Physical Medicine and Rehabilitation: Trends and Applications

Stroke recovery is a journey. Stroke survivors can face many consequences that may last the rest of their lives. Assessment of initial impairments allows reasonable prediction of biological spontaneous recovery at 3 to 6 months for a majority of survivors. In real-world clinical practice, stroke survivors continue to improve their motor function beyond the spontaneous recovery period, but management plans for maximal recovery are not well understood. A model within the international classification of functioning (ICF) theoretical framework is proposed to systematically identify opportunities and potential barriers to maximize and realize the potentials of functional recovery from the acute to chronic stages and to maintain their function in the chronic stages. Health conditions of individuals, medical and neurological complications can be optimized under the care of specialized physicians. This permits stroke survivors to participate in various therapeutic interventions. Sufficient doses of appropriate interventions at the right time is critical for stroke motor rehabilitation. It is important to highlight that combining interventions is likely to yield better clinical outcomes. Caregivers, including family members, can assist and facilitate targeted therapeutic exercises for these individuals and can help stroke survivors comply with medical plans (medications, visits), and provide emotional support. With health optimization, comprehensive rehabilitation, support from family and caregivers and a commitment to a healthy lifestyle, many stroke survivors can overcome barriers and achieve potentials of maximum recovery and maintain their motor function in chronic stages. This ICF recovery model is likely to provide a guidance through the journey to best achieve stroke recovery potentials. Full article

Across traumatic brain injury (TBI) severities, a geriatric TBI tsunami has emerged. Mixed outcomes are reported for elderly TBI with positive functional improvements with acute inpatient rehabilitation. We studied the effect of age at TBI on discharge functional outcomes, levels of independence and length of stay. A retrospective analysis of Asian TBI patients during inpatient rehabilitation over a 4-year period was conducted. Independent variables included admission GCS, post-traumatic amnesia (PTA) duration and injury subtypes. Primary outcomes were discharge Functional Independence Measure (Td-FIM) and FIM gain. In total, 203 datasets were analysed; 60.1% (122) were aged ≥65 years (older), while 39.9% (81) were <65 years (younger). At discharge, older TBI had a significantly lower Td-FIM by 15 points compared to younger (older 90/126 vs. younger 105/126, p < 0.001). Median FIM gains (younger 27 vs. older 23, p = 0.83) and rehabilitation LOS (older 29.5 days vs. younger 27.5 days, p = 0.79) were similar for both age groups. Older TBIs had significantly lower independence (Td-FIM category ≥ 91) levels (49.4% older vs. 63.9% younger, p = 0.04), higher institutionalisation rates (23.5% older vs. 10.7% younger, p = 0.014) and need for carers (81.5% older vs. 66.4% younger, p = 0.019) on discharge. Although 77% of older TBI patients returned home, a significantly higher proportion needed care. This study supports the functional benefits of TBI rehabilitation in increasing independence regardless of age without incurring longer inpatient rehabilitation days. Full article

Background: Haemorrhagic stroke, accounting for 10–20% of all strokes, often requires decompressive surgery as a life-saving measure for cases with massive oedema and raised intracranial pressure. This study was conducted to compare the demographics, characteristics and rehabilitation profiles of patients with severe haemorrhagic stroke who were managed surgically versus those who were managed non-surgically. Methods: A single-centre retrospective study of electronic medical records was conducted over a 3-year period from 1 January 2018 to 31 December 2020. The inclusion criteria were first haemorrhagic stroke, age of >18 years and an admission Functional Independence Measure (FIM™) score of 18–40 upon admission to the rehabilitation centre. The primary outcome measure was discharge FIM™. Secondary outcome measures included modified Rankin Scale (mRS), rehabilitation length of stay (RLOS) and complication rates. Results: A total of 107 patients’ records were analysed; 45 (42.1%) received surgical intervention and 62 (57.9%) patients underwent non-surgical management. Surgically managed patients were significantly younger than non-surgical patients, with a mean age of [surgical 53.1 (SD 12) vs. non-surgical 61.6 (SD 12.3), p = 0.001]. Admission FIM was significantly lower in the surgical vs. non-surgical group [23.7 (SD6.7) vs. 26.71 (SD 7.4), p = 0.031). However, discharge FIM was similar between both groups [surgical 53.91 (SD23.0) vs. non-surgical 57.0 (SD23.6), p = 0.625). Similarly, FIM gain (surgical 30.1 (SD 21.1) vs. non-surgical 30.3 (SD 21.1), p = 0.094) and RLOS [surgical 56.2 days (SD 21.5) vs. non-surgical 52.0 days (SD 23.4), p = 0.134) were not significantly different between groups. The majority of patients were discharged home (surgical 73.3% vs. non-surgical 74.2%, p = 0.920) despite a high level of dependency. Conclusions: Our findings suggest that patients with surgically managed haemorrhagic stroke, while older and more dependent on admission to rehabilitation, achieved comparable FIM gains, discharge FIM and discharge home rates after ~8 weeks of rehabilitation. This highlights the importance of rehabilitation, especially for surgically managed haemorrhagic stroke patients. Full article

Background: The minimum clinically important difference (MCID) for the St George’s Respiratory Questionnaire (SGRQ) is debated in chronic obstructive pulmonary disease (COPD) quality-of-life (QoL) assessments. This study aimed to determine whether there is a difference in predictors of clinically significant improvement between the traditional (value of 4) and newly proposed MCID SGRQ (value of 7) after climatic rehabilitation treatment. Climatic rehabilitation treatment consists of two main parts: climatotherapy, which typically involves the controlled exposure of individuals to natural environmental elements, and climatic rehabilitation, which includes other therapeutic factors such as physical activities as well as educating the patient to change their lifestyle. Methods: This study included 90 consecutive patients diagnosed with COPD who underwent structured complex pulmonary rehabilitation in High Tatras, part of the Carpathian Mountains. The examination before and after treatment included spirometry, QoL assessment using the SGRQ, 6 min walk test (6-MWT), and the Borg, Beck and Zung scale. Results: Patients showed statistically significant improvement after the intervention in FEV1, FEV1/FVC, 6-MWT, (p < 0.001), anxiety scores, depression, and improvement in dyspnoea both before and after the 6-MWT (p < 0.001). For both MCID for SGRQ levels 4 and 7, we confirmed the same predictors of clinical improvement for bronchial obstruction grade (spirometry) and exercise capacity (6-MWT), for quality of life in activity score and total score. Conclusion. The results suggest that both the proposed MCID for SGRQ values could be sufficient to assess the clinical significance of the achieved change in health status when assessing the need for pulmonary rehabilitation comprising climatotherapy in patients with COPD. Full article

Background: This study investigated the incidence, characteristics and functional outcomes associated with unplanned Acute Care Unit Readmissions (ACUR) during inpatient traumatic brain injury (TBI) rehabilitation in an Asian cohort. Methods: A retrospective review of electronic medical records from a single rehabilitation unit was conducted from 1 January 2012 to 31 December 2014. Inclusion criteria were first TBI, aged >18 years, admitted <6 months of TBI. ACUR were characterized into neurological, medical or neurosurgical subtypes. The main outcome measure was discharge and Functional Independence Measure (FIM™). Secondary outcomes included rehabilitation length of stay (RLOS). Results: Of 121 eligible TBI records, the incidence of ACUR was 14% (n = 17), comprising neurologic (76.5%) and medical (23.5%) subtypes occurring at median of 13 days (IQR 6, 28.5) after rehabilitation admission. Patients without ACUR had a significantly higher admission mean (SD) FIM score compared to those with ACUR (FIM ACUR-negative 63.4 (21.1) vs. FIM ACUR-positive 50.53(25.4), p = 0.026). Significantly lower discharge FIM was noted in those with ACUR compared to those without. (FIM ACUR-positive 65.8(31.4) vs. FIM ACUR-negative 85.4 (21.1), p = 0.023) Furthermore, a significant near-doubling of RLOS was noted in ACUR patients compared to non-ACUR counterparts (ACUR-positive median 55 days (IQR 34.50, 87.50) vs. ACUR-negative median 28 days (IQR 16.25, 40.00), p = 0.002). Conclusions: This study highlights the significant negative functional impact and lengthening of rehabilitation duration of ACUR on inpatient rehabilitation outcome for TBI. Full article

Background: This study aimed to compare acute injury and rehabilitation characteristics for traumatic brain injury (TBI) inpatients during the pre and post COVID-19 pandemic periods. Methods: A retrospective study of TBI inpatients between 1 April 2018 and 31 December 2019 (pre COVID-19 period), and 1 July 2020 and 31 March 2022 (post COVID-19 period) was performed to compare demographics, premorbid comorbidity, TBI characteristics, rehabilitation complications, admission and discharge functional independence measure (FIM^®), length of stay and discharge status. Results: A total of 187 data sets were analyzed (82 pre COVID-19 and 105 post COVID-19). Post COVID-19 TBI inpatients were older by 11 years (pre COVID-19 mean 55 years vs. post COVID-19 mean 66 years, and p < 0.001), with 23% higher female inpatients (pre COVID-19 13.4% vs. post COVID-19 36.2%, and p < 0.001) and 25% higher presence of comorbidities (pre COVID-19 52.4% vs. post COVID-19 77.1%, and p < 0.001). In the post COVID-19 group, total discharge FIM (Td-FIM) was significantly lower by ~12 points (pre COVID-19 94.5 vs. post COVID-19 82, and p = 0.011), Td-FIM ≥ 91 was lower by ~18% (pre COVID-19 53.7% vs. post COVID-19 36.2%, and p = 0.017), and the need for caregivers increased by ~17% (pre COVID-19 68% vs. post COVID-19 85.4%, and p = 0.006) Conclusions: Our findings signal a demographic shift towards older, frailer TBI with lower functional independence levels post COVID-19. Full article

In this retrospective study, we used data from the hospital information system (HIS) to evaluate the influence of the COVID-19 pandemic on rehabilitation care at the University Hospital of Ostrava (UHO). From March 2020 to December 2021, 5173 COVID-19 cases were hospitalized at UHO. Cases within individual groups and categories are shown in a flowchart. The average patient age was 64.9 ± 16.9 years. The mean BMI value was 30.6 ± 6.8 in the rehabilitated group, which was significantly higher compared to that among the non-rehabilitated cases 29.1 ± 6.9 (p < 0.001). Among the admitted patients, 16.6% required artificial pulmonary ventilation (APV), 1.8% extracorporeal membrane oxygenation (ECMO), and 11.9% high-flow oxygenation (HF). The days of rehabilitation ranged from 1–102 days. Among all rehabilitated patients, 92.0% (n = 1302) had a hospitalization duration ranging from 1–15 days and 8.0% (n = 114) longer than 15 days. Overall, rehabilitation care plays an important role in providing exercise, mobilization, and rehabilitation interventions to survivors of critical illness associated with COVID-19, enabling the early and functional return to home, and it must, therefore, be integrated into the clinical care of patients with COVID-19. Full article

Low back pain is a serious threat to human health and the illness jeopardizes the human workforce and pressurizes the health system in the community. Low back pain might be related to piriformis syndrome (PS), which is a disorder presented as muscular spasm and hypertrophy that is strongly associated with piriformis thickness. Nevertheless, the relationship between piriformis thickness and morphological and functional changes of the gluteal muscles in PS remains unclear. This study aimed to investigate the association between the thickness, strength, and activation of piriformis and gluteus muscles (maximus and medius) among low back pain (LBP) patients with and without PS. This is a case-control study conducted at HSNZ and UiTM from 2019–2020. A total number of 91 participants (LBP + PS (n = 36), LBP − PS (n = 24), and healthy (n = 31)) were recruited in this study. Negative radiography, specific symptoms, and a positive PS test were applied for PS diagnoses. The thickness, strength, and activation of piriformis and gluteus muscles were measured using ultrasonography (USG) and a surface electromyogram, respectively. Resultantly, the one-way ANOVA test demonstrated no significant difference in piriformis thickness between LBP + PS and LBP − PS (p > 0.01). Piriformis thickness was inversely correlated with gluteus maximus strength (r = −0.4, p < 0.05) and positively correlated with gluteus medius activation (r = 0.48, p < 0.01) in LBP + PS. Stepwise linear regression for LBP + PS revealed a significant association between piriformis thickness and gluteus maximus strength (R = −0.34, accounted for 11% of the variance) and gluteus medius activation in prone lying with the hip in an externally rotated, abducted, and extended (ERABEX) position (R = 0.43, accounted for 23% of the variance). With the adjustment of age and gender, piriformis thickness, gluteus maximus strength, and gluteus medius activation in prone lying with hip ERABEX demonstrated a significant association, but no independent effect of age and gender was detected within the range. Meanwhile, a significant association between piriformis thickness and gluteus maximus thickness was observed (R = 0.44, accounted for 19% of the variance) in the LBP − PS group. These findings may assist to elucidate the actions and functions of piriformis and gluteus muscle in LBP with and without PS. Full article

Patients with mitral valve prolapse (MVP) have been reported to have exercise intolerance. However, the underlying pathophysiological mechanisms and their physical fitness remain unclear. We aimed to determine the exercise capacity of patients with MVP through the cardiopulmonary exercise test (CPET). We retrospectively collected the data of 45 patients with a diagnosis of MVP. Their CPET and echocardiogram results were compared with 76 healthy individuals as primary outcomes. No significant differences regarding the patient’s baseline characteristics and echocardiographic data were found between the two groups, except for the lower body mass index (BMI) of the MVP group. Patients in the MVP group demonstrated a similar peak metabolic equivalent (MET), but a significantly lower peak rate pressure product (PRPP) (p = 0.048). Patients with MVP possessed similar exercise capacity to healthy individuals. The reduced PRPP may indicate compromised coronary perfusion and subtle left ventricular function impairment. Full article

Background: Understanding balance ability and assessing the risk of possible falls are very important for elderly rehabilitation. The Mini-Balanced Evaluation System Test (Mini-BESTest) is an important survey for older adults to evaluate subject balance, but it is not easy to complete due to various limitations of physical activities, including occasional fear of injury. A center of pressure (CoP) signal can be extracted from a force pressure plate with a short recording time, and it is relatively achievable to ask subjects to stand on a force pressure plate in a clinical environment. The goal of this study is to estimate the cutoff score of Mini-BESTest scores from CoP data. Methods: CoP signals from a human balance evaluation database with data from 75 people were used. Time domain, frequency domain, and nonlinear domain parameters of 60 s CoP signals were extracted to classify different cutoff point scores for both linear regression and a decision tree algorithm. Classification performances were evaluated by accuracy and area under a receiver operating characteristic curve. Results: The correlation coefficient between real and estimated Mini-BESTest scores by linear regression is 0.16. Instead of linear regression, binary classification accuracy above or below a cutoff point score was developed to examine the CoP classification performance for Mini-BESTest scores. The decision tree algorithm is superior to regression analysis among scores from 16 to 20. The highest area under the curve is 0.76 at a cutoff point score of 21 for the CoP measurement condition of eyes opened on the foam, and the corresponding classification accuracy is 76.15%. Conclusions: CoP measurement is a potential tool to estimate corresponding balance and fall survey scores for elderly rehabilitation and is useful for clinical users. Full article

Complex regional pain syndrome (CRPS) is characterized by pain, limited range of motion, swelling, skin changes, vasomotor instability, and patchy bone demineralization. Conservative management strategies for CRPS include physical and occupational therapy, psychosocial and behavioral therapy, and pharmacotherapy. However, some patients still experience CRPS symptoms after receiving conventional treatments. Therefore, botulinum toxin (BoNT) has been applied to patients with CRPS in several trials considering its analgesic effect in musculoskeletal and neuropathic pain; however, the results were controversial. We conducted the study to explore the effectiveness and safety of BoNT in patients with complex regional pain syndrome (CRPS). A search was performed using the following electronic databases up to 19 October 2022: PubMed, Embase, and Cochrane Library. We included both randomized controlled trials and nonrandomized controlled studies involving patients with complex regional pain syndrome managed with botulinum toxin. Cochrane risk-of-bias tool and Joanna Briggs Institute Critical Appraisal Checklist were used for quality assessment for randomized controlled trials and quasi-experimental studies. Only randomized controlled trials entered the meta-analysis. The primary outcome was the visual analogue scale of pain presented as a weighted mean difference (WMD) and 95% confidence interval (CI). The secondary outcome was the risk of adverse events presented as an odds ratio (OR) with 95% CI. We analyzed eight articles with 176 patients, including three randomized controlled trials with 62 participants. The age of the patients ranged from 23.8 to 51 years old. The duration of the disease ranged from 2.2 to 11.8 years. The proportion of females ranged from 16.6% to 100%. The route of administration of BoNT included: (1) lumbar sympathetic block (LSB), (2) intramuscular injection, (3) subcutaneous or intradermal injection (SC/ID). Improvement in pain was revealed in six studies, and adverse events were all self-limited and temporary. Meta-analysis revealed a significant reduction in pain at the first follow-up between 3 weeks to 1 month after intervention (WMD, −1.036, 95% CI, −1.673 to −0.400) but not at the second follow-up between 2 to 3 months after treatment (WMD, −0.895, 95% CI, −2.249 to 0.458). Subgroup analyses between LSB and SC/ID were nonsignificant at both follow-up periods (p = 0.422, 0.139). The risk of adverse events was similar between the BoNT and control group (OR, 0.698, 95% CI, 0.136 to 3.581). In conclusion, BoNT may be effective and safe for alleviating pain in patients with CRPS. However, we could not draw definite conclusions due to small sample size and high between-study heterogeneity. The limited number of participants may conceal the possibility of serious adverse events. Further large-scale randomized controlled trials are warranted to delineate the role of BoNT in CRPS. Full article

To investigate the impact on physical performance and walking abilities associated with fall risk and disability in the senior population, we created a telerehabilitation system. This is a multi-site, community setting, pre–post experimental study. We recruited participants from four rural areas in Thailand. All participants received eight weeks of tele-exercise, three sessions per week, via the telerehabilitation system. After the intervention, all participants underwent the Short Physical Performance Battery (SPPB), Timed Up and Go (TUG) test, and the six-minute walk test (6MWT) using a wearable sensor system. A total of 123 participants participated in the study and 2 participants dropped out while conducting the study, thus 121 participants were included in the analysis. In comparison to the baseline, we discovered a considerable improvement in the SPPB score (0.65 ± 0.22, p < 0.001), TUG (−1.70 ± 0.86, p < 0.001), and 6MWT (10.23 ± 7.33, p = 0.007). Our study demonstrates the benefits of telerehabilitation on SPPB, TUG, and 6MWT related to disabilities and fall risk. This telerehabilitation technology demonstrated its viability in the community environment and demonstrated its capacity to offer fundamental components of remote rehabilitation services within the healthcare system. Full article

(1) Background: Heart failure is a complex disease leading to functional disability. Cardiopulmonary exercise testing (CPET) is the gold standard in assessing aerobic capacity and formulating function-based prognostic stratification; however, patients with acute heart failure after medical treatment usually remain with markedly reduced exercise capacity, leading to early termination of CPET with submaximal testing results. The current study aimed to assess the cardiorespiratory fitness and characteristics of CPET variables of patients after acute heart failure treatment and determine potential CPET variables with prognostic value. (2) Methods: We recruited patients during hospitalization after management of acute heart failure, and pre-discharge CPET was performed. All enrolled patients were followed for one year for major adverse cardiovascular events (MACE). (3) Results: 85 patients were enrolled, with average left ventricular ejection fraction of 30.52%, and peak oxygen consumption of 10.85 mL/min/kg at baseline. The one-year MACE was 50%. Oxygen uptake efficiency slope (OUES) was a significant event predictor, with lower one-year MACE in those with OUES ≥ 1.25 (p < 0.001). Cox regression analysis showed a 5.421-fold increased risk of MACE in those with OUES < 1.25 (p = 0.004). (4) Conclusions: The current results suggested OUES is a significant prognostic indicator in patients with acute heart failure. This also emphasized the critical role of CPET in patients with heart failure for prognostic stratification. Full article

Objectives: This study aimed to investigate the safety and efficacy of high-definition transcranial alternating current stimulation (HD-tACS) to the left primary motor cortex (M1) in the treatment of fibromyalgia (FM) patients. Methods: In this randomized, double-blind, sham-controlled clinical trial, patients with FM were recruited in a teaching hospital. Thirty-eight patients were randomized to active HD-tACS (n = 19) or sham stimulation (n = 19). Active stimulation included a daily session of 20-min stimulation of 1 mA HD-tACS over the left M1 for ten sessions in two weeks. The primary outcome was the change in pain intensity and quality of life, assessed using the numeric rating scale (NRS) and the fibromyalgia impact questionnaire (FIQ) at baseline and after two weeks of treatment. Secondary outcomes included other core symptoms of FM (psychological distress, sleep quality, hyperalgesia measured by pressure pain threshold) and changes in biomarkers’ total Tau and Aβ1-42. All analyses were based on intention-to-treat for a significance level of p < 0.05. Results: Of the 38 randomized patients, 35 completed the study. After two weeks, HD-tACS induced a significant reduction in FIQ score post-treatment. However, there were no significant differences in NRS and FIQ scores compared to sham stimulation. Most adverse events were mild in severity. Nevertheless, one patient receiving HD-tACS attempted suicide during the trial. Conclusions: These results suggest that HD-tACS may effectively reduce pain, psychological distress, and symptom impacts in FM patients. However, we found no significant differences between the two groups. Future studies investigating HD-tACS in FM are warranted. Full article

The aims of this study were to compare inpatient rehabilitation outcomes between acute stroke subtypes of Cerebral Infarction (CI) and Intracerebral Hemorrhage (ICH), and to determine the predictors of discharge outcomes. A retrospective study of stroke inpatients was carried out using the discharge Functional Independence Measure (FIM) as the primary outcome measure. Relationships between stroke subtype, rehabilitation impairments, and medical complications on FIM -gain were analyzed. Altogether, 280 datasets including 211 (75.4%) CI and 69 (24.6%) ICH were analyzed. ICH patients were significantly younger than CI patients (55 years ICH vs. 64.0 years CI years, p < 0.001), had a 10-fold higher proportion needing ICU admission (ICH 82.6% vs. CI 7.6%, p < 0.001), and had significantly lower total admission FIM scores (67 points ICH vs. 74 CI points, p = 0.006), with lower motor-FIM scores in particular (38 points ICH vs. 48 points CI, p = 0.003). Significant functional improvements after inpatient rehabilitation, i.e., FIM gain, occurred regardless of stroke subtype (FIM-ICH Δ 27 vs. FIM-CI Δ 21, p = 0.05). Despite significantly worse initial stroke severity, ICH patients achieved similar functional gains, independence levels, and return-home rates compared with their CI counterparts after inpatient rehabilitation. Full article

Although primary brain tumors are relatively rare, they cause significant morbidity and mortality due to the high rates of neurological impairment. The purpose of this study was to examine the physical and functional outcomes of patients with primary brain tumors who had undergone inpatient rehabilitation. This was a retrospective study which recruited 163 patients who had been admitted for inpatient rehabilitation. Rehabilitation outcomes, including the Functional Independence Measure (FIM) and Glasgow Outcome Scale (GOS), were recorded up to 1 year post-discharge. The majority of patients (79.1%) had low-grade (WHO Class I-II) tumors, 35 (21.5%) were diagnosed with GBM and 52 (31.9%) had recurrent brain tumors. Rehabilitation outcomes were sustained, with 125 (76.7%) and 113 (69.3%) patients having a GOS of ≥4 at 6 months and 1 year after discharge, respectively. A GOS of ≥4 at 1 year was negatively associated with high-grade tumors (p < 0.001) and radiotherapy (p = 0.028), and positively associated with a higher discharge FIM motor score (p < 0.001) and the presence of a caregiver after discharge (p = 0.034). Our study demonstrates significant positive functional benefits from 4 weeks of inpatient neuro-oncological rehabilitation for patients with primary brain tumors, as well as the importance of supportive care from caregivers. Full article

Background: Stroke and spinal cord injury are neurological disorders that cause disability and exert tremendous social and economic effects. Robot-assisted training (RAT), which may reduce spasticity, is widely applied in neurorehabilitation. The combined effects of RAT and antispasticity therapies, such as botulinum toxin A injection therapy, on functional recovery remain unclear. This review evaluated the effects of combined therapy on functional recovery and spasticity reduction. Materials and Methods: Studies evaluating the efficacy of RAT and antispasticity therapy in promoting functional recovery and reducing spasticity were systemically reviewed. Five randomized controlled trials (RCTs) were included. The modified Jadad scale was applied for quality assessment. Functional assessments, such as the Berg Balance Scale, were used to measure the primary outcome. Spasticity assessments, such as the modified Ashworth Scale, were used to measure the secondary outcome. Results: Combined therapy improves functional recovery in the lower limbs but does not reduce spasticity in the upper or lower limbs. Conclusions: The evidence supports that combined therapy improves lower limb function but does not reduce spasticity. The considerable risk of bias among the included studies and the enrolled patients who did not receive interventions within the golden period of intervention are two major factors that should be considered when interpreting these results. Additional high-quality RCTs are required. Full article