Overall Low Risk Of Bias Research Articles

Impact of active placebo controls on estimated drug effects in randomised trials: a systematic review of trials with both active placebo and standard placebo.

An estimated 60% of pharmacological randomised trials use placebo control interventions to blind (i.e. mask) participants. However, standard placebos do not control for perceptible non-therapeutic effects (i.e. side effects) of the experimental drug, which may unblind participants. Trials rarely use active placebo controls, which contain pharmacological compounds designed to mimic the non-therapeutic experimental drug effects in order to reduce the risk of unblinding. A relevant improvement in the estimated effects of active placebo compared with standard placebo would imply that trials with standard placebo may overestimate experimental drug effects. We aimed to estimate the difference in drug effects when an experimental drug is compared with an active placebo versus a standard placebo control intervention, and to explore causes for heterogeneity. In the context of a randomised trial, this difference in drug effects can be estimated by directly comparing the effect difference between the active placebo and standard placebo intervention. We searched PubMed, CENTRAL, Embase, two other databases, and two trial registries up to October 2020. We also searched reference lists and citations and contacted trial authors. We included randomised trials that compared an active placebo versus a standard placebo intervention. We considered trials both with and without a matching experimental drug arm. We extracted data, assessed risk of bias, scored active placebos for adequacy and risk of unintended therapeutic effect, and categorised active placebos as unpleasant, neutral, or pleasant. We requested individual participant data from the authors of four cross-over trials published after 1990 and one unpublished trial registered after 1990. Our primary inverse-variance, random-effects meta-analysis used standardised mean differences (SMDs) of active versus standard placebo for participant-reported outcomes at earliest post-treatment assessment. A negative SMD favoured the active placebo. We stratified analyses by trial type (clinical or preclinical) and supplemented with sensitivity and subgroup analyses and meta-regression. In secondary analyses, we investigated observer-reported outcomes, harms, attrition, and co-intervention outcomes. We included 21 trials (1462 participants). We obtained individual participant data from four trials. Our primary analysis of participant-reported outcomes at earliest post-treatment assessment resulted in a pooled SMD of -0.08 (95% confidence interval (CI) -0.20 to 0.04; I2 = 31%; 14 trials), with no clear difference between clinical and preclinical trials. Individual participant data contributed 43% of the weight of this analysis. Two of seven sensitivity analyses found more pronounced and statistically significant differences; for example, in the five trials with low overall risk of bias, the pooled SMD was -0.24 (95% CI -0.34 to -0.13). The pooled SMD of observer-reported outcomes was similar to the primary analysis. The pooled odds ratio (OR) for harms was 3.08 (95% CI 1.56 to 6.07), and for attrition, 1.22 (95% CI 0.74 to 2.03). Co-intervention data were limited. Meta-regression found no statistically significant association with adequacy of the active placebo or risk of unintended therapeutic effect. We did not find a statistically significant difference between active and standard placebo control interventions in our primary analysis, but the result was imprecise and the CI compatible with a difference ranging from important to irrelevant. Furthermore, the result was not robust, because two sensitivity analyses produced a more pronounced and statistically significant difference. We suggest that trialists and users of information from trials carefully consider the type of placebo control intervention in trials with high risk of unblinding, such as those with pronounced non-therapeutic effects and participant-reported outcomes.

Intracycle Velocity Variation in Swimming: A Systematic Scoping Review.

Intracycle velocity variation is a swimming relevant research topic, focusing on understanding the interaction between hydrodynamic propulsive and drag forces. We have performed a systematic scoping review to map the main concepts, sources and types of evidence accomplished. Searches were conducted in the PubMed, Scopus and Web of Science databases, as well as the Biomechanics and Medicine in Swimming Symposia Proceedings Book, with manual searches, snowballing citation tracking, and external experts consultation. The eligibility criteria included competitive swimmers' intracycle velocity variation assessment of any sex, distance, pace, swimming technique and protocol. Studies' characteristics were summarized and expressed in an evidence gap map, and the risk of bias was judged using RoBANS. A total of 76 studies, corresponding to 68 trials involving 1440 swimmers (55.2 and 34.1% males and females), were included, with only 20 (29.4%) presenting an overall low risk of bias. The front crawl was the most studied swimming technique and intracycle velocity variation was assessed and quantified in several ways, leading to extremely divergent results. Researchers related intracycle velocity variation to coordination, energy cost, fatigue, technical proficiency, velocity, swimming techniques variants and force. Future studies should focus on studying backstroke, breaststroke and butterfly at high intensities, in young, youth and world-class swimmers, as well as in IVV quantification.

Persistent knee extension deficits are common after anterior cruciate ligament reconstruction: a systematic review and meta-analysis of randomised controlled trials.

Knee extension deficits complicate recovery from ACL injury and reconstruction; however, the incidence of knee extension loss is not well defined. The aim of this review was to identify the incidence of loss of extension (LOE) following ACL rupture and reconstruction, explore the definitions of knee extension deficits reported and identify prognostic factors affecting LOE incidence. A systematic search was conducted in Medline, Cochrane Library and PEDro for studies in publication up to November 2021, with no restrictions on publication year. References were screened and assessed for inclusion using predetermined eligibility criteria. Randomised controlled trials (RCTs) that quantified knee angle, loss of extension or incidence of extension deficit were included for quality assessment and data extraction. Statistical summaries were generated and meta-analyses performed in two parts to examine: (i) the probability of a datapoint being zero incidence compared to a nonzero incidence and (ii) the relationship between the predictors and nonzero LOE incidence. A sample of 15,494 studies were retrieved using the search criteria, with 53 studies meeting eligibility criteria. The pooled results from 4991 participants were included for analysis, with 4891 participants who had undergone ACLR. The proportion of included studies judged at an overall low risk of bias was small (7.8%). The observed group and study were the most important predictors for whether a datapoint reported an incidence of extension deficit. Time to follow-up (P < 0.001) and graft type (P = 0.02) were found to have a significant influence on nonzero LOE incidence (%). Covariate adjusted estimates of average LOE indicated 1 in 3 patients presenting with LOE at 12month follow-up, reducing to 1 in 4 at 2years. This review examined the definitions for the measurement and interpretation of postoperative knee extension and established the trajectory of knee extension deficit after ACL injury and reconstruction. While factors associated with loss of extension were identified, the exact trajectory of knee extension deficits was difficult to infer due to discrepancies in measurement techniques and patient variation. On average, 1 in 3 patients may present with loss of extension of at least 3 degrees at 12-month follow-up, decreasing to 1 in 4 at 2years. These results may be used by clinicians as an upper threshold for acceptable complication rates following ACLR. Future work should focus on LOE as a clinically relevant complication of ACL injury and treatment with appropriate attention to standardisation of definitions, measurements and better understanding of natural history. CRD42018092295. Level I.

Complication Rates in Osteotome and Drill Techniques in External Auditory Canal Exostoses: A Systematic Review and Meta-Analysis.

To assess and compare complication rates of symptomatic external auditory canal (EAC) exostoses treated with drill versus osteotome canalplasty. PubMed/Medline, OVID, EMBASE, Web of Science, Google Scholar. A systematic review and meta-analysis in accordance with PRISMA guidelines and standardized bias assessment using the JBI critical appraisal checklist was performed. Studies containing original outcome data on drill and osteotome canalplasty were included. The primary study outcome was complication rates. Fifteen studies were included, encompassing 1399 total patients (1788 ears) with 530 and 1258 ears in the osteotome and drill groups, respectively. Ten studies used a drill, 2 used an osteotome, and 3 used both. The most frequently reported complications were tympanic membrane (TM) perforation (osteotome group: 5.3% [95% CI: 1.7%-10.9%]; drill group: 3.8% [1.5%-7.1%]), sensorineural hearing loss (SNHL) (0.69% [0.07%-1.9%]; 4.3% [2.2%-7.0%]), and postoperative stenosis (1.1% [0.0005%-4.3%]; 4.1% [1.9%-7.0%]). Use of the osteotome was associated with a lower rate of SNHL (P < .05) and stenosis (P < .05), and a higher rate of TM perforation (P < .05). Heterogeneity of the studies included in the analyzed complications ranged from moderate to high. Level of evidence in the included studies ranged from 2b to 4 and all studies had an overall low risk of bias. While an osteotome technique may increase the risk of TM perforation, drill canaloplasty may increase the risk of SNHL and postoperative stenosis in EAC exostectomy. The exact quantity of hearing loss could not be definitively evaluated. Additional research with participant randomization is needed to assess clinical efficacy. Level 8.

Impact of Physical Rehabilitation on Bone Biomarkers in Non-Metastatic Breast Cancer Women: A Systematic Review and Meta-Analysis.

Rehabilitation might improve bone health in breast cancer (BC) patients, but the effects on bone biomarkers are still debated. Thus, this meta-analysis of randomized controlled trials (RCTs) aims at characterizing the impact of rehabilitation on bone health biomarkers in BC survivors. On 2 May 2022, PubMed, Scopus, Web of Science, Cochrane, and PEDro were systematically searched for RCTs assessing bone biomarker modifications induced by physical exercise in BC survivors. The quality assessment was performed with the Jadad scale and the Cochrane risk-of-bias tool for randomized trials (RoBv.2). Trial registration number: CRD42022329766. Ten studies were included for a total of 873 patients. The meta-analysis showed overall significant mean difference percentage decrease in collagen type 1 cross-linked N-telopeptide (NTX) serum level [ES: -11.65 (-21.13, -2.17), p = 0.02)] and an increase in bone-specific alkaline phosphatase (BSAP) levels [ES: +6.09 (1.56, 10.62). According to the Jadad scale, eight RCTs were considered high-quality studies. Four studies showed a low overall risk of bias, according to RoBv.2. The significant effects of rehabilitation on bone biomarkers suggested a possible implication for a precision medicine approach targeting bone remodeling. Future research might clarify the role of bone biomarkers monitoring in rehabilitation management of cancer treatment induced bone-loss.

Efficacy of prophylactic pre-operative desmopressin administration during functional endoscopic sinus surgery for chronic rhinosinusitis: A systematic review and meta-analysis of randomised placebo-controlled trials.

To examine the efficacy of prophylactic desmopressin versus placebo among patients undergoing functional endoscopic sinus surgery (FESS). Systematic review and meta-analysis of randomised controlled trials (RCTs). The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, Scopus, and Web of Science databases were screened from inception until 18 March 2022. Patients undergoing FESS. Primary efficacy endpoints comprised intraoperative blood loss, visual clarity, and operation time. Secondary endpoints comprised side effects. The efficacy endpoints were summarised as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Five RCTs comprising 380 patients (desmopressin=191 patients and placebo=189 patients) were included. Collectively, the included RCTs had an overall low risk of bias. The pooled results showed that the mean intraoperative blood loss (n= 5 RCTs, MD=-37.97 ml, 95% CI [-56.97, -18.96], p < .001), 5-point Boezaart scores (n= 2 RCTs, MD=-.97, 95% CI [-1.21, -.74], p < .001), and 10-point Boezaart scores (n= 2 RCTs, MD=-3.00, 95% CI [-3.61, -2.40], p < .001) were significantly reduced in favour of the desmopressin group compared with the placebo group. Operation time did not significantly differ between both groups (n= 5 RCTs, MD=-3.73 min, 95% CI [-14.65, 7.18], p= .50). No patient in both groups developed symptomatic hyponatremia (n= 3 RCTs, 194 patients) or thromboembolic events (n= 2 RCTs, 150 patients). Among patients undergoing FESS, prophylactic administration of desmopressin does not correlate with significant clinical benefits. Data on safety is limited. Future research may explore the synergistic antihaemorrhagic efficacy and safety of tranexamic acid (TXA) plus desmopressin versus TXA alone among patients undergoing FESS.

Effectiveness and cost effectiveness of palliative care interventions in people with chronic heart failure and their caregivers: a systematic review

BackgroundChronic heart failure is a common condition, and its prevalence is expected to rise significantly over the next two decades. Research demonstrates the increasing multidimensional needs of patients and caregivers. However, access to palliative care services for this population has remained poor. This systematic review was to provide an evidence synthesis of the effectiveness and cost-effectiveness of palliative care interventions for people with chronic heart failure and their caregivers.MethodsRelevant publications were identified via electronic searches of MEDLINE, Embase, PsychInfo, CINAHL, CENTRAL and HMIC from inception to June 2019. Grey literature databases, reference list, and citations of key review articles were also searched. Quality was assessed using the Revised Cochrane Risk of Bias Tool.ResultsOf the 2083 records, 18 studies were identified including 17 having randomised controlled trial (RCT) designs and one mixed methods study with an RCT component. There was significant heterogeneity in study settings, control groups, interventions delivered, and outcome measures used. The most commonly assessed outcome measures were functional status (n = 9), psychological symptoms (n = 9), disease-specific quality of life (n = 9), and physical symptom control (n = 8). The outcome measures with the greatest evidence for benefit included general and disease-specific quality of life, psychological symptom control, satisfaction with care, physical symptom control, medical utilisation, and caregiver burden. Moreover, the methodological quality of these studies was mixed, with only four having an overall low risk of bias and the remaining studies either demonstrating high risk of bias (n = 10) or showing some concerns (n = 4) due to small sample sizes and poor retention. Only two studies reported on economic costs. Both found statistically significant results showing the intervention group to be more cost effective than the control group, but the quality of both studies was at high risk of bias.ConclusionsThis review supports the role of palliative care interventions in patients with chronic heart failure and their caregivers across various outcomes, particularly quality of life and psychological wellbeing. Due to the highly heterogeneous nature of palliative care interventions, it is not possible to provide definitive recommendations as to what guise palliative care interventions should take to best support the complex care of this population. Considerable future research, particularly focusing on quality of care after death and the caregiver population, is warranted.

Efficacy of different clinical assessment measures of hyperacusis: a systematic review.

Hyperacusis is the hypersensitivity to auditory stimuli that would typically not affect those with hearing sensitivity within normal limits. The prevalence of hyperacusis in the general population has been estimated to range from 9% to 15%. There is no universally accepted definition for what defines hyperacusis amongkindred illnesses of poor sound tolerance. As a result, hyperacusis prevalence varies more, which has an impact on both assessment and treatment. This study aims to determine the efficacy of the different clinical assessment measures of hyperacusis in assessing hyperacusis through a systematic review. A review and reference of literature were done on hyperacusis, and assessment measures were used. A review of 23 articles was conducted to highlight these measures used. Most selected studies included retrospective, prospective, survey, and experimental designs. Study quality reported an overall low risk of bias. This review reports the summary and the current evidence of clinical assessment measures used for diagnosing hyperacusis. This review highlights a protocol that may be used in the clinical diagnosis of hyperacusis. It also shows the necessity to standardize and validate assessment measures for the younger population.

Diagnostic test accuracy of novel biomarkers for lupus nephritis-An overview of systematic reviews.

IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with multiorgan inflammatory involvement and a mortality rate that is 2.6-fold higher than individuals of the same age and sex in the general population. Approximately 50% of patients with SLE develop renal impairment (lupus nephritis). Delayed diagnosis of lupus nephritis is associated with a higher risk of progression to end-stage renal disease, the need for replacement therapy, and mortality. The initial clinical manifestations of lupus nephritis are often discrete or absent and are usually detected through complementary tests. Although widely used in clinical practice, their accuracy is limited. A great scientific effort has been exerted towards searching for new, more sensitive, and specific biomarkers in recent years. Some systematic reviews have individually evaluated new serum and urinary biomarkers tested in patients with lupus nephritis. This overview aimed to summarize systematic reviews on the accuracy of novel serum and urinary biomarkers for diagnosing lupus nephritis in patients with SLE, discussing how our results can guide the clinical management of the disease and the direction of research in this area.MethodsThe research question is “What is the accuracy of the new serum and urinary biomarkers studied for the diagnosis of LN in patients with SLE?”. We searched for systematic reviews of observational studies evaluating the diagnostic accuracy of new serum or urinary biomarkers of lupus nephritis. The following databases were included: PubMed, EMBASE, BIREME/LILACS, Scopus, Web of Science, and Cochrane, including gray literature found via Google Scholar and PROQUEST. Two authors assessed the reviews for inclusion, data extraction, and assessment of the risk of bias (ROBIS tool).ResultsTen SRs on the diagnostic accuracy of new serum and urinary BMs in LN were selected. The SRs evaluated 7 distinct BMs: (a) antibodies (anti-Sm, anti-RNP, and anti-C1q), (b) cytokines (TWEAK and MCP-1), (c) a chemokine (IP-10), and (d) an acute phase glycoprotein (NGAL), in a total of 20 review arms (9 that analyzed serum BMs, and 12 that analyzed BMs in urine). The population evaluated in the primary studies was predominantly adults. Two SRs included strictly adults, 5 reviews also included studies in the paediatric population, and 4 did not report the age groups. The results of the evaluation with the ROBIS tool showed that most of the reviews had a low overall risk of bias.ConclusionsThere are 10 SRs of evidence relating to the diagnostic accuracy of serum and urinary biomarkers for lupus nephritis. Among the BMs evaluated, anti-C1q, urinary MCP-1, TWEAK, and NGAL stood out, highlighting the need for additional research, especially on LN diagnostic panels, and attempting to address methodological issues within diagnostic accuracy research. This would allow for a better understanding of their usefulness and possibly validate their clinical use in the future.RegistrationThis project is registered on the International Prospective Registry of Systematic Reviews (PROSPERO) database (CRD42020196693).

Prognostic Value of Myocardial Blush Grade in ST-elevation MI: A Systematic Review and Meta-analysis

Background: Ineffective myocardial perfusion despite angiographic success after angioplasty occurs frequently and is associated with an increased risk of mortality. Hence, this study determined whether myocardial perfusion measured by myocardial blush grade (MBG) identifies ST-elevation MI (STEMI) patients at high risk for poor outcomes after successful angioplasty. Methods: The search employed strategies designed for research databases. An article was eligible if it included adults who underwent coronary angioplasty for STEMI, post-angioplasty MBG was assessed, and mortality or major adverse cardiovascular events (MACE) were determined. Risk for bias was assessed using the Quality In Prognosis Studies tool and forest plots in a Mantel-Haenszel fixed effects model were created using RevMan5.4. Results/discussion: Eight observational studies with an overall low risk of bias were included, involving 8,044 patients. MBG 0/1 with no to poor myocardial perfusion had a negative prognostic value for mortality (OR 2.68; 95% CI [2.22–3.23]) and MACE (OR 1.20; 95% CI [1.01–1.41]). Furthermore, MBG 2 with moderate myocardial perfusion and MBG 3 with normal myocardial perfusion were associated with increased survival with a logHR of 0.47 (95% CI [0.43–0.52]) and 0.20 percutaneous coronary intervention (95% CI [0.18–0.23]). These results imply MBG is a useful prognostic marker for STEMI patients. Conclusion: MBG 0/1 after primary angioplasty is a strong negative prognostic marker for long-term all-cause mortality and MACE among STEMI patients, and a post-primary angioplasty MBG of 2 or 3 is a robust prognostic marker for long-term survival.

Vagus nerve stimulation for focal seizures.

This is an updated version of the Cochrane Review published in 2015. Epilepsy is a chronic neurological disorder, characterised by recurring, unprovoked seizures. Vagus nerve stimulation (VNS) is a neuromodulatory treatment that is used as an adjunctive therapy for treating people with drug-resistant epilepsy. VNS consists of chronic, intermittent electrical stimulation of the vagus nerve, delivered by a programmable pulse generator. To evaluate the efficacy and tolerability of VNS when used as add-on treatment for people with drug-resistant focal epilepsy. For this update, we searched the Cochrane Register of Studies (CRS), and MEDLINE Ovid on 3 March 2022. We imposed no language restrictions. CRS Web includes randomised or quasi-randomised controlled trials from the Specialised Registers of Cochrane Review Groups, including Epilepsy, CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We considered parallel or cross-over, randomised, double-blind, controlled trials of VNS as add-on treatment, which compared high- and low-level stimulation (including three different stimulation paradigms: rapid, mild, and slow duty-cycle), and VNS stimulation versus no stimulation, or a different intervention. We considered adults or children with drug-resistant focal seizures who were either not eligible for surgery, or who had failed surgery. We followed standard Cochrane methods, assessing the following outcomes: 1. 50% or greater reduction in seizure frequency 2. Treatment withdrawal (any reason) 3. Adverse effects 4. Quality of life (QoL) 5. Cognition 6. Mood We did not identify any new studies for this update, therefore, the conclusions are unchanged. We included the five randomised controlled trials (RCT) from the last update, with a total of 439 participants. The baseline phase ranged from 4 to 12 weeks, and double-blind treatment phases from 12 to 20 weeks. We rated two studies at an overall low risk of bias, and three at an overall unclear risk of bias, due to lack of reported information about study design. Effective blinding of studies of VNS is difficult, due to the frequency of stimulation-related side effects, such as voice alteration. The risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.73 (95% confidence interval (CI) 1.13 to 2.64; 4 RCTs, 373 participants; moderate-certainty evidence), showing that high frequency VNS was over one and a half times more effective than low frequency VNS. The RR for treatment withdrawal was 2.56 (95% CI 0.51 to 12.71; 4 RCTs, 375 participants; low-certainty evidence). Results for the top five reported adverse events were: hoarseness RR 2.17 (99% CI 1.49 to 3.17; 3 RCTs, 330 participants; moderate-certainty evidence); cough RR 1.09 (99% CI 0.74 to 1.62; 3 RCTs, 334 participants; moderate-certainty evidence); dyspnoea RR 2.45 (99% CI 1.07 to 5.60; 3 RCTs, 312 participants; low-certainty evidence); pain RR 1.01 (99% CI 0.60 to 1.68; 2 RCTs; 312 participants; moderate-certainty evidence); paraesthesia 0.78 (99% CI 0.39 to 1.53; 2 RCTs, 312 participants; moderate-certainty evidence). Results from two studies (312 participants) showed that a small number of favourable QOL effects were associated with VNS stimulation, but results were inconclusive between high- and low-level stimulation groups. One study (198 participants) found inconclusive results between high- and low-level stimulation for cognition on all measures used. One study (114 participants) found the majority of participants showed an improvement in mood on the Montgomery-Åsberg Depression Rating Scale compared to baseline, but results between high- and low-level stimulation were inconclusive. We found no important heterogeneity between studies for any of the outcomes. VNS for focal seizures appears to be an effective and well-tolerated treatment. Results of the overall efficacy analysis show that high-level stimulation reduced the frequency of seizures better than low-level stimulation. There were very few withdrawals, which suggests that VNS is well tolerated. Adverse effects associated with implantation and stimulation were primarily hoarseness, cough, dyspnoea, pain, paraesthesia, nausea, and headache, with hoarseness and dyspnoea more likely to occur with high-level stimulation than low-level stimulation. However, the evidence for these outcomes is limited, and of moderate to low certainty. Further high-quality research is needed to fully evaluate the efficacy and tolerability of VNS for drug-resistant focal seizures.

Inhaled nitric oxide for treating pain crises in people with sickle cell disease.

Inhaled nitric oxide for treating pain crises in people with sickle cell disease.

Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure.

Adjunctive steroid therapy versus antibiotics alone for acute endophthalmitis after intraocular procedure.

Clinical non-effectiveness of clopidogrel use for peripheral artery disease in patients with CYP2C19 polymorphisms: a systematic review.

To conduct a systematic review to identify studies that assessed the association between CYP2C19 polymorphisms and clinical outcomes in peripheral artery disease (PAD) patients who took clopidogrel. We systematically searched Ovid EMBASE, PubMed, and Web of Science from November 1997 (inception) to September 2020. We included observational studies evaluating how CYP2C19 polymorphism is associated with clopidogrel's effectiveness and safety among patients with PAD. We extracted relevant information details from eligible studies (e.g., study type, patient population, study outcomes). We used the Risk of Bias in Non-randomized Studies-of Interventions (ROBINS-I) Tool to assess the risk of bias for included observational studies. The outcomes of interest were the effectiveness and safety of clopidogrel. The effectiveness outcomes included clinical ineffectiveness (e.g., restenosis). The safety outcomes included bleeding and death related to the use of clopidogrel. We identified four observational studies with a sample size ranging from 50 to 278. Outcomes and comparison groups of the studies varied. Three studies (75%) had an overall low risk of bias. All included studies demonstrated that carrying CYP2C19 loss of function (LOF) alleles was significantly associated with reduced clinical effectiveness and safety of clopidogrel. Our systematic review showed an association between CYP2C19 LOF alleles and reduced functions of clopidogrel. The use of CYP2C19 testing in PAD patients prescribed clopidogrel may help improve the clinical outcomes. However, based on the limited evidence, there is a need for randomized clinical trials in PAD patients to test both the effectiveness and safety outcomes of clopidogrel.

Preliminary efficacy of optimal pharmacotherapy and patient views in multiple myeloma.

e20006 Background: As new agents are approved for multiple myeloma (MM) and existing drugs become generic, treatments that represent optimal use of healthcare funds need to be reassessed. A therapeutic review was initiated to compare the clinical and cost-effectiveness of treatments for newly diagnosed (NDMM) patients who are ineligible for stem cell transplantation and those who are relapsed and/or are refractory (RRMM). This abstract reports on the clinical efficacy of treatments for both populations along with patient experiences, expectations, and perspectives of treatment for MM. Methods: A systematic literature search of randomized controlled phase III trials (RCTs), published between January 1996 and April 2021, that met the eligibility criteria in either population were included. Two network meta-analyses (NMA), one per population, were conducted to compare the efficacy across treatments for the primary endpoint of progression-free survival (PFS). PFS was defined as the time from randomization to either disease progression or death. A random-effects model was used in both populations to estimate the hazard ratio (HR) and 95% credible intervals (CrIs) for PFS. Myeloma Canada conducted seven surveys between January 2016 and May 2021 that addressed expectations when selecting a treatment option in MM. A literature search of qualitative studies published between January 2016 and May 2021 was conducted on patients’ perspectives and experiences on treatment decisions in MM. Results: There were 29 RCTs in each NMA with an overall low risk of bias. The NDMM NMA identified 11 regimens that had numerically lower hazards for PFS compared to lenalidomide + dexamethasone (Rd), with HRs ranging from 0.38 to 0.99. The RRMM network showed 15 regimens that had numerically lower hazards for PFS compared to Rd, with HRs ranging from 0.44 to 0.99. Due to the wide 95% CrIs, conclusions on differences in PFS for each population are limited. Myeloma Canada collated data from 2,297 survey respondents. Ten qualitative studies of low to moderate quality were included. The survey data and qualitative studies found that choosing a treatment must involve a holistic approach beyond the efficacy of a therapy. Conclusions: The uncertainty in both NMAs limit firm conclusions on differences in PFS across treatment options in each population. Among the survey respondents, socioeconomic status was unclear which may influence patients’ expectations and preferences for treatment decisions in MM. Insufficient reporting in the qualitative studies makes it unclear how a patient’s treatment decisions changes over time. For Canadian payers to optimize the funding of treatment options available in MM, the results from the NMAs combined with Canadian real-world evidence will inform the development of an economic model to assess the cost-effectiveness of treatment sequences in NDMM.

Artificial Intelligence in Laryngeal Endoscopy: Systematic Review and Meta-Analysis.

Background: Early diagnosis of laryngeal lesions is necessary to begin treatment of patients as soon as possible to preserve optimal organ functions. Imaging examinations are often aided by artificial intelligence (AI) to improve quality and facilitate appropriate diagnosis. The aim of this study is to investigate diagnostic utility of AI in laryngeal endoscopy. Methods: Five databases were searched for studies implementing artificial intelligence (AI) enhanced models assessing images of laryngeal lesions taken during laryngeal endoscopy. Outcomes were analyzed in terms of accuracy, sensitivity, and specificity. Results: All 11 studies included presented an overall low risk of bias. The overall accuracy of AI models was very high (from 0.806 to 0.997). The accuracy was significantly higher in studies using a larger database. The pooled sensitivity and specificity for identification of healthy laryngeal tissue were 0.91 and 0.97, respectively. The same values for differentiation between benign and malignant lesions were 0.91 and 0.94, respectively. The comparison of the effectiveness of AI models assessing narrow band imaging and white light endoscopy images revealed no statistically significant differences (p = 0.409 and 0.914). Conclusion: In assessing images of laryngeal lesions, AI demonstrates extraordinarily high accuracy, sensitivity, and specificity.

Pleasurable ways to spontaneously expulse distal ureteral stones: A systematic review and meta-analysis of randomized controlled trials

ABSTRACT Introduction Numerous non-invasive ways of managing distal ureteral stones have been recommended, such as administering treatments to inhibit receptors responsible for ureteral tone and peristaltic movement frequency. Nitric oxide, which is released during penile erection, causes smooth muscle relaxation by inhibiting the non-adrenergic non-cholinergic (NANC) nerves of the distal ureter and ureterovesical junction. Bladder neck contraction followed by relaxation, occurring during orgasm and ejaculation could also facilitate the passage of stones. However, the exact role of sexual activities involving these mechanisms has yet to be established. Objective This review aimed to evaluate the efficacy of sexual acts, including sexual intercourse and masturbation, to promote distal ureteral stones expulsion based on the findings of relevant randomized controlled trials (RCT)s. Methods A systematic search adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was performed in the Embase, Scopus, and Medline databases in July 2021. The initial search generated 50 articles. The articles were screened based on the eligibility criteria. Their quality was assessed using the Cochrane Risk of Bias (RoB) tool 2 for randomized trials. Measured outcomes included stone expulsion rate, expulsion time, analgesic injections frequency, and the need for a ureteroscopic (URS) lithotripsy. A fixed effects model was used for analyzing parameters with homogeneity among studies, whereas a random effects model was used for heterogenous studies. The odds ratio (OR) and mean difference (MD) among studies were displayed in forest plots using the Review Manager software version 5.4.1. Results A total of five RCTs with an overall low risk of bias, consisting of 406 subjects, were included in this review. Four studies evaluated sexual intercourse and one study evaluated masturbation. Both interventions were instructed to be performed for three to four times a week. The stone expulsion rate was higher in the sexual activity group compared to the control group at the two-week follow-up (OR 5.77 95%CI 3.70 - 9.01, p&amp;lt;0.00001) and four-week follow-up (OR 4.44 95%CI 2.73 - 7.23, p&amp;lt;0.00001) with a significantly lower expulsion time of the sexual activity group (MD -3.79 95% CI -6.38 - -1.20, p=0.004). The number of subjects requiring additional analgesic injections (MD -0.62 95% CI -1.03 - -0.21, p=0.003) and URS lithotripsy (OR 0.22 95% CI 0.13 – 0.37, p&amp;lt;0.00001) was also lower in the sexual activity group compared to the control group. Conclusions Performing sexual intercourse or masturbation for three to four times a week is beneficial for promoting spontaneous expulsion of distal ureteral stones. It could also reduce the use of analgesic injections and the need for a URS lithotripsy.

P289 The effectiveness of interventions to reduce psychological distress in patients with autoimmune rheumatic conditions: a systematic review of effectiveness

Abstract Background/Aims Autoimmune rheumatic conditions are multisystem chronic disorders associated with increased psychological distress. Consequences include poor medication adherence and high levels of disease activity. Psychological interventions may reduce distress and change health behaviours. We aimed to determine the effectiveness of interventions for psychological distress in patients with autoimmune rheumatic conditions. Methods This was a systematic review of effectiveness which included randomised controlled trials of psychological interventions in adults with autoimmune rheumatic conditions. We searched MEDLINE, BNI, CINAHL, EMBASE, EMCARE, PsycINFO, NICE Evidence and The Cochrane Library. Two reviewers screened titles and abstracts and assessed the methodological quality of the included studies using Cochrane Risk of Bias 2 tool. Data were extracted by one reviewer and checked by a second. In each study, the effectiveness data were determined by extracting the reported means (and standard deviation) for each group and calculating the standardised mean differences using RevMan 5.4 software (The Cochrane Collaboration, 2020). The data on primary outcomes (anxiety and depression) are reported here. Results The search identified 96 studies. The process of screening and assessing for eligibility resulted in 20 studies for inclusion. Of these, one study had an overall low risk of bias and 19 had ‘some concerns’, mainly due to inadequate blinding and no information on pre-specified analysis plan. Only eight studies reported the effects on anxiety and 10 studies reported on depression. These studies included 919 patients in total. Most interventions were based on cognitive behavioural therapy and the context of delivery ranged from face-to-face individualised treatment to online group therapy. They often included education on topics such as stress and fatigue. Interventions often trained participants to develop skills in relaxation, problem-solving, and thought reframing. Goal setting and action planning were common to help participants make behaviour changes and apply their learning. Table 1 summarises disease group, type of intervention, comparator, outcome measure, and effects. Conclusion Conclusion: Most interventions were effective in reducing anxiety and depression in autoimmune rheumatic conditions. However, given the clinical heterogeneity and ‘some concerns’ about the included quality of studies, more work is needed to understand the mechanisms of the intervention effectiveness. Disclosure J. Hulley-Mills: None. C. Sliverthorne: None. B. Jones: None. J. Hooper: None. J. Robson: None. E. Dures: None. J. Daniels: None. M. Thompson: None. M. Ndosi: None.

Two-way text message interventions and healthcare outcomes in Africa: Systematic review of randomized trials with meta-analyses on appointment attendance and medicine adherence.

The growing access to mobile phones in Africa has led to an increase in mobile health interventions, including an increasing number of two-way text message interventions. However, their effect on healthcare outcomes in an African context is uncertain. This systematic review aims to landscape randomized trials involving two-way text message interventions and estimate their effect on healthcare outcomes. We searched Medline, Embase, Cochrane Central Register of Controlled Trials, The Global Health Library (up to 12 August 2021) and trial registries (up to 24 April 2020). Published and unpublished trials conducted in Africa comparing two-way text message interventions with standard care and/or one-way text message interventions were included. Trials that reported dichotomous effect estimates on healthcare appointment attendance and/or medicine adherence were assessed for risk of bias and included in meta-analyses. Results of other outcomes were reported descriptively. We included 31 trials (28,563 participants) all set in Sub-Saharan Africa with a wide range of clinical conditions. Overall, ten different trials were included in the primary meta-analyses, and two of these had data on both medicine adherence and appointment attendance. An additional two trials were included in sensitivity analyses. Of the 12 included trials, three were judged as overall low risk of bias and nine as overall high risk of bias trials. Two-way text messages did not improve appointment attendance, RR: 1.03; 95% CI: 0.95-1.12, I2 = 53% (5 trials, 4374 participants) but improved medicine adherence compared to standard care, RR: 1.14, 95% CI: 1.07-1.21, I2 = 8% (6 trials, 2783 participants). Two-way text messages seemingly improve medicine adherence but has an uncertain effect on appointment attendance compared to standard care. PROSPERO CRD42020175810.

Assessment of the reporting quality of resistance training interventions in randomised controlled trials for lower limb tendinopathy: A systematic review

Objectives 1. To describe what exercises and intervention variables are used in resistance training interventions in randomised controlled trials for lower limb tendinopathy 2. To assess completeness of reporting as assessed by the Consensus on Exercise Reporting Template (CERT) and the Toigo and Boutellier framework. 3. To assess the implementation of scientific resistance training principles. 4. To assess therapeutic quality of exercise interventions with the i-CONTENT tool. Data sources We searched MEDLINE, CINAHL, AMED, EMBase, SPORTDiscus, and the Cochrane library databases. Review methods Systematic review of randomised controlled trials that reported using resistance exercises for lower limb tendinopathies. Results We included 109 RCTs. Eccentric heel drops were the most common exercise (43 studies), followed by isotonic heel raises (21), and single leg eccentric decline squats (18). Reporting of exercise descriptor items from the Toigo and Boutellier framework ranged from 0–13, with an average score of 9/13, and only 7 studies achieved a full 13/13. Reporting of items from the CERT ranged from 0–18, with an average score of 14/19. No study achieved a full 19/19, however 5 achieved 18/19. Scoring for resistance training principles ranged from 1–10, with only 11 studies achieving 10/10. Reporting across studies for the i-CONTENT tool ranged from 2–7, with an average score of 5 across included studies. A total of 19 studies achieved a full 7/7 score. Less than 50% of studies achieved an overall low risk of bias, highlighting the methodological concerns throughout studies. Conclusion The reporting of exercise descriptors and intervention content was generally high across RCTs for lower limb tendinopathy, with most allowing exercise replication. However, reporting for some tendinopathies and content items such as adherence was poor, limiting optimal translation to clinical practice.