Secukinumab sustains early patient-reported outcome benefits through 1 year: Results from 2 phase III randomized placebo-controlled clinical trials comparing secukinumab with etanercept.

BACKGROUND: Psoriasis is a chronic condition with negative impact on patients' quality of life that most often requires lifelong effective and safe treatment. OBJECTIVE: This analysis focused on the effect of secukinumab treatment on patient-reported health-related quality of life as assessed by the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis. METHODS: The proportion of subjects achieving DLQI score 0/1 response at week 24, time to DLQI score 0/1 response, and sustained DLQI score 0/1 response up to week 52 were compared between secukinumab and etanercept. RESULTS: Of 1470 subjects, 1144 received secukinumab and 326 received etanercept. DLQI score 0/1 response rates were significantly higher for secukinumab than for etanercept at week 24. The median time to DLQI score 0/1 response was significantly shorter for secukinumab versus etanercept (12 vs 24 weeks; P < .01). The majority of secukinumab-treated subjects achieved DLQI score 0/1 response at week 24 and sustained it through week 52 along with a 90% to 100% reduction in the Psoriasis Area and Severity Index total score response. LIMITATIONS: Placebo comparisons are limited during the maintenance period because of rerandomization at week 12. CONCLUSION: Secukinumab treatment provided faster and greater sustained improvements in quality of life than etanercept over 52 weeks, consistent with greater clinical response.

Economic burden of comorbidities in psoriasis patients in the United States: results from a retrospective U.S. database.

BACKGROUND: Psoriasis is a multifactorial, inflammatory, skin disease associated with various comorbidities. The cost of those comorbidities is not well characterized. The present study assesses the incremental burden of comorbidities on healthcare resource utilization, direct costs and indirect costs associated with short-term disabilities among patients with psoriasis in the United States. METHODS: A retrospective, U.S. cohort analysis was conducted using a large claims database. Adult psoriasis patients with at least two diagnoses of psoriasis during the years 2010 and 2011 (one psoriasis diagnosis had to happen in the year 2010) and with continuous enrollment of medical and pharmacy benefits in the years 2010 and 2011 were included. Psoriasis patients were categorized and compared according to the presence or absence of pre-selected comorbidities in the year 2010. Adjusted annual direct (costs associated with outpatient, emergency room, and inpatient claims, and outpatient pharmacy claims) and indirect costs (short-term disabilities) was assessed in patients with and without comorbidities using a regression analysis, controlling for age, gender, and psoriasis severity in year 2010. RESULTS: In total, 56,406 patients (mean [SD]) age, 51.6 [14.6] years) were included in the analysis. The most prevalent comorbidities were hypertension (34.3%), hyperlipidemia (33.5%), cardiovascular disease (17.7%), diabetes (14.2%), and psoriatic arthritis (9.9%). Psoriasis patients with comorbidities used more healthcare resources than those without comorbidities. The incidence rate ratio (IRR) (95% CI) for patients with cardiovascular disease was 1.5 (1.4 - 1.5) for outpatient visits, 2.6 (2.4 - 2.8) for hospitalizations, and 2.3 (2.2 - 2.5) for ER visits, showing higher IRRs across all three types of resource use. The mean annual adjusted direct cost differences (i.e., incremental adjusted costs) in psoriasis patients with and without comorbidities were $9914.3, $8386.5, and $8275.1 for psoriatic arthritis, peripheral vascular disease, and cardiovascular disease, respectively. The mean annual incremental adjusted indirect costs of short-term disabilities were $1333, $1195, $994.9, and $996.6 for cerebrovascular disease, obesity, peripheral vascular disease, and depression, respectively. CONCLUSION: The presence of comorbidities was associated with higher healthcare resource utilization and costs among patients with psoriasis.

Association of lower urinary tract symptoms and the metabolic syndrome: results from the Boston area community health survey.

PURPOSE: In this study we investigated the relationship between lower urinary tract symptoms as defined by the American Urological Association symptom index and the metabolic syndrome, and determined the relationship between individual symptoms comprising the American Urological Association symptom index and the metabolic syndrome. MATERIALS AND METHODS: The Boston Area Community Health Survey used a 2-stage cluster design to recruit a random sample of 2,301 men 30 to 79 years old. Analyses were conducted on 1,899 men who provided blood samples. Urological symptoms comprising the American Urological Association symptom index were included in the analysis. The metabolic syndrome was defined using a modification of the Adult Treatment Panel III guidelines. The association between lower urinary tract symptoms and the metabolic syndrome was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models. RESULTS: Increased odds of the metabolic syndrome were observed in men with mild to severe symptoms (American Urological Association symptom index 2 to 35) compared to those with an American Urological Association symptom index score of 0 or 1 (multivariate OR 1.68, 95% CI 1.21-2.35). A statistically significant association was observed between the metabolic syndrome and a voiding symptom score of 5 or greater (multivariate adjusted OR 1.73, 95% CI 1.06-2.80) but not for a storage symptom score of 4 or greater (multivariate adjusted OR 0.94, 95% CI 0.66-1.33). Increased odds of the metabolic syndrome were observed even with mild symptoms, primarily for incomplete emptying, intermittency and nocturia. These associations were observed primarily in younger men (younger than 60 years) and were null in older men (60 years old or older). CONCLUSIONS: The observed association between urological symptoms and the metabolic syndrome provides further evidence of common underlying factors between lower urinary tract symptoms and chronic conditions outside the urinary tract.

Whole-Genome Sequencing Snapshot of Clinically Relevant Carbapenem-Resistant Gram-Negative Bacteria from Wastewater in Serbia.

Wastewater (WW) is considered a source of antibiotic-resistant bacteria with clinical relevance and may, thus, be important for their dissemination into the environment, especially in countries with poor WW treatment. To obtain an overview of the occurrence and characteristics of carbapenem-resistant Gram-negative bacteria (CR-GNB) in WW of Belgrade, we investigated samples from the four main sewer outlets prior to effluent into international rivers, the Sava and the Danube. Thirty-four CR-GNB isolates were selected for antimicrobial susceptibility testing (AST) and whole-genome sequencing (WGS). AST revealed that all isolates were multidrug-resistant. WGS showed that they belonged to eight different species and 25 different sequence types (STs), seven of which were new. ST101 K. pneumoniae (blaCTX-M-15/blaOXA-48) with novel plasmid p101_srb was the most frequent isolate, detected at nearly all the sampling sites. The most frequent resistance genes to aminoglycosides, quinolones, trimethroprim-sulfamethoxazole, tetracycline and fosfomycin were aac(6')-Ib-cr (55.9%), oqxA (32.3%), dfrA14 (47.1%), sul1 (52.9%), tet(A) (23.5%) and fosA (50%), respectively. Acquired resistance to colistin via chromosomal-mediated mechanisms was detected in K. pneumoniae (mutations in mgrB and basRS) and P. aeruginosa (mutation in basRS), while a plasmid-mediated mechanism was confirmed in the E. cloacae complex (mcr-9.1 gene). The highest number of virulence genes (>300) was recorded in P. aeruginosa isolates. Further research is needed to systematically track the occurrence and distribution of these bacteria so as to mitigate their threat.

Quality of life assessment of cabozantinib in patients with advanced hepatocellular carcinoma in the CELESTIAL trial.

BACKGROUND: The CELESTIAL trial (NCT01908426) demonstrated overall survival benefit for cabozantinib versus placebo in patients with advanced hepatocellular carcinoma (aHCC) who had received prior sorafenib treatment. This analysis of CELESTIAL compared the impact of cabozantinib versus placebo on health-related quality of life (HRQoL). MATERIALS AND METHODS: Health status was assessed using the EuroQol five-dimension five-level (EQ-5D-5L) questionnaire over the 800-day follow-up period. EQ-5D-5L health states were mapped to health utility scores using reference values for the UK population. Quality-adjusted life years (QALYs) were calculated for each treatment group as the area under the curve for the plot of health utility score over time. The between-treatment group difference in restricted mean QALYs was calculated by generalized linear models and adjusted for baseline differences. A difference of 0.08 in health utility score (or in QALY) was deemed a minimally important difference and to be clinically significant. RESULTS: At week 5, the difference in mean health utility score between cabozantinib and placebo was -0.097 (95% confidence interval [95% CI]: -0.126, -0.067; p ≤ 0.001). Between-group differences in health utility scores diminished over time and were generally non-significant. The cabozantinib group accrued more QALYs than the placebo group over follow-up. Differences in mean QALYs (cabozantinib minus placebo) were statistically and clinically significant, ranging from +0.092 (95% CI: 0.016, 0.169) to +0.185 (95% CI: 0.126, 0.243) in favour of cabozantinib, depending on the reference value set used. CONCLUSIONS: These HRQoL findings support a positive benefit-risk profile for cabozantinib in previously treated patients with aHCC.

Comparative Efficacy of Cabozantinib and Ramucirumab After Sorafenib for Patients with Hepatocellular Carcinoma and Alpha-fetoprotein ≥ 400 ng/mL: A Matching-Adjusted Indirect Comparison.

INTRODUCTION: Cabozantinib and ramucirumab are approved for the treatment of adults with hepatocellular carcinoma (HCC) following prior sorafenib treatment; ramucirumab is restricted to use in patients with serum alpha-fetoprotein (AFP) ≥ 400 ng/mL. This matching-adjusted indirect comparison evaluated the efficacy and safety of both drugs after sorafenib in patients with HCC and AFP ≥ 400 ng/mL. METHODS: Individual patient data (IPD) from the CELESTIAL trial (cabozantinib) and population-level data from the REACH-2 trial (ramucirumab) were used. To align with REACH-2, the CELESTIAL population was limited to patients who received first-line sorafenib only and had baseline serum AFP ≥ 400 ng/mL. The IPD from CELESTIAL were weighted to balance the distribution of 11 effect-modifying baseline characteristics with those of REACH-2. Overall survival (OS; primary endpoint) and progression-free survival (PFS) were compared for the CELESTIAL (matching-adjusted) and REACH-2 populations using weighted Kaplan-Meier (KM) curves and parametric (OS, Weibull; PFS, log-logistic) modeling. Rates of treatment-related adverse events (TRAEs) and TRAE-related discontinuations were also compared. RESULTS: After matching and weighting, baseline characteristics were balanced between populations (REACH-2, N = 292; CELESTIAL, effective sample size = 105). Weighted KM estimates for OS (median [95% CI]) were not significantly different between cabozantinib and ramucirumab (10.6 [9.5-17.3] months versus 8.7 [7.3-10.8] months; p = 0.104), but PFS was significantly longer for cabozantinib than for ramucirumab (5.5 [4.6-7.4] months versus 2.8 [2.7-4.1] months; p = 0.016). Parametric modeling results were consistent with the weighted KM analysis. Rates of some grade 3 or 4 TRAEs were lower with ramucirumab than with cabozantinib; however, TRAE-related discontinuation rates were similar (p = 0.271). CONCLUSION: In this MAIC, cabozantinib significantly prolonged median PFS compared with ramucirumab after prior sorafenib treatment in patients with HCC and AFP ≥ 400 ng/mL; rates of some grade 3 or 4 TRAEs were lower with ramucirumab than cabozantinib but related discontinuation rates were not significantly different between treatments. TRIAL REGISTRATION: Clinical trials.gov identifiers: CELESTIAL trial (NCT01908426) and REACH-2 trial (NCT02435433). These slides can be retrieved under Electronic Supplementary Material.

A microsimulation of the cost-effectiveness of maraviroc for antiretroviral treatment-experienced HIV-infected individuals.

PURPOSE: Maraviroc (MVC) is the first approved CCR5 antagonist. The aim of this study was to explore the cost-effectiveness of MVC in treatment-experienced or treatment-resistant HIV-infected adults. METHODS: The validated HIV microsimulation model ARAMIS was used to predict clinical and economic outcomes of treating patients with optimized background therapy (OBT) alone, as compared to a strategy of testing for the patient's viral tropism and treating with OBT with or without (+/-) MVC in a cohort corresponding to the MOTIVATE screening cohort. RESULTS: Compared to treatment with OBT alone, a treatment strategy of OBT +/- MVC (twice daily) according to tropism test result was predicted to increase CD4+ cell count after 5 years (from mean 249 to 360 cells/microL), undiscounted life expectancy (7.6 to 8.9 years), and quality-adjusted life years (QALYs; from 4.99 to 5.71) for an additional $40,500, giving an incremental cost-effectiveness ratio of $56,400 per QALY gained. The result was relatively insensitive to alternative clinical and cost assumptions within reasonable ranges, but for individuals with HIV susceptible to only two or fewer components of OBT, the ICER decreased to $52,000 per QALY gained. CONCLUSION: MVC is cost-effective, especially among individuals with few remaining options for active antiretroviral therapy.

Comparative Efficacy of Cabozantinib and Regorafenib for Advanced Hepatocellular Carcinoma.

BACKGROUND: No trials have compared cabozantinib and regorafenib for the second-line treatment of advanced hepatocellular carcinoma (HCC). OBJECTIVES: Conduct a matching-adjusted indirect comparison (MAIC) of the efficacy and safety of second-line cabozantinib and regorafenib in patients with advanced HCC and disease progression after prior sorafenib. METHODS: The CELESTIAL and RESORCE trials were used for indirect comparison of second-line cabozantinib and regorafenib in advanced HCC. Population-level data were available for RESORCE, individual patient data (IPD) for CELESTIAL. To align with RESORCE, the CELESTIAL population was limited to patients who received first-line sorafenib only. To minimize potential effect-modifying population differences, the CELESTIAL IPD were weighted to balance the distribution of clinically relevant baseline characteristics with those of RESORCE. Overall survival (OS) and progression-free survival (PFS) were evaluated for the matching-adjusted second-line CELESTIAL population and compared with those for RESORCE using weighted Kaplan-Meier curves and parametric modeling. Rates of grade 3/4 treatment-emergent adverse events (TEAEs) affecting > 5% of patients in any study arm were compared. RESULTS: In the matching-adjusted second-line populations (CELESTIAL, effective sample size = 266; RESORCE, n = 573), median (95% confidence interval) OS was similar for cabozantinib and regorafenib (11.4 [8.9-17.0] versus 10.6 [9.1-12.1] months; p = 0.3474, log-rank test). Median PFS was longer for cabozantinib than regorafenib (5.6 [4.9-7.3] versus 3.1 [2.8-4.2] months; p = 0.0005, log-rank test). There was a trend for lower rates of some grade 3/4 TEAEs with regorafenib than with cabozantinib, which may reflect the exclusion of sorafenib-intolerant patients from RESORCE but not from CELESTIAL, a difference that the MAIC methods could not remove. Only diarrhea rates were statistically significantly lower for regorafenib (p ≤ 0.001). CONCLUSIONS: Cabozantinib may achieve similar OS and prolonged PFS compared with regorafenib in patients with progressive advanced HCC after prior sorafenib.

Cabozantinib and regorafenib are treatments approved for some patients with advanced hepatocellular carcinoma (HCC), a type of liver cancer, after disease progression despite prior sorafenib treatment. Cabozantinib, regorafenib and sorafenib are tyrosine kinase inhibitors (TKIs), meaning that they slow cancer progression by targeting specific ways that tumors grow. Cabozantinib and regorafenib offer benefits to patients compared with placebo (i.e., no treatment) for those who have progressed despite sorafenib treatment. No clinical studies have compared cabozantinib and regorafenib directly. This study compared the efficacy and safety of cabozantinib and regorafenib using data from trials of each drug versus placebo: CELESTIAL for cabozantinib and RESORCE for regorafenib. These two trials were similar­both involved patients with progressive advanced HCC who had received previous cancer treatment. There were some important differences, but these were minimized using statistical methods (matching and adjustments/"weighting") allowing outcomes to be meaningfully compared. One difference that could not be removed by the statistical methods was that patients who were intolerant to prior sorafenib were excluded from RESORCE but were eligible for the CELESTIAL trial. In the otherwise matched populations, treatment with cabozantinib was associated with similar overall survival and significantly longer progression-free survival than regorafenib. Rates of diarrhea were significantly lower for regorafenib than cabozantinib, suggesting that regorafenib may be better tolerated, but this may reflect the exclusion of sorafenib-intolerant patients from RESORCE. These findings cannot replace a head-to-head study, but may help in guiding decision-making between cabozantinib and regorafenib in patients with progressive advanced HCC after soraftenib treatment.

Association of urological symptoms and chronic illness in men and women: contributions of symptom severity and duration--results from the BACH Survey.

PURPOSE: We investigated the association between lower urinary tract symptoms and chronic illness, such as heart disease, diabetes, hypertension and depression, in men and women. In addition, we determined whether a dose-response relationship exists in the association between the severity and duration of urological symptoms and major chronic illnesses. MATERIALS AND METHODS: The Boston Area Community Health Survey used a multistage stratified design to recruit a random sample of 5,503 adults who were 30 to 79 years old. Urological symptoms in the American Urological Association symptom index were included in analysis. RESULTS: Statistically significant associations that were consistent by gender were observed between depression and all urological symptoms. Nocturia of any degree of severity or duration was associated with heart disease in men and with diabetes in women. In men a dose-response relationship was observed for the association of symptom severity and/or the duration of urinary intermittency and frequency with heart disease, and for the association of urinary urgency with diabetes. In women a history of heart disease was associated with a weak stream and straining, while a history of hypertension was associated with urgency and a weak stream. CONCLUSIONS: Results indicate a dose-response relationship in the association of the severity and duration of urological symptoms with major chronic illnesses. An association between urinary symptoms and depression was observed in men and women. In contrast, the association between lower urinary tract symptoms and heart disease, diabetes or hypertension varied by gender, suggesting different mechanisms of association in men and women.

Association of lower urinary tract symptoms and the metabolic syndrome: results from the Boston Area Community Health Survey.

PURPOSE: In this study we investigated the relationship between lower urinary tract symptoms as defined by the American Urological Association symptom index and the metabolic syndrome, and determined the relationship between individual symptoms comprising the American Urological Association symptom index and the metabolic syndrome. MATERIALS AND METHODS: The Boston Area Community Health Survey used a 2-stage cluster design to recruit a random sample of 2,301 men 30 to 79 years old. Analyses were conducted on 1,899 men who provided blood samples. Urological symptoms comprising the American Urological Association symptom index were included in the analysis. The metabolic syndrome was defined using a modification of the Adult Treatment Panel III guidelines. The association between lower urinary tract symptoms and the metabolic syndrome was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models. RESULTS: Increased odds of the metabolic syndrome were observed in men with mild to severe symptoms (American Urological Association symptom index 2 to 35) compared to those with an American Urological Association symptom index score of 0 or 1 (multivariate OR 1.68, 95% CI 1.21-2.35). A statistically significant association was observed between the metabolic syndrome and a voiding symptom score of 5 or greater (multivariate adjusted OR 1.73, 95% CI 1.06-2.80) but not for a storage symptom score of 4 or greater (multivariate adjusted OR 0.94, 95% CI 0.66-1.33). Increased odds of the metabolic syndrome were observed even with mild symptoms, primarily for incomplete emptying, intermittency and nocturia. These associations were observed primarily in younger men (younger than 60 years) and were null in older men (60 years old or older). CONCLUSIONS: The observed association between urological symptoms and the metabolic syndrome provides further evidence of common underlying factors between lower urinary tract symptoms and chronic conditions outside the urinary tract.

Lower urinary tract symptoms and sexual health: the role of gender, lifestyle and medical comorbidities.

OBJECTIVE: To investigate the association between urological symptoms and self-reported measures of sexual activity, desire and function in large representative samples of men and women in the Boston Area Community Health (BACH) survey. SUBJECTS AND METHODS: The BACH survey is a racially and ethnically diverse random sample of 5503 community-dwelling residents aged 30-79 years, of Boston, MA, USA. Urological symptoms and sexual function were assessed in men and women at baseline using validated self-report measures, i.e. the International Prostate Symptom Score (IPSS), International Index of Erectile Function, and Female Sexual Function Index. Bivariate and multivariate analyses were conducted to assess the degree of association of sexual function measures with LUTS and other common urological problems in men and women in the BACH sample, controlling for the effects of age, medical comorbidities, and lifestyle factors. RESULTS: Urological symptoms were associated with a significant decrease in sexual activity and function in both men and women. Women were more likely to report low sexual desire than men. Low sexual desire was associated with depression, nocturia and prostatitis in men. Erectile dysfunction in men was significantly associated with LUTS, nocturia and prostatitis in bivariate associations, and with prostatitis in multivariate analyses, controlling for the effects of diabetes and other comorbidities. In the multivariate analysis in women, sexual dysfunction was primarily associated with depression and inversely with alcohol use. CONCLUSION: Sexual activity and function were diminished in both men and women with urological symptoms, although women reported more sexual problems overall than men, and the profile of risk factors and comorbidities was different across genders.

Urological symptom clusters and health-related quality-of-life: results from the Boston Area Community Health Survey.

OBJECTIVE To determine whether urological symptom clusters, as identified in previous studies, were associated with health-related quality-of-life (HRQoL) and use of healthcare. SUBJECTS AND METHODS The Boston Area Community Health Survey is a population-based epidemiological study of 2301 male and 3201 female residents of Boston, MA, USA, aged 30-79 years. Baseline data collected from 2002 to 2005 were used in this analysis. Data on 14 urological symptoms were used for the cluster analysis, and five derived symptom clusters among men and four among women were used in multivariate linear regression models (adjusted for age group, race/ethnicity, and comorbidity) to determine their association with physical (PCS-12) and mental health component scores (MCS-12) calculated from the Medical Outcomes Study 12-item Short Form Survey. RESULTS For both men and women, being in the most symptomatic cluster was associated with decrements in the PCS-12 score (men, cluster 5, -10.42; women, cluster 4, -9.80; both P < 0.001) and the MCS-12 score (men, cluster 5, -9.35; women, cluster 4, -6.24; both P < 0.001) compared with the asymptomatic groups. Both men and women in these most symptomatic clusters appeared to have adequate access to healthcare. CONCLUSION For men and women, those with the most urological symptoms reported poorer HRQoL in two domains after adjusting for age and comorbidity, and despite adequate access to care.

Implications of recent epidemiology studies for the clinical management of lower urinary tract symptoms.

Lower urinary tract symptoms (LUTS) include storage, voiding, and postmicturition symptoms, and occur commonly in both men and women. Findings from two recent epidemiological studies, the Epidemiology of LUTS study and the Boston Area Community Health survey, further extend the understanding of the prevalence of individual LUTS, the overlap of LUTS in men and women, the associations of LUTS with other comorbid conditions, the impact of LUTS on health-related quality of life (HRQL), and the relationships between frequency and bother of LUTS and treatment-seeking behaviour. Examining the clinical implications of these findings might provide directions to physicians for managing their patients with LUTS. For example, common findings of separate patient groups spanning a spectrum from those with typically one urinary symptom of mild to moderate severity to those with multiple more severe LUTS and frequent comorbidities might further encourage the diagnosis and treatment of comorbid conditions as a standard part of the management of patients with LUTS. Likewise, understanding that the impact of LUTS on HRQL and the degree of bother, rather than the frequency of LUTS, are significant drivers for treatment seeking might aid in assisting patients to make decisions about treatment.

Beyond the cluster: methodological and clinical implications in the Boston Area Community Health survey and EPIC studies.

OBJECTIVE: To test the replicability and robustness of findings about urological symptoms in men and women, classified using an objective statistical method, cluster analysis, by planned sensitivity analyses conducted within and across two large, epidemiological studies of lower urinary tract symptoms. METHODS: Sensitivity analyses were used to assess the effects of: (i) the number of urological symptoms included in the cluster analysis; (ii) the use of ordinal vs dichotomous scaling of responses; (iii) the type of cluster analysis used (hierarchical vs non-hierarchical; random vs nonrandom seeds); and (iv) the distance metric (median difference vs root mean square) of the resulting clusters. These sensitivity analyses were conducted independently in each of the two studies, with results systematically compared using Cramer's V statistic. Contingency tables were also used to assess the frequency of transitions or change in classification from one method to another. RESULTS: There were marked similarities in the cluster profiles in men and women across the two studies. For both men and women, the largest clusters consisted of low-frequency, single-symptom profiles, with urinary frequency and urgency symptoms reported by both genders. There was a multiple, mixed and highly symptomatic cluster profile in both genders in the Boston Area Community Health (BACH) and EPIC studies. The sensitivity analyses showed stability across both BACH and EPIC studies, and varying cluster methods and solutions (Cramer's V, 0.37-0.93). CONCLUSION: Sensitivity analyses show that cluster profiles are quite robust from EPIC to BACH, and that gender profiles within studies are relatively consistent across the methods and variables examined. Further studies are needed to investigate the mechanisms of action and clinical management implications of these findings.

Symptoms and Functional Limitations in the First Year Following a Myocardial Infarction: A Qualitative Study.

BACKGROUND AND OBJECTIVES: This qualitative interview study was designed to highlight the symptoms and functional limitations experienced by patients in the year following a myocardial infarction (MI). This information can support the use or development of patient-reported outcome (PRO) instruments in the post-MI population. METHODS: Individual face-to-face interviews were conducted with 38 participants who had experienced an MI (with or without ST segment elevation) within the past month to <6 months (n = 17), or 6 months to ≤12 months (n = 21). Using content and thematic analysis, patient reports of symptoms and functional limitations were coded and then grouped into categories. The specific content and frequency of the symptom and functional limitation reports were summarized. RESULTS: Nearly half of all symptom expressions were related to fatigue. Within this fatigue category, patients reported experiencing general tiredness, as well as a loss of physical energy, mental energy, and/or motivation. Chest pain and discomfort, sleep disruption, and shortness of breath were also frequently reported. Additionally, patients reported emotional effects, including worry and depression, as well as a negative impact on relationships and social activities. CONCLUSIONS: Patients reported a wide variety of symptoms and functional limitations after an MI. Fatigue was the most commonly reported symptom and included several specific dimensions related to tiredness. Consideration of these concepts associated with the patient's experience following an MI may yield novel endpoints for use in clinical trials and better therapies.

Clinical outcomes, health resource use, and cost in patients with early versus late dual or triple anti-platelet treatment for acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) guidelines recommend early dual anti-platelet therapy (thienopyridines + acetylsalicylic acid [aspirin]). However, triple therapy (thienopyridines + aspirin + glycoprotein IIb/IIIa receptor inhibitors [GRIs]) has shown benefit in clinical trials. OBJECTIVE: This study assessed real-world ACS treatment patterns and outcomes in the acute care setting. STUDY DESIGN: A retrospective analysis of patients admitted to hospital with ACS (index event) from January 2007 to December 2009 was conducted (Thomson's MarketScan Hospital Drug Database). PATIENTS: Eligible patients were ≥18 years of age, of either sex, and had primary admission and discharge diagnoses of ACS. OUTCOME MEASURES: Cohorts were defined by anti-platelet treatment and then by the timing of treatment initiation (early initiation: within ≤2 days of admission; late initiation: ≥2 days post-admission). Patient characteristics, clinical outcomes, resource utilization, and costs were assessed using descriptive statistics. RESULTS: A total of 249,907 eligible patients were placed into four treatment cohorts (aspirin assumed for all patients): aspirin only; clopidogrel only (dual therapy); GRI only (dual therapy); and clopidogrel + GRI (triple therapy). Patients in the 'clopidogrel-only' cohort were more likely to be older, female, and have more co-morbidities than those in other cohorts; stroke (6.2 %) and re-hospitalization (15.4 %) rates were higher than in the 'GRI-only' and 'triple therapy' cohorts. The GRI-only cohort had higher major bleeding rates (3.3 %), mortality (7.6 %), and costs ($US21,975 [year 2010 values]) than the clopidogrel-only and triple-therapy cohorts. Late initiation cohorts were more likely to be older, female, and have more co-morbidities than early initiation cohorts. Major bleeding was more likely with GRI-only patients (regardless of initiation timing) than with other cohorts. Late-treated clopidogrel-only patients had higher rates of stroke (6.9 %), ACS-related re-admissions (6.1 %), and all-cause re-admissions (15.9 %) than other cohorts. Late treatment was associated with longer length of stay and significantly higher costs. CONCLUSIONS: Real-world anti-platelet treatment patterns are consistent with ACS guidelines recommending early initiation and selective GRI use. In contrast to recommendations, some outcomes were improved with triple therapy compared with dual therapy.

Association of C-reactive protein and lower urinary tract symptoms in men and women: results from Boston Area Community Health survey.

OBJECTIVES: To determine whether an association exists between C-reactive protein (CRP) levels and lower urinary tract symptoms (LUTS) as assessed by the American Urological Association Symptom Index (AUA-SI) among both men and women, and to determine the association of CRP levels with the individual urologic symptoms comprising the AUA-SI among both men and women. METHODS: The Boston Area Community Health survey used a multistage stratified design to recruit a random sample of 5502 adults aged 30-79 years. Blood samples were obtained from 3752 participants. The analyses were conducted on 1898 men and 1854 women with complete data on CRP levels. Overall LUTS was defined as an AUA-SI of >or=8 (moderate to severe LUTS). The urologic symptoms comprising the AUA-SI were included in the analysis as reports of fairly often to almost always vs non/rarely/a few times. RESULTS: A statistically significant association was observed between the CRP levels and overall LUTS among both men and women. The pattern of associations between the individual symptoms and CRP levels varied by sex. Nocturia and straining were associated with greater CRP levels among men, and incomplete emptying and weak stream were associated with greater CRP levels among women. CONCLUSIONS: The results of this study have demonstrated an association between CRP levels and LUTS in both men and women. The dose-response relationship between increased CRP levels and an increased odds of LUTS supports the hypothesized role of inflammatory processes in the etiology of LUTS.