Observational Cohort Database Research Articles

Long-Term Safety of Roflumilast in Patients with Chronic Obstructive Pulmonary Disease, a Multinational Observational Database Cohort Study.

This study evaluated the long-term safety of roflumilast in patients with chronic obstructive pulmonary disease or chronic bronchitis using electronic healthcare databases from Germany, Norway, Sweden, and the United States (US). The study population consisted of patients aged ≥40 years who had been exposed to roflumilast and a matched cohort unexposed to roflumilast. The matching was based on sex, age, calendar year of cohort entry date (2010-2011, 2012, or 2013), and a propensity score that included variables such as demographics, markers of chronic obstructive pulmonary disease (COPD) severity and morbidity, and comorbidities. In comparison to the unexposed matched cohort (never use), three exposure definitions were used for the exposed matched cohort: ever use, use status (current, recent, past use), and cumulative duration of use. The main outcome was 5-year all-cause mortality. Cox regression models were used to estimate crude and adjusted hazard ratios (HRs) and 95% confidence intervals (CI). 112,541 unexposed and 23,239 exposed patients across countries were included. Some variables remained unbalanced after matching, indicating higher COPD disease severity among the exposed patients. Adjusted HRs of 5-year all-cause mortality for "ever use" of roflumilast, compared to "never use", were 1.12 (95% CI, 1.08-1.17) in Germany, 1.00 (95% CI, 0.92-1.08) in Norway, 0.98 (95% CI, 0.92-1.04) in Sweden, and 1.16 (95% CI, 1.12-1.20) in the US. Compared to never users, there was a decrease in 5-year mortality risk observed among "current users" in Germany (HR: 0.93, 95% CI: 0.88-0.98), Norway (HR: 0.77, 95% CI: 0.67-0.87), and Sweden (HR: 0.80, 95% CI: 0.73-0.88). There was no observed increase in 5-year mortality risk with the use of roflumilast in Sweden or Norway. A small increase in 5-year mortality risk was observed in Germany and the US in the ever versus never comparison, likely due to residual confounding by indication.

Sleep Characteristics in Pediatric Anti-N-methyl-d-aspartate (NMDA) Receptor Encephalitis: A Retrospective Cohort Study.

Background: Rates of sleep problems in children with anti-N-methyl-d-aspartate (NMDA) receptor encephalitis are unknown. Methods: We used a retrospective observational cohort database of children with a diagnosis of NMDA receptor encephalitis at a single freestanding institution. One-year outcomes were assessed with the pediatric modified Rankin Score (mRS), with 0 to 2 as good and 3 or greater as poor outcome. Results: Ninety-five percent (39/41) of children with NMDA receptor encephalitis had sleep dysfunction at onset; 34% (11/32) reported sleep problems at 1 year. Sleep problems at onset and propofol use were not associated with poor outcomes at 1 year. Poor sleep at 1 year correlated with mRS scores (range 2-5) at 1 year. Discussion: High rates of sleep dysfunction occur in children with NMDA receptor encephalitis. Persistent sleep problems at 1 year may correlate with outcomes as assessed by mRS at 1 year. Further studies comparing the relationship of poor sleep with outcomes in NMDA receptor encephalitis are needed.

Cluster analysis categorizes five phenotypes of pulmonary tuberculosis

Tuberculosis (TB) has a heterogeneous phenotype, which makes it challenging to diagnose. Our study aimed to identify TB phenotypes through cluster analysis and compare their initial symptomatic, microbiological and radiographic characteristics. We systemically collected data of notified TB patients notified in Korea and constructed a prospective, observational cohort database. Cluster analysis was performed using K-means clustering, and the variables to be included were determined by correlation network. A total of 4,370 subjects with pulmonary TB were enrolled in the study. Based on the correlation network, age and body mass index (BMI) were selected for the cluster analysis. Five clusters were identified and characterised as follows: (1) middle-aged overweight male dominance, (2) young-aged relatively female dominance without comorbidities, (3) middle-aged underweight male dominance, (4) overweight elderly with comorbidities and (5) underweight elderly with comorbidities. All clusters had distinct demographic and symptomatic characteristics. Initial microbiologic burdens and radiographic features also varied, including the presence of cavities and bilateral infiltration, which reflect TB-related severity. Cluster analysis of age and BMI identified five phenotypes of pulmonary TB with significant differences at initial clinical presentations. Further studies are necessary to validate our results and to assess their clinical implications.

Impact of subcallosal artery origin and A1 asymmetry on surgical outcomes of anterior communicating artery aneurysms.

Surgical clipping of anterior communicating artery (ACoA) aneurysms remains challenging due to their complex anatomy. Anatomical risk factors for ACoA aneurysm surgery require further elucidation. The aim of this study is to investigate whether proximity of the midline perforating artery, subcallosal artery (SubCA), and associated anomaly of the ACoA complex affect functional outcomes of ACoA aneurysm surgery. A total of 92 patients with both unruptured and ruptured ACoA aneurysms, who underwent surgical clipping, were retrospectively analyzed from a multicenter, observational cohort database. Association of ACoA anatomy with SubCA origin at the aneurysmal neck under microsurgical observation was analyzed in the interhemispheric approach subgroup (n = 56). Then, we evaluated whether anatomical factors associated with SubCA neck origin affected surgical outcomes in the entire cohort (both interhemispheric and pterional approaches, n = 92). In the interhemispheric approach cohort, combination of A1 asymmetry and aneurysmal size ≥ 5.0mm was stratified to have the highest probability of the SubCA neck origin by a decision tree analysis. Then, among the entire cohort using either interhemispheric or pterional approach, combination of A1 asymmetry and aneurysmal size ≥ 5.0mm was significantly associated with poor functional outcomes by multivariable logistic regression analysis (OR 6.76; 95% CI 1.19-38.5; p = 0.03) as compared with A1 symmetry group in the acute subarachnoid hemorrhage settings. Combination of A1 asymmetry and larger aneurysmal size was significantly associated with SubCA aneurysmal neck origin and poor functional outcomes in ACoA aneurysm surgery. Interhemispheric approach may be proposed to provide a wider and unobstructed view of SubCA for ACoA aneurysms with this high-risk anatomical variant.

COPD Exacerbation History and Impact on Future Exacerbations - 8-Year Retrospective Observational Database Cohort Study from Germany.

BackgroundRecent studies evaluating the predictive value of different variables on future exacerbations suggest exacerbation history as the strongest predictor. We examined the effect of exacerbation history on subsequent events in a large sample population with over 250,000 COPD patients using up to 8 years of longitudinal healthcare data from Germany.MethodsPatients 40 years or older with any COPD diagnosis in primary or secondary care were included from 2011 to 2017 (index period) from healthcare insurance claims (Germany; WIG2 research database), with 12 months before index date as baseline and at least 12-month follow-up. Exacerbations during baseline were defined as moderate (treatment with oral corticosteroids or antibiotics, J01AA, J01CA) or severe (emergency visit or hospitalization).ResultsPatients without (category A), with one moderate (category B), or with either one severe or several baseline exacerbations (category C) experienced an average of 0.9 (CI 0.9–0.9), 1.9 (CI 1.9–1.9), and 6.3 (CI 6.1–6.3) exacerbations during the first 3 years of follow-up, respectively. By 8 years, 87.0% (CI 86.6–87.4), 70.5% (CI 69.9–71.0) and 49.1% (CI 48.9–49.3) of category C, B and A patients had experienced a subsequent exacerbation.ConclusionBaseline exacerbations increased the likelihood of, and reduced time to subsequent exacerbations. Even patients without baseline exacerbations experienced exacerbations within three years, emphasizing the importance of adequate treatment in patients with less severe disease presentation as well.

Roxadustat in treating anemia in dialysis patients (ROAD): protocol and rationale of a multicenter prospective observational cohort study

BackgroundRoxadustat has been shown effective in treating patients with anemia due to chronic kidney disease. However, its long-term effect on clinical outcomes and socioeconomic burden and safety remains unclear.Methods/DesignThis is a multicenter, prospective, longitudinal observational cohort study assessing if Roxadustat improves prognosis in dialysis patients. Primary outcomes will be major adverse cardiovascular events (MACE), defined as composites of cardiovascular death, myocardial infarction, cerebral infarction, hospitalization because of heart failure; all-cause mortality, and annual economic costs in two years. The data will be collected via Research electronic data capture (REDCap) based database as well as software-based dialysis registry of Sichuan province. The primary outcomes for the ROAD study participants will be compared with those in the dialysis registry cohort. Data at baseline and study follow up will also be compared to assess the association between Roxadustat and long-term clinical outcomes.DiscussionThe main objective of this study is to the assess long-term association of Roxadustat on MACE, all-cause mortality, socio-economic burden, safety in dialysis patients, which will provide guidance for designing further large randomized controlled trials to investigate this clinic question.Study registrationThe study has been registered in Chinese Clinical Trials Registry (ROAD, ROxadustat in treating Anemia in Dialysis patients, registration number ChiCTR1900025765) and provincial observational cohort database (Renal disEAse observational CoHort database, REACH, ChiCTR1900024926), registered 07 September 2019, http://www.chictr.org.cn.

Statins for atherosclerotic cardiovascular disease prevention in people living with HIV in Thailand: a cost-effectiveness analysis.

IntroductionPeople living with HIV (PLHIV) have an elevated risk of atherosclerotic cardiovascular disease (CVD) compared to their HIV‐negative peers. Expanding statin use may help alleviate this burden. However, the choice of statin in the context of antiretroviral therapy is challenging. Pravastatin and pitavastatin improve cholesterol levels in PLHIV without interacting substantially with antiretroviral therapy. They are also more expensive than most statins. We evaluated the cost‐effectiveness of pravastatin and pitavastatin for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy.MethodsWe developed a discrete‐state microsimulation model that randomly selected (with replacement) individuals from the TREAT Asia HIV Observational Database cohort who were aged 40 to 75 years, receiving antiretroviral therapy in Thailand, and not using lipid‐lowering therapy. The model simulated each individual’s probability of experiencing CVD. We evaluated: (1) treating no one with statins; (2) treating everyone with pravastatin 20mg/day (drug cost 7568 Thai Baht ($US243)/year) and (3) treating everyone with pitavastatin 2 mg/day (drug cost 8182 Baht ($US263)/year). Direct medical costs and quality‐adjusted life‐years (QALYs) were assigned in annual cycles over a 20‐year time horizon and discounted at 3% per year. We assumed the Thai healthcare sector perspective.ResultsPravastatin was estimated to be less effective and less cost‐effective than pitavastatin and was therefore dominated (extended) by pitavastatin. Patients receiving pitavastatin accumulated 0.042 additional QALYs compared with those not using a statin, at an extra cost of 96,442 Baht ($US3095), giving an incremental cost‐effectiveness ratio of 2,300,000 Baht ($US73,812)/QALY gained. These findings were sensitive to statin costs and statin efficacy, pill burden, and targeting of PLHIV based on CVD risk. At a willingness‐to‐pay threshold of 160,000 Baht ($US5135)/QALY gained, we estimated that pravastatin would become cost‐effective at an annual cost of 415 Baht ($US13.30)/year and pitavastatin would become cost‐effective at an annual cost of 600 Baht ($US19.30)/year.ConclusionsNeither pravastatin nor pitavastatin were projected to be cost‐effective for the primary prevention of CVD among PLHIV in Thailand who are not currently using lipid‐lowering therapy. We do not recommend expanding current use of these drugs among PLHIV in Thailand without substantial price reduction.

Impact of Upper Limb Function and Employment Status on Return to Work of Blue-Collar Workers after Stroke

Background and PurposeReturn to work (RTW) after stroke is the ultimate goal of the working population to achieve economic independence and well-being. Previous studies have reported lower RTW rates of blue-collar workers versus white-collar workers. Thus, investigating predictive factors for RTW of blue-collar workers is meaningful to improve RTW after stroke. Here, we investigate the physical, cognitive, and social factors associated with the RTW of blue-collar workers after stroke. MethodsPoststroke rehabilitation data for 71 patients aged 15-64 years who had been active blue-collar workers at stroke onset were analyzed from a single-center observational cohort database. Baseline characteristics, social background factors, and quantitative assessments of the upper limb, lower limb, and cognitive functions at discharge were analyzed to identify any association with RTW. Receiver operating characteristic curve analysis was performed to determine the optimal cutoff value of continuous valuables with significant associations. ResultsFunctional upper limb represented by an increasing Simple Test for Evaluating hand Function (STEF) score was independently associated with RTW of blue-collar workers by multivariable logistic regression analysis (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.14; p = .017). Correlation with self-employment status was also significant compared to that with employee status (OR, 185; 95% CI, 1.05-32400; p = .048). The cutoff value of the 100-point scale STEF to discriminate between RTW and non-RTW was 82. ConclusionsFunctional upper limb and self-employment status were independent predictors for the RTW of blue-collar workers after stroke.

The influence of age-associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV.

IntroductionMultiple comorbidities among HIV‐positive individuals may increase the potential for polypharmacy causing drug‐to‐drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age‐associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age‐associated comorbidities on therapeutic outcomes of cART in HIV‐positive adults in Asian countries.MethodsPatients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in‐line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure.ResultsThe incidence of virologic failure was 7.72/100 person‐years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age‐related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person‐years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities.ConclusionsIn our Asia regional cohort, age‐associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response.

Association of Perforator Infarction with Clinical Courses and Outcomes Following Surgical Clipping of Ruptured Anterior Communicating Artery Aneurysms.

Perforator infarction is a procedure-related complication of surgical clipping of ruptured anterior communicating artery (ACoA) aneurysms. Patients with perforator infarction may present with specific clinical features. The aim of this study was to elucidate incidence, risk factors, clinical course, and outcomes of perforator infarction following surgical clipping of ruptured ACoA aneurysms. Retrospective analysis was performed of 104 patients from a single-center, observational cohort database who underwent surgical clipping for ruptured ACoA aneurysm. Risk factors of perforator infarction were identified. Correlation of perforator infarction with clinical course during hospitalization was investigated, focusing on dysfunction of hypothalamus and cerebral limbic system. We also evaluated any associations between perforator infarction and poor outcomes. Perforator infarction was observed in 24 (23.1%) patients. Use of temporary clip (P= 0.019, χ2 test) and intraoperative rupture (P < 0.001, χ2 test) were significantly associated with perforator infarction. Patients with perforator infarction had increased likelihood of hyponatremia (odds ratio 6.41 [95% confidence interval 2.27-18.1], P < 0.001) and insufficient oral intake (odds ratio 6.53 [95% confidence interval 1.80-23.7], P= 0.004) in the subacute stage of subarachnoid hemorrhage by multivariate analyses. Perforator infarction was an independent risk factor of poor functional outcomes at 3 months (modified Rankin Scale score 3-6; odds ratio 5.29 [95% confidence interval 1.62-17.2], P= 0.006). Perforator infarction following surgical clipping of ruptured ACoA aneurysms caused region-specific complications, including hyponatremia and insufficient oral intake, and was associated with poor functional outcomes.

Abstract TP417: Plasma D-dimer Elevation Predicts Poor Functional Outcomes Through Systemic Complications After Aneurysmal Subarachnoid Hemorrhage

Introduction: Plasma D-dimer levels elevate during acute stage of aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor functional outcomes. However, the mechanism in which D-dimer elevation on admission affects functional outcomes remains unknown. Hypothesis: We hypothesize that D-dimer levels on admission are correlated with systemic complications rather than neurological complications, and therefore have an additive predictive value on conventional risk factors for poor functional outcomes. Methods: A total of 187 patients with aneurymal SAH were retrospectively analyzed from a single center, observational cohort database. Correlations of plasma D-dimer levels on admission with patients’ characteristics, initial presentation, neurological complications, and systemic complications were identified. We also evaluated additive value of D-dimer elevation on admission for poor functional outcomes by comparing predictive models with and without D-dimer. Result and Conclusions: D-dimer elevation on admission was associated with increasing age, women, and severity of SAH. Patients with higher D-dimer levels had increased likelihood of nosocomial infections (OR 1.22 [95% CI 1.07-1.39], p = 0.004), serum sodium disorders (OR 1.11 [95% CI 1.01-1.23], p = 0.033), and cardiopulmonary complications (OR 1.20 [95% CI 1.04-1.37], p = 0.01) by multivariable analysis. D-dimer elevation was an independent risk factor of poor functional outcomes (modified Rankin scale 3-6, OR 1.50 [95% CI 1.15-1.95], p = 0.003). A novel prediction model with D-dimer had significantly better discrimination ability for poor outcomes than conventional models without D-dimer, evaluated by C statistics, net reclassification improvement, and integrated discrimination improvement methods. These results suggest that elevated D-dimer levels on admission were independently correlated with systemic complications, and had an additive value for outcome prediction on conventional risk factors after aneurysmal SAH.

Plasma D-dimer may predict poor functional outcomes through systemic complications after aneurysmal subarachnoid hemorrhage.

OBJECTIVE Plasma D-dimer levels elevate during acute stages of aneurysmal subarachnoid hemorrhage (SAH) and are associated with poor functional outcomes. However, the mechanism in which D-dimer elevation on admission affects functional outcomes remains unknown. The aim of this study is to clarify whether D-dimer levels on admission are correlated with systemic complications after aneurysmal SAH, and to investigate their additive predictive value on conventional risk factors for poor functional outcomes. METHODS A total of 187 patients with aneurysmal SAH were retrospectively analyzed from a single-center, observational cohort database. Correlations of plasma D-dimer levels on admission with patient characteristics, initial presentation, neurological complications, and systemic complications were identified. The authors also evaluated the additive value of D-dimer elevation on admission for poor functional outcomes by comparing predictive models with and without D-dimer. RESULTS D-dimer elevation on admission was associated with increasing age, female sex, and severity of SAH. Patients with higher D-dimer levels had increased likelihood of nosocomial infections (OR 1.22 [95% CI 1.07-1.39], p = 0.004), serum sodium disorders (OR 1.11 [95% CI 1.01-1.23], p = 0.033), and cardiopulmonary complications (OR 1.20 [95% CI 1.04-1.37], p = 0.01) on multivariable analysis. D-dimer elevation was an independent risk factor of poor functional outcome (modified Rankin Scale Score 3-6, OR 1.50 [95% CI 1.15-1.95], p = 0.003). A novel prediction model with D-dimer had significantly better discrimination ability for poor outcomes than conventional models without D-dimer. CONCLUSIONS Elevated D-dimer levels on admission were independently correlated with systemic complication, and had an additive value for outcome prediction on conventional risk factors after aneurysmal SAH.

Risk of new onset autoimmune disease in 9- to 25-year-old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom

ABSTRACTTo assess the risk of autoimmune disease (AD) in 9–25 year-old women within 1 year after the first AS04-HPV-16/18vaccine dose, a retrospective, observational database cohort study was conducted using CPRD GOLD. From CPRD GOLD 4 cohorts (65,000 subjects each) were retrieved: 1 exposed female cohort (received ≥1 AS04-HPV-16/18 vaccine dose between Sep2008–Aug2010) and 3 unexposed cohorts: historical female (Sep2005–Aug2007), concurrent male, and historical male. Co-primary endpoints were confirmed neuroinflammatory/ophthalmic AD and other AD, secondary endpoints were confirmed individual AD. Risk of new onset of AD was compared between cohorts (reference: historical cohort) using Poisson regression. The main analysis using confirmed cases showed no neuroinflammatory/ophthalmic AD cases in the female exposed cohort. Incidence rate ratio (IRR) (95% CI) of other AD was 1.41 (0.86 to 2.31) in female and 1.77 (0.94 to 3.35) in male cohorts when compared to the female and male historical cohort, respectively. Secondary endpoints were evaluated for diseases with >10 cases, which were Crohn's disease (IRR: 1.21 [0.37 to 3.95] for female and 4.22 [0.47 to 38.02] for male cohorts), autoimmune thyroiditis (IRR: 3.75 [1.25 to 11.31] for female and no confirmed cases for male cohorts) and type 1 diabetes (IRR: 0.30 [0.11 to 0.83] for female and 2.46 [1.08 to 5.60] for male cohorts). Analysis using confirmed and non-confirmed cases showed similar results, except for autoimmune thyroiditis in females, IRR: 1.45 (0.79 to 2.64). There was no evidence of an increased risk of AD in women aged 9 to 25 years after AS04-HPV-16/18 vaccination.

Incidence of syphilis seroconversion among HIV-infected persons in Asia: results from the TREAT Asia HIV Observational Database.

IntroductionOutbreaks of syphilis have been described among HIV-infected men who have sex with men (MSM) in Western communities, whereas reports in Asian countries are limited. We aimed to characterize the incidence and temporal trends of syphilis among HIV-infected MSM compared with HIV-infected non-MSM in Asian countries.MethodsPatients enrolled in the TREAT Asia HIV Observational Database cohort and with a negative non-treponemal test since enrolment were analyzed. Incidence of syphilis seroconversion, defined as a positive non-treponemal test after previously testing negative, was evaluated among patients at sites performing non-treponemal tests at least annually. Factors associated with syphilis seroconversion were investigated at sites doing non-treponemal testing in all new patients and subsequently testing routinely or when patients were suspected of having syphilis.ResultsWe included 1010 patients from five sites that performed non-treponemal tests in all new patients; those included had negative non-treponemal test results during enrolment and subsequent follow-ups. Among them, 657 patients were from three sites conducting regular non-treponemal testing. The incidence of syphilis seroconversion was 5.38/100 person-years (PY). Incidence was higher in MSM than non-MSM (7.64/100 PY vs. 2.44/100 PY, p<0.001). Among MSM, the incidence rate ratio (IRR) for every additional year from 2009 was 1.19 (p=0.051). MSM status (IRR 3.48, 95% confidence interval (CI) 1.88–6.47), past syphilis diagnosis (IRR 5.15, 95% CI 3.69–7.17) and younger age (IRR 0.84 for every additional 10 years, 95% CI 0.706–0.997) were significantly associated with syphilis seroconversion.ConclusionsWe observed a higher incidence of syphilis seroconversion among HIV-infected MSM and a trend to increasing annual incidence. Regular screening for syphilis and targeted interventions to limit transmission are needed in this population.

Impact of Aneurysm Projection on Intraoperative Complications During Surgical Clipping of Ruptured Posterior Communicating Artery Aneurysms.

Surgical clipping of ruptured posterior communicating artery (PCoA) aneurysms is a well-established procedure to date. However, preoperative factors associated with procedure-related risk require further elucidation. To investigate the impact of the direction of aneurysm projection on the incidence of procedure-related complications during surgical clipping of ruptured PCoA aneurysms. A total of 65 patients with ruptured PCoA aneurysms who underwent surgical clipping were retrospectively analyzed from a single-center, prospective, observational cohort database in this study. The aneurysms were categorized into lateral and posterior projection groups, depending on direction of the dome. Characteristics and operative findings of each projection group were identified. We also evaluated any correlation of aneurysm projection with the incidence of procedure-related complications. Patients with ruptured PCoA aneurysms with posterior projection more likely presented with good-admission-grade subarachnoid hemorrhage (P = .01, χ test) and were less to also have intracerebral hematoma (P = .01). These aneurysms were found to be associated with higher incidence of intraoperative rupture (P = .02), complex clipping with fenestrated clips (P = .02), and dense adherence to PCoA or its perforators (P = .04) by univariate analysis. Aneurysms with posterior projection were also correlated with procedure-related complications, including postoperative cerebral infarction or hematoma formation (odds ratio, 5.87; 95% confidence interval, 1.11-31.1; P = .04) by multivariable analysis. Ruptured PCoA aneurysms with posterior projection carried a higher risk of procedure-related complications of surgical clipping than those with lateral projection.

Treatment and disease outcomes of migrants from low- and middle-income countries in the Australian HIV Observational Database cohort

ABSTRACTPeople from culturally and linguistically diverse backgrounds, including low- and middle-income countries, account for a third of new HIV diagnoses in Australia and are a priority for HIV prevention and treatment programs. We describe the demographic and clinical characteristics of participants in the Australian HIV Observational Database (AHOD) and compare disease outcomes, progression to AIDS and treatment outcomes of those born in low- and middle-income countries, with those born in high-income countries and Australia. All participants enrolled in AHOD sites where country of birth is routinely collected were included in the study. Age, CD4 count, HIV viral load, antiretroviral therapy, hepatitis co-infection, all-cause mortality and AIDS illness were analysed. Of 2403 eligible participants, 77.3% were Australian born, 13.7% born in high-income countries and 9.0% born in middle- or low-income countries. Those born in Australia or high-income countries were more likely to be male (96%) than those from middle- or low-income countries (76%), p < .0001 and more likely to have acquired HIV via male to male sexual contact (77%; 79%) compared with those from middle- or low-income countries (50%), p < .0001. At enrolment, mean CD4 cell count was higher in Australian born (528 cells/µL) than both those born in high-income countries (468 cells/µL) and those born in middle- and low-income countries (451 cells/µL), p < .0001; whereas the mean HIV RNA level (log10 copies/mL) was similar in all three groups (4.44, 4.76 and 4.26, respectively), p = .19.There was no difference in adjusted incidence risk ratios for all-cause mortality and AIDS incidence in all three groups, p = .39. These findings reflect successful outcomes of people born in low- and middle-income countries once engaged in HIV care.

Opioid Medication Practices Observed in Chronic Pain Patients Presenting for All-Causes to Emergency Departments: Prevalence and Impact on Health Care Outcomes.

Chronic pain is a significant health problem that affects an estimated 100 million American adults (aged ≥ 18 years). Chronic pain affects more individuals than heart disease, stroke, diabetes, and cancer combined. Chronic pain sufferers cost up to $635 billion annually in medical treatment and lost productivity. Opioids are commonly used to treat chronic pain, but their metabolic interactions with concurrently prescribed medications for concomitant disease burdens can affect potency and efficacy of pain therapy. Additionally, misuse of short-acting opioids (SAOs) for chronic pain versus breakthrough pain can create gaps in pain relief. These potentially suboptimal prescribing practices may contribute to the high economic impact associated with chronic pain. To examine the prevalence of suboptimal opioid therapy and the associated health care costs resulting from these prescribing practices in real-world patients presenting for all-causes to the emergency department (ED). This retrospective observational database cohort analysis used the linked Premier-Optum database and included patients with ED visits from 2006 to 2010 having ≥ 60 days supply of opioids in the 75 days prior to the visit. Suboptimal prescribing practices were identified as patients with (a) drug-drug exposures (DDEs), defined as cytochrome P-450 (CYP-450)-metabolized opioids prescribed concurrently with CYP-450 inhibitors or inducers and/or (b) monotherapy with SAOs. Comorbid conditions and principal diagnoses were documented. Readmission rates to the ED and hospital within 72 hours as well as ≤ 30, ≤ 45, ≤ 60, and ≤ 90 days were computed. Total costs for health care were calculated, and reimbursement rates were normalized using 2011 Medicare severity diagnosis-related group (MS-DRG) and CPT-4 information. Nonparametric bootstrapping to adjust for patient comorbidities was applied to cost data. Of the 9,214 patients identified with chronic pain, potentially suboptimal medication practices prior to the index ED visit were found for 8,539 (92.6%) patients. These appeared to be corrected in 345 (4.0%) patients before leaving the ED. Of 675 (7.3%) patients without prior DDE or exclusive use of SAOs, 345 (51.1%) patients were discharged with one of these. Of the 8,352 patients who left the ED with DDE or exclusive use of SAOs, 1,525 (18.3%) left with a DDE without exclusive SAO use; 4,812 (57.6%) left with both DDE and exclusive SAO use; and 2,015 (24.1%) left with only exclusive SAO use. Only 862 (9.3%) patients from the entire cohort left the ED without DDE or exclusive SAO use. Patients identified with suboptimal opioid use were aged 50 ± 13.5 years and were predominantly female (64.0%). Hypertension (44.0%), fluid and electrolyte disorders (32.7%), chronic pulmonary disease (22.8%), depression (19.6%), diabetes without chronic complications (16.2%), and drug abuse (15.6%) were the most prevalent comorbid conditions identified. The most prevalent principal diagnoses involved symptoms and signs of ill-defined conditions (36.5%), injury and poisoning (18.2%), and diseases of the musculoskeletal system (13.2%). The majority of revisits to the ED and hospital admissions occurred within 72 hours (73.6%) of the index visit and within 30 days (70%), respectively. When adjusted total costs were compared for all patients whose opioid use included DDE versus those without, a significantly greater cost (P less than 0.05) was observed at every time period except ≤ 72 hours. Respective mean increases in costs were $581, $689, $773, and $1,275 at 30, 45, 60, and 90 days. Exclusive SAO use with or without DDE resulted in a significant increase (P less than 0.05) in mean costs at all times: $214 at 72 hours; $836 at 30 days; $1,023 at 45 days; $1,022 at 60 days; and $1,536 at 90 days. This study identified potentially suboptimal opioid prescribing practices in a real-world population presenting for all-causes to the ED. The observed rate of ED revisits and inpatient admissions in these patients was associated with increased health care costs. These findings suggest that the ED has the future potential to serve as an ideal setting to identify and correct such practices, thereby improving patient care and reducing resource use and beneficiary costs.

Intrasylvian hematoma caused by ruptured middle cerebral artery aneurysms predicts recovery from poor-grade subarachnoid hemorrhage.

Intrasylvian hematoma (ISH) is a subtype of intracranial hematoma caused by aneurysmal rupture and often presents with a poor initial neurological grade; it is not well studied. The aim of this study was to elucidate outcomes of aneurysmal subarachnoid hemorrhage (SAH) with ISH. Data for 97 patients with poor-grade SAH (World Federation of Neurosurgical Societies Grade IV or V) were retrospectively analyzed from a single-center, prospective, observational cohort database. Ultra-early surgical clipping, removal of hematoma, external decompression for brain swelling, and prevention of vasospasm by cisternal irrigation with milrinone were combined as an aggressive treatment. Characteristics and clinical courses of SAH with ISH were identified. The authors also evaluated any correlations between poor admission-grade SAH and ISH with good functional outcome. Patients with poor admission-grade SAH and with ISH were more likely to have initial cerebral edema (p < 0.001, Mann-Whitney U-test), which significantly resolved overtime (p < 0.001, Mann-Whitney U-test). These patients had a better chance of functional survival (modified Rankin Scale scores of 1-3; OR 5.75; 95% CI 1.36-24.3; p = 0.017) at 6 months after hospital discharge, after adjustment for potential confounders such as younger age and better initial neurological grade by multivariable analysis. ISH predicted good functional recovery from poor-grade aneurysmal SAH.

A clinical prediction tool for targeted pre-antiretroviral therapy creatinine testing applied to the TREAT Asia HIV observational database cohort.

A clinical prediction tool for targeted pre-antiretroviral therapy creatinine testing applied to the TREAT Asia HIV observational database cohort.

Drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors for rheumatoid arthritis in Japanese patients on low-dose methotrexate or without methotrexate

Objectives. The purpose of this study was to explore drug retention rates of second biologic agents after switching from tumor necrosis factor inhibitors (TNFi) in clinical practice in patients with rheumatoid arthritis (RA) on low-dose methotrexate (MTX) or without MTX.Methods. A total of 169 RA patients who had been withdrawn from first-course TNFi therapy and received a different TNFi or tocilizumab (TCZ) as a second biologic agent were selected from the Tsurumai Biologics Communication Registry, an observational cohort database. Retention rates of second biologic treatment were compared by the type of first TNFi and second biologic agents.Results. Eighty-six patients received first-course infliximab (IFX) or adalimumab (ADA) therapy, and 83 patients received first-course etanercept (ETN) therapy. The former group had a significantly higher retention rate (IFX, 81.1%; ADA, 83.3%) of the second biologic therapy compared to the latter (56.6%, p < 0.001, log-rank test). Drug retention rates of the second biologic agent after switching from IFX/ADA were significantly higher with ETN (90.0%) and TCZ (94.7%) than with ADA/IFX (59.3%). Drug retention rates of the second biologic agent after switching from ETN were significantly higher with TCZ (75.9%) than with ADA/IFX (46.3%). The differences were significant even after adjusting for baseline clinical variables using the Cox proportional hazards model.Conclusions. Drug retention rates of IFX and ADA after switching from the first TNFi were significantly lower compared to those of ETN and TCZ in patients on low-dose MTX or without MTX.