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Advances in Therapy Aug 2022A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy of brolucizumab relative to other anti-vascular... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy of brolucizumab relative to other anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) at 1 and 2 years, and overall safety and injection frequency of each treatment.
METHODS
An SLR identifying randomized controlled trials (RCTs) published before June 2021 according to a pre-specified protocol was followed by a Bayesian NMA to compare brolucizumab (6 mg q12w/q8w) against sham and all relevant anti-VEGF regimens. Pooled mean injection frequency, serious adverse ocular events, and discontinuation rates were estimated for each treatment regimen.
RESULTS
Nineteen RCTs were included in NMA base-case analysis. Brolucizumab (6 mg q12w/q8w) with loading-phase (LP) demonstrated superior best-corrected visual acuity (BCVA) gains to sham both at year 1 (mean difference 16.8 [95%CrI 13.3, 20.4]) and year 2 (mean difference 21.2 [95%CrI 17.4, 25.0]) and was comparable to other anti-VEGFs. Brolucizumab (6 mg q12w/q8w) also showed superior retinal thickness reduction to most comparators including ranibizumab (0.5 mg q4w; year 1 mean difference - 50.1 [95%CrI - 70.3, - 29.8]; year 2 mean difference - 49.5 [95%CrI - 70.8, - 28.6]), aflibercept (2 mg q8w; year 1 mean difference - 39.7 [95%CrI - 52.9, - 26.4]; year 2 mean difference - 35.0 [95%CrI - 49.1, - 21.4]), and faricimab (6 mg q16w/q8w; year 1 mean difference - 27.6 [95%CrI - 42.3, - 12.8]). Brolucizumab (6 mg q12w/q8w) showed similar rates of treatment discontinuation and serious and overall adverse events (both years). At year 2, pooled annualized injection frequency was lowest for brolucizumab (6 mg q12w/q8w) and highest for ranibizumab (0.5 mg q4w) at 5.7 and 11.5 injections annually, respectively.
CONCLUSION
Among all licensed anti-VEGF treatments, brolucizumab showed superior reduction in retinal thickness and comparable BCVA gains and discontinuation rates, despite having the lowest injection frequency. The current study provides the most up-to-date, robust comparison of treatments for nAMD.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child, Preschool; Humans; Infant; Intravitreal Injections; Macular Degeneration; Network Meta-Analysis; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 35678996
DOI: 10.1007/s12325-022-02193-3 -
Cureus May 2022The current review aimed to critically and systematically evaluate the available evidence regarding the effectiveness of periodontally accelerated osteogenic... (Review)
Review
The Effectiveness of Periodontally Accelerated Osteogenic Orthodontics (PAOO) in Accelerating Tooth Movement and Supporting Alveolar Bone Thickness During Orthodontic Treatment: A Systematic Review.
The current review aimed to critically and systematically evaluate the available evidence regarding the effectiveness of periodontally accelerated osteogenic orthodontics (PAOO) in accelerating orthodontic tooth movement and supporting the alveolar bone. Additionally, this review aimed to analyze the untoward effects of this procedure and the patient-reported outcome measures. A comprehensive electronic search was performed on 10 databases in addition to a manual search to retrieve all relevant studies. Randomized controlled trials (RCTs) were only included in this review. The interventional group was the PAOO procedure, whereas the control group was either a non-accelerated traditional fixed orthodontic treatment or an accelerated treatment using any other intervention. The Cochrane risk of bias tool for randomized controlled trials (RoB 2) was employed to estimate the risk of bias in the included studies. The current review included eight RCTs evaluating 175 participants (63 males and 112 females) with a mean age ranging from 18.8 to 29.6 years. Five of them assessed the effectiveness of PAOO versus traditional orthodontic treatment, i.e. without any adjuvant surgical intervention. At the same time, the remaining three studies evaluated the effectiveness of PAOO versus corticotomy-only as an adjunctive procedure. The PAOO accelerated the leveling and alignment stage from 39% to 47% and accelerated the retraction of the upper anterior teeth from 41% to 61% compared to conventional orthodontic treatment. One study only indicated that PAOO reduced treatment time by 30.3% versus a corticotomy-only as an adjunctive procedure. No significant side effects have been reported with the PAOO procedure. The PAOO procedure was effective in accelerating orthodontic movement and tended to increase the thickness of the alveolar bone. But most periodontal outcome measures regarding PAOO application were not comprehensively covered in the included trials.
PubMed: 35582021
DOI: 10.7759/cureus.24985 -
Orthopaedic Journal of Sports Medicine Mar 2023Some studies have suggested that running increases the risk of knee osteoarthritis (OA), while others believe it serves a protective function. (Review)
Review
BACKGROUND
Some studies have suggested that running increases the risk of knee osteoarthritis (OA), while others believe it serves a protective function.
PURPOSE
To perform an updated systematic review of the literature to determine the effects of running on the development of knee OA.
STUDY DESIGN
Systematic review; Level of evidence, 4.
METHODS
A systematic review was performed by searching the PubMed, Cochrane Library, and Embase databases to identify studies evaluating the effect of cumulative running on the development of knee OA or chondral damage based on imaging and/or patient-reported outcomes (PROs). The search terms used were "knee AND osteoarthritis AND (run OR running OR runner)." Patients were evaluated based on plain radiographs, magnetic resonance imaging (MRI), and PROs (presence of knee pain, Health Assessment Questionnaire-Disability Index, and the Knee injury and Osteoarthritis Outcome Score).
RESULTS
Seventeen studies (6 level 2 studies, 9 level 3 studies, and 2 level 4 studies), with 7194 runners and 6947 nonrunners, met the inclusion criteria. The mean follow-up time was 55.8 months in the runner group and 99.7 months in the nonrunner group. The mean age was 56.2 years in the runner group and 61.6 years in the nonrunner group. The overall percentage of men was 58.5%. There was a significantly higher prevalence of knee pain in the nonrunner group ( < .0001). Although 1 study found a significantly higher prevalence of osteophytes in the tibiofemoral (TF) and patellofemoral (PF) joints within the runner group, multiple studies found no significant differences in the prevalence of radiographic knee OA (based on TF/PF joint-space narrowing or Kellgren-Lawrence grade) or cartilage thickness on MRI between runners and nonrunners ( > .05). One study found a significantly higher risk of knee OA progressing to total knee replacement among nonrunners (4.6% vs 2.6%; = .014).
CONCLUSION
In the short term, running is not associated with worsening PROs or radiological signs of knee OA and may be protective against generalized knee pain.
PubMed: 36875337
DOI: 10.1177/23259671231152900 -
Ultrasound in Obstetrics & Gynecology :... Apr 2021Maternal diabetes in pregnancy is associated with structural anomalies of the fetal heart, as well as hypertrophy and functional impairment. This systematic review and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Maternal diabetes in pregnancy is associated with structural anomalies of the fetal heart, as well as hypertrophy and functional impairment. This systematic review and meta-analysis aimed to estimate the effect of maternal diabetes on fetal cardiac function as measured by prenatal echocardiography.
METHODS
We performed a search of the EMBASE, PubMed and The Cochrane Library databases, from inception to 4 July 2019, for studies evaluating fetal cardiac function using echocardiography in pregnancies affected by diabetes compared with uncomplicated pregnancies. Outcome measures were cardiac hypertrophy and diastolic, systolic and overall cardiac function as assessed by various ultrasound parameters. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data on interventricular septal (IVS) thickness, myocardial performance index (MPI) and E/A ratio were pooled for the meta-analysis using random-effects models. For pregnancies with diabetes, results were reported overall and according to whether diabetes was pregestational (PDM) or gestational (GDM). Results were also stratified according to the trimester in which fetal cardiac assessment was performed.
RESULTS
Thirty-nine studies were included, comprising data for 2276 controls and 1925 women with pregnancy affected by diabetes mellitus (DM). Of these, 1120 had GDM, 671 had PDM and in 134 cases diabetes type was not specified. Fetal cardiac hypertrophy was more prevalent in diabetic pregnancies than in non-diabetic controls in 21/26 studies, and impaired diastolic function was observed in diabetic pregnancies in 22/28 studies. The association between DM and systolic function was inconsistent, with 10/25 studies reporting no difference between cases and controls, although more recent studies measuring cardiac deformation, i.e. strain, did show decreased systolic function in diabetic pregnancies. Of the studies measuring overall fetal cardiac function, the majority (14/21) found significant impairment in diabetic pregnancies. Results were similar when stratified according to GDM or PDM. These effects were already present in the first trimester, but were most profound in the third trimester. Meta-analysis of studies performed in the third trimester showed, compared with controls, increased IVS thickness in both PDM (mean difference, 0.75 mm (95% CI, 0.56-0.94 mm)) and GDM (mean difference, 0.65 mm (95% CI, 0.39-0.91 mm)) pregnancies, decreased E/A ratio in PDM pregnancies (mean difference, -0.09 (95% CI, -0.15 to -0.03)), no difference in E/A ratio in GDM pregnancies (mean difference, -0.01 (95% CI, -0.02 to 0.01)) and no difference in MPI in either PDM (mean difference, 0.04 (95% CI, -0.01 to 0.09)) or GDM (mean difference, 0.03 (95% CI, -0.01 to 0.06)) pregnancies.
CONCLUSIONS
The findings of this review show that maternal diabetes is associated with fetal cardiac hypertrophy, diastolic dysfunction and overall impaired myocardial performance on prenatal ultrasound, irrespective of whether diabetes is pregestational or gestational. Further studies are needed to demonstrate the relationship with long-term outcomes. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Adult; Diabetes, Gestational; Echocardiography; Female; Fetal Heart; Humans; Pregnancy; Pregnancy Trimesters; Pregnancy in Diabetics; Ultrasonography, Prenatal
PubMed: 32730637
DOI: 10.1002/uog.22163 -
Advances in Therapy Dec 2023A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
A systematic literature review (SLR) and network meta-analysis (NMA) were conducted to evaluate the comparative efficacy, durability and safety of faricimab, used in a Treat & Extend (T&E) regime with intervals up to every 16 weeks (Q16W), relative to other therapies currently in use for treatment of diabetic macular oedema (DME). Of particular interest were anti-vascular endothelial growth factor (VEGF) therapies applied in flexible dosing regimens such as Pro re nata (PRN) and T&E, which are the mainstay in clinical practice.
METHODS
An SLR identifying randomised controlled trials (RCTs) published before August 2021 was conducted, followed by a Bayesian NMA comparing faricimab T&E treatment to aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), change in central subfield thickness (CST), injection frequency, ocular adverse events (AE) and all-cause discontinuation, all of which were evaluated at 12 months. Subgroup analyses including patients' naïve to anti-VEGF were conducted where feasible.
RESULTS
Twenty-six studies identified in the SLR were included in the NMA. Most importantly for decision making in clinical practise, faricimab T&E was associated with a statistically greater (95% credible intervals exclude zero) and clinically meaningful decrease in retinal thickness compared to all other flexible dosing regimens (greater retinal drying by 55-125 microns). Anatomical outcomes determine treatment efficacy and retreatment of patients. The NMA also showed a statistically greater increase in mean change in BCVA for faricimab T&E vs. flexible regimens using ranibizumab and bevacizumab (increase of 4.4-4.8 letters) as well as a numerical improvement vs. aflibercept PRN (two letters, 95% credible intervals including zero). Accordingly, the injection frequency was numerically lower versus other treatments using flexible dosing regimens (decrease by 0.92-1.43 injections). The analyses also indicated that the safety profile of faricimab T&E was comparable to those of ranibizumab and aflibercept, which have well-established safety profiles, with similar results for the number of all-cause discontinuations.
CONCLUSION
Faricimab provides a new treatment option in DME with dual-pathway inhibition of VEGF and angiopoeitin-2 (Ang-2). To the authors' knowledge, this is the first indirect comparison of faricimab T&E in DME. The analyses indicate that faricimab T&E is associated with superior retinal drying along with numerically fewer injections compared to all other treatments given in flexible dosing regimens. It also showed superior visual acuity outcomes compared to ranibizumab and bevacizumab.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Vascular Endothelial Growth Factor A
PubMed: 37751021
DOI: 10.1007/s12325-023-02675-y -
Surgical Outcomes after Colorectal Surgery for Endometriosis: A Systematic Review and Meta-analysis.Journal of Minimally Invasive Gynecology Mar 2021To assess the impact of type of surgery for colorectal endometriosis-rectal shaving or discoid resection or segmental colorectal resection-on complications and surgical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the impact of type of surgery for colorectal endometriosis-rectal shaving or discoid resection or segmental colorectal resection-on complications and surgical outcomes.
DATA SOURCES
We performed a systematic review of all English- and French-language full-text articles addressing the surgical management of colorectal endometriosis, and compared the postoperative complications according to surgical technique by meta-analysis. The PubMed, Clinical Trials.gov, Cochrane Library, and Web of Science databases were searched for relevant studies published before March 27, 2020. The search strategy used the following Medical Subject Headings terms: ("bowel endometriosis" or "colorectal endometriosis") AND ("surgery for endometriosis" or "conservative management" or "radical management" or "colorectal resection" or "shaving" or "full thickness resection" or "disc excision") AND ("treatment", "outcomes", "long term results" and "complications").
METHODS OF STUDY SELECTION
Two authors conducted the literature search and independently screened abstracts for inclusion, with resolution of any difference by 3 other authors. Studies were included if data on surgical management (shaving, disc excision, and/or segmental resection) were provided and if postoperative outcomes were detailed with at least the number of complications. The risk of bias was assessed according to the Cochrane recommendations.
TABULATION, INTEGRATION, AND RESULTS
Of the 168 full-text articles assessed for eligibility, 60 were included in the qualitative synthesis. Seventeen of these were included in the meta-analysis on rectovaginal fistula, 10 on anastomotic leakage, 5 on anastomotic stenosis, and 9 on voiding dysfunction <30 days. The mean complication rate according to shaving, disc excision, and segmental resection were 2.2%, 9.7%, and 9.9%, respectively. Rectal shaving was less associated with rectovaginal fistula than disc excision (odds ratio [OR] = 0.19; 95% confidence interval [CI], 0.10-0.36; p <.001; I = 33%) and segmental colorectal resection (OR = 0.26; 95% CI, 0.15-0.44; p <.001; I = 0%). No difference was found in the occurrence of rectovaginal fistula between disc excision and segmental colorectal resection (OR = 1.07; 95% CI, 0.70-1.63; p = .76; I = 0%). Rectal shaving was less associated with leakage than disc excision (OR = 0.22; 95% CI, 0.06-0.73; p = .01; I = 86%). No difference was found in the occurrence of leakage between rectal shaving and segmental colorectal resection (OR = 0.32; 95% CI, 0.10-1.01; p = .05; I = 71%) or between disc excision and segmental colorectal resection (OR = 0.32; 95% CI, 0.30-1.58; p = .38; I = 0%). Disc excision was less associated with anastomotic stenosis than segmental resection (OR = 0.15; 95% CI, 0.05-0.48; p = .001; I = 59%). Disc excision was associated with more voiding dysfunction <30 days than rectal shaving (OR = 12.9; 95% CI, 1.40-119.34; p = .02; I = 0%). No difference was found in the occurrence of voiding dysfunction <30 days between segmental resection and rectal shaving (OR = 3.05; 95% CI, 0.55-16.87; p = .20; I = 0%) or between segmental colorectal and discoid resections (OR = 0.99; 95% CI, 0.54-1.85; p = .99; I = 71%).
CONCLUSION
Colorectal surgery for endometriosis exposes patients to a risk of severe complications such as rectovaginal fistula, anastomotic leakage, anastomotic stenosis, and voiding dysfunction. Rectal shaving seems to be less associated with postoperative complications than disc excision and segmental colorectal resection. However, this technique is not suitable for all patients with large bowel infiltration. Compared with segmental colorectal resection, disc excision has several advantages, including shorter operating time, shorter hospital stay, and lower risk of postoperative bowel stenosis.
Topics: Adult; Colon, Sigmoid; Databases, Factual; Digestive System Surgical Procedures; Endometriosis; Female; Humans; Laparoscopy; Middle Aged; Postoperative Complications; Prognosis; Rectal Diseases; Rectovaginal Fistula; Rectum; Treatment Outcome
PubMed: 32841755
DOI: 10.1016/j.jmig.2020.08.015 -
Journal of Athletic Training May 2020To determine the effects of an eccentric hamstrings strength-training program, performed for at least 4 weeks by healthy adults, on muscle architecture and eccentric... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the effects of an eccentric hamstrings strength-training program, performed for at least 4 weeks by healthy adults, on muscle architecture and eccentric strength.
DATA SOURCES
A systematic search was performed up to October 2018 in the following electronic databases: PubMed, PEDro, CINAHL and SPORTDiscus. Combinations of the following search terms were used: , , , , , , , , , , and .
STUDY SELECTION
Included articles were randomized controlled trials that allowed comparisons between isolated eccentric strength training of the biceps femoris muscle and other programs.
DATA EXTRACTION
Data from the included studies were extracted by 2 independent reviewers. These data included the study design, participant characteristics, inclusion and exclusion criteria of clinical studies, exercise and intervention characteristics, outcome measures, and the main results of the study. When meta-analysis was possible, we performed quantitative analysis. Ten randomized controlled trials were included.
DATA SYNTHESIS
Limited to moderate evidence indicated that eccentric strength training was associated with an increase in fascicle length (mean difference [MD] = 1.97; 95% confidence interval [CI] = 1.48, 2.46), an increase in muscle thickness (MD = 0.10; 95% CI = 0.06, 0.13), and a decrease in pennation angle (MD = 2.36; 95% CI = 1.61, 3.11). Conflicted to moderate evidence indicated that eccentric hamstrings strength was increased after eccentric strength training compared with concentric strength training (standardized mean difference [SMD] = 1.06; 95% CI = 0.26, 1.86), usual level of activity (SMD = 2.72; 95% CI = 1.68, 3.77), and static stretching (SMD = 0.39; 95% CI = -0.97, 1.75).
CONCLUSIONS
In healthy adults, an eccentric strength-training program produced architectural adaptations on the long head of the biceps femoris muscle and increased eccentric hamstrings strength.
Topics: Adaptation, Physiological; Adult; Athletic Injuries; Hamstring Muscles; Humans; Muscle Strength; Resistance Training
PubMed: 32216654
DOI: 10.4085/1062-6050-194-19 -
Circulation Aug 2020To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk.
METHODS
We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach.
RESULTS
We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients.
CONCLUSIONS
The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
Topics: Carotid Artery, Common; Carotid Intima-Media Thickness; Female; Heart Disease Risk Factors; Humans; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Stroke
PubMed: 32546049
DOI: 10.1161/CIRCULATIONAHA.120.046361 -
The Cochrane Database of Systematic... May 2021The World Health Organization (WHO) recommends that people of all ages take regular and adequate physical activity. If unable to meet the recommendations due to health...
BACKGROUND
The World Health Organization (WHO) recommends that people of all ages take regular and adequate physical activity. If unable to meet the recommendations due to health conditions, international guidance advises being as physically active as possible. Evidence from community interventions of physical activity indicate that people living with medical conditions are sometimes excluded from participation in studies. In this review, we considered the effects of activity-promoting interventions on physical activity and well-being in studies, as well as any adverse events experienced by participants living with inherited or acquired neuromuscular diseases (NMDs). OBJECTIVES: To assess the effects of interventions designed to promote physical activity in people with NMD compared with no intervention or alternative interventions.
SEARCH METHODS
On 30 April 2020, we searched Cochrane Neuromuscular Specialised Register, CENTRAL, Embase, MEDLINE, and ClinicalTrials.Gov. WHO ICTRP was not accessible at the time.
SELECTION CRITERIA
We considered randomised or quasi-randomised trials, including cross-over trials, of interventions designed to promote physical activity in people with NMD compared to no intervention or alternative interventions. We specifically included studies that reported physical activity as an outcome measure. Our main focus was studies in which promoting physical activity was a stated aim but we also included studies in which physical activity was assessed as a secondary or exploratory outcome.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane procedures.
MAIN RESULTS
The review included 13 studies (795 randomised participants from 12 studies; number of participants unclear in one study) of different interventions to promote physical activity. Most studies randomised a minority of invited participants. No study involved children or adolescents and nine studies reported minimal entry criteria for walking. Participants had one of nine inherited or acquired NMDs. Types of intervention included structured physical activity support, exercise support (as a specific form of physical activity), and behaviour change support that included physical activity or exercise. Only one included study clearly reported that the aim of intervention was to increase physical activity. Other studies reported or planned to analyse the effects of intervention on physical activity as a secondary or exploratory outcome measure. Six studies did not report results for physical activity outcomes, or the data were not usable. We judged 10 of the 13 included studies at high or unclear risk of bias from incomplete physical activity outcome reporting. We did not perform a meta-analysis for any comparison because of differences in interventions and in usual care. We also found considerable variation in how studies reported physical activity as an outcome measure. The studies that reported physical activity measurement did not always clearly report intention-to-treat (ITT) analysis or whether final assessments occurred during or after intervention. Based on prespecified measures, we included three comparisons in our summary of findings. A physical activity programme (weight-bearing) compared to no physical activity programme One study involved adults with diabetic peripheral neuropathy (DPN) and reported weekly duration of walking during and at the end of a one-year intervention using a StepWatch ankle accelerometer. Based on the point estimate and low-certainty evidence, intervention may have led to an important increase in physical activity per week; however, the 95% confidence interval (CI) included the possibility of no difference or an effect in either direction at three months (mean difference (MD) 34 minutes per week, 95% CI -92.19 to 160.19; 69 participants), six months (MD 68 minutes per week, 95% CI -55.35 to 191.35; 74 participants), and 12 months (MD 49 minutes per week, 95% CI -75.73 to 173.73; 70 participants). Study-reported effect estimates for foot lesions and full-thickness ulcers also included the possibility of no difference, a higher, or lower risk with intervention. A sensor-based, interactive exercise programme compared to no sensor-based, interactive exercise programme One study involved adults with DPN and reported duration of walking over 48 hours at the end of four weeks' intervention using a t-shirt embedded PAMSys sensor. It was not possible to draw conclusions about the effectiveness of the intervention from the very low-certainty evidence (MD -0.64 hours per 48 hours, 95% CI -2.42 to 1.13; 25 participants). We were also unable to draw conclusions about impact on the Physical Component Score (PCS) for quality of life (MD 0.24 points, 95% CI -5.98 to 6.46; 35 participants; very low-certainty evidence), although intervention may have made little or no difference to the Mental Component Score (MCS) for quality of life (MD 5.10 points, 95% CI -0.58 to 10.78; 35 participants; low-certainty evidence). A functional exercise programme compared to a stretching exercise programme One study involved adults with spinal and bulbar muscular atrophy and reported a daily physical activity count at the end of 12 weeks' intervention using an Actical accelerometer. It was not possible to draw conclusions about the effectiveness of either intervention (requiring compliance) due to low-certainty evidence and unconfirmed measurement units (MD -8701, 95% CI -38,293.30 to 20,891.30; 43 participants). Functional exercise may have made little or no difference to quality of life compared to stretching (PCS: MD -1.10 points, 95% CI -5.22 to 3.02; MCS: MD -1.10 points, 95% CI -6.79 to 4.59; 49 participants; low-certainty evidence). Although studies reported adverse events incompletely, we found no evidence of supported activity increasing the risk of serious adverse events.
AUTHORS' CONCLUSIONS
We found a lack of evidence relating to children, adolescents, and non-ambulant people of any age. Many people living with NMD did not meet randomised controlled trial eligibility criteria. There was variation in the components of supported activity intervention and usual care, such as physical therapy provision. We identified variation among studies in how physical activity was monitored, analysed, and reported. We remain uncertain of the effectiveness of promotional intervention for physical activity and its impact on quality of life and adverse events. More information is needed on the ITT population, as well as more complete reporting of outcomes. While there may be no single objective measure of physical activity, the study of qualitative and dichotomous change in self-reported overall physical activity might offer a pragmatic approach to capturing important change at an individual and population level.
Topics: Bias; Exercise; Health Promotion; Humans; Muscle Stretching Exercises; Neuromuscular Diseases; Outcome Assessment, Health Care; Quality of Life; Randomized Controlled Trials as Topic; Resistance Training; Time Factors; Walking
PubMed: 34027632
DOI: 10.1002/14651858.CD013544.pub2 -
The Cochrane Database of Systematic... Mar 2020Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease, which is the more prevalent form of dry eye disease. Intense pulsed light (IPL)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Meibomian gland dysfunction (MGD) is the major cause of evaporative dry eye disease, which is the more prevalent form of dry eye disease. Intense pulsed light (IPL) therapy, involving treatment of the skin near the eyelids, has emerged as a potential treatment for MGD.
OBJECTIVES
To evaluate the effectiveness and safety of intense pulsed light (IPL) for the management dry eye disease resulting from meibomian gland dysfunction (MGD).
SEARCH METHODS
We searched CENTRAL, MEDLINE (Ovid), Embase Ovid and three trial registers for eligible clinical trials on 1 August 2019. There were no restrictions on publication status, date or language.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) studying the effectiveness or safety of IPL for treating MGD.
DATA COLLECTION AND ANALYSIS
Our outcomes of interest were the change from baseline in subjective dry eye symptoms, adverse events, changes to lipid layer thickness, tear break-up time (TBUT), tear osmolarity, eyelid irregularity, eyelid telangiectasia, meibomian gland orifice plugging, meibomian gland dropout, corneal sodium fluorescein staining and conjunctival lissamine green staining. Two review authors independently screened abstracts and full-text articles, extracted data from eligible RCTs and judged the risk of bias using the Cochrane tool. We reached consensus on any disagreements by discussion. We summarised the overall certainty of the evidence using the GRADE Working Group approach.
MAIN RESULTS
We included three RCTs, one from New Zealand, one from Japan and one from China, published between 2015 and 2019. Together, these trials enrolled 114 adults (228 eyes). Two studies used a paired-eye (inter-eye comparison) design to evaluate the effects of a sham (control) IPL treatment relative to an actual IPL treatment. One study randomised individuals to either an IPL intervention combined with meibomian gland expression (MGX), or MGX alone (standard therapy). The study follow-up periods ranged from 45 days to nine months. None of the trials were at low risk of bias in all seven domains. The first authors of two included studies were in receipt of funding from patents or the manufacturers of IPL devices. The funding sources and declaration of interests were not given in the report of the third included trial. All three trials evaluated the effect of IPL on dry eye symptoms, quantified using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. Pooling data from two trials that used a paired-eye design, the summary estimate for these studies indicated little to no reduction in dry eye symptoms with IPL relative to a sham intervention (mean difference (MD) -0.33 units, 95% confidence interval (CI) -2.56 to 1.89; I² = 0%; 2 studies, 144 eyes). The other study was not pooled as it had a unit-of-analysis error, but reported a reduction in symptoms in favour of IPL (MD -4.60, 95% CI -6.72 to -2.48; 84 eyes). The body of evidence for this outcome was of very low certainty, so we are uncertain about the effect of IPL on dry eye symptoms. There were no relevant combinable data for any of the other secondary outcomes, thus the effect of IPL on clinical parameters relevant to dry eye disease are currently unclear. For sodium fluorescein TBUT, two studies indicated that there may be an improvement in favour of IPL (MD 2.02 seconds, 95% CI 0.87 to 3.17; MD 2.40 seconds, 95% CI 2.27 to 2.53; 172 eyes total; low-certainty evidence). We are uncertain of the effect of IPL on non-invasive tear break-up time (MD 5.51 seconds, 95% CI 0.79 to 10.23; MD 3.20, 95% CI 3.09 to 3.31 seconds; two studies; 140 eyes total; very low-certainty evidence). For tear osmolarity, one study indicated that there may be an improvement in favour of IPL (MD -7.00 mOsmol/L, 95% -12.97 to -1.03; 56 eyes; low-certainty evidence). We are uncertain of the effect of IPL on meibomian gland orifice plugging (MD -1.20 clinical units, 95% CI -1.24 to -1.16; 84 eyes; very low-certainty evidence). We are uncertain of the effect of IPL on corneal sodium fluorescein staining. One study reported no evidence of a difference between the IPL and sham intervention arms at three months of follow-up (P = 0.409), and a second study reported data favouring IPL (MD -1.00 units, 95% CI -1.07 to -0.93 units; 172 eyes in total; very low-certainty evidence). We considered the incidence of adverse events at the study endpoint, as a measure of safety. As most trials did not specifically report adverse events, the safety of IPL as a treatment for MGD could also not be determined with any certainty. Very low-certainty results from individual studies suggest some adverse effects that may be experienced by participants, include mild pain and burning, and the potential for partially losing eyelashes (due to clinician error).
AUTHORS' CONCLUSIONS
This systematic review finds a scarcity of RCT evidence relating to the effectiveness and safety of IPL as a treatment for MGD. Whether IPL is of value for modifying the symptoms or signs of evaporative dry eye disease is currently uncertain. Due to a lack of comprehensive reporting of adverse events, the safety profile of IPL in this patient population is also unclear. The current limitations in the evidence base should be considered by clinicians using this intervention to treat MGD, and outlined to individuals potentially undergoing this procedure with the intent of treating dry eye disease. The results of the 14 RCTs currently in progress will be of major importance for establishing a more definitive answer regarding the effectiveness and safety of IPL for treating MGD. We intend to update this review when results from these trials become available.
Topics: Dry Eye Syndromes; Humans; Intense Pulsed Light Therapy; Meibomian Gland Dysfunction; Randomized Controlled Trials as Topic
PubMed: 32182637
DOI: 10.1002/14651858.CD013559