Factors Associated With Outcomes of Patients With Primary Sclerosing Cholangitis and Development and Validation of a Risk Scoring System.

We sought to identify factors that are predictive of liver transplantation or death in patients with primary sclerosing cholangitis (PSC), and to develop and validate a contemporaneous risk score for use in a real-world clinical setting. Analyzing data from 1,001 patients recruited to the UK-PSC research cohort, we evaluated clinical variables for their association with 2-year and 10-year outcome through Cox-proportional hazards and C-statistic analyses. We generated risk scores for short-term and long-term outcome prediction, validating their use in two independent cohorts totaling 451 patients. Thirty-six percent of the derivation cohort were transplanted or died over a cumulative follow-up of 7,904 years. Serum alkaline phosphatase of at least 2.4 × upper limit of normal at 1 year after diagnosis was predictive of 10-year outcome (hazard ratio [HR] = 3.05; C = 0.63; median transplant-free survival 63 versus 108 months; P < 0.0001), as was the presence of extrahepatic biliary disease (HR = 1.45; P = 0.01). We developed two risk scoring systems based on age, values of bilirubin, alkaline phosphatase, albumin, platelets, presence of extrahepatic biliary disease, and variceal hemorrhage, which predicted 2-year and 10-year outcomes with good discrimination (C statistic = 0.81 and 0.80, respectively). Both UK-PSC risk scores were well-validated in our external cohort and outperformed the Mayo Clinic and aspartate aminotransferase-to-platelet ratio index (APRI) scores (C statistic = 0.75 and 0.63, respectively). Although heterozygosity for the previously validated human leukocyte antigen (HLA)-DR*03:01 risk allele predicted increased risk of adverse outcome (HR = 1.33; P = 0.001), its addition did not improve the predictive accuracy of the UK-PSC risk scores. Conclusion: Our analyses, based on a detailed clinical evaluation of a large representative cohort of participants with PSC, furthers our understanding of clinical risk markers and reports the development and validation of a real-world scoring system to identify those patients most likely to die or require liver transplantation.

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial.

Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of 'personalized' therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4-5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02759120.

Infective endocarditis is associated with worse outcomes in stroke: A Thailand National Database Study.

BACKGROUND: There is lack of data on the association between infective endocarditis (IE) and outcomes of mortality and complications in stroke. We aimed to compare characteristics and outcomes of stroke patients with and without IE. METHODS: We retrospectively examined the above association using data obtained from an insurance database which covers ~75% of the Thai population. All hospitalised strokes between 8 January 2003 and 31 December 2013 were included in the current study. Characteristics and outcomes were compared between stroke patients with or without IE, and then between two main stroke types. Multiple logistic regression models including propensity score-matched analyses were constructed to assess study outcomes controlling for age, sex, stroke type and comorbidities. RESULTS: A total of 590 115 stroke patients (mean (SD) age = 64.2 ± 13.7 years; ischaemic = 51.7%; haemorrhagic = 32.6%; undetermined = 15.7%) were included, of whom 2129 (0.36%) had stroke associated with IE. After adjustment, we found that IE was significantly associated with the following complications: arrhythmias (adjusted odds ratio (95% CI) 6.94 (6.29-7.66)), sepsis (1.24 (1.01-1.52)), pneumonia (1.34 (1.17-1.53)), respiratory failure (1.43 (1.24-1.66)) and in-hospital mortality (1.29 (1.13-1.47)) (P for all <.001). Patients with haemorrhagic stroke with IE had poorer outcomes for in-hospital mortality and respiratory failure compared with their counterparts with ischaemic stroke. Propensity score-matched analysis showed similar results. CONCLUSIONS: Our results suggest that stroke patients with IE differ from that of the general stroke population and these patients have worse outcomes. Future studies are needed to determine the best treatment strategies for stroke patients with IE.

Effect of Co-trimoxazole (Trimethoprim-Sulfamethoxazole) vs Placebo on Death, Lung Transplant, or Hospital Admission in Patients With Moderate and Severe Idiopathic Pulmonary Fibrosis: The EME-TIPAC Randomized Clinical Trial.

Importance: Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited treatment options. Patients with IPF have altered lung microbiota, with bacterial burden within the lungs associated with mortality; previous studies have suggested benefit with co-trimoxazole (trimethoprim-sulfamethoxazole). Objective: To determine the efficacy of co-trimoxazole in patients with moderate and severe IPF. Design, Setting, and Participants: Double-blind, placebo-controlled, parallel randomized trial of 342 patients with IPF, breathlessness (Medical Research Council dyspnea scale score >1), and impaired lung function (forced vital capacity ≤75% predicted) conducted in 39 UK specialist interstitial lung disease centers between April 2015 (first patient visit) and April 2019 (last patient follow-up). Interventions: Study participants were randomized to receive 960 mg of oral co-trimoxazole twice daily (n = 170) or matched placebo (n = 172) for between 12 and 42 months. All patients received 5 mg of folic acid orally once daily. Main Outcomes and Measures: The primary outcome was time to death (all causes), lung transplant, or first nonelective hospital admission. There were 15 secondary outcomes, including the individual components of the primary end point respiratory-related events, lung function (forced vital capacity and gas transfer), and patient-reported outcomes (Medical Research Council dyspnea scale, 5-level EuroQol 5-dimension questionnaire, cough severity, Leicester Cough Questionnaire, and King's Brief Interstitial Lung Disease questionnaire scores). Results: Among 342 individuals who were randomized (mean age, 71.3 years; 46 [13%] women), 283 (83%) completed the trial. The median (interquartile range) duration of follow-up was 1.02 (0.35-1.73) years. Events per person-year of follow-up among participants randomized to the co-trimoxazole and placebo groups were 0.45 (84/186) and 0.38 (80/209), respectively, with a hazard ratio of 1.2 ([95% CI, 0.9-1.6]; P = .32). There were no statistically significant differences in other event outcomes, lung function, or patient-reported outcomes. Patients in the co-trimoxazole group had 696 adverse events (nausea [n = 89], diarrhea [n = 52], vomiting [n = 28], and rash [n = 31]) and patients in the placebo group had 640 adverse events (nausea [n = 67], diarrhea [n = 84], vomiting [n = 20], and rash [n = 20]). Conclusions and Relevance: Among patients with moderate or severe IPF, treatment with oral co-trimoxazole did not reduce a composite outcome of time to death, transplant, or nonelective hospitalization compared with placebo. Trial Registration: ISRCTN Identifier: ISRCTN17464641.

Parkinson's disease and patient related outcomes in stroke: A matched cohort study.

OBJECTIVE: To evaluate post-stroke outcomes in patients with Parkinson's disease (PD). METHODS: A matched cohort study was performed. Stroke patients with PD and non-PD controls were extracted from the Thailand Universal Insurance Database. Logistic regressions were used to evaluate the association between PD and in-hospital outcomes (mortality and complications). The PD-associated long-term mortality was evaluated using Royston-Parmar models. RESULTS: A total of 1967 patients with PD were identified between 2003 and 2015 and matched to controls (1:4) by age, sex, admission year, and stroke type. PD patients had decreased odds of in-hospital death: OR (95% CI) 0.66 (0.52 - 0.84) and 0.61 (0.43 - 0.85) after ischaemic and haemorrhagic strokes, respectively. PD was associated with a length-of-stay greater than median (4 days) after both stroke types: 1.37 (1.21 - 1.56) and 1.45 (1.05 - 2.00), respectively. Ischaemic stroke patients with PD also had increased odds of developing pneumonia, sepsis and AKI: 1.52 (1.2 - 1.83), 1.54 (1.16 - 2.05), and 1.33 (1.02 - 1.73). In haemorrhagic stroke patients, PD was associated with pneumonia: 1.89 (1.31 - 2.72). Survival analyses showed that PD was protective against death in the short term (HR=0.66; 95% CI 0.53-0.83 ischaemic, and HR=0.50; 95% CI 0.37 - 0.68 haemorrhagic stroke), but leads to an increased mortality risk approximately 1 and 3 months after ischaemic and haemorrhagic stroke, respectively. CONCLUSION: PD is associated with a reduced mortality risk during the first 2-4 weeks post-admission but an increased risk thereafter, in addition to increased odds of in-hospital complications and prolonged hospitalisation.

Blood pressure differences between home monitoring and daytime ambulatory values and their reproducibility in treated hypertensive stroke and TIA patients.

BACKGROUND: Guidelines recommend ambulatory or home blood pressure monitoring to improve hypertension diagnosis and monitoring. Both these methods are ascribed the same threshold values, but whether they produce similar results has not been established in certain patient groups. METHODS: Adults with mild/moderate stroke or transient ischemic attack (N = 80) completed 2 sets of ambulatory and home blood pressure monitoring. Systolic and diastolic blood pressure values from contemporaneous measurements were compared, and the limits of agreement were assessed. Exploratory analyses for predictive factors of any difference were conducted. RESULTS: Daytime ambulatory blood pressure values were consistently lower than home values, the mean difference in systolic blood pressure for initial ambulatory versus first home monitoring was -6.6 ± 13.5 mm Hg (P≤.001), and final ambulatory versus second home monitoring was -7.1 ± 11.0mm Hg (P≤.001). Mean diastolic blood pressure differences were -2.1 ± 8.5mm Hg (P=.03) and -2.0 ± 7.2mm Hg (P=.02). Limits of agreement for systolic blood pressure were -33.0 to 19.9mm Hg and -28.7 to 14.5mm Hg for the 2 comparisons and for DBP were -18.8 to 14.5mm Hg and -16.1 to 12.2mm Hg, respectively. The individual mean change in systolic blood pressure difference was 11.0 ± 8.3mm Hg across the 2 comparisons. No predictive factors for these differences were identified. CONCLUSIONS: Daytime ambulatory systolic and diastolic blood pressure values were significantly lower than home monitored values at both time points. Differences between the 2 methods were not reproducible for individuals. Using the same threshold value for both out-of-office measurement methods may not be appropriate in patients with cerebrovascular disease.

Myocardial infarction after acute ischaemic stroke: Incidence, mortality and risk factors.

OBJECTIVES: To determine the risk factor profiles associated with post-acute ischaemic stroke (AIS) myocardial infarction (MI) over long-term follow-up. METHODS: This observational study includes prospectively identified AIS patients (n = 9840) admitted to a UK regional centre between January 2003 and December 2016 (median follow-up: 4.72 years). Predictors of post-stroke MI during follow-up were examined using logistic and Cox regression models for in-hospital and post-discharge events, respectively. MI incidence was determined using a competing risk non-parametric estimator. The influence of post-stroke MI on mortality was examined using Cox regressions. RESULTS: Mean age (SD) of study participants was 77.3 (12.2) years (48% males). Factors associated with in-hospital MI (OR [95% CI]) were increasing blood glucose (1.80 [1.17-2.77] per 10 mmol/L), total leucocyte count (1.25 [1.01-1.54] per 10 × 109 /L) and CRP (1.05 [1.02-1.08] per 10 mg/L increase). Age (HR [95% CI] = 1.03 [1.01-1.06]), coronary heart disease (1.59 [1.01-2.50]), chronic kidney disease (2.58 [1.44-4.63]) and cancers (1.76 [1.08-2.89]) were associated with incident MI between discharge and one-year follow-up. Age (1.02 [1.00-1.03]), diabetes (1.96 [1.38-2.65]), congestive heart failure (2.07 [1.44-2.99]), coronary heart disease (1.81 [1.31-2.50]), hypertension [1.86 (1.24-2.79)] and peripheral vascular disease (2.25 [1.40-3.63]) were associated with incident MI between 1 and 5 years after discharge. Diabetes (2.01 [1.09-3.72]), hypertension (3.69 [1.44-9.45]) and peripheral vascular disease (2.46 [1.02-5.98]) were associated with incident MI between 5 and 10 years after discharge. Cumulative MI incidence over 10 years was 5.4%. MI during all follow-up periods (discharge-1, 1-5, 5-10 years) was associated with increased risk of death (respective HR [95% CI] = 3.26 [2.51-4.15], 1.96 [1.58-2.42] and 1.92 [1.26-2.93]). CONCLUSIONS: In conclusion, prognosis is poor in post-stroke MI. We highlight a range of potential areas to focus preventative efforts.

Pneumonia and Risk of Serious Adverse Outcomes in Hospitalized Strokes in Thailand.

BACKGROUND: The impact of stroke associated pneumonia (SAP) on stroke complications is not well understood; we aimed to study the association between SAP and adverse outcomes including in-hospital mortality, prolonged length of stay and the risk of developing common serious complications (sepsis, respiratory failure, and convulsions). METHODS: We retrospectively analyzed data from a cohort of 610,668 stroke patients drawn from the Universal Coverage Health Security Scheme (a national insurance database) in Thailand which covers ∼80% of the Thai population. Patients were hospitalized between October 2004 and January 2013. RESULTS: Pneumonia was present in 9.6 % (n = 58,586) of patients. Aspiration pneumonia was present in 6.2% (n = 38,060) and nonaspiration pneumonia in 3.4% (n = 20,526). After adjusting for age, sex, stroke type, and comorbidities, patients with SAP had significantly higher odds of in-hospital mortality (odds ratio [OR] 2.90: 2.83-2.96), long length of stay (OR 13.11: 12.83-13.40), sepsis (OR 8.49: 8.22-8.76), respiratory failure (OR 4.37: 4.27-4.48), and convulsions (OR 2.09: 2.00-2.17). On subanalysis, patients with nonaspiration pneumonia were found to have higher odds of adverse outcomes compared to aspiration pneumonia; the corresponding ORs (95% confidence interval) for above outcomes were 1.25 (1.21-1.30), 2.40 (2.32-2.49), 1.34 (1.28-1.40), 1.80 (1.73-1.88), and 1.19 (1.11-1.28), respectively. CONCLUSIONS: SAP is associated with higher odds of inpatient mortality, long length of stay, and risk of developing serious stroke complications. Nonaspiration pneumonia is associated with significantly higher likelihood of adverse outcomes compared to aspiration pneumonia in this patient population. Early identification and treatment of SAP is vital in reducing adverse outcomes in acute stroke.

Cognitive profile and determinants of poor cognition in people without dementia in Parkinson's disease.

Background: The Montreal Cognitive Assessment (MoCA) has been recommended as a cognitive screening tool for clinical practice and research in Parkinson's disease (PD), yet no normative data have been published for MoCA in PD without dementia. Methods: We undertook a pooled secondary analysis of data from two studies (one cross-sectional design and one clinical trial) conducted in the East of England region. All participants were aged 18 years or over, met UK Brain Bank criteria for PD and did not have clinical dementia. Cognitive status was assessed using MoCA at baseline in both studies. The influences of age, gender, disease duration, medication load (LEDD) and mood (HADS) on cognition were examined using regression analysis. Results: Data from 101 people with PD without dementia were available (mean age 71 years, 66% men). Median (IQR) MoCA was 25(22, 27). Age was found as the only predictor of MoCA in this sample. People aged over 71 had poorer MoCA (Beta=0.6 (95%CI 0.44, 0.82)) and an increased odds of MoCA <26 (Beta=0.29 (95%CI 0.12, 0.70)) as well as poorer scores on several MoCA sub-domains. Conclusion: We present the normative data for MoCA in people with PD without clinical dementia. Age appeared to be the only associated factor for lower level of cognition, suggestive of Mild cognitive impairment in PD (PD-MCI) in PD without clinical diagnosis of dementia.

Does self-monitoring and self-management of blood pressure after stroke or transient ischemic attack improve control? TEST-BP, a randomized controlled trial.

The therapeutic benefit of self-monitoring blood pressure in stroke patients is uncertain. We investigated the effect of self-monitoring with or without guided antihypertensive management compared with usual care in patients with a recent cerebrovascular event. No between-group differences in blood pressure at outcome were found, but blood pressure self-monitoring and management was well tolerated.

Association Between Statin Use After Diagnosis of Esophageal Cancer and Survival: A Population-Based Cohort Study.

BACKGROUND & AIMS: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), commonly prescribed in the primary and secondary prevention of cardiovascular disease, promote apoptosis and limit proliferation of esophageal cancer cell lines. We investigated whether statin use after a diagnosis of esophageal cancer is associated with reduced esophageal cancer-specific and all-cause mortality. METHODS: We identified a cohort of 4445 men and women in the United Kingdom diagnosed with esophageal cancer from January 2000 through November 2009 using the General Practice Research Database. The National Cancer Registry and Office of National Statistics datasets established the histologic subtype and cancer-specific mortality, respectively. Cox proportional hazard regression analysis with time-dependent exposures estimated the association between statin use after diagnosis and esophageal cancer-specific and all-cause mortality. RESULTS: The median survival time of the entire cohort was 9.2 months (interquartile range [IQR], 3.7-23.2 mo). Among subjects who used statins after a diagnosis of esophageal cancer, the median survival time was 14.9 months (IQR, 7.1-52.3 mo) compared with 8.1 months for nonusers (IQR, 3.3-20 mo). In the entire cohort, statin use after diagnosis was associated with a decreased risk of esophageal cancer-specific mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44-0.86) and all-cause mortality (HR, 0.67; 95% CI, 0.58-0.77). In patients with esophageal adenocarcinoma, statin use after diagnosis was associated with a decreased risk of esophageal cancer-specific mortality (HR, 0.61; 95% CI 0.38-0.96) and all-cause mortality (HR, 0.63; 95% 0.43-0.92). This effect was not observed in patients with esophageal squamous cell carcinoma. There was no evidence for effect modification of these associations with statin use before the cancer diagnosis. CONCLUSIONS: In a large population-based cohort, statin use after a diagnosis of esophageal adenocarcinoma, but not esophageal squamous cell carcinoma, was associated with reduced esophageal cancer-specific and all-cause mortality.

The effect of co-trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial.

AIMS: Co-trimoxazole maintains a well-established role in the treatment of Pneumocystis jirovecii and Toxoplasma gondii, as well as urinary tract infections. Observational studies report hyperkalaemia to be associated with co-trimoxazole, which may stem from an amiloride-like potassium-sparing effect. The current study investigated changes in serum potassium in patients without acute infections, and the influence of concomitant antikaliuretic drugs on this effect. METHODS: A post hoc analysis was carried out of a randomized controlled trial in patients with interstitial lung disease who were assigned to placebo or 960 mg co-trimoxazole twice daily. Serum potassium and creatinine were measured at baseline, 6 weeks, and 6, 9 and 12 months. The primary outcome was the difference in mean serum potassium concentrations between co-trimoxazole and placebo at 6 weeks. RESULTS: Mean serum potassium levels were similar at baseline: 4.24 (± 0.44) mmol l-1 in the 87 co-trimoxazole group participants and 4.25 (± 0.39) mmol l-1 in the 83 control participants. Co-trimoxazole significantly increased mean serum potassium levels at 6 weeks, with a difference between means compared with placebo of 0.21 mmol l-1 [95% confidence interval (CI) 0.09, 0.34; P = 0.001). This significant increase in serum potassium was detectable even after exclusion of patients on antikaliuretic drugs, with a difference between means for co-trimoxazole compared with placebo of 0.23 mmol l-1 (95% CI 0.09, 0.38; P = 0.002). There were 5/87 (5.7%) patients on co-trimoxazole whose serum potassium concentrations reached ≥5.5 mmol l-1 during the study period. CONCLUSIONS: Co-trimoxazole significantly increases serum potassium concentration, even in participants not using antikaliuretic drugs. While the magnitude of increase was often minor, a small proportion in our outpatient cohort developed hyperkalaemia of clinical importance.

Closure methods of the appendix stump for complications during laparoscopic appendectomy.

BACKGROUND: Laparoscopic appendectomy is amongst the most common general surgical procedures performed in the developed world. Arguably, the most critical part of this procedure is effective closure of the appendix stump to prevent catastrophic intra-abdominal complications from a faecal leak into the abdominal cavity. A variety of methods to close the appendix stump are used worldwide; these can be broadly divided into traditional ligatures (such as intracorporeal or extracorporeal ligatures or Roeder loops) and mechanical devices (such as stapling devices, clips, or electrothermal devices). However, the optimal method remains unclear. OBJECTIVES: To compare all surgical techniques now used for appendix stump closure during laparoscopic appendectomy. SEARCH METHODS: In June 2017, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 6) in the Cochrane Library, MEDLINE Ovid (1946 to 14 June 2017), Embase Ovid (1974 to 14 June 2017), Science Citation Index - Expanded (14 June 2017), China Biological Medicine Database (CBM), the World Health Organization International Trials Registry Platform search portal, ClinicalTrials.gov, Current Controlled Trials, the Chinese Clinical Trials Register, and the EU Clinical Trials Register (all in June 2017). We searched the reference lists of relevant publications as well as meeting abstracts and Conference Proceedings Citation Index to look for additional relevant clinical trials. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared mechanical appendix stump closure (stapler, clips, or electrothermal devices) versus ligation (Endoloop, Roeder loop, or intracorporeal knot techniques) for uncomplicated appendicitis. DATA COLLECTION AND ANALYSIS: Two review authors identified trials for inclusion, collected data, and assessed risk of bias independently. We performed the meta-analysis using Review Manager 5. We calculated the odds ratio (OR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs). MAIN RESULTS: We included eight randomised studies encompassing 850 participants. Five studies compared titanium clips versus ligature, two studies compared an endoscopic stapler device versus ligature, and one study compared an endoscopic stapler device, titanium clips, and ligature. In our analyses of primary outcomes, we found no differences in total complications (OR 0.97, 95% CI 0.27 to 3.50, 8 RCTs, very low-quality evidence), intraoperative complications (OR 0.93, 95% CI 0.34 to 2.55, 8 RCTs, very low-quality evidence), or postoperative complications (OR 0.80, 95% CI 0.21 to 3.13, 8 RCTs, very low-quality evidence) between ligature and all types of mechanical devices. However, our analyses of secondary outcomes revealed that use of mechanical devices saved approximately nine minutes of total operating time when compared with use of a ligature (mean difference (MD) -9.04 minutes, 95% CI -12.97 to -5.11 minutes, 8 RCTs, very low-quality evidence). However, this finding did not translate into a clinically or statistically significant reduction in inpatient hospital stay (MD 0.02 days, 95% CI -0.12 to 0.17 days, 8 RCTs, very low-quality evidence). Available information was insufficient for reliable comparison of total hospital costs and postoperative pain/quality of life between the two approaches. Overall, evidence across all analyses was of very low quality, with substantial potential for confounding factors. Given the limitations of all studies in terms of bias and the low quality of available evidence, a clear conclusion regarding superiority of any one particular type of mechanical device over another is not possible. AUTHORS' CONCLUSIONS: Evidence is insufficient at present to advocate omission of conventional ligature-based appendix stump closure in favour of any single type of mechanical device over another in uncomplicated appendicitis.

Derivation and Validation of a Novel Prognostic Scale (Modified-Stroke Subtype, Oxfordshire Community Stroke Project Classification, Age, and Prestroke Modified Rankin) to Predict Early Mortality in Acute Stroke.

BACKGROUND AND PURPOSE: The stroke subtype, Oxfordshire Community Stroke Project classification, age, and prestroke modified Rankin (SOAR) score is a prognostic scale proposed for early mortality prediction after acute stroke. We aimed to evaluate whether including a measure of initial stroke severity (National Institutes of Health Stroke Scale and modified-SOAR [mSOAR] scores) would improve the prognostic accuracy. METHODS: Using Anglia Stroke and Heart Clinical Network data, 2008 to 2011, we assessed the performance of SOAR and mSOAR against in-hospital mortality using area under the receiver operating curve statistics. We externally validated the prognostic utility of SOAR and mSOAR using an independent cohort data set from Glasgow. We described calibration using Hosmer-Lemeshow goodness-of-fit test. RESULTS: A total of 1002 patients were included in the derivation cohort, and 105 (10.5%) died as inpatients. The area under the receiver operating curves for outcome of early mortality derived from the SOAR and mSOAR scores were 0.79 (95% confidence interval, 0.75-0.84) and 0.83 (95% confidence interval, 0.79-0.86), respectively (P=0.001). The external validation data set contained 1012 patients with stroke; of which, 121 (12.0%) patients died within 90 days. The mSOAR scores identified the risk of early mortality ranging from 3% to 42%. External validation of mSOAR score yielded an area under the receiver operating curve of 0.84 (95% confidence interval, 0.82-0.88) for outcome of early mortality. Calibration was good (P=0.70 for the Hosmer-Lemeshow test). CONCLUSIONS: Adding National Institutes of Health Stroke Scale data to create a modified-SOAR score improved prognostic utility in both derivation and validation data sets. The mSOAR may have clinical utility by using easily available data to predict mortality.

Rheumatic Mitral Valve Disease Is Associated With Worse Outcomes in Stroke: A Thailand National Database Study.

BACKGROUND AND PURPOSE: Rheumatic valvular heart disease is associated with the increased risk of cerebrovascular events, although there are limited data on the prognosis of patients with rheumatic mitral valve disease (RMVD) after stroke. METHODS: We examined the association between RMVD and both serious and common cardiovascular and noncardiovascular (respiratory and infective) complications in a cohort of hospitalized stroke patients based in Thailand. Factors associated with in-hospital mortality were also explored. Data were obtained from a National Insurance Database. All hospitalized strokes between October 1, 2004, and January 31, 2013, were included in the current study. Characteristics and outcomes were compared for RMVD and non-RMVD patients. Logistic regression, propensity score matching, and multivariate models were used to assess study outcomes. RESULTS: In total, 594 681 patients (mean [SD] age=64 [14.5] years) with a diagnosis of stroke (ischemic=306 154; hemorrhagic=195 392; undetermined=93 135) were included in this study, of whom 5461 had RMVD. Results from primary analyses showed that after ischemic stroke, and controlling for potential confounding covariates, RMVD was associated (P<0.001) with increased odds for cardiac arrest (odds ratio [95% confidence interval]=2.13 [1.68-2.70]), shock (2.13 [1.64-2.77]), arrhythmias (1.70 [1.21-2.39]), respiratory failure (2.09 [1.87-2.33]), pneumonia (2.00 [1.81-2.20]), and sepsis (1.39 [1.19-1.63]). In hemorrhagic stroke patients, RMVD was associated with increased odds (fully adjusted model) for respiratory failure (1.26 [1.01-1.57]), and in patients with undetermined stroke, RMVD was associated with increased odds (fully adjusted analyses) for shock (3.00 [1.46-6.14]), respiratory failure (2.70 [1.91-3.79]), and pneumonia (2.42 [1.88-3.11]). CONCLUSIONS: RMVD is associated with the development of cardiac arrest, shock, arrhythmias, respiratory failure, pneumonia, and sepsis after acute stroke.

Consumption of Fish Oil Providing Amounts of Eicosapentaenoic Acid and Docosahexaenoic Acid That Can Be Obtained from the Diet Reduces Blood Pressure in Adults with Systolic Hypertension: A Retrospective Analysis.

BACKGROUND: Although many randomized controlled trials (RCTs) have examined the effects of the n-3 (ω-3) fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) on blood pressure (BP) and vascular function, the majority have used doses of EPA+DHA of >3 g/d, which are unlikely to be achieved by dietary manipulation. OBJECTIVE: The objective was to examine, by using a retrospective analysis from a multicenter RCT, the impact of recommended EPA+DHA intakes achievable through diet on systolic and diastolic BPs and microvascular function in adults in the United Kingdom. METHODS: In a double-blind, placebo-controlled RCT, healthy men and women (n = 312) consumed a control oil or fish oil (FO) providing 0.7 or 1.8 g EPA+DHA/d, in random order, each for 8 wk. Fasting BP and microvascular function (using laser Doppler iontophoresis) were assessed and plasma collected for the quantification of markers of vascular function. Participants were retrospectively genotyped for the endothelial nitric oxide synthase (eNOS) rs1799983 variant. RESULTS: No effects of n-3 fatty acid treatment or any treatment × eNOS genotype interactions were evident in the group as a whole for any of the clinical or biochemical outcomes. Assessment of response according to hypertension status at baseline indicated a significant (P = 0.046) FO-induced reduction (mean: 5 mm Hg) in systolic BP, specifically in those with isolated systolic hypertension (n = 31). No dose response was observed. CONCLUSIONS: These findings indicate that in adults with isolated systolic hypertension, daily doses of EPA+DHA as low as 0.7 g show clinically meaningful BP reductions, which, at a population level, could be associated with lower cardiovascular disease risk. Confirmation of findings in an RCT in which participants are prospectively recruited on the basis of BP status is required to draw definite conclusions.

Incidentally Raised Cardiac Troponin I Has a Worse Prognosis in Older Patients Compared to Those with Normal Cardiac Troponin I and Patients with Acute Coronary Syndrome: A Cohort Study.

BACKGROUND: Incidentally elevated cardiac troponin I (cTnI) levels are common in acutely unwell older patients. However, little is known about how this impacts on the prognosis of these patients. OBJECTIVE: We aimed to investigate whether incidentally elevated cTnI levels (group 1) are associated with poorer outcome when compared to age- and sex-matched patients without an elevated cTnI level (group 2), and to patients diagnosed with acute coronary syndrome (group 3). PATIENTS AND METHODS: This prospective, matched cohort study placed patients ≥75 years old who were admitted to a University teaching hospital into groups 1-3, based on the cTnI levels and underlying diagnosis. Outcomes were compared between the groups using mixed-effects regression models and adjusted for renal function and C-reactive protein. All-cause mortality at discharge, at 1 month and 3 months, alongside the length of hospital stay (LOS), were recorded. RESULTS: In total, 315 patients were included, with 105 patients in each of the 3 groups. The mean age was 84.8 ± 5.5 years, with 41.9% males. All patients were followed up for 3 months. The percent all-cause mortality at discharge and the LOS for groups 1, 2 and 3 were 12.4, 3.8 and 8.6% and 11.2, 8.5 and 7.7 days, respectively. Group 1 had significantly increased mortality at 3 months [odds ratio (OR) 2.80, 95% confidence interval (CI) 1.12-6.96; p = 0.040] and LOS (OR 1.39, 95% CI 1.08-1.79; p = 0.008) compared to group 2 and did not differ significantly when compared to 3-month mortality (OR 2.39, 95% CI 0.91-6.29; p = 0.079) or LOS (OR 1.26, 95% CI 0.96-1.66; p = 0.097) in group 3. CONCLUSION: There is a significant association between an incidental rise in cTnI level with mortality and LOS in older patients. Further research is required to evaluate whether a more systematic management of these patients would improve the prognosis.

Statin use is associated with reduced risk of histologic subtypes of esophageal cancer: a nested case-control analysis.

BACKGROUND & AIMS: Most patients with esophageal adenocarcinoma (EAC) or squamous cell cancer (ESCC) present with advanced, incurable disease. Statins have reported anti-carcinogenic effects and may be chemoprotective. We investigated the association between regular use of statins and the main histologic subtypes of esophageal malignancy (EAC, esophagogastric junctional adenocarcinoma, and ESCC) in the UK general population. METHODS: We identified all individuals in the UK General Practice Research Database diagnosed with esophageal cancer from 2000 through 2009. Patients were linked to the National Cancer Registry to confirm histologic subtypes. Each patient was matched with up to 4 controls for age, sex, and practice. We performed a nested case-control analysis using conditional logistic regression to estimate the risk of each subtype with regular statin use, adjusted for body mass index, smoking, alcohol intake, and concomitant use of medications. RESULTS: In total, 581 participants with EAC, 213 with esophagogastric junctional adenocarcinoma, and 332 with ESCC were matched to 2167, 783, and 1242 controls, respectively. Regular statin use was inversely associated with development of EAC (odds ratio = 0.58; 95% confidence interval: 0.39-0.87) (with significant dose and duration responses) and esophagogastric junctional adenocarcinoma (odds ratio = 0.29; 95% confidence interval: 0.09-0.92) (with high-dose use only). Statin use for 1-4 years was inversely associated with ESCC (odds ratio = 0.51; 95% confidence interval: 0.27-0.98). CONCLUSIONS: In a nested case-control analysis of a UK population-based cohort, statin use was inversely associated with histologic subtypes of esophageal cancer. Randomized controlled trials are warranted to determine whether statins have chemopreventive effects in high-risk groups.

Knee orthoses for treating patellofemoral pain syndrome.

BACKGROUND: Patellofemoral pain syndrome (PFPS) is a painful musculoskeletal condition, which is characterised by knee pain located in the anterior aspect (front) and retropatellar region (behind) of the knee joint. Various non-operative interventions are suggested for the treatment of this condition. Knee orthoses (knee braces, sleeves, straps or bandages) are worn over the knee and are thought to help reduce knee pain. They can be used in isolation or in addition to other treatments such as exercise or non-steroidal anti-inflammatory medications. OBJECTIVES: To assess the effects (benefits and harms) of knee orthoses (knee braces, sleeves, straps or bandages) for treating PFPS. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (11 May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015 Issue 5), MEDLINE (1946 to 8 May 2015), EMBASE (1980 to 2015 Week 18), SPORTDiscus (1985 to 11 May 2015), AMED (1985 to 8 May 2015), CINAHL (1937 to 11 May 2015), PEDro (1929 to June 2015), trial registries and conference proceedings. SELECTION CRITERIA: Randomised and quasi-randomised controlled clinical trials evaluating knee orthoses for treating people with PFPS. Our primary outcomes were pain and function. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility, assessed study risk of bias and extracted data. We calculated mean differences (MD) or, where pooling data from different scales, standardised mean differences (SMD) with 95% confidence intervals (CI) for continuous outcomes and risk ratios (RR) with 95% CIs for binary outcomes. We pooled data using the fixed-effect model. MAIN RESULTS: We included five trials (one of which was quasi-randomised) that reported results for 368 people who had PFPS. Participants were recruited from health clinics in three trials and were military recruits undergoing training in the other two trials. Although no trials recruited participants who were categorised as elite or professional athletes, military training does comprise intensive exercise regimens. All five trials were at high risk of bias, including performance bias reflecting the logistical problems in these trials of blinding of participants and care providers. As assessed using the GRADE approach, the available evidence for all reported outcomes is 'very low' quality. This means that we are very uncertain about the results.The trials covered three different types of comparison: knee orthosis and exercises versus exercises alone; one type of orthosis versus another; and knee orthosis versus exercises. No trials assessed the mode of knee orthosis use, such as whether the orthosis was worn all day or only during physical activity. Two trials had two groups; two trials had three groups; and one trial had four groups.All five trials compared a knee orthosis (knee sleeve, knee brace, or patellar strap) versus a 'no treatment' control group, with all participants receiving exercises, either through a military training programme or a home-based exercise programme. There is very low quality evidence of no clinically important differences between the two groups in short-term (2 to 12 weeks follow-up) knee pain based on the visual analogue scale (0 to 10 points; higher scores mean worse pain): MD -0.46 favouring knee orthoses, 95% CI -1.16 to 0.24; P = 0.19; 234 participants, 3 trials). A similar lack of clinically important difference was found for knee function (183 participants, 2 trials). None of the trials reported on quality of life measures, resource use or participant satisfaction. Although two trials reported on the impact on sporting or occupational participation, one trial (35 participants) did not provide data split by treatment group on the resumption of sport activity and the other reported only on abandonment of military training due to knee pain (both cases were allocated a knee orthosis). One trial (59 participants, 84 affected knees) recording only adverse events in the two knee orthoses (both were knee sleeves) groups, reported 16 knees (36% of 44 knees) had discomfort or skin abrasion.Three trials provided very low quality evidence on single comparisons of different types of knee orthoses: a knee brace versus a knee sleeve (63 participants), a patella strap with a knee sleeve (31 participants), and a knee sleeve with a patellar ring versus a knee sleeve only (44 knees). None of three trials found an important difference between the two types of knee orthosis in pain. One trial found no clinically important difference in function between a knee brace and a knee sleeve. None of the three trials reported on quality of life, resource use or participant satisfaction. One trial comparing a patella strap with a knee sleeve reported that both participants quitting military training due to knee pain were allocated a knee sleeve. One poorly reported trial found three times as many knees with adverse effects (discomfort or skin abrasion) in those given knee sleeves with a patella ring than those given knee sleeves only.One trial compared a knee orthosis (knee brace) with exercise (66 participants). It found very low quality evidence of no clinically important difference between the two intervention groups in pain or knee function. The trial did not report on quality of life, impact on sporting or occupational participation, resource use, participant satisfaction or complications. AUTHORS' CONCLUSIONS: Overall, this review has found a lack of evidence to inform on the use of knee orthoses for treating PFPS. There is, however, very low quality evidence from clinically heterogeneous trials using different types of knee orthoses (knee brace, sleeve and strap) that using a knee orthosis did not reduce knee pain or improve knee function in the short term (under three months) in adults who were also undergoing an exercise programme for treating PFPS. This points to the need for good-quality clinically-relevant research to inform on the use of commonly-available knee orthoses for treating PFPS.