Factors Predicting Nonadherence to Treatment Recommendations for Patients With Chronic Low Back Pain in India: A Cross-Sectional Survey.

OBJECTIVE: The purpose of this study was to examine patients' expectations and factors that influence adherence to physiotherapists' treatment recommendations on chronic low back pain (CLBP). METHOD: One hundred and forty seven patients with CLBP were included in this study. Predictive indicators including demographic information, views, expectations, and opinions regarding the health status and treatment expectations of patients were derived from questionnaires. The dependent outcome variables were the absence of trust in treatment recommendations provided by physiotherapists, the anticipation of treatment recommendations based on patient expectations, and the resistance to modifying expectations despite efforts by physiotherapists to persuade otherwise. The study was carried out between April 2022 and January 2023 in 2 regions located in India. RESULTS: Multivariate regression analyses show that age, expectations about diagnosis, preference for passive therapies and medical care, and information seeking behavior emerged as independent predictors of a lack of trust in physiotherapists' treatment recommendations. The information-seeking behavior of the patients' alone predicted the anticipation of treatment recommendations based on patient expectations and the reluctance to alter those expectations despite the physiotherapists' persuasion. CONCLUSION: Our results suggest that information seeking behavior is the most consistent independent predictor of treatment expectations that will align with physiotherapist recommendations. This indicates the importance of screening for such factors and the importance of patient education to optimize the management of CLBP. However, larger studies incorporating all variables associated with patient expectations in similar patient populations are needed to confirm these results.

Impact of total occlusion of culprit artery in acute non-ST elevation myocardial infarction: a systematic review and meta-analysis.

AIMS: Total occlusion (TO) of the culprit artery usually presents with ST-elevation myocardial infarction. A subset of patients with TO present as non-ST segment elevation myocardial infarction (NSTEMI) without classic ST-elevation on the electrocardiogram. This may lead to delay in identification of these patients and further management. We performed a meta-analysis to estimate the difference in outcomes between totally occluded and non-occluded culprit arteries in patients with NSTEMI. METHODS AND RESULTS: Our literature search yielded seven studies with 40 777 patients. The outcomes assessed were clinical presentation (Killip class), left ventricular ejection fraction, time to angiography, major cardiac adverse events (MACE) and all-cause mortality. The generic inverse or Mantel-Haenszel method was used to pool relevant outcomes and the mean difference (MD) or relative risk (RR) was calculated. A total of 10 415 (25.5%) patients had an occluded culprit artery with a predominant infero-lateral distribution (40% right coronary and 33% left circumflex artery). There was an increased risk of both MACE (short-term RR: 1.41; CI: 1.17, 1.70; P = 0.0003; I2 = 26%; medium- to long-term RR: 1.32; CI: 1.11, 1.56; P = 0.001; I2 = 25%) and all-cause mortality (short-term RR: 1.67; CI: 1.31, 2.13; P < 0.0001; I2 = 41%; medium to long-term RR: 1.42; CI: 1.08, 1.86; P = 0.01; I2 = 32%) with TO of the culprit artery. CONCLUSION: Our meta-analysis suggests that patients with NSTEMI who demonstrate a totally occluded culprit vessel on coronary angiography are at higher risk of mortality and major adverse cardiac events. Better risk stratification tools are needed to identify such high-risk acute coronary syndrome patients to facilitate earlier revascularization and potentially to improve outcomes.

Mortality Effect of ICD in Primary Prevention of Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Implantation of an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) is controversial in view of the recent DANISH trial which suggested no benefit with ICD for primary prevention in patients with non-ischemic cardiomyopathy (NICMP). METHODS: We conducted a meta-analysis of randomized control trials studying the role of ICD in primary prevention of SCD in patients with NICMP. Only six studies were identified after the application of inclusion/exclusion criteria. RESULTS: Pooling of these randomized trials showed a statistically significant benefit of using ICDs in patients with NICMP [OR 0.76 (0.64 - 0.91), I2 = 0%]. Sensitivity analysis did not show a statistically significant mortality benefit of ICD in NICMP in trials which had adequate beta blocker, ACE/ARB and aldosterone receptor blocker (ALD-RB) use [OR 0.70 (0.41, 1.19), I2 = 70%]. CONCLUSION: The DANISH trial's failure to show mortality benefit may be due to the significant number of patients who had CRT. Our meta-analysis studied the independent effect of ICDs and showed them to be associated with net mortality benefits in patients who are not on optimal guideline directed medical therapy; especially the patients not on ALD-RB.

Left dominant circulation increases mortality in acute coronary syndrome: A systematic review and meta-analysis of observational studies involving 255,718 patients.

BACKGROUND: The effect of coronary dominance on mortality in patients with acute coronary syndrome (ACS) remains unclear. We performed a meta-analysis to evaluate the effect of coronary dominance in patients with ACS. METHODS: Several data sources were searched for studies which compared studies that compared outcomes between right and left dominant coronary circulation in patients with ACS. The measured outcomes were in-hospital, 30-day or long-term mortality as reported in individual studies. The Generic inverse variance method was used in a random-effects model to pool mortality as an outcome. Odds ratio (OR) was calculated for mortality in the left dominant circulation relative to a right dominant one. Sub-group analysis was performed after stratification of mortality by duration. RESULTS: A total of 5 studies with 8 comparisons and 255,718 participants revealed an increased risk mortality (OR = 1.27 (95% CI: 1.13 - 1.42; P < 0.0001; I(2) = 34%). Sub-group analysis revealed that the increased risk was evident at all time periods after the ACS; in-hospital (OR = 1.37; 95% CI: 1.07 - 1.76; P = 0.01; I(2) = 50%), at 30 days (OR = 1.69; 95% CI: 1.14 - 2.52; P = 0.009; I(2) = 18%) and long-term (OR = 1.15; 95% CI: 1.03 - 1.28; P = 0.01; I(2) = 0%). CONCLUSIONS: In this meta-analysis we found that there is an increased risk of mortality with LD coronary circulation in patients with ACS. The knowledge of coronary dominance may not only be helpful as an incremental prognostic factor beyond pre-procedural risk scores in all patients with ACS, but may also aid in clinical decision making in a subset of these patients. © 2015 Wiley Periodicals, Inc.

Azithromycin and Risk of Cardiovascular Death: A Meta-Analytic Review of Observational Studies.

Recent evidence, though conflicting, suggests an association between azithromycin use and cardiovascular death. We conducted a systematic review and meta-analysis to evaluate the effect of azithromycin on risk of death. Multiple databases were searched. Authors independently screened and extracted the data from studies. Primary outcome of interest was risk of death (cardiovascular and/or noncardiovascular). Subgroup analyses were conducted to explore the source of a possible heterogeneity. Random effects model meta-analysis and hazards ratio (HR) were used to pool the data and calculate the overall effect estimate, respectively. Eight hundred twenty-eight citations, identified with 5 cohort studies that involved 2,246,178 episodes of azithromycin use, met our inclusion criteria. Azithromycin use was not associated with higher risk of death from any cause, HR = 0.99 [confidence interval (CI), 0.82-1.19], I = 54%, or cardiovascular cause, HR = 1.15 (CI, 0.66-2.00), I = 64%, but there was a moderate degree of heterogeneity. Subgroup analyses have shown no increased risk of death with azithromycin use in younger population with zero degree of heterogeneity, HR = 0.85 (CI, 0.66-1.09), I = 0%. However, current use of azithromycin (within 1-5 days of therapy) was associated with a higher risk of death among older population with mild degree of heterogeneity, HR = 1.64 (CI, 1.23-2.19), I = 4%. In summary, azithromycin use was not associated with higher risk of death particularly in younger population. Nevertheless, older population might be at higher risk of death with current use of azithromycin, and an alternative therapy should probably be considered.

Incidental myocardial infarct on conventional nongated CT: a review of the spectrum of findings with gated CT and cardiac MRI correlation.

OBJECTIVE: Myocardial infarctions (MIs) are frequently evident on routine chest or abdominal CT, even when studies are not performed for cardiac-specific indications. However, the telltale signs of an MI may be easily overlooked. Herein, we present the spectrum of appearances of MIs, including areas of fat attenuation, myocardial calcifications, focal areas of wall thinning or aneurysm formation, and perfusion abnormalities. Thrombi, especially when present at the apex of the left ventricle, may also suggest an MI. CONCLUSION: The increased use of CT in the evaluation of patients for a variety of indications gives the radiologist the unique opportunity to recognize findings consistent with MI in patients who may not have a prior diagnosis of ischemic heart disease.

Random forest analysis reveals taxa predictive of Prunus replant disease in peach root microbiomes.

Successive plantings of Prunus species produce suboptimal growth and yield in many California soils due to a poorly understood soilborne disease complex, Prunus replant disease (PRD). We explored the hypothesis that PRD is mediated by microbial taxa in roots of Nemaguard peach, a rootstock for almond and other stone fruits. In a greenhouse bioassay, portions of 10 replant soils were treated with fumigation or pasteurization or left untreated as a control before being planted with peach seedlings. Ten weeks after planting, seedlings were considered PRD-affected if their top fresh weights in the control were significantly reduced, compared to the weights in pasteurization and fumigation treatments; plants with equivalent top weights in all treatments were considered to be non-affected. The roots were washed from the soil, frozen, extracted for total DNA, and used for metabarcoding of rRNA gene amplicons from bacteria, fungi, and oomycetes. High-throughput amplicon sequencing revealed that root microbial community shifts resulted from preplant treatments, and specific taxa were associated with PRD induction among controls. Random forest (RF) analysis discriminated effectively between PRD-affected and non-affected root communities. Among the 30 RF top-ranked amplicon sequence variant (ASV) predictors, 26 were bacteria, two were oomycetes, and two were fungi. Among them, only Streptomyces scabiei, Steroidobacter denitrificans, Streptomyces bobili, and Pythium mamillatum had root abundances ≥5% that were either associated positively (former two ASVs) or negatively (latter two) with PRD. Thus, our findings were consistent with microbial mediation of PRD in roots and suggested taxa that may be involved in the mediation.

Characterization of soils conducive and non-conducive to Prunus replant disease.

Successive orchard plantings of almond and other Prunus species exhibit reduced growth and yield in many California soils. This phenomenon, known as Prunus replant disease (PRD), can be prevented by preplant soil fumigation or anaerobic soil disinfestation, but its etiology is poorly understood and its incidence and severity are hard to predict. We report here on relationships among physicochemical variables, microbial community structure, and PRD induction in 25 diverse replant soils from California. In a greenhouse bioassay, soil was considered to be "PRD-inducing" when growth of peach seedlings in it was significantly increased by preplant fumigation and pasteurization, compared to an untreated control. PRD was induced in 18 of the 25 soils, and PRD severity correlated positively with soil exchangeable-K, pH, %clay, total %N, and electrical conductivity. The structure of bacterial, fungal, and oomycete communities differed significantly between the PRD-inducing and non-inducing soils, based on PERMANOVA of Bray Curtis dissimilarities. Bacterial class MB-A2-108 of phylum Actinobacteria had high relative abundances among PRD-inducing soils, while Bacteroidia were relatively abundant among non-inducing soils. Among fungi, many ASVs classified only to kingdom level were relatively abundant among PRD-inducing soils whereas ASVs of Trichoderma were relatively abundant among non-inducing soils. Random forest classification effectively discriminated between PRD-inducing and non-inducing soils, revealing many bacterial ASVs with high explanatory values. Random forest regression effectively accounted for PRD severity, with soil exchangeable-K and pH having high predictive value. Our work revealed several biotic and abiotic variables worthy of further examination in PRD etiology.

Childhood esophagitis: then and now.

OBJECTIVES: It is not known whether the prevalence of childhood esophagitis has changed over time. In children, the intraepithelial eosinophil is considered the hallmark of esophageal inflammation. This study compares the prevalence of intraepithelial eosinophils in esophageal biopsies obtained from 1980-1988 and 2001-2002. PATIENTS AND METHODS: This study reevaluated all of the esophageal biopsies obtained at a single center during 2 periods: 1980-1988 and 2001-2002. Histological appearances were characterized and eosinophils per high-power field were quantified. RESULTS: In total, 1058 esophageal biopsies from 510 subjects were reviewed. Between 1980 and 1988, 247 biopsies from 188 subjects were evaluated. Of these, 62 subjects met the criteria for esophageal disease, and 106 had no specific pathological changes. Between 2001 and 2002, 811 biopsies from 322 subjects were evaluated. Of these, 132 subjects met the criteria for esophageal disease, and 182 had no specific pathological changes. A statistically significant increase in the prevalence of esophageal inflammatory disease was observed comparing the recent group with the remote group. Eosinophilic esophagitis is thought to be distinct from other types of esophagitis in pathogenesis, epidemiology, histology, and treatment. Some suggest the prevalence of eosinophilic esophagitis has increased in recent years. We sought evidence for an increase in histological changes consistent with eosinophilic esophagitis. No matter whether histology consistent with eosinophilic esophagitis was defined as 25, 20, 15, or 10 eosinophils per high-power field, no increase in prevalence was found. CONCLUSIONS: This study demonstrated no evidence for a change in the density of eosinophilic infiltrates in esophageal biopsies during the 22-year study period. The study showed a statistically significant increase in the prevalence of esophageal inflammatory disease across the same period.

Vascular Physics: Explaining the Nature of Escape Veins and When to Use Endovascular Ligation.

Small branching veins that arise from the venous outflow of surgical arterial-venous fistulas (AVFs) are frequently seen during fistulograms performed to evaluate for poorly functioning AVFs. It is hypothesized that the presence of escape veins can decrease the performance of native AVFs during hemodialysis by diverting flow. Though interventional methods for exclusion of escape veins are effective, the mechanism of disruption these small branching vessels cause on flow through AVFs is unknown. Furthermore, an objective method for identifying escape veins that cause significantly diminished venous flow has not been defined. The following describes the detrimental nature of escape veins using tenants of physics and electrical circuitry. Subsequently, the proceeding study shows the identification of small branching escape veins in patients during fistulography. Intravascular pressure measurements were obtained proximal and distal to the ostium of the offending collaterals in these patients. Escape veins causing a pressure gradient of at least 5 mmHg were treated, and pressure measurements were repeated following intervention. The patients were entered into a database and hemodialysis blood flow rates were monitored to determine if escape vein intervention increased AVF performance.

Comparison of Causes and Associated Costs of 30-Day Readmission of Transcatheter Implantation Versus Surgical Aortic Valve Replacement in the United States (A National Readmission Database Study).

Our current knowledge about comparative differences in 30-day readmissions and the impact of readmissions on overall costs after transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) is largely derived from clinical trials. The objectives of this study were to compare readmissions and costs for TAVI and SAVR in a nationally representative population-based sample. The Healthcare Cost and Utilization Project's National Readmission Database was used for the study. Hierarchical multivariable regression analyses were used to examine differences in the propensity score 1:1 matched cohort. The matched cohort included 4,682 patients who survived index procedures done from January through November 2013. Compared with SAVR, the rate of 30-day readmission was not significantly different for endovascular TAVI (16% vs 18%; p = 0.19); and was higher for the transapical TAVI (22% vs 17%; p <0.01) group. The 30-day cumulative costs were higher for the 2 endovascular TAVI ($51,025 vs $46,228; p = 0.03) and transapical TAVI ($59,575 vs $45,792; p <0.01). In multivariable analyses, the risk of 30-day readmission was similar for endovascular TAVI (odds ratio [OR] 0.93; 95% confidence interval [CI] 0.78 to 1.12) and was 27% higher for transapical TAVI (OR 1.27; 95% CI 1.02 to 1.57). Cumulative costs (index plus readmission costs) were 13% (ß 0.13; 95% CI 0.10 to 0.15) and 19% (ß 0.19; 95% CI 0.16 to 0.23) higher for the endovascular TAVI and transapical TAVI, respectively. In conclusion, the rate of readmissions was similar for endovascular TAVI and SAVR but the costs were 26% higher for TAVI than for SAVR.

Meta-analysis of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Left Main Coronary Artery Disease.

Despite the increase in use of percutaneous coronary intervention (PCI) in left main coronary disease, its efficacy compared with coronary artery bypass grafting (CABG) is unclear. We performed a meta-analysis of randomized controlled trials to assess the optimal revascularization strategy. Our search yielded 8 studies reporting relevant outcomes that were pooled using the inverse variance method, and the hazard ratio (HR) was calculated. The primary outcome was all-cause mortality, myocardial infarction (MI), or stroke (major adverse cardiac events [MACE]), and the secondary outcome was death/MI/stroke/repeat revascularization (expanded MACE). Differences in outcomes classified by follow-up duration (early: 0 to 1 year; late: 3 to 5 years) or anatomical complexity of coronary artery disease (SYNTAX score) were investigated. Our results suggest no difference in either early or late MACE (early: HR 0.81; 95% confidence interval [CI] 0.63 to 1.05; late: HR 1.12; 95% CI 0.80 to 1.56) or expanded MACE (early: HR 1.03; 95% CI 0.69 to 1.52; late: HR 1.16; 95% CI 0.95 to 1.43) between the 2 groups. There was an increased risk of expanded MACE with a high SYNTAX score for PCI (HR 1.47; 95% CI 1.13 to 1.92) at late follow-up. There were comparable rates of all-cause mortality and nonprocedural MI between the 2 groups with increased rates of repeat revascularization with PCI throughout the follow-up and higher rates of stroke with coronary artery bypass grafting early in the follow-up period. In conclusion, our analysis suggests that CABG may be preferable in patients with left main disease and high SYNTAX scores, assuming they are at low surgical risk, and PCI may be an acceptable alternative in patients with low-intermediate SYNTAX scores.

Stent thrombosis with bioabsorbable polymer drug-eluting stents: insights from the Food and Drug Administration database.

BACKGROUND: SYNERGY, a bioabsorbable polymer-based, everolimus-eluting stent (BP-DES), recently received regulatory approval in the USA for use in percutaneous coronary interventions. Yet, information on the safety of BP-DES in routine clinical practice is limited. Our aim was to compare the safety of the recently approved BP-DES with current durable polymer drug-eluting stents (DP-DES) by analyzing adverse events, namely, stent thrombosis (ST), reported to the Manufacturer and User Facility Device Experience (MAUDE) database. MATERIALS AND METHODS: The MAUDE database requires nationwide mandatory notification for adverse events on devices approved for clinical use. This database was searched for adverse events reported between 1 October 2015 and 25 December 2016, encountered after the placement of either BP-DES or DP-DES. Only those adverse events were included where the exposure period to the stents was comparable after the index procedure. Of all the adverse events reported, the event of interest was ST. RESULTS: A total of 951 adverse events were reported. ST occurred in 48/951 of all events, 31/309 and 17/642 when BP-DES or DP-DES were used, respectively (P=0.00001). Of the 31 ST events with BP-DES, 68% (21/31) occurred within less than or equal to 24 h of the index procedure and 52% (16/31) occurred within less than or equal to 2 h. CONCLUSION: Our results raise the possibility of an increased risk of ST, particularly early ST (within 24 h), with the recently approved BP-DES. However, because of the inherent limitations of reporting within the MAUDE database, these data merely highlight a potential need for additional surveillance and randomized trials to assess further the safety of the bioabsorbable platform.

Mechanical Thrombectomy for Middle Cerebral Artery Division Occlusions: A Systematic Review and Meta-Analysis.

BACKGROUND: Middle cerebral artery division (M2) occlusion was significantly underrepresented in recent mechanical thrombectomy (MT) randomized controlled trials, and the approach to this disease remains heterogeneous. OBJECTIVE: To conduct a systematic review and meta-analysis of outcomes at 90 days among patients undergoing MT for M2 middle cerebral artery (MCA) occlusions. METHODS: Five clinical databases were searched from inception through September 2016. Observational studies reporting 90-day modified Rankin Scale scores for patients undergoing MT for M2 MCA occlusions with an M1 MCA control group were selected. The primary outcome of interest was good clinical outcome 90 days after MT of an M1 or M2 MCA occlusion. Secondary outcomes of interest included mortality and excellent clinical outcome, recanalization rates, significant intracerebral hemorrhage, and procedural complications. RESULTS: A total of 323 publications were identified, and 237 potentially relevant articles were screened. Six studies were included in the analysis (M1 = 1,203, M2 = 258; total n = 1,461). We found no significant differences in good clinical outcomes (1.10 [95% CI, 0.83-1.44]), excellent clinical outcomes (1.07 [0.65-1.79]), mortality at 3 months (0.85 [0.58-1.24]), recanalization rates (1.06 [0.32-3.48]), and significant intracranial hemorrhage (1.19 [0.61-2.30]). CONCLUSIONS: MT of M2 MCA occlusions is as safe as that of main trunk MCA occlusions, and comparable in terms of clinical outcomes and hemorrhagic complications. Randomized clinical trials are needed to assess the impact of MT in patients with M2 occlusions, given that M1 MCA occlusions have different natural histories than M2 occlusions.

Thirty-Day Readmission Rate and Costs After Percutaneous Coronary Intervention in the United States: A National Readmission Database Analysis.

BACKGROUND: The association of short-term readmissions after percutaneous coronary intervention (PCI) on healthcare costs has not been well studied. METHODS AND RESULTS: The Healthcare Cost and Utilization Project National Readmission Database encompassing 722 US hospitals was used to identify index PCI cases in patients ≥18 years old. Hierarchical regression analyses were used to examine the factors associated with risk of 30-day readmission and higher cumulative costs. We evaluated 206 869 hospitalized patients who survived to discharge after PCI from January through November 2013 and analyzed readmissions over 30 days after discharge. A total of 24 889 patients (12%) were readmitted within 30 days, with rates ranging from 6% to 17% across hospitals. Among the readmitted patients, 13% had PCI, 2% had coronary artery bypass surgery, and 3% died during the readmission. The most common reasons for readmission included nonspecific chest pain/angina (24%) and heart failure (11%). Mean cumulative costs were higher for those with readmissions ($39 634 versus $22 058; P<0.001). The multivariable analyses showed that readmission increased the log10 cumulative costs by 45% (ß: 0.445; P<0.001). There was no significant difference in cumulative costs by the type of insurance. CONCLUSIONS: In a national sample of inpatient PCI cases, 30-day readmissions were associated with a significant increase in cumulative costs. The majority of readmissions were because of low-risk chest pain that did not require any intervention. Ongoing effort is warranted to recognize and mitigate potentially preventable post-PCI readmissions.

Complete Chloroplast Genome of Nicotiana otophora and its Comparison with Related Species.

Nicotiana otophora is a wild parental species of Nicotiana tabacum, an interspecific hybrid of Nicotiana tomentosiformis and Nicotiana sylvestris. However, N. otophora is least understood as an alternative paternal donor. Here, we compared the fully assembled chloroplast (cp) genome of N. otophora and with those of closely related species. The analysis showed a cp genome size of 156,073 bp and exhibited a typical quadripartite structure, which contains a pair of inverted repeats separated by small and large single copies, containing 163 representative genes, with 165 microsatellites distributed unevenly throughout the genome. Comparative analysis of a gene with known function across Nicotiana species revealed 76 protein-coding sequences, 20 tRNA sequences, and 3 rRNA sequence shared between the cp genomes. The analysis revealed that N. otophora is a sister species to N. tomentosiformis within the Nicotiana genus, and Atropha belladonna and Datura stramonium are their closest relatives. These findings provide a valuable analysis of the complete N. otophora cp genome, which can identify species, elucidate taxonomy, and reconstruct the phylogeny of genus Nicotiana.

Device closure of patent foramen ovale versus medical therapy in cryptogenic stroke: a systematic review and meta-analysis.

OBJECTIVES: This study sought to perform a meta-analysis of randomized controlled trials comparing device closure with medical therapy in the prevention of recurrent neurological events in patients with cryptogenic stroke and patent foramen ovale. BACKGROUND: The optimal strategy for secondary prevention of cryptogenic stroke with a patent foramen ovale is unclear. METHODS: Several databases were searched from their inception to March 2013, which yielded 3 eligible studies. The results were pooled as per the different patient populations defined in the studies:-intention-to-treat, per-protocol, and as-treated cohorts. A generic inverse method was used based on time-to-event outcomes in a fixed-effect model. A supplementary analysis pooled the results from only 2 trials (RESPECT [Randomized Evaluation of Recurrent Stroke Comparing PFO Closure to Established Current Standard of Care Treatment] and PC Trial [Randomized Clinical Trial Comparing the Efficacy of Percutaneous Closure of Patent Foramen Ovale (PFO) With Medical Treatment in Patients With Cryptogenic Embolism]) as a similar device was used in them. RESULTS: Our meta-analysis yielded effect-estimate hazard ratios of 0.67 (95% confidence interval [CI]: 0.44 to 1.00, I(2) = 0%) in the intention-to-treat cohort, 0.62 (95% CI: 0.40 to 0.95). I(2) = 0%) in the per-protocol cohort, and 0.61 (95% CI: 0.40 to 0.95, I(2) = 38%) in the as-treated cohort, showing beneficial effects of device closure. The results became more robust with pooled results from RESPECT and the PC Trial: The effect-estimate hazard ratios being 0.54 (95% CI: 0.29 to 1.01, I(2) = 0%), 0.48 (95% CI: 0.24 to 0.94, I(2) = 26%), and 0.42 (95% CI: 0.21 to 0.84, I(2) = 26%) in the intention-to-treat, per-protocol, and as-treated populations, respectively. CONCLUSIONS: Our meta-analysis suggests that PFO closure is beneficial as compared to medical therapy in the prevention of recurrent neurological events. This meta-analysis helps to further strengthen the role of device closure in cryptogenic stroke.