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The Cochrane Database of Systematic... Feb 2024Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Methotrexate has broad immunomodulatory properties and is the most commonly used... (Review)
Review
BACKGROUND
Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Methotrexate has broad immunomodulatory properties and is the most commonly used disease-modifying antirheumatic drug (DMARD). This is an update of a 2001 Cochrane review. It supports a living guideline for children and young people with JIA.
OBJECTIVES
To assess the benefits and harms of methotrexate for children and young people with juvenile idiopathic arthritis.
SEARCH METHODS
The Australian JIA Living Guideline Working Group created a registry of all randomised controlled trials (RCTs) of JIA by searching CENTRAL, MEDLINE, Embase, and trials registries. The date of the most recent search of online databases was 1 February 2023.
SELECTION CRITERIA
We searched for RCTs that compared methotrexate with placebo, no treatment, or another DMARD (with or without concomitant therapies) in children and young people (aged up to 18 years) with JIA.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. The main comparison was methotrexate versus placebo. Our outcomes were treatment response, sustained clinically inactive disease, function, pain, participant global assessment of well-being, serious adverse events, and withdrawals due to adverse events. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified three new trials in this update, bringing the total number of included RCTs to five (575 participants). Three trials evaluated oral methotrexate versus placebo, one evaluated methotrexate plus intra-articular glucocorticoid (IAGC) therapy versus IAGC therapy alone, and one evaluated methotrexate versus leflunomide. Doses of methotrexate ranged from 5 mg/m/week to 15 mg/m/week in four trials, and participants in the methotrexate group of the remaining trial received 0.5 mg/kg/week. Trial size varied from 31 to 226 participants. The average age of participants ranged from four to 10 years. Most participants were females and most had nonsystemic JIA. The study that evaluated methotrexate plus IAGC therapy versus IAGC therapy alone recruited children and young people with the oligoarticular disease subtype of JIA. Two placebo-controlled trials and the trial of methotrexate versus leflunomide were adequately randomised and blinded, and likely not susceptible to important biases. One placebo-controlled trial may have been susceptible to selection bias due to lack of adequate reporting of randomisation methods. The trial investigating the addition of methotrexate to IAGC therapy was susceptible to performance and detection biases. Methotrexate versus placebo Methotrexate compared with placebo may increase the number of children and young people who achieve treatment response up to six months (absolute difference of 163 more per 1000 people; risk ratio (RR) 1.67, 95% confidence interval (CI) 1.21 to 2.31; I = 0%; 3 trials, 328 participants; low-certainty evidence). However, methotrexate compared with placebo may have little or no effect on pain as measured on an increasing scale of 0 to 100 (mean difference (MD) -1.10 points, 95% CI -9.09 to 6.88; 1 trial, 114 participants), improvement in participant global assessment of well-being (absolute difference of 92 more per 1000 people; RR 1.23, 95% CI 0.88 to 1.72; 1 trial, 176 participants), occurrence of serious adverse events (absolute difference of 5 fewer per 1000 people; RR 0.63, 95% CI 0.04 to 8.97; 3 trials, 328 participants), and withdrawals due to adverse events (RR 3.46, 95% CI 0.60 to 19.79; 3 trials, 328 participants) up to six months. We could not estimate the absolute difference for withdrawals due to adverse events because there were no withdrawals in the placebo group. All outcomes were reported within six months of randomisation. We downgraded the certainty of the evidence to low for all outcomes due to indirectness (suboptimal dosing of methotrexate and diverse outcome measures) and imprecision (few participants and low event rates). No trials reported function or the number of participants with sustained clinically inactive disease. Serious adverse events included liver derangement, abdominal pain, and inadvertent overdose. Methotrexate plus intra-articular corticosteroid therapy versus intra-articular corticosteroid therapy alone Methotrexate plus IAGC therapy compared with IAGC therapy alone may have little or no effect on the probability of sustained clinically inactive disease or the rate of withdrawals due to adverse events up to 12 months in children and young people with the oligoarticular subtype of JIA (low-certainty evidence). We could not calculate the absolute difference in withdrawals due to adverse events because there were no withdrawals in the control group. We are uncertain if there is any difference between the interventions in the risk of severe adverse events, because none were reported. The study did not report treatment response, function, pain, or participant global assessment of well-being. Methotrexate versus an alternative disease-modifying antirheumatic drug Methotrexate compared with leflunomide may have little or no effect on the probability of treatment response or on function, participant global assessment of well-being, risk of serious adverse events, and rate of withdrawals due to adverse events up to four months. We downgraded the certainty of the evidence for all outcomes to low due to imprecision. The study did not report pain or sustained clinically inactive disease.
AUTHORS' CONCLUSIONS
Oral methotrexate (5 mg/m/week to 15 mg/m/week) compared with placebo may increase the number of children and young people achieving treatment response but may have little or no effect on pain or participant global assessment of well-being. Oral methotrexate plus IAGC injections compared to IAGC injections alone may have little or no effect on the likelihood of sustained clinically inactive disease among children and young people with oligoarticular JIA. Similarly, methotrexate compared with leflunomide may have little or no effect on treatment response, function, and participant global assessment of well-being. Serious adverse events due to methotrexate appear to be rare. We will update this review as new evidence becomes available to inform the living guideline.
Topics: Child; Female; Humans; Adolescent; Aged; Child, Preschool; Male; Methotrexate; Arthritis, Juvenile; Leflunomide; Australia; Antirheumatic Agents; Glucocorticoids; Pain
PubMed: 38334147
DOI: 10.1002/14651858.CD003129.pub2 -
Breastfeeding Medicine : the Official... Oct 2023African American women continue to experience low rates of breastfeeding initiation as well as low rates of exclusive breastfeeding for 6 months. Research has indicated... (Review)
Review
African American women continue to experience low rates of breastfeeding initiation as well as low rates of exclusive breastfeeding for 6 months. Research has indicated that there are several social determinants that impact breastfeeding rates, but there is a dearth of literature that allows African American women to give voice to their experiences. In addition, research has shown women, infant, and children (WIC) participants to have lower breastfeeding rates than non-WIC eligible women. The aim of this systematic review was to examine the relationship between WIC program participation and breastfeeding initiation and duration among non-Hispanic African American/Black women. The approach for this review used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Four online databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Library, MEDLINE, and SCOPUS, were used to search for peer-reviewed articles and grey literature. Two hundred eighteen articles were retrieved through the database search and underwent initial screening, yielding 59 potential eligible articles. Full-text articles were further reviewed and 11 met the inclusion criteria and were included in this systematic review. Included studies show mixed results regarding the association between WIC participation and breastfeeding initiation, but there is a general negative association between WIC participation and breastfeeding duration, especially among Black women.
Topics: Infant; Female; Child; Humans; Breast Feeding; Black or African American
PubMed: 37856661
DOI: 10.1089/bfm.2023.0091 -
The Cochrane Database of Systematic... May 2024Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue may expedite wound healing. There are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue may expedite wound healing. There are numerous methods of debridement available, but no consensus on which one is most effective for surgical wounds.
OBJECTIVES
To assess the effects of different methods of debridement on the rate of debridement and healing of surgical wounds.
SEARCH METHODS
In October 2021, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL. To identify additional studies, we searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies, reviews, meta-analyses, and health technology reports. There were no restrictions on language, date of publication, or study setting.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that enrolled people with a surgical wound that required debridement, and reported time to complete wound debridement or time to wound healing, or both.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, risk of bias assessment using the RoB 1 tool, data extraction, and GRADE assessment of the certainty of evidence.
MAIN RESULTS
In this fourth update, we identified one additional study for inclusion. The review now includes six studies, with 265 participants, aged three to 91 years. Five studies were published between 1979 and 1990 and one published in 2014. The studies were carried out in hospital settings in China, Denmark, Belgium, and the UK. Six studies provided six comparisons. Due to the heterogeneity of studies, it was not appropriate to conduct meta-analyses. Four studies evaluated the effectiveness of dextranomer beads/paste; however, each study used a different comparator (Eusol-soaked dressings, 10% aqueous polyvinylpyrrolidone, 0.1% chloramine-soaked packs, and silicone foam elastomer dressing). One study compared streptokinase/streptodornase with saline-soaked dressings, and one compared endoscopic surgical debridement with conventional 'open' surgical debridement. Five studies reported time to complete debridement (reported as time to a clean wound bed) and three reported time to complete healing. One study reported effect estimates (surgical debridement via endoscopy versus surgical debridement) for time to a clean wound bed and time to complete wound healing, and it was possible to calculate effect estimates for one other study (dextranomer paste versus silicone foam elastomer) for time to complete wound healing. For the other four studies that did not report effect estimates, it was not possible to calculate time to a clean wound bed or time to complete wound healing due to missing variance and participant exclusions. None of the included studies reported outcomes pertaining to proportion of wounds completely healed, rate of reduction in wound size, rate of infection, or quality of life. All studies had unclear or high risk of bias for at least one key domain. Dextranomer paste/beads (autolytic debridement) compared with four different comparators Four studies compared dextranomer paste or beads with Eusol-soaked gauze (20 participants), 10% aqueous polyvinylpyrrolidone (40 participants), 0.1% chloramine-soaked dressings (28 participants), or silicone foam elastomer (50 participants). There is very low-certainty evidence that there may be no clear difference in time to a clean wound bed between dextranomer beads and Eusol gauze. The study did not report adverse events. There is very low-certainty evidence that there may be no difference in time to a clean wound bed between dextranomer paste and 10% aqueous polyvinylpyrrolidone gauze. There was low-certainty evidence that there may be no difference in deaths and serious adverse events. There may be a difference in time until the wounds were clinically clean and time to complete wound healing between dextranomer paste and 0.1% chloramine favouring 0.1% chloramine, but we are very uncertain. There is low-certainty evidence that there may be no difference in deaths and serious adverse events. There is very low-certainty evidence that there may be no difference in time to complete healing between dextranomer beads and silicone foam elastomer. The study did not report adverse events. Streptokinase/streptodornase solution (enzymatic) compared with saline-soaked dressings One study (21 participants) compared enzymatic debridement with saline-soaked dressings. There is low-certainty evidence that there may be no difference in time to a clean wound bed or secondary suture between streptokinase/streptodornase and saline-soaked dressings. There is very low-certainty evidence that there may be no difference in deaths and serious adverse events. Surgical debridement via endoscopic ('keyhole') surgery compared with surgical debridement by 'open' surgery (the wound is opened using a scalpel) One study (106 participants) reported time to complete wound healing and time to a clean wound bed. There is low-certainty evidence that there may be a reduction in time to complete wound healing and very low-certainty evidence that there may be no difference in time to a clean wound bed with surgical debridement via endoscopy compared to 'open' surgical debridement. The study did not report adverse events. Overall, the evidence was low to very low-certainty for all outcomes. Five included studies were published before 1991 and investigated treatments that are no longer available. Worldwide production of dextranomer products has been discontinued, except for dextranomer paste, which is currently only available in South Africa. Furthermore, Eusol, used in one study as the comparator to dextranomer, is rarely used due to risk of harmful effects on healthy tissue and the enzymatic agent streptokinase/streptodornase is no longer available worldwide.
AUTHORS' CONCLUSIONS
Evidence for the effects of different methods of debridement on complete wound debridement and healing of surgical wounds remains unclear. Adequately powered, methodologically robust RCTs evaluating contemporary debridement interventions for surgical wounds are needed to guide clinical decision-making.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Humans; Middle Aged; Young Adult; Bandages; Bias; Debridement; Randomized Controlled Trials as Topic; Surgical Wound; Surgical Wound Infection; Time Factors; Wound Healing
PubMed: 38712723
DOI: 10.1002/14651858.CD006214.pub5 -
The Journal of Maternal-fetal &... Dec 2023Transcervical resection of adhesion (TCRA) and postoperative adjuvant estrogen and progestin are the main treatments for cavity adhesions, but the recurrence rate after... (Meta-Analysis)
Meta-Analysis Review
The effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion: a systematic review and meta-analysis.
BACKGROUND
Transcervical resection of adhesion (TCRA) and postoperative adjuvant estrogen and progestin are the main treatments for cavity adhesions, but the recurrence rate after surgery is still high. It was showed that aspirin could promote endometrial proliferation and repair after TCRA in patients with severe cavity adhesions, but the effect on reproduction was uncertain.
OBJECTIVE
To assess the effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion.
METHODS
The databases used included Cumulative Index to PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang database. Studies published before June 2022 were included. Each participant received an aspirin-based intervention aimed at improving uterine status, which was compared to a sham intervention. The primary outcome measure was a change in endometrium thickness. Secondary outcomes included uterine artery resistance index, blood flow index, and endometrial arterial resistance index.
RESULT
A total of 19 studies ( = 1361 participants) that met the inclusion criteria were included in this study. The aspirin-based intervention was strongly associated with better clinical outcome at second-look endometrium thickness (MD 0.81, CI 0.46-1.16; < .00001) and blood flow Index (FI) (MD 4.1, CI 2.3-5.9; < .00001). Besides, the analysis of arterial pulsatility index (PI) showed a significantly reduced after transcervical resection of adhesion (MD -0.9, CI -1.2 to 0.6; < .00001); whereas no significant difference was found in endometrial arterial resistance index (RI) (95% CI, -0.30 to 0.01; = .07).
CONCLUSION
Our study proved the effect of aspirin on uterine arterial blood flow and endometrium in moderate and severe intrauterine adhesion after transcervical resection of adhesion. However, the review requires evidence from additional randomized controlled trials and high-quality research. More strictly designed research studies are needed to assess the effectiveness of aspirin administration after transcervical resection of adhesion.
Topics: Female; Humans; Aspirin; Uterine Artery; Uterine Diseases; Endometrium; Uterus
PubMed: 37286223
DOI: 10.1080/14767058.2023.2209818 -
Journal of the American Academy of... Jul 2024To evaluate the reporting of race/ethnicity data in randomized controlled trials (RCTs) of attention-deficit/hyperactivity disorder (ADHD) medications. Secondary... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-Analysis: Reporting and Representation of Race/Ethnicity in 310 Randomized Controlled Trials of Attention-Deficit/Hyperactivity Disorder Medications.
OBJECTIVE
To evaluate the reporting of race/ethnicity data in randomized controlled trials (RCTs) of attention-deficit/hyperactivity disorder (ADHD) medications. Secondary objectives were to estimate temporal trends in the reporting, and to compare the pooled prevalence of racial/ethnic groups in RCTs conducted in the US to national estimates.
METHOD
We drew on, adapted, and updated the search of a network meta-analysis by Cortese et al. (2018) up to March 2022. We calculated the percentage of RCTs reporting data on race/ethnicity of participants in the published article or in related unpublished material. Temporal trends were estimated with logistic regression. The pooled prevalence of each racial/ethnic group across US RCTs was calculated using random-effects model meta-analyses.
RESULTS
We retained 310 RCTs (including 44,447 participants), of which 231 were conducted in children/adolescents, 78 in adults, and 1 in both. Data on race/ethnicity were reported in 59.3% of the RCTs (75% of which were conducted in children/adolescents and 25% in adults) in the published article, and in unpublished material in an additional 8.7% of the RCTs. Reporting improved over time. In the US RCTs, Asian and White individuals were under- and overrepresented, respectively, compared to national estimates in the most recent time period considered.
CONCLUSION
More than 30% of the RCTs of ADHD medications retained in this review did not include data on race/ethnicity in their published or unpublished reports, and more than 40% in their published articles, even though reporting improved over time. Results should inform investigators, authors, editors, regulators, and study participants in relation to efforts to tackle inequalities in ADHD research.
PLAIN LANGUAGE SUMMARY
A systematic review of 310 randomized controlled trials for attention-deficit/hyperactivity disorder (ADHD) medications found that race/ethnicity were reported in only 30% of trials. Compared to national estimates, Asian individuals were underrepresented and non-Hispanic Whites individuals were overrepresented, drawing attention to the inequities in participation in ADHD research.
DIVERSITY & INCLUSION STATEMENT
One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
STUDY PREREGISTRATION INFORMATION
Reporting and representation of race/ethnicity in double blind randomised controlled trials of medications for ADHD; https://osf.io/; hfgz8.
Topics: Humans; Attention Deficit Disorder with Hyperactivity; Randomized Controlled Trials as Topic; Child; Adolescent; United States; Adult; Ethnicity
PubMed: 37890665
DOI: 10.1016/j.jaac.2023.09.544 -
Public Health Nutrition Dec 2023Aligning with the United Nations Convention on the Rights of the Child, amplification of children's voice in food practice research aims to inform initiatives that cater... (Review)
Review
OBJECTIVE
Aligning with the United Nations Convention on the Rights of the Child, amplification of children's voice in food practice research aims to inform initiatives that cater to children's needs and thus improve nutritional outcomes. The aim of this study was to describe children's (aged 6-11 years) involvement across qualitative research investigating their food practice perspectives.
DESIGN
A scoping review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR). Six electronic databases were searched up until March 2023 (Cochrane, CINAHL, Embase, ERIC, Medline and PsychInfo). The Wellcome Framework for young people's involvement in health research guided data extraction. Data were described according to inclusiveness, geography, food-related study topic, research stage and method, and child involvement.
RESULTS
The search identified 120 peer-reviewed studies (134 papers). Active participation was only seen within research implementation stages (i.e. data collection ( 134), analysis ( 31), dissemination ( 9) and re-design ( 7)). More passive forms of participation were identified in research design stages (i.e. agenda setting, resourcing and design). Studies that utilised participatory research methodologies and developmentally appropriate and engaging methods (e.g. PhotoVoice) saw more active participation by children.
CONCLUSION
This review identified a lack of opportunities for children's active participation in all stages of food practice research. Without a radical shift towards providing these opportunities, food and nutrition initiatives, policies or further research that do not meet the needs of children's food-related worlds will continue to be developed. Instead, researchers and their institutions need to advocate for and, where possible, provide voluntary opportunities for children to actively participate in food practice research.
Topics: Child; Humans; Adolescent; Food; Qualitative Research
PubMed: 37746758
DOI: 10.1017/S1368980023001891 -
The Cochrane Database of Systematic... Nov 2023A groin hernia is a collective name for inguinal and femoral hernias, which can present acutely with incarceration or strangulation of the hernia sac content, requiring... (Review)
Review
BACKGROUND
A groin hernia is a collective name for inguinal and femoral hernias, which can present acutely with incarceration or strangulation of the hernia sac content, requiring emergency treatment. Timely repair of emergency groin hernias is crucial due to the risk of reduced blood supply and thus damage to the bowel, but the optimal surgical approach is unclear. While mesh repair is the standard treatment for elective hernia surgery, using mesh for emergency groin hernia repair remains controversial due to the risk of surgical site infection.
OBJECTIVES
To assess the benefits and harms of mesh compared with non-mesh in emergency groin hernia repair in adult patients with an inguinal or femoral hernia.
SEARCH METHODS
On 5 August 2022, we searched the following databases: CENTRAL, MEDLINE Ovid, and Embase Ovid, as well as two trial registers for ongoing and completed trials. Additionally, we performed forward and backward citation searches for the included trials and relevant review articles. We searched without any language or publication restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing mesh with non-mesh repair in emergency groin hernia surgery in adults. We included any mesh and any non-mesh repairs. All studies fulfilling the study, participant, and intervention criteria were included irrespective of reported outcomes.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodology. We presented dichotomous data as risk ratios (RR) with 95% confidence intervals (CI). We based missing data analysis on best- and worst-case scenarios. For outcomes with sufficiently low heterogeneity, we performed meta-analyses using the random-effects model. We analysed subgroups when feasible, including the degree of contamination. We used RoB 2 for risk of bias assessment, and summarised the certainty of evidence using GRADE.
MAIN RESULTS
We included 15 trials randomising 1241 participants undergoing emergency groin hernia surgery with either mesh (626 participants) or non-mesh hernia repair (615 participants). The studies were conducted in China, the Middle East, and South Asia. Most patients were men, and most participants had an inguinal hernia (41 participants had femoral hernias). The mean/median age in the mesh group ranged from 35 to 70 years, and from 41 to 69 years in the non-mesh group. All studies were performed in a hospital emergency setting (tertiary care) and lasted for 11 to 139 months, with a median study duration of 31 months. The majority of the studies only included participants with clean to clean-contaminated surgical fields. For all outcomes, we considered the certainty of the evidence to be very low, mainly downgraded due to high risk of bias (due to deviations from intended intervention and missing outcome data), indirectness, and imprecision. Mesh hernia repair may have no effect on or slightly increase the risk of 30-day surgical site infections (RR 1.66, 95% CI 0.96 to 2.88; I² = 21%; 2 studies, 454 participants) when compared with non-mesh hernia repair, but the evidence is very uncertain. The evidence is also very uncertain about the effect of mesh hernia repair compared with non-mesh hernia repair on 30-day mortality (RR 1.38, 95% CI 0.58 to 3.28; 1 study, 208 participants). In summary, the results showed 70 more (from 5 fewer to 200 more) surgical site infections and 29 more (from 32 fewer to 175 more) deaths within 30 days of mesh hernia repair per 1000 participants compared with non-mesh hernia repair. The evidence is very uncertain about 90-day surgical site infections after mesh versus non-mesh hernia repair (RR 1.00, 95% CI 0.15 to 6.64; 1 study, 60 participants; very low-certainty evidence). No 30-day recurrences were recorded, and mesh hernia repair may not reduce recurrence within one year (RR 0.19, 95% CI 0.04 to 1.03; I² = 0%; 2 studies, 104 participants; very low-certainty evidence). Within 30 days of hernia repair, no meshes were removed from clean to clean-contaminated fields, but 6.7% of meshes (1 study, 208 participants) were removed from contaminated to dirty surgical fields. Among the four studies reporting 90-day mesh removal, no events occurred. We were not able to identify any studies reporting complications classified according to the Clavien-Dindo Classification or reoperation for complications within 30 days of repair.
AUTHORS' CONCLUSIONS
Our results show that in terms of 30-day surgical site infections, 30-day mortality, and hernia recurrence within one year, the evidence for the use of mesh hernia repair compared with non-mesh hernia repair in emergency groin hernia surgery is very uncertain. Unfortunately, firm conclusions cannot be drawn due to very low-certainty evidence and meta-analyses based on small-sized and low-quality studies. There is a need for future high-quality RCTs or high-quality registry-based studies if RCTs are unfeasible.
Topics: Male; Adult; Humans; Middle Aged; Aged; Female; Surgical Wound Infection; Hernia, Inguinal; Hernia, Femoral; Herniorrhaphy; Surgical Mesh; Groin
PubMed: 38009575
DOI: 10.1002/14651858.CD015160.pub2 -
European Journal of Pain (London,... Apr 2024The magnitude of placebo effects from physical and psychological 'sham' is unknown but could impact efficacy trials and treatment understanding. To quantify placebo... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The magnitude of placebo effects from physical and psychological 'sham' is unknown but could impact efficacy trials and treatment understanding. To quantify placebo effects, this systematic review of three-armed randomised controlled trials (RCTs) of physical and psychological interventions for pain compared outcomes in 'sham' control intervention and non-exposure arms.
METHODS
RCTs with treatment, 'sham' control intervention, and non-exposure groups were included, enrolling adults with any pain. A protocol was pre-registered (PROSPERO: CRD42023413324), and twelve databases searched from 2008 to July 2023. Trial methods and blinding were analysed descriptively and risk of bias assessed. Meta-analysis of pain measures at short-, medium- and long-term was performed with random-effects models of standardised mean differences (SMD).Studies were sub-grouped according to control intervention type.
RESULTS
Seventeen RCTs were included. The average short-term placebo effect was small (0.21 SMD, 0.1-0.33 95% CI, p = 0.0002, 1440 participants). It showed no heterogeneity (Tau = 0.1, I = 11%, p = 0.3), preventing meta-regression analyses of effect modifiers. However, sub-group analyses revealed larger placebo effects in manual control interventions compared to disabled devices and miscellaneous control interventions. Overall, placebo analgesia accounted for 39% of treatments' short-term effectiveness. No placebo effects were found at medium-term (7 RCTs, 381 participants) or long-term follow-up (3 RCTs, 173 participants).
CONCLUSIONS
The observed placebo analgesia has mechanistic and methodological implications, though its clinical importance may be limited. Control intervention design affects placebo effects, highlighting the importance of considering methodology in RCT interpretation. Review limitations include a small number of long-term studies and sample heterogeneity.
SIGNIFICANCE
This systematic review directly quantifies placebo effects from physical and psychological 'sham' control interventions and compares them to treatments' overall effectiveness. By doing so, the review enhances our understanding of placebo effects, their relative contribution in clinical trials, and their susceptibly to trial design. It poses further questions regarding the influence of blinding, participant expectations, and features of the therapeutic context. Overall, the insights provided by this review carry methodological significance and are important for the interpretation and synthesis of efficacy trials in this field.
Topics: Adult; Humans; Analgesia; Pain
PubMed: 37985188
DOI: 10.1002/ejp.2205 -
The Cochrane Database of Systematic... Oct 2023Overactive bladder (OAB) is a common chronic and bothersome condition. Bladder training is widely prescribed as a first-line treatment for OAB, but the efficacy has been... (Review)
Review
BACKGROUND
Overactive bladder (OAB) is a common chronic and bothersome condition. Bladder training is widely prescribed as a first-line treatment for OAB, but the efficacy has been systematically evaluated for urinary incontinence rather than OAB alone.
OBJECTIVES
To evaluate the benefits and harms of bladder training for treating adults with OAB compared to no treatment, anticholinergics, β3-adrenoceptor agonists, or pelvic floor muscle training (PFMT) alone or in combination.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 6 November 2022.
SELECTION CRITERIA
We included randomized controlled trials involving adults aged 18 years or older with non-neurogenic OAB. We excluded studies of participants whose symptoms were caused by factors outside the urinary tract (e.g. neurologic disorders, cognitive impairment, gynecologic diseases).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. participant-reported cure or improvement, 2. symptom- and condition-related quality of life (QoL), and 3.
ADVERSE EVENTS
Secondary outcomes included 4. participant-reported satisfaction, 5. number of incontinence episodes, 6. number of urgency episodes, and 7. number of micturition episodes. For the purpose of this review, we considered two time points: immediately after the treatment (early phase) and at least two months after the treatment (late phase). We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included 15 trials with 2007 participants; participants in these trials were predominantly women (89.3%). We assessed the risk of bias of results for primary and secondary outcomes, which across all studies was similar and predominantly of high risk of bias, and none were at low risk of bias. The certainty of evidence was low to very low, with some moderate, across measured outcomes. Bladder training versus no treatment: three studies involving 92 participants compared bladder training to no treatment. The evidence is very uncertain about the effects of bladder training on cure or improvement at the early phase (risk ratio (RR) 17.00, 95% confidence interval (CI) 1.13 to 256.56; 1 study, 18 participants; very low-certainty evidence). Bladder training may reduce the number of incontinence episodes (mean difference (MD) -1.86, 95% CI -3.47 to -0.25; 1 study, 14 participants; low-certainty evidence). No studies measured symptom- and condition-related QoL, number of adverse events, participant-reported satisfaction, number of urgency episodes, or number of micturition episodes in the early phase. Bladder training versus anticholinergics: seven studies (602 participants) investigated the effects of bladder training versus anticholinergic therapy. Bladder training may be more effective than anticholinergics on cure or improvement at the early phase (RR 1.37, 95% CI 1.10 to 1.70; 4 studies, 258 participants; low-certainty evidence). The evidence is very uncertain about the effects of bladder training on symptom- and condition-related QoL (standardized mean difference (SMD) -0.06, 95% CI -0.89 to 0.77; 2 studies, 117 participants; very low-certainty evidence). Although the evidence is very uncertain, there were fewer adverse events in the bladder training group than in the anticholinergics group (RR 0.03, 95% CI 0.01 to 0.17; 3 studies, 187 participants; very low-certainty evidence). The evidence is very uncertain about the effects of the number of incontinence episodes per 24 hours (MD 0.36, 95% CI -0.27 to 1.00; 2 studies, 117 participants; very low-certainty evidence), the number of urgency episodes per 24 hours (MD 0.70, 95% CI -0.62 to 2.02; 2 studies, 92 participants; very low-certainty evidence), and the number of micturition episodes per 24 hours (MD -0.35, 95% CI -1.90 to 1.20; 3 studies, 175 participants; very low-certainty evidence). No studies measured participant-reported satisfaction in the early phase. Bladder training versus PFMT: three studies involving 203 participants compared bladder training to PFMT. The evidence is very uncertain about the different effects between bladder training and PFMT on symptom- and condition-related QoL at the early phase (SMD 0.10, 95% CI -0.19 to 0.40; 2 studies, 178 participants; very low-certainty evidence). There were no adverse events in either group at the early phase (1 study, 97 participants; moderate-certainty evidence). The evidence is uncertain about the effects of the number of incontinence episodes per 24 hours (MD 0.02, 95% CI -0.35 to 0.39, 1 study, 81 participants; low-certainty evidence) and very uncertain about the number of micturition episodes per 24 hours (MD 0.10, 95% CI -1.44 to 1.64; 1 study, 81 participants; very low-certainty evidence). No studies measured cure or improvement, participant-reported satisfaction, or number of urgency episodes in the early phase. Although we were interested in studies examining bladder training versus β3-adrenoceptor agonists, in combination with β3-adrenoceptor agonists versus β3-adrenoceptor agonists alone, and in combination with PFMT versus PFMT alone, we did not identify any eligible studies for these comparisons.
AUTHORS' CONCLUSIONS
This review focused on the effect of bladder training to treat OAB. However, most of the evidence was low or very-low certainty. Based on the low- or very low-certainty evidence, bladder training may cure or improve OAB compared to no treatment. Bladder training may be more effective to cure or improve OAB than anticholinergics, and there may be fewer adverse events. There may be no difference in efficacy or safety between bladder training and PFMT. More well-designed trials are needed to reach a firm conclusion.
Topics: Female; Adult; Humans; Male; Urinary Bladder, Overactive; Quality of Life; Electric Stimulation Therapy; Urinary Bladder; Pelvic Floor; Urinary Incontinence; Cholinergic Antagonists; Receptors, Adrenergic
PubMed: 37811598
DOI: 10.1002/14651858.CD013571.pub2 -
International Journal of Stroke :... May 2024In patients surviving stroke, approximately 15% and 60% exhibit concurrent diabetes mellitus and overweight/obesity, respectively, necessitating heightened secondary... (Review)
Review
BACKGROUND
In patients surviving stroke, approximately 15% and 60% exhibit concurrent diabetes mellitus and overweight/obesity, respectively, necessitating heightened secondary prevention efforts. Despite glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrating improved outcomes for those with diabetes mellitus or obesity, their underutilization persists among eligible individuals. This systematic review and meta-analysis investigated the impact of GLP-1 RAs on stroke risk. The findings aim to optimize the implementation of this therapeutic strategy in patients surviving stroke with diabetes mellitus or obesity.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we systematically reviewed MEDLINE and Scopus until 15 November 2023. Eligible studies included randomized cardiovascular outcome trials (CVOTs) with individuals, with or without type 2 diabetes, randomized to either GLP-1 RA or placebo. The outcomes were total strokes, non-fatal strokes, and fatal strokes. Analyses were conducted using RevMan 5.4.1.
RESULTS
Among 1369 screened studies, 11 were eligible, encompassing 82,140 participants (34.6% women) with a cumulative follow-up of 247,596 person-years. In the GLP-1 RAs group, the stroke rate was significantly lower compared to placebo (RR: 0.85, 95% CI: 0.77-0.93; NNT: 200), showing no heterogeneity or interaction with administration frequency (daily vs weekly). In addition, the GLP-1 RAs group exhibited a significantly lower rate of non-fatal strokes compared to placebo (RR: 0.87, 95% CI: 0.79-0.95; NNT: 250), with no heterogeneity or interaction based on administration frequency, route (oral vs subcutaneous), or diabetes presence.
CONCLUSION
In this meta-analysis of 11 CVOTs with 82,140 participants, GLP-1 RAs demonstrated a 16% relative reduction in stroke risk compared to placebo. This finding may increase implementation of GLP-1 RAs by stroke specialists in individuals with stroke and comorbid diabetes mellitus or obesity.
DATA ACCESS STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
PubMed: 38676552
DOI: 10.1177/17474930241253988