The independent contribution of Pseudomonas aeruginosa infection to long-term clinical outcomes in bronchiectasis.

Pseudomonas aeruginosa is responsible for chronic infection in many bronchiectasis patients but it is not known whether it is associated with worse clinical outcomes independent of the underlying severity of disease.This study analysed data from 2596 bronchiectasis patients included from 10 different bronchiectasis clinical centres across Europe and Israel, with a 5-year follow-up period. Prevalence of P. aeruginosa chronic infection and its independent impact on exacerbations, hospitalisations, quality of life and mortality was assessed.The prevalence of P. aeruginosa chronic infection was 15.0% (n=389). P. aeruginosa was associated with a higher mortality in a univariate analysis (hazard ratio (HR) 2.02; 95% (confidence interval) CI 1.53-2.66; p<0.0001) but an independent impact on mortality was not found in a multivariate analysis (HR 0.98; 95% CI 0.70-1.36; p=0.89). P. aeruginosa was independently associated with increased mortality only in patients with frequent exacerbations (two or more per year) (HR 2.03; 95% CI 1.36-3.03; p=0.001). An independent association with worse quality of life of 7.46 points (95% CI 2.93-12.00; p=0.001) was found in a multivariable linear regression. P. aeruginosa was therefore found to be independently associated with exacerbation frequency, hospital admissions and worse quality of life. Mortality was increased in patients with P. aeruginosa particularly in the presence of frequent exacerbations.

Antithrombin concentrates may benefit cardiopulmonary bypass patients with suspected heparin resistance: A retrospective analysis of real-world data.

Background: Heparin resistance is a common complication of surgical patients requiring anticoagulation, such as those undergoing cardiopulmonary bypass (CPB). Treatments to address heparin resistance include supplementation of antithrombin (AT) or fresh frozen plasma (FFP). This retrospective database analysis compared key outcomes in suspected heparin-resistant patients undergoing CPB treated with AT or FFP. Methods: De-identified United States electronic health records (Cerner Health Facts®) were queried. International Classification of Diseases (ICD-9/10) codes were used to determine CPB procedures and FFP administration. AT administration was identified using medication data, while a combination of lab and medication data examining activated clotting times detected heparin resistance in FFP patients. Adult inpatients (≥18 years old) seen between 2001 and 2018 were included. Differences in mortality, intensive care unit (ICU) length of stay (LOS), and hospital-free days (using a 30-day post-discharge period) were assessed with univariate models as well as adjusted logistic regression models controlling for patient characteristics and Charlson Comorbidity Index (CCI) scores. Results: Of the 502 patients identified, 247 received AT and 255 received FFP. The FFP cohort was associated with a higher CCI compared to the AT cohort (3.3 ± 2.4 vs. 2.3 ± 2.0, P < .001). The AT cohort was associated with a 71% (Odds Ratio [OR]: 0.29, 95% Confidence Interval [CI]: P = .003) and 66% (OR: 0.34, 95% CI: P = .01) reduction in mortality when compared to FFP using univariate and adjusted logistic regression models, respectively. Similarly, use of AT also showed a 22% shorter ICU LOS (P = .02) and 10% more hospital-free days in the 30 days following discharge (P = .004) according to the univariate models, though statistical significance was absent within adjusted models in both ICU LOS (P = .08) and hospital-free days (P = .53). Conclusions: Compared to FFP, AT use suggests a reduction in the odds of mortality in suspected heparin-resistant patients undergoing CPB, though larger prospective studies are necessary to elucidate potential differences in hospital-free days or ICU LOS across treatment modalities.

Pseudomonas aeruginosa associated with severity of non-cystic fibrosis bronchiectasis measured by the modified bronchiectasis severity score (BSI) and the FACED: The US bronchiectasis and NTM Research Registry (BRR) study.

RATIONALE: Non-cystic fibrosis bronchiectasis (NCFB) is characterized by dilated bronchi, poor mucus clearance and susceptibility to bacterial infection. Pseudomonas aeruginosa (PA) is one of the most frequently isolated pathogens in patients with NCFB. The purpose of this study was to evaluate the association between presence of PA and disease severity in patients within the US Bronchiectasis and Nontuberculous mycobacteria (NTM) Research Registry (BRR). METHODS: Baseline US BRR data from adult patients with NCFB collected between 2008 and 2018 was used for this study. The presence of PA was defined as one or more positive PA cultures within two years prior to enrollment. Modified Bronchiectasis Severity Index (m-BSI) and modified FACED (m-FACED) were computed to evaluate severity of bronchiectasis. Unadjusted and multivariable multinomial regression models were used to assess the association between presence of PA and severity of bronchiectasis. RESULTS: Average age of the study participants (n = 1831) was 63.7 years (SD = 14.1), 91.5% white, and 78.8% female. Presence of PA was identified in 25.4% of the patients. Patients with presence of PA had significantly lower mean pre-bronchodilator FEV1% predicted compared to those without PA (62.8% vs. 73.7%, p < .0001). In multivariate analyses, patients with presence of PA had significantly greater odds for having high (ORadj = 6.15 (95%CI:3.98-9.50) and intermediate (ORadj = 2.06 (95%CI:1.37-3.09) severity vs. low severity on m-BSI. CONCLUSION: The presence of PA is common in patients with NCFB within the Bronchiectasis and NTM Research Registry. Severity of bronchiectasis is significantly greater in patients with PA which emphasizes high burden of the disease.

Comorbidity Associations with AATD Among Commercially Insured and Medicare Beneficiaries with COPD in the US.

Introduction: Alpha-1 antitrypsin deficiency (AATD) is often not identified in patients with chronic obstructive pulmonary disease (COPD) until advanced stages of disease, despite the availability of genetic testing. While clinical practice guidelines provide recommendations on patients who should be tested, more refined algorithms are needed to identify COPD patients who are likely candidates for AATD testing and to prevent delays in diagnosis and treatment. The objective of this study was to identify comorbid associations with AATD among patients diagnosed with COPD in the United States. Methods: Using data from the 2012-2017 PharMetrics Plus Administrative Claims Database and 2011-2014 Medicare Fee for Service 5% Sample, patients with COPD (ICD-9-CM: 491.xx, 492.xx, or 496, ICD-10-CM J41, J42, J43, J44) and AATD (ICD-9-CM: 273.4, ICD-10-CM: E88.01) were identified. Patient demographic and diagnostic characteristics were assessed. Logistic regression models were developed to identify significant predictors of AATD. Results: A cohort of 344,528 Medicare beneficiaries with COPD (of which 302 (0.09%) also had two diagnoses of AATD) and a cohort of 340,259 commercially insured patients with COPD (of which 1076 (0.3%) also had a diagnosis of AATD) were constructed. Associations with AATD identified in both models included ICD-9-CM and ICD-10-CM codes for chronic pulmonary heart disease, chronic liver disease and cirrhosis, and liver transplant. Discussion: Significant associations with a diagnosis of AATD among patients with COPD were consistently represented in each of the datasets evaluated, which suggests meaningful comorbidity implications in AATD patients. These findings reinforce the need to test individuals with COPD for AATD as early as possible to help reduce the development of associated comorbid conditions.

Effects on violence of laws and policies facilitating the transfer of youth from the juvenile to the adult justice system: a report on recommendations of the Task Force on Community Preventive Services.

The independent, nonfederal Task Force on Community Preventive Services (Task Force), which directs the development of the Guide to Community Preventive Services (Community Guide), conducted a systematic review of published scientific evidence concerning the effectiveness of laws and policies that facilitate the transfer of juveniles to the adult criminal justice system to determine whether these transfers prevent or reduce violence among youth who have been transferred and among the juvenile population as a whole. For this review, transfer is defined as placing juveniles aged <18 years under the jurisdiction of the adult criminal justice system. The review followed Community Guide methods for conducting a systematic review of literature and for providing recommendations to public health decision makers. Available evidence indicates that transfer to the adult criminal justice system typically increases rather than decreases rates of violence among transferred youth. Available evidence was insufficient to determine the effect of transfer laws and policies on levels of violent crime in the overall juvenile population. On the basis of these findings, the Task Force recommends against laws or policies facilitating the transfer of juveniles to the adult criminal justice system for the purpose of reducing violence.

The effectiveness of universal school-based programs for the prevention of violent and aggressive behavior: a report on recommendations of the Task Force on Community Preventive Services.

Universal school-based programs to reduce or prevent violent behavior are delivered to all children in classrooms in a grade or in a school. Similarly, programs targeted to schools in high-risk areas (defined by low socioeconomic status or high crime rates) are delivered to all children in a grade or school in those high-risk areas. During 2004-2006, the Task Force on Community Preventive Services (Task Force) conducted a systematic review of published scientific evidence concerning the effectiveness of these programs. The results of this review provide strong evidence that universal school-based programs decrease rates of violence and aggressive behavior among school-aged children. Program effects were demonstrated at all grade levels. An independent meta-analysis of school-based programs confirmed and supplemented these findings. On the basis of strong evidence of effectiveness, the Task Force recommends the use of universal school-based programs to prevent or reduce violent behavior.

Impact of a Health Management Program on Healthcare Outcomes among Patients on Augmentation Therapy for Alpha 1-Antitrypsin Deficiency: An Insurance Claims Analysis.

INTRODUCTION: Alpha 1-antitrypsin deficiency (AATD) is a genetic disorder which reduces serum alpha 1-antitrypsin (AAT or alpha1-proteinase inhibitor, A1PI) and increases the risk of chronic obstructive pulmonary disease (COPD). Management strategies include intravenous A1PI augmentation, and, in some cases, a health management program (Prolastin Direct®; PD). OBJECTIVES: This study compared clinical and economic outcomes between patients with and without PD program participation. METHODS: This retrospective study included commercial and Medicare Advantage health insurance plan members with ≥ 1 claim with diagnosis codes for COPD and ≥ 1 medical or pharmacy claim including A1PI (on index date). Outcomes were compared between patients receiving only Prolastin® or Prolastin®-C (PD cohort) and patients who received a different brand without PD (Comparator cohort). Demographic and clinical characteristics were captured during 6 months pre-index. Post-index exacerbation episodes and healthcare utilization and costs were compared between cohorts. RESULTS: The study sample comprised 445 patients (n = 213 in PD cohort; n = 232 in Comparator cohort), with a mean age 55.5 years, 50.8% male, and 78.9% commercially insured. The average follow-up was 822 days (2.25 years), and the average time on A1PI was 747 days (2.04 years). Few differences were observed in demographic or clinical characteristics. Adjusting for differences in patient characteristics, the rate of severe exacerbation episodes was reduced by 36.1% in the PD cohort. Adjusted total annual all-cause costs were 11.4% lower, and adjusted mean respiratory-related costs were 10.6% lower in the PD cohort than the Comparator cohort. Annual savings in all-cause total costs in the PD cohort relative to the Comparator cohort was US$25,529 per patient, largely due to significantly fewer and shorter hospitalizations. CONCLUSIONS: These results suggest that comprehensive health management services may improve both clinical and economic outcomes among patients with COPD and AATD who receive augmentation therapy. FUNDING: Grifols Shared Services of North America, Inc.

Effects on violence of laws and policies facilitating the transfer of juveniles from the juvenile justice system to the adult justice system: a systematic review.

The independent, nonfederal Task Force on Community Preventive Services (Task Force), which directs development of the Guide to Community Preventive Services (Community Guide), has conducted a systematic review of published scientific evidence concerning the effectiveness of laws and policies that facilitate the transfer of juveniles to the adult criminal justice system, on either preventing or reducing violence (1) among those youth who experience the adult criminal system or (2) in the juvenile population as a whole. This review focuses on interpersonal violence. Violence may lead to the juvenile's initial arrest and entry into the justice system and, for those who are arrested, may be committed subsequent to exiting the justice system. Here transfer is defined as the placement of juveniles aged less than 18 years under the jurisdiction of the adult criminal justice system, rather than the juvenile justice system, following arrest. Using the methods developed by the Community Guide to conduct a systematic review of literature and provide recommendations to public health decision makers, the review team found that transferring juveniles to the adult justice system generally increases, rather than decreases, rates of violence among transferred youth. Evidence was insufficient for the Task Force on Community Preventive Services to determine the effect of such laws and policies in reducing violent behavior in the overall juvenile population. Overall, the Task Force recommends against laws or policies facilitating the transfer of juveniles from the juvenile to the adult judicial system for the purpose of reducing violence.

Effectiveness of universal school-based programs to prevent violent and aggressive behavior: a systematic review.

Universal, school-based programs, intended to prevent violent behavior, have been used at all grade levels from pre-kindergarten through high school. These programs may be targeted to schools in a high-risk area-defined by low socioeconomic status or high crime rate-and to selected grades as well. All children in those grades receive the programs in their own classrooms, not in special pull-out sessions. According to the criteria of the systematic review methods developed for the Guide to Community Preventive Services (Community Guide), there is strong evidence that universal, school-based programs decrease rates of violence among school-aged children and youth. Program effects were consistent at all grade levels. An independent, recently updated meta-analysis of school-based programs confirms and supplements the Community Guide findings.

Healthcare Cost and Utilization before and after Diagnosis of Pseudomonas aeruginosa among Patients with Non-Cystic Fibrosis Bronchiectasis in the U.S.

Non-cystic fibrosis bronchiectasis (NCFBE) is a rare, chronic lung disease characterized by bronchial inflammation and permanent airway dilation. Chronic infections with P. aeruginosa have been linked to higher morbidity and mortality. To understand the impact of P. aeruginosa in NCFBE on health care costs and burden, we assessed healthcare costs and utilization before and after P. aeruginosa diagnosis. Using data from 2007 to 2013 PharMetrics Plus administrative claims, we included patients with ≥2 claims for bronchiectasis and >1 claim for P. aeruginosa; then excluded those with a claim for cystic fibrosis. Patients were indexed at first claim for P. aeruginosa and were required to have >12 months before and after the index P. aeruginosa. The mean differences in utilization and costs were assessed using paired Student's t-tests for statistical significance. Mean total healthcare costs per patient were $36,213 pre-P. aeruginosa diagnosis versus $67,764 post-P. aeruginosa, an increase of 87% (p < 0.0001). Inpatient costs represented the largest proportion of total healthcare costs post-P. aeruginosa (54%) with an increase of four hospitalizations per patient (p < 0.0001). NCFBE patients with evidence of P. aeruginosa incur substantially greater healthcare costs and utilization after P. aeruginosa diagnosis. Future research should explore methods of earlier identification of NCFBE patients with P. aeruginosa, as this may lead to fewer severe exacerbations, thereby resulting in a reduction in hospitalizations and healthcare costs.

Estimating health and economic benefits from using prescription omega-3 fatty acids in patients with severe hypertriglyceridemia.

Patients with increased triglyceride levels compared to those with normal levels are at higher risk for coronary heart disease. In patients with severe (≥500 mg/dl) hypertriglyceridemia (SHTG), clinical trials have demonstrated that prescription ω-3 fatty acids (P-OM3s) 4 g/day can decrease triglyceride levels by 45%. However, the precise health and economic benefits of decreasing SHTG with P-OM3 are unknown. We used the previously validated Archimedes model to simulate a 20-year trial involving subjects 45 to 75 years old with SHTG. The trial consisted of an intervention arm (P-OM3 4 g/day) and a control arm. Simulation results for the control arm indicated that subjects with SHTG are at about 2 times higher risk for myocardial infarction than those with normal triglyceride levels. Using estimates from previous epidemiologic studies and meta-analyses with OM3s, the model predicted 29% to 36% decreases in various measurements of adverse cardiac events for the intervention arm. The model also predicted a decrease in ischemic stroke of 24% (95% confidence interval 15 to 33). For the 20-year simulated trial, the cost per quality-adjusted life-year gained for the currently available P-OM3 approved by the Food and Drug Administration was $47,000. Results remained robust under different clinical assumptions. In our model P-OM3 was effective in decreasing triglyceride levels and cardiovascular disease risk in patients with SHTG. In conclusion, P-OM3 medication is cost effective in our simulated trial and comparable to other cost-effective cardiovascular interventions.