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Gait disturbance and imbalance are the major symptoms of Parkinson disease (PD), with fall being the most undesirable consequence. However, few effective evidence-based treatments are available for alleviating these symptoms and preventing falls. Cholinesterase inhibitors (ChEIs) are a well-established treatment for PD dementia with possible impacts on gait, balance, and fall reduction. The present study involved a meta-analysis of randomized controlled trials (RCTs) to investigate the effects of ChEIs on gait, balance, and fall in patients with PD. We searched for studies using the PubMed, Embase, and Web of Science databases. The major outcomes were effects on gait parameters, balance, and fall. This study was registered with PROSPERO (CRD42021254733). Five RCTs were included in the present meta-analysis. ChEIs did not significantly increase gait speed in PD patients (mean difference [MD]: 0.03 m/s, 95% confidence interval [CI]: −0.02 to 0.07, p = 0.29). However, ChEI treatment significantly decreased step or stride variability during the single task (standard MD: −0.43, 95% CI = −0.79 to −0.06, p = 0.02). Regarding fall and balance, trending but nonsignificant beneficial effects were observed with ChEI treatment. In conclusion, although ChEI treatment did not significantly improve gait speed and reduce fall, it can significantly reduce step or stride variability. Considering that gait disorder is a challenging issue in patients with PD and that ChEIs are generally tolerable, the present meta-analysis may provide more evidence for the benefit of ChEIs on PD gait disturbance as an alternative treatment consideration.

Context: Athletes must maintain their peak state of strength. Previous studies have investigated the effect of low-level laser therapy (LLLT) on muscular performance. A previous systematic review and meta-analysis has investigated this issue in healthy participants but not in physically active athletes. Objective: To investigate whether LLLT can improve muscular performance and soreness recovery in athletes. Data Sources: PubMed, EMBASE, and Cochrane Library. Study Selection: Published randomized controlled trials and crossover studies till December 2020. Study Design: Systematic review and meta-analysis. Level of Evidence: Level 3. Data Extraction: Assessment of study quality was rated using the risk of bias assessment method for randomized trials (Cochrane Handbook for Systematic Reviews of Interventions). Results: A total of 24 studies were included. LLLT application before exercise significantly improved lower-limb muscle strength in 24-hour, 48-hour, 96-hour, and 8-week follow-up groups. Furthermore, decreased soreness index, serum creatine kinase concentrations, interleukin-6, and thiobarbituric acid reactive substance concentrations and a trend toward the improvement of contract repetition number and VO2 kinetic outcomes were observed. Conclusion: Although a definite therapeutic effect of LLLT is yet to be established, the current evidence supports that LLLT use improves muscular performance in physically active athletes. Additional trials with large sample sizes and robust design should be conducted before strong recommendations are made.

Background Hand-foot syndrome (HFS) is a specific adverse effect of certain chemotherapy that may lead to dosage reduction or chemotherapy discontinuation in patients with cancer. Topical urea cream may reduce symptom severity in patients with HFS. However, these studies have not provided consonant results. Objective To determine the effectiveness of urea cream, we conducted a meta-analysis of clinical trials to evaluate the prevention and treatment of HFS. Methods PubMed, EMBASE, and Cochrane Library databases were searched for studies published before September 2020. The study registered at PROSPERO (CRD 42020203164). Incidence of HFS reported in studies at any grade and at second grade or greater was assessed within 3 to 12 weeks. Secondary outcomes were time to HFS, incidence of skin-related adverse events, chemotherapy dose reduction, and quality of life. Results Seven trials involving 1387 patients were reviewed. In the prophylactic subgroup, patients with urea cream intervention showed a significantly lower incidence of HFS at second grade or greater (risk ratio, 0.72; 95% confidence interval, 0.58-0.90) and a nonsignificant lower incidence of any-grade HFS (risk ratio, 0.79; 95% confidence interval, 0.58-1.08) than those not receiving urea cream intervention. Conclusions Urea cream has advantages to reduce the incidence of severe HFS. Implications for practice Urea cream is a safe and viable topical prevention strategy that can reduce the incidence of high-grade HFS in patients undergoing chemotherapy. We recommend a routine treatment option before chemotherapy for the patients.

Background The need for patients to wear compression stockings after varicose vein surgery and the duration of compressions tocking therapy has been debated. This study isa meta-analysis of randomized controlled trials (RCTs) to determine the optimal duration of compression stocking therapy after endovenous thermal ablation (ETA) of the great saphenous vein. Methods The PubMed, Embase, and Cochrane Library databases were searched before January 2019. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random effects model. The primary outcome was the severity of pain in the postoperative period. Secondary outcomes were quality of life (QoL), leg volume, bruising scores, consumptionof analgesic agents, recovery time off work, satisfaction, and the incidence rates of postoperative complications including paresthesia and phlebitis. Results Five RCTsinvolving775 patients were reviewed. The long-duration (1–2 weeks) group significantly reduced postoperative pain at 1 week (mean difference [MD] 1.19; 95% confidence interval [CI]: 0.58–1.80) and recovery time off work (MD: 1.01 day, 95% CI: 0.06–1.96)when compared with the short-duration (24–48 h) group. However, the mean pain scores at 2 (0.1; 95% CI: 0–0.2) and 6 weeks postoperatively (−0.3; 95% CI: −1.09-0.49) did not differ significantly between the two groups. Moreover, the incidence rates of complication, paresthesia, and phlebitis did not differ significantly between the short-duration and long-duration groups. Conclusion The use of compression therapy for a long time (1–2 weeks) is better than short-term (24–48 h) use in terms of postoperative pain at 1 week and recovery off work. Hence, we recommend the prescription of 1-week compression stocking therapy after ETA in routine clinical practice. However, the available evidence is of variable quality, further well-structured RCTs with improved standardization of compression treatment, types of stockings, and target populations are warranted.

Simple Summary Parkinson’s disease (PD) is a common neurodegenerative disease that manifests as motor dysfunction and nonmotor symptoms (NMSs). Apart from motor symptoms, NMSs include sleep disorders, neuropsychiatric problems, and cognitive impairment, which negatively influence patients’ daily lives and caregivers. Disturbances of the sleep cycle also worsen overall health, causing dysregulation of cortisol and melatonin secretion. Furthermore, bright light therapy (BLT) is a well-known treatment for circadian rhythm sleep disorders, seasonal affective disorders, and dementia-related sleep disturbances under the regulation of circadian rhythm by melatonin, a chronological pacemaker. BLT is also applied to treat depressive symptoms and bipolar disorder through unknown mechanisms. The present study, at first, conducted a literature review, which found that a few non-controlled studies demonstrated improvements in motor symptoms and NMSs in PD. Secondly, the present study performed a meta-analysis of the randomized controlled trials which treated the PD patients with BLT. The results revealed that BLT nonsignificantly alleviated symptoms of depression and sleep disorders in patients with PD. However, the inconsistency between BLT protocols, such as varied timing, dosages, and treatment durations, may render BLT’s efficacy challenging to demonstrate, and future RCTs must be obtained. Abstract Sleep disorders and depression are significant nonmotor symptoms (NMSs) of Parkinson disease (PD). However, few effective, evidence-proven medical treatments are available for alleviating these symptoms. Bright light therapy (BLT) is a well-established treatment for circadian rhythm sleep disorders and seasonal affective disorder. The present study conducted a literature review for the effect of BLT on PD, especially a meta-analysis of randomized controlled trials (RCTs). We searched for studies using the PubMed and Cochrane Library databases. The major outcomes were the effects on sleep and depression. The effect on motor symptoms was also analyzed as a secondary outcome. This study was registered with PROSPERO (CRD42020204454). Six studies were included in the literature review only, and the other five RCTs were included in the meta-analysis. Despite the positive effects of BLT on PD patients, which were demonstrated in noncontrolled studies, in the meta-analysis of the RCTs, BLT did not significantly improve the depressive symptoms (standardized mean difference (SMD): −0.15, 95% confidence interval (CI): −0.48 to 0.17, p = 0.36) and excessive daytime sleepiness (EDS) (SMD: −0.12, 95% CI: −0.49 to 0.25, p = 0.53) in PD patients. Regarding motor symptoms, no significant beneficial effects were conferred (SMD: −0.11, 95% CI: −0.44 to 0.21, p = 0.49). In conclusion, BLT did not significantly alleviate depression and sleepiness. The inconsistency between BLT protocols, such as the varied timing, dosages, and treatment durations, may render BLT’s efficacy difficult to demonstrate. The small effect size obtained from the present meta-analysis indicates that future RCTs are necessary, for which BLT protocols are standardized and more patients are enrolled to determine whether a significant therapeutic benefit was conferred.

Background Trismus is a common complication of cancer treatment, particularly radiotherapy, for head and neck cancer. We investigated whether exercise therapy could prevent or manage limited mouth opening in patients before or after the cancer treatment. Methods We performed a systematic review and meta-analysis to evaluate the effectiveness of exercise therapy combined with a jaw-mobilizing device in the prevention and treatment of cancer treatment-induced trismus. The electronic databases PubMed, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials were searched for articles on trismus published before July 2020 with no language restrictions. The primary outcome for prevention was trismus incidence. The treatment outcome for trismus was the improvement of maximal interincisal opening (MIO). Results Thirteen randomized controlled trials (RCTs) involving 733 patients were identified. Six studies assessed MIO and found that exercise therapy adjuvant to the use of a jaw-mobilizing device significantly improved the MIO from 4.48 (95% confidence interval [CI] = 0.20, 8.75) to 14.20 (95% CI = 10.73, 17.67) mm. Seven studies evaluating the preventive outcome of incidence of trismus found no significant difference between standard usual care and exercise therapy adjuvant to the use of a jaw-mobilizing device (risk ratio = 1.20; 95% CI = 0.61, 2.34). Conclusions The current evidence from RCTs revealed that exercise therapy can lead to MIO improvement following the development of cancer treatment-induced trismus, but does not prevent trismus in patients being treated for head and neck cancer. The clinical exercise programs used in the studies were heterogeneous; therefore, additional high-quality RCTs are required.

Tremor is a common movement disorder. Essential tremor (ET) is the most common etiology of tremor, while hands tremor is the most disabling type of tremor. This study aimed to explore the effects of Botulinum toxin (BoNT) on tremor within 6 weeks of treatment, and the muscular weakness adverse effect within 6 weeks specifically in randomized controlled trials. PubMed, Embase, and Cochrane Library databases were searched. Tremor severity and grip strength after BoNT treatment were investigated. BoNT significantly attenuated hand tremor severity in patients with either essential tremor (ET), Parkinson’s disease or multiple sclerosis (Standardized mean difference [SMD] = −0.59, 95% confidence interval [CI], −0.95 to −0.24, p = 0.001, I2 = 46%). Regarding people with ET, BoNT significantly reduced their tremor severity, including hands tremor and head tremor within 6 weeks of treatment (SMD = −0.58, 95% CI, −0.28 to −0.88, p = 0.002, I2 = 0%). Electromyography (EMG) but not anatomical guidance BoNT injection provided significant benefit on the relief of tremor in both conditions. The principal adverse event was weakness, but it did not worse within 6 weeks of BoNT treatment (SMD = −0.35, 95% CI, −0.83 to 0.12, p = 0.07, I2 = 57%), as assessed by the subjective grip strength. In conclusion, BoNT was an effective treatment for the hand tremor and ET, and EMG guidance injection was preferred. In addition, the muscular weakness adverse effect was not significant.

Objective Anxiety and depression are major psychiatric nonmotor symptoms (NMSs) of Parkinson disease (PD). Although several studies have investigated the effects of psychotherapeutic interventions, particularly cognitive-behavioral therapy (CBT), for alleviating anxiety and depression in patients with PD, the findings have been inconclusive because of the small sample size and the lack of a unified protocol for such treatments. Thus, the present meta-analysis of randomized controlled trials (RCTs) was conducted to assess the effect of psychotherapy on PD-related anxiety and depression. Design Systematic review and meta-analysis. Setting and Participants Relevant RCTs were extracted from PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases. This study was registered in PROSPERO under the number CRD 42020165052. Measures The primary and secondary outcomes were changes in the anxiety score and depressive symptoms, respectively. Results Fourteen RCTs including 507 patients with PD were analyzed. The interventions were classified as CBT and non-CBT. CBT significantly reduced anxiety at the end of the study (standardized mean difference = −0.85, 95% confidence interval = −1.12 to −0.58, P Conclusion and Implications CBT is effective for the management of anxiety and depression in patients with PD. Routine treatment for patients with this condition is strongly recommended.

Objective Lymphoedema characterised by the persistent accumulation of the interstitial fluid in peripheral tissues post breast cancer treatments. Photobiomodualtion therapy (PBMT) is widely used as supportive care in patients with breast cancer or breast cancer-related lymphoedema (BCRL). This systematic review and meta-analysis analysed the effectiveness and safety of PBMT for the treatment of BCRL. Method PubMed, EMBASE, PEDro, SCOPUS, CINAHL, and Cochrane Central Register of Controlled Trials were searched for RCTs on PBMT published before July 2019. Randomised controlled trials (RCTs) that evaluated the efficacy of PBMT on BCRL were included. The primary outcome was the arm circumference or volume, and secondary outcomes were grip strength and pain scores. This study is registered with PROSPERO (number CRD 42018102107). Results We reviewed nine RCTs that included 316 patients and six studies for mata-analysis. We found no significant difference in the reduction of the arm circumference or arm volume after treatment, one month, and three month follow-up between the PBMT and control groups. Studies revealed no significant differences in the reduction in grip strength and pain scores at 0, 1, 2, and 3 month between the PBMT and control groups. Conclusions Although PBMT demonstrated a slight improvement in reducing arm circumference and arm volume, the results of our meta-analysis did not show significant benefits in relieving of lymphoedema. Further trials are needed to recruit more participants, and to evaluate the long-term efficacy and safety of PBMT in management of breast cancer-related lymphoedema.

Objective This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. Methods PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. Results We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. Conclusions Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.

Background Endotracheal intubation (ETI) is a procedure widely performed for several clinical indications. In typical ETI, an endotracheal tube is placed into a patient's trachea with the help of a malleable metal rod covered with a clear plastic sheath (called a stylet). However, another intubation aid, a bougie (also named a gum elastic bougie or endotracheal tube introducer), was also introduced in the clinical setting to improve the efficacy of conventional ETI. Methods This study performed a systematic review and meta-analysis of randomized controlled trials to compare the efficacy of bougie and stylet approaches in ETI. PubMed, Embase, and Cochrane Library databases were searched for studies published before November 2018. Randomized controlled trials comparing the clinical outcomes of bougie and stylet approaches in patients who underwent orotracheal intubation were included. Meta-analyses were conducted by using a random effects model, and treatment efficacy was measured by evaluating the first-attempt success rate and intubation duration. Results A total of 5 randomized controlled trials and 1,038 patients were included. Although a bougie resulted in a better first-attempt success rate, no significant difference was observed between the approaches (risk ratios, 1.03; 95% confidence interval, 0.85-1.24). Moreover, no significant differences were observed in the intubation duration and esophageal intubation rate between the bougie and stylet approaches. Conclusion Endotracheal intubation performed with a bougie was not superior over ETI performed with a stylet. Therefore, intubation approaches should be selected by considering personal preference and clinician expertise. Level of evidence Systematic review and meta-analysis, level II.

Purpose Aromatase inhibitor (AI)-induced arthralgia (AIA) is a common side effect that may lead to premature discontinuation of effective hormonal therapy in patients with breast cancer. Acupuncture may relieve joint pain in patients with AIA. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effectiveness of acupuncture in pain relief in AIA. Methods The PubMed, Embase, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry were searched for studies published before February 2017. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random effect model. Pain was assessed using the Brief Pain Inventory (BPI) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3–4, 6–8, and 12 weeks. Secondary outcomes included disability level, upper extremity function, physical performance, and quality of life. Results Five trials involving 181 patients were reviewed. Significant pain reduction was observed after 6–8 weeks of acupuncture treatment. Patients receiving acupuncture showed a significant decrease in the BPI worst pain score (weighted mean difference [WMD]: −3.81, 95% confidence interval [CI]: −5.15 to −2.47) and the WOMAC pain score (WMD: −130.77, 95% CI: −230.31 to −31.22) after 6–8 weeks of treatment. One of the 4 trials reported 18 minor adverse events in 8 patients during 398 intervention episodes. Conclusion Acupuncture is a safe and viable nonpharmacologic treatment that may relieve joint pain in patients with AIA. Additional studies involving a higher number of RCTs are warranted.

Study design A meta-analysis. Objective The aim of this study was to perform a comprehensive search of current literature and conduct a meta-analysis of randomized controlled trials (RCTs) to assess the neck pain relieving effect of intermittent cervical traction (ICT). Summary of background data Neck pain is a common and disabling problem with a high prevalence in general population. It causes a considerable burden on the health care system with a substantial expenditure. ICT is a common component of physical therapy for neck pain in the outpatient clinic. However, the evidence regarding the effectiveness of ICT for neck pain is insufficient. Methods Data were obtained from the PubMed, Cochrane Library, Embase, and Scopus databases from the database inception date to July 02, 2016. RCTs reporting the effects of ICT on neck pain, including those comparing the effects of ICT with those of a placebo treatment, were included. Two reviewers independently reviewed the studies, conducted a risk of bias assessment, and extracted data. The data were pooled in a meta-analysis by using a random-effects model. Results The meta-analysis included seven RCTs. The results indicated that patients who received ICT for neck pain had significantly lower pain scores than those receiving placebos did immediately after treatment (standardized mean difference = -0.26, 95% confidence interval = -0.46 to -0.07). The pain scores during the follow-up period and the neck disability index scores immediately after treatment and during the follow-up period did not differ significantly. Conclusion ICT may have a short-term neck pain-relieving effect. Some risks of bias were noted in the included studies, reducing the evidence level of this meta-analysis. Additional high-quality RCTs are required to clarify the long-term effects of ICT on neck pain. Level of evidence 1.

Background In 2014, the American Society of Clinical Oncology published an updated clinical practice guideline on axillary lymph node dissection (ALND) for early-stage breast cancer patients. However, these recommendations have been challenged because they were based on data from only one randomized controlled trial (RCT). We evaluated the rationale of these recommendations by systematically reviewing RCTs using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Methods We searched articles in the PubMed, EMBASE, CINAHL, Scopus, and Cochrane databases. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were recurrence rate and surgical complications of axillary dissection. The quality of evidence was assessed using the GRADE profiler. Results Five eligible studies were retrieved and analyzed. We divided sentinel lymph node (SLN) metastasis into two categories: SLN micrometastasis and SLN macrometastasis. In patients with 1 or 2 SLN micrometastasis, no significant difference was observed in OS, DFS, or recurrence rate between the ALND and non-ALND groups. For patients with 1 or 2 SLN marcometastasis, only one trial with a moderate risk of bias was included, and non-ALND was the preferred management overall. However, ALND might be appropriate for patients who placed a greater emphasis on longer-term survival at any cost. Conclusion We recommend non-ALND management for early breast cancer patients with 1 or 2 SLN micrometastasis or macrometastasis on the basis of a systematic review of the current evidence conducted using the GRADE system. However, the optimal practice of evidence-based medicine should incorporate patient preferences, particularly when evidence is limited.

Background Mutans streptococci (MS) are the major causative bacteria involved in human dental decay. Habitual consumption of xylitol has been proved to reduce MS levels in saliva and plaque. Aim To evaluate the effect of the maternal use of xylitol gum on MS reduction in infants. Design A structured literature review and meta-analysis. A random effects model was used to assess the relative risks of the incidence of MS in the saliva or plaque of children who were 6, 9, 12, 18, and 24 months old. Results We reviewed 11 RCTs derived from 5 research teams that included 601 mothers. Our results indicated that the incidence of MS in the saliva or plaque of the infants was significantly reduced in the xylitol group (risk ratio: 0.54; 95% confidence interval: 0.39–0.73, at 12–18 months) and (risk ratio: 0.56; 95% confidence interval: 0.40–0.79, at 36 months) compared with the control groups. The long-term effect of maternal xylitol gum exposure on their children's dental caries was controversial. Conclusion Habitual xylitol consumption by mothers with high MS levels was associated with a significant reduction in the mother–child transmission of salivary MS.

Objective The optimal duration of compression therapy following varicose vein surgery of the great saphenous vein (GSV) remains controversial. Therefore, the aim of this study was to evaluate different durations of compression therapy after varicose vein surgery and their outcomes. Design A systematic review and meta-analysis of randomized controlled trials (RCTs). Methods Outcomes from short-duration (3–10 d) and long-duration (3–6 wk) compression therapy after GSV stripping and phlebectomies were evaluated. Pain was assessed post surgery using a visual analog scale. Secondary outcomes included leg volume, complications, and the duration of absenteeism from work. Results We identified 4 RCTs published between 1991 and 2009 that evaluated 686 patients. We observed non-significant differences in postoperative pain scores between the long-duration and short-duration groups, with a weighted mean difference of −0.03 (95% confidence interval (CI): −0.53 to 0.47) at 4 weeks, and −0.01 (95% CI: −0.31 to 0.33) at 6 weeks, postoperatively. We also observed non-significant differences in the incidence of postoperative complications (risk ratio: 0.84, 95% CI: 0.60–1.18), and changes in leg volume, 4 weeks postoperatively ( P = .18) between the groups. Conclusion Our study results indicate that there are no benefits to long-term compression therapy after varicose vein surgery of the GSV regarding postoperative pain, leg volume, incidence of complications, and duration of absenteeism from work.

Background Lymphedema is a common complication of axillary dissection for breast cancer. We investigated whether manual lymphatic drainage (MLD) could prevent or manage limb edema in women after breast-cancer surgery. Methods We performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) to evaluate the effectiveness of MLD in the prevention and treatment of breast-cancer-related lymphedema. The PubMed, EMBASE, CINAHL, Physiotherapy Evidence Database (PEDro), SCOPUS, and Cochrane Central Register of Controlled Trials electronic databases were searched for articles on MLD published before December 2012, with no language restrictions. The primary outcome for prevention was the incidence of postoperative lymphedema. The outcome for management of lymphedema was a reduction in edema volume. Results In total, 10 RCTs with 566 patients were identified. Two studies evaluating the preventive outcome of MLD found no significant difference in the incidence of lymphedema between the MLD and standard treatment groups, with a risk ratio of 0.63 and a 95% confidence interval (CI) of 0.14 to 2.82. Seven studies assessed the reduction in arm volume, and found no significant difference between the MLD and standard treatment groups, with a weighted mean difference of 75.12 (95% CI, −9.34 to 159.58). Conclusions The current evidence from RCTs does not support the use of MLD in preventing or treating lymphedema. However, clinical and statistical inconsistencies between the various studies confounded our evaluation of the effect of MLD on breast-cancer-related lymphedema.