0.72).
PMC10119738
Conclusions and Relevance
Results of this trial showed that participants who received an 80-minute PBT intervention experienced a statistically nonsignificant 22% reduction in daily-life fall rates. There was no significant effect on other daily-life fall-related metrics; however, a statistically significant decrease in falls was found in the laboratory setting.
PMC10119738
Trial Registration
ClinicalTrials.gov Identifier:
PMC10119738
Introduction
injuries
Falling is the leading cause of injuries in older adults, and the associated costs of treatment and rehabilitation burden society substantially.The recently published world guidelines for fall prevention highlight PBT as a future research priority.
PMC10119738
Methods
PMC10119738
Study Design, Setting, and Participants
neurological disease, osteoporosis-related fractures, cognitive impairment, fracture, Parkinson or multiple sclerosis, osteoporosis
NEUROLOGICAL DISEASE, OSTEOPOROSIS
This assessor-blinded, parallel-group (1:1 ratio) RCT was conducted between March 2021 and December 2022 at a laboratory in Aalborg University in Denmark. The trial protocol was approved by the North Denmark Region Committee on Health Research Ethics and the Danish Data Protection Agency. All participants provided written informed consent. The trial protocol (Individuals were recruited through radio and television advertisements and snowball sampling from March through November 2021. Eligible individuals were 65 years or older, community dwelling, and able to walk without a walking aid. Individuals were excluded if they (1) had any of the following self-reported conditions: orthopedic surgery within the past 12 months, osteoporosis or osteoporosis-related fractures (low-impact hip, spine, or wrist fracture), or progressive neurological disease (eg, Parkinson or multiple sclerosis); (2) had an unstable medical condition that prevented safe participation; (3) had a severe cognitive impairment (score <8 in the Short Orientation-Memory-Concentration Test); or (4) were currently participating in another fall prevention trial.
PMC10119738
Randomization and Interventions
After the pretraining assessments, participants were randomized in a 1:1 ratio to either the PBT (intervention) group or control group (
PMC10119738
Participant Flowchart
PBT indicates perturbation-based balance training.All participants in the PBT group were assigned to four 20-minute PBT sessions, and participants in the control group were assigned to 4 treadmill walking training sessions; the initial 2 training sessions were performed on the same day immediately after the pretraining assessments. A week later, the third training session was completed, whereas the fourth was conducted after 6 months (
PMC10119738
Training Schedule
sudden small deceleration
POSITIVE
The figure illustrates the arrangement of the training sessions (A). During slip perturbations (B), the participant walked at their preferred walking speed when a sudden acceleration reversed the direction of the belt movement before the belt returned to the preferred walking speed. During trip perturbations (C), the participant walked at their preferred walking speed when a sudden small deceleration followed by a larger backward acceleration occurred before the belt returned to the preferred walking speed. Positive belt speed values (B and C) indicate the belt movement direction during regular walking. PBT indicates perturbation-based balance training; TW, treadmill walking; TWT, treadmill walking training.
PMC10119738
Perturbation-Based Balance Training (Intervention)
anxiety
Each of the 4 PBT sessions lasted approximately 20 minutes and consisted of 40 perturbations (20 to each leg) delivered on a uniformly moving treadmill with no lateral rails (Split 70/157/ASK; Woodway). A safety harness prevented participants from falling to the ground if they could not regain balance after a perturbation. Participants experienced only slips in the first session, only trips in the second session, and randomly ordered slips and trips (mixed perturbations) in the third and fourth sessions (The perturbation intensity was adjusted based on participants’ preferred walking speed and was divided into 5 levels with progressively longer durations (slip) or greater accelerations (trip). The intensity was increased after every fourth perturbation if (1) the combined rating of perceived anxiety and difficulty was 4 or less, (2) the participant avoided falling during the previous 4 perturbations, and (3) the participant was comfortable increasing the intensity. However, if any criterion was not met, the intensity remained unchanged (for protocol tailoring, see eAppendix 1 in
PMC10119738
Treadmill Walking Training (Control)
In each of the 4 treadmill walking training sessions, the control participants performed 20 minutes of treadmill walking at their preferred walking speed. The duration of these walks matched the PBT group's time on the treadmill.
PMC10119738
Outcome Assessment
fracture, fractures, injury or unpleasantness
ADVERSE EVENTS, EVENT
This RCT’s primary outcome was the daily-life fall rates that were collected from fall calendars for the 12 months after the third training session. A fall was defined as “an unexpected event in which the participant comes to rest on the ground, floor, or lower level.”Secondary outcomes included the proportion of participants experiencing at least 1 fall and recurrent falls, time to first fall, fall-related fractures, fall-related injuries, fall-related health care contacts, and daily-life slip and trip falls. A fall-related fracture was a radiologically confirmed fracture from a fall.At the pretraining and posttraining assessments and the 6-month and 12-month follow-up, laboratory falls were evaluated by exposing participants to level-1 slip and trip perturbations. These perturbations were recorded in slow motion (100 fps [frames per second]) with a camera (Canon M200; Canon Inc) that was positioned 2 m away, perpendicular to the center of the treadmill. The video recordings were reviewed by a blinded research assistant to determine whether the participants experienced a fall. An attempt was categorized as a fall when the participant's body posture was in a falling mode that was clearly and unambiguously stopped by the safety harness. The laboratory fall rate (number of laboratory falls per exposed perturbation) was used for analysis. The personnel responsible for the training sessions (J.E.N.) registered all adverse events related to the intervention, including any injury or unpleasantness.
PMC10119738
Statistical Analysis
REGRESSION, SENSITIVITY
An a priori sample size calculation was performed using a Poisson regression model in G*Power, version 3.1.9.4 (University of Kiel). To detect a significant (2-sided α = .05) difference between groups of 50% from a base fall rate of 0.85 with 80% power and an expected 20% dropout, a total of 140 participants, with 70 in each group, was needed. The expected effect size of 50% was based on previous PBT reports.The statistical analyses were conducted in collaboration with an external statistician according to a preregistered statistical analysis plan using Stata, version 17.0 (StataCorp LLC). The analyses were based on the intention-to-treat principle. Two-sided Between-group differences in count outcomes were analyzed using a negative binomial regression with person-years of follow-up as an offset variable. We applied the negative binomial regression as the data fit better with this model than with the preregistered Poisson regression with bootstrapping. A sensitivity analysis using the preregistered approach was conducted. Binary daily-life fall outcomes were evaluated using Poisson regression with robust error variance.Preregistered sensitivity analyses were conducted for each daily-life fall outcome, adjusting for age, sex, and previous falls and following the per-protocol principle, among participants who completed at least 75% of the training sessions. Sensitivity analyses that were decided after data collection included fall rates after stratifying participants based on their fall history and laboratory fall rates after multiple imputations.
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Results
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Enrollment and Adherence
Of the 199 individuals screened for eligibility, 140 were included (mean [SD] age, 72 [5] years; 79 females [56%] and 61 males [44%]) and randomized to either the PBT or control group (
PMC10119738
Baseline Characteristics of Participants
Frailty
Abbreviation: PBT, perturbation-based balance training.Tilburg Frailty Indicator: score range of 0 to 15, with a lower score indicating less frailty.Vulnerable Elders-13 Survey: score range of 0 to 10, with a lower score indicating less vulnerable.Short Falls Efficacy Scale: score range of 7 to 28, with a lower score indicating less concern about falling.Short Orientation-Memory-Concentration Test: score range of 0 to 28, with a higher score indicating better performance.Short Physical Performance Battery: score range of 0 to 12, with a higher score indicating better performance.Time to complete the Trail Making Test Part A was subtracted from Part B time, with less time indicating better executive function.The PBT group completed 90% and the control group completed 93% of the assigned training sessions. At least 75% (per-protocol criterion) of the training sessions were completed by 90% of the PBT group and 97% of the control group.At 12 months, the PBT group had returned 99% (71.5 person-years) and the control group had returned 97% (70.4 person-years) of fall calendars. Nineteen participants (27%) in the PBT group and 25 participants (36%) in the control group had missing laboratory fall data. Data were treated as missing at random because the reasons for missing data and the demographic characteristics of participants with missing data were similar between the 2 groups (eTables 1 and 2 in
PMC10119738
Daily-Life and Laboratory Falls
For the primary outcome, 62 falls in the PBT group (rate of falls per person-year of follow-up: 0.90; 95% CI, 0.58-1.21) and 78 in the control group (rate of falls per person-year of follow-up: 1.14; 95% CI, 0.76-1.52) were reported, resulting in a nonsignificant 22% relative between-group difference in fall rates (incidence rate ratio [IRR], 0.78; 95% CI, 0.48-1.27) (
PMC10119738
Comparison of the Number of Falls in the Intervention and Control Groups
PBT indicates perturbation-based balance training.
PMC10119738
Daily-Life Fall Results From Intention-to-Treat Analysis After 12 Months
EVENTS
Abbreviations: HR, hazard ratio; IRR, incidence rate ratio; NA, not applicable; PBT, perturbation-based balance training; RR, risk ratio.Primary outcome. The rate is the falls per person-year of follow-up.Not enough events to conduct analysis.The laboratory fall rates were similar at baseline but were significantly lower in the PBT group than in the control group at the posttraining assessment (IRR, 0.20; 95% CI, 0.10-0.41), 6-month follow-up (IRR, 0.47; 95% CI, 0.26-0.86), and 12-month follow-up (IRR, 0.37; 95% CI, 0.19-0.72). All laboratory fall rate results are shown in eTable 3 in
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Sensitivity Analyses
REGRESSION
The Poisson regression with bootstrapping yielded results that were comparable to those of the negative binomial regression for all count outcomes (eAppendix 3 in
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Safety
knee injury, injuries
ADVERSE EVENTS
No serious adverse events were reported in the present RCT. Nevertheless, 2 injuries occurred during PBT: a knee injury and a muscle strain in the thigh. The participant with the knee injury had 1 appointment with the general practitioner, but none of the injuries required any further health care treatment. An overview of the adverse events is available in eTable 7 in
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Discussion
In this trial of a 4-session treadmill PBT intervention, there was not a statistically significant decrease in daily-life fall rates among community-dwelling older adults compared with those in the control group. There was, however, a significant reduction in laboratory fall rates associated with PBT.The significant decrease in laboratory fall rates found in this study aligns with results of previous PBT studies.Of the 4 RCTs with a primary aim of investigating the effects of PBT on daily-life falls,While treadmill PBT did not show significant decreases in daily-life falls, overground PBT may be more effective.
PMC10119738
Limitations
This trial has several limitations. First, participants were unblinded to group randomization due to the nature of training interventions. Given that the initial fall reporting was a participant-reported outcome, the lack of blinding may have contributed to fewer falls reported in the PBT group. However, daily-life falls were collected according to the recommendations of the Prevention of Falls Network Europe.
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Conclusions
In this RCT, participants who received an 80-minute PBT intervention experienced a statistically nonsignificant 22% reduction in daily-life fall rates. There was no significant effect on other daily-life fall-related metrics; however, a statistically significant decrease in falls was found in the laboratory setting. Further studies are warranted to corroborate this effect.
PMC10119738
Aims/hypothesis
NOCTURNAL HYPOGLYCAEMIA
It is generally recommended to reduce basal insulin doses after exercise to reduce the risk of post-exercise nocturnal hypoglycaemia. Based on its long
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Methods
hypoglycaemia, diabetes
TYPE 1 DIABETES, HYPOGLYCAEMIA, DIABETES
The ADREM study (Adjustment of insulin Degludec to Reduce post-Exercise (nocturnal) hypoglycaeMia in people with diabetes) was a randomised controlled, crossover study in which we compared 40% dose reduction (D40), or postponement and 20% dose reduction (D20-P), with no dose adjustment (CON) in adults with type 1 diabetes at elevated risk of hypoglycaemia, who performed a 45 min aerobic exercise test in the afternoon. All participants wore blinded continuous glucose monitors for 6 days, measuring the incidence of (nocturnal) hypoglycaemia and subsequent glucose profiles.
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Results
We recruited 18 participants (six women, age 38 ± 13 years, HbA
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Conclusions/interpretation
EVENTS, TYPE 1 DIABETES, NOCTURNAL HYPOGLYCAEMIA
Post-exercise adjustment of degludec does not mitigate the risk of subsequent nocturnal hypoglycaemia in people with type 1 diabetes. Although reducing degludec reduced next-day time below range, this did not translate into fewer hypoglycaemic events, while postponing degludec should be avoided because of increased time above range. Altogether, these data do not support degludec dose adjustment after a single exercise bout.
PMC9988601
Trial registration
EudraCT number 2019-004222-22
PMC9988601
Funding
The study was funded by an unrestricted grant from Novo Nordisk, Denmark.
PMC9988601
Graphical abstract
PMC9988601
Supplementary Information
The online version of this article (10.1007/s00125-023-05893-9) contains peer-reviewed but unedited supplementary material.
PMC9988601
Keywords
PMC9988601
Introduction
TYPE 1 DIABETES MELLITUS
Regular physical exercise is recommended for people with type 1 diabetes mellitus given its beneficial effects on general well-being, cardiometabolic health and insulin requirements [Insulin degludec is a second-generation long-acting insulin analogue with a much longer
PMC9988601
Methods
PMC9988601